BioMed Research International: Nephrology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Oral Tori in Chronic Hemodialysis Patients Tue, 31 Mar 2015 13:15:12 +0000 Background. This study investigated the epidemiology of torus palatinus (TP) and torus mandibularis (TM) in hemodialysis patients and analyzed the influences of hyperparathyroidism on the formation of oral tori. Method. During 2013, 119 hemodialysis patients were recruited for dental examinations for this study. Results. The prevalence of oral tori in our sample group was high at 33.6% (40 of 119). The most common location of tori was TP (70.0%), followed by TM (20.0%), and then both TP and TM (10.0%). Of the 40 tori cases, most (67.5%) were <2 cm in size; moreover, the majority (52.5%) were flat in shape. In symmetry, most (70.0%) occurred in the midline, followed by bilateral sides (20.0%). Notably, the levels of intact parathyroid hormone did not differ in patients with or without tori (). Furthermore, patients with tori did not differ from patients without tori in inflammatory variables such as log high-sensitivity C-reactive protein () or nutritional variables such as albumin (). Finally, there were no differences between patients with and without tori in adequacy of dialysis (). Conclusions. Neither hyperparathyroidism nor inflammation malnutrition syndrome was found to contribute to the formation of oral tori in chronic hemodialysis patients. Further studies are warranted. Pei-Jung Chao, Huang-Yu Yang, Wen-Hung Huang, Cheng-Hao Weng, I-Kuan Wang, Aileen I. Tsai, and Tzung-Hai Yen Copyright © 2015 Pei-Jung Chao et al. All rights reserved. Long-Term Clinical Practice Experience with Cinacalcet for Treatment of Hypercalcemic Hyperparathyroidism after Kidney Transplantation Tue, 10 Mar 2015 11:03:41 +0000 Within this prospective, open-label, self-controlled study, we evaluated the long-term effects of the calcimimetic cinacalcet on calcium and phosphate homeostasis in 44 kidney transplant recipients (KTRs) with hypercalcemic hyperparathyroidism by comparing biochemical parameters of mineral metabolism between pre- and posttreatment periods. Results are described as mean differences (95% CIs) between pre- and posttreatment medians that summarize all repeated measurements of a parameter of interest between the date of initial hypercalcemia and cinacalcet initiation (median of 1.6 (IQR: 0.6–3.8) years) and up to four years after treatment start, respectively. Cinacalcet was initiated after 1.8 (0.8–4.7) years posttransplant and maintained for 6.2 (3.9–7.6) years. It significantly decreased total serum calcium (−0.30 (−0.34 to −0.26) mmol/L, ) and parathyroid hormone levels (−79 (−103 to −55) pg/mL, ). Serum levels of inorganic phosphate (Pi) and renal tubular reabsorption of phosphate to glomerular filtration rate (TmP/GFR) increased simultaneously (Pi: 0.19 (0.15–0.23) mmol/L, , TmP/GFR: 0.20 (0.16–0.23) mmol/L, ). In summary, cinacalcet effectively controlled hypercalcemic hyperparathyroidism in KTRs in the long-term and increased low Pi levels without causing hyperphosphatemia, pointing towards a novel indication for the use of cinacalcet in KTRs. Ursula Thiem, Alois Gessl, and Kyra Borchhardt Copyright © 2015 Ursula Thiem et al. All rights reserved. Bone Marrow Pathology Predicts Mortality in Chronic Hemodialysis Patients Tue, 24 Feb 2015 12:44:06 +0000 Introduction. A bone marrow biopsy is a useful procedure for the diagnosis and staging of various hematologic and systemic diseases. The objective of this study was to investigate whether the findings of bone marrow studies can predict mortality in chronic hemodialysis patients. Methods. Seventy-eight end-stage renal disease patients on maintenance hemodialysis underwent bone marrow biopsies between 2000 and 2011, with the most common indication being unexplained anemia followed by unexplained leukocytosis and leukopenia. Results. The survivors had a higher incidence of abnormal megakaryocyte distribution , band and segmented cells , and lymphoid cells than the nonsurvivors. The overall mortality rate was 38.5% (30/78), and the most common cause of mortality was sepsis (83.3%) followed by respiratory failure (10%). In multivariate Cox regression analysis, both decreased (OR 3.714, 95% CI 1.671–8.253, ) and absent (OR 9.751, 95% CI 2.030–45.115, ) megakaryocyte distribution (normal megakaryocyte distribution as the reference group), as well as myeloid/erythroid ratio (OR 1.054, CI 1.012–1.098, ), were predictive of mortality. Conclusion. The results of a bone marrow biopsy can be used to assess the pathology, and, in addition, myeloid/erythroid ratio and abnormal megakaryocyte distribution can predict mortality in chronic hemodialysis patients. Cheng-Hao Weng, Kuan-Ying Lu, Ching-Chih Hu, Wen-Hung Huang, I-Kwan Wang, and Tzung-Hai Yen Copyright © 2015 Cheng-Hao Weng et al. All rights reserved. Aortic Arch Calcification Predicts the Renal Function Progression in Patients with Stage 3 to 5 Chronic Kidney Disease Wed, 28 Jan 2015 06:15:36 +0000 Introduction. The presence of aortic arch calcification (AoAC) and cardiomegaly on chest radiography has been demonstrated as important risk factors for cardiovascular mortality in patients with chronic kidney disease (CKD). However, the interrelationship among AoAC, cardiomegaly, and renal function progression remains unclear. The aim of this study is to assess whether AoAC and cardiomegaly are independently associated with the renal function progression in patients with stages 3–5 CKD. Methods. We retrospectively determined AoAC and cardiomegaly by chest X-ray in 237 patients, followed up for at least three years without entering dialysis and classified into 4 groups according to the presence or absence of AoAC and cardiomegaly. The change in renal function was measured by the slope of estimated glomerular filtration rate (eGFR). Results. Of the 237 patients, the rate of eGFR decline was significantly higher in the group with coexistence of AoAC and cardiomegaly than any other groups. Baseline AoAC and proteinuria were independently associated with eGFR decline. AoAC were independently determined by age, eGFR slope, and cardiomegaly. Conclusions. The coexistence of AoAC and cardiomegaly is associated with faster eGFR decline. AoAC is an independent determinant of renal outcomes in patients with CKD stages 3–5. Lung-Chih Li, Yueh-Ting Lee, Yi-Wei Lee, Chia-An Chou, and Chien-Te Lee Copyright © 2015 Lung-Chih Li et al. All rights reserved. Solid Phase-Based Cross-Matching as Solution for Kidney Allograft Recipients Pretreated with Therapeutic Antibodies Thu, 15 Jan 2015 06:33:36 +0000 In order to select recipients without donor-specific anti-HLA antibodies, the complement-dependent cytotoxicity crossmatch (CDC-CM) was established as the standard procedure about 40 years ago. However, the interpretability of this functional assay strongly depends on the vitality of isolated donors’ lymphocytes. Since the application of therapeutic antibodies for the immunosuppressive regimen falsifies the outcome of the CDC-crossmatch as a result of these antibodies’ complement-activating capacity in the recipients’ sera, we looked for an alternative methodical approach. We here present 27 examples of AB0 blood group-incompatible living kidney allograft recipients who, due to their treatment with the humanized chimeric monoclonal anti-CD20 antibody Rituximab, did not present valid outcomes of CDC-based pretransplant cross-matching. Additionally, four cases of posttransplant cross-matching after living kidney allografting and consequent treatment with the therapeutic anti-CD25 antibody Basiliximab (Simulect) due to acute biopsy-proven rejection episodes are presented and compared regarding CDC- and ELISA-based crossmatch outcomes. In all cases, it became evident that the classical CDC-based crossmatch was completely unfeasible for the detection of donor-specific anti-HLA antibodies, whereas ELISA-based cross-matching not requiring vital cells was not artificially affected. We conclude that ELISA-based cross-matching is a valuable tool to methodically circumvent false positive CDC-based crossmatch results in the presence of therapeutically applied antibodies. Gerald Schlaf, Susanne Apel, Anja Wahle, and Wolfgang W. Altermann Copyright © 2015 Gerald Schlaf et al. All rights reserved. Intradialytic Hypotension and Cardiac Remodeling: A Vicious Cycle Wed, 14 Jan 2015 14:32:21 +0000 Hemodynamic instability during hemodialysis is a common but often underestimated issue in the nephrologist practice. Intradialytic hypotension, namely, a decrease of systolic or mean blood pressure to a certain level, prohibits the safe and smooth achievement of ultrafiltration and solute removal goal in chronic dialysis patients. Studies have elucidated the potential mechanisms involved in the development of Intradialytic hypotension, including excessive ultrafiltration and loss of compensatory mechanisms for blood pressure maintenance. Cardiac remodeling could also be one important piece of the puzzle. In this review, we intend to discuss the role of cardiac remodeling, including left ventricular hypertrophy, in the development of Intradialytic hypotension. In addition, we will also provide evidence that a bidirectional relationship might exist between Intradialytic hypotension and left ventricular hypertrophy in chronic dialysis patients. A more complete understanding of the complex interactions in between could assist the readers in formulating potential solutions for the reduction of both phenomena. Chia-Ter Chao, Jenq-Wen Huang, and Chung-Jen Yen Copyright © 2015 Chia-Ter Chao et al. All rights reserved. Acute Kidney Injury Tue, 06 Jan 2015 08:06:41 +0000 Raúl Lombardi, Emmanuel A. Burdmann, Alejandro Ferreiro, and Fernando Liaño Copyright © 2015 Raúl Lombardi et al. All rights reserved. Midkine: A Novel and Early Biomarker of Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions Mon, 05 Jan 2015 07:12:59 +0000 We tested the hypothesis whether midkine could represent an early biomarker of contrast-induced acute kidney injury (CIAKI) in 89 patients with normal serum creatinine undergoing PCI. Midkine, serum and urinary NGAL, and cystatin C were evaluated before and 2, 4, 8, 24, and 48 hours after PCI using commercially available kits. Serum creatinine was assessed before and 24 and 48 hours after PCI. We found a significant rise in serum midkine as early as after 2 hours () when compared to the baseline values. It was also significantly higher 4 hours after PCI and then returned to the baseline values after 24 hours and started to decrease after 48 hours. When contrast nephropathy was defined as an increase in serum creatinine by >25% of the baseline level 48 hours after PCI, the prevalence of CIN was 10%. Patients with CIN received significantly more contrast agent (), but durations of PCI were similar. Midkine was significantly higher 2, 4, and 8 hours after PCI in patients with CIN. Since the “window of opportunity” is narrow in CIAKI and time is limited to introduce proper treatment after initiating insult, particularly when patients are discharged within 24 hours after the procedure, midkine needs to be investigated as a potential early marker for renal ischemia and/or nephrotoxicity. Jolanta Malyszko, Hanna Bachorzewska-Gajewska, Ewa Koc-Zorawska, Jacek S. Malyszko, Grazyna Kobus, and Slawomir Dobrzycki Copyright © 2015 Jolanta Malyszko et al. All rights reserved. Chronic Kidney Disease Requiring Healthcare Services: A New Approach to Evaluate Epidemiology of Renal Disease Thu, 20 Nov 2014 07:11:32 +0000 Background. Screening-based CKD estimates may not provide a sufficient insight into the impact of CKD on the use of healthcare resources in clinical practice. The aim of this study was to evaluate the epidemiology of “medicalized” CKD, that is, CKD requiring healthcare services, in an outpatient setting. Design, Setting, Participants, and Measurements. This is a retrospective, longitudinal population-based study conducted in a large general practice setting in Southern Italy (Caserta) using a healthcare database. Over 2006–2011, all patients with a CKD diagnosis, either through CKD-related indications of use associated with drug prescriptions or through CKD-related hospital discharge diagnoses/procedures, were identified using this database. The prevalence of “medicalized” CKD in the general population of Caserta was estimated by age, gender, and calendar year. Results. Overall, 1,989 (1.3%) patients with a diagnosis of CKD were identified from 2006–2011 in the Caserta general population. The one year prevalence increased from 0.9% in 2006 to 1.6% in 2011, which is much lower compared to previous screening-based studies. The prevalence was slightly higher in males and increased significantly with advancing age (in 2011, 0.2% in ≤44 years old versus 9.2% in >80 years old). Conclusions. The findings of this study suggest that, in the general population, the prevalence of “medicalized” CKD is lower compared to the screening-based CKD prevalence. Gianluca Trifirò, Janet Sultana, Francesco Giorgianni, Ylenia Ingrasciotta, Michele Buemi, Marco Muscianisi, Daniele Ugo Tari, Margherita Perrotta, Valeria Canale, Vincenzo Arcoraci, and Domenico Santoro Copyright © 2014 Gianluca Trifirò et al. All rights reserved. Chronic Kidney Disease and Upper Tract Urothelial Carcinomas Thu, 11 Sep 2014 06:13:45 +0000 Li-Jen Wang, Joëlle L. Nortier, Bin Tean Teh, Cheng-Keng Chuang, and Shen-Yang Lee Copyright © 2014 Li-Jen Wang et al. All rights reserved. A Network Meta-Analysis on Randomized Trials Focusing on the Preventive Effect of Statins on Contrast-Induced Nephropathy Sun, 07 Sep 2014 09:25:22 +0000 Contrast-induced nephropathy is a common complication of iodinated contrast administration. Statins may reduce the risk of contrast-induced nephropathy, but data remain inconclusive. We summarized the evidence based on statins for the prevention of contrast-induced nephropathy with a network meta-analysis. Randomized trials focusing on statins were searched and pooled with random-effect odds ratios. A total of 14 trials (6,160 patients) were included, focusing on atorvastatin (high/low dose), rosuvastatin (high dose), simvastatin (high/low dose), and placebo or no statin therapy before contrast administration. The risk of contrast-induced nephropathy was reduced by atorvastatin high dose and rosuvastatin high dose, with no difference between these two agents. Results for atorvastatin low dose and simvastatin (high/low dose) in comparison to placebo were inconclusive. Atorvastatin and rosuvastatin administered at high doses and before iodinated contrast administration have a consistent and beneficial preventive effect on contrast-induced nephropathy and may actually halve its incidence. Mariangela Peruzzi, Leonardo De Luca, Henrik S. Thomsen, Enrico Romagnoli, Fabrizio D’Ascenzo, Massimo Mancone, Gennaro Sardella, Luigi Lucisano, Antonio Abbate, Giacomo Frati, and Giuseppe Biondi-Zoccai Copyright © 2014 Mariangela Peruzzi et al. All rights reserved. Emerging Biomarkers in Renal Damage Wed, 03 Sep 2014 08:36:38 +0000 Pasquale Ditonno, Cees van Kooten, Loreto Gesualdo, Giuseppe Grandaliano, and Giuseppe Lucarelli Copyright © 2014 Pasquale Ditonno et al. All rights reserved. Angiotensin II Removes Kidney Resistance Conferred by Ischemic Preconditioning Thu, 28 Aug 2014 05:10:26 +0000 Ischemic preconditioning (IPC) by ischemia/reperfusion (I/R) renders resistance to the kidney. Strong IPC triggers kidney fibrosis, which is involved in angiotensin II (AngII) and its type 1 receptor (AT1R) signaling. Here, we investigated the role of AngII/AT1R signal pathway in the resistance of IPC kidneys to subsequent I/R injury. IPC of kidneys was generated by 30 minutes of bilateral renal ischemia and 8 days of reperfusion. Sham-operation was performed to generate control (non-IPC) mice. To examine the roles of AngII and AT1R in IPC kidneys to subsequent I/R, IPC kidneys were subjected to either 30 minutes of bilateral kidney ischemia or sham-operation following treatment with AngII, losartan (AT1R blocker), or AngII plus losartan. IPC kidneys showed fibrotic changes, decreased AngII, and increased AT1R expression. I/R dramatically increased plasma creatinine concentrations in non-IPC mice, but not in IPC mice. AngII treatment in IPC mice resulted in enhanced morphological damage, oxidative stress, and inflammatory responses, with functional impairment, whereas losartan treatment reversed these effects. However, AngII treatment in non-IPC mice did not change I/R-induced injury. AngII abolished the resistance of IPC kidneys to subsequent I/R via the enhancement of oxidative stress and inflammatory responses, suggesting that the AngII/AT1R signaling pathway is associated with outcome in injury-experienced kidney. Hee-Seong Jang, Jee In Kim, Jinu Kim, Jeen-Woo Park, and Kwon Moo Park Copyright © 2014 Hee-Seong Jang et al. All rights reserved. Multiple Analytical Approaches Demonstrate a Complex Relationship of Genetic and Nongenetic Factors with Cisplatin- and Carboplatin-Induced Nephrotoxicity in Lung Cancer Patients Thu, 28 Aug 2014 00:00:00 +0000 Background. Cisplatin and carboplatin cause nephrotoxicity by forming platinum-DNA adducts and lead to cell death. Methods. One-hundred and sixteen Taiwanese lung cancer patients who received cisplatin or carboplatin more than twice were recruited, and their genotypes were determined. The risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage kidney disease (RIFLE) criteria were used to evaluate the occurrence of nephrotoxicity. A logistic regression, multiple regression with a classification and regression tree (CART), and the Framingham study risk score were used to analyze interactions between genetic and nongenetic factors in producing platinum-induced nephrotoxicity. Results. ERCC1 118C and TP53 72Arg polymorphisms were associated with increased risks of platinum-induced nephrotoxicity. Other risk factors found included the platinum type, baseline serum creatinine (Scr), coadministration of vinorelbine, and the number of chemotherapy cycles. The overall prediction rate of the CART was 82.7%, with a sensitivity of 0.630 and specificity of 0.896. The Framingham study risk prediction model contained 7 factors. Its prediction rate was 84.5%, with a sensitivity of 0.643 and specificity of 0.909. Conclusions. Genetic polymorphisms of ERCC1 and TP53 are risk factors for nephrotoxicity. The CART analysis may provide a clinically applicable model to predict the risk of cisplatin- and carboplatin-induced nephrotoxicity. H. Eugene Liu, Kuan-Jen Bai, Yu-Chen Hsieh, Ming-Chih Yu, Chun-Nin Lee, Jer-Hua Chang, Han-Lin Hsu, Pei-Chih Lu, and Hsiang-Yin Chen Copyright © 2014 H. Eugene Liu et al. All rights reserved. A Higher Frequency of CD4+CXCR5+ T Follicular Helper Cells in Adult Patients with Minimal Change Disease Wed, 27 Aug 2014 10:34:07 +0000 Background. T follicular helper (TFH) cells are involved in the humoral immune responses. This study is aimed at examining the frequencies of different subsets of CD4+CXCR5+ TFH cells in adult patients with minimal change disease (MCD). Methods. A total of 27 patients and 14 healthy controls (HC) were characterized for the levels of sera cytokines, inducible T-cell costimulator (ICOS), and programmed death 1 (PD-1) of positive TFH cells by flow cytometry. The level of sera IL-21 was examined; 24 h urinary protein and eGFR were calculated. The potential correlation between the frequency of different subsets of TFH cells and the values of clinical measures in MCD patients were analyzed. Results. The frequency of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+, and CD4+CXCR5+PD-1+ TFH cells and the levels of sera IL-17A, IFN-γ, IL-2, IL-10, IL-4, and IL-21 were significantly higher in MCD patients () than that in the HC group. Furthermore, the percentages of circulating CD4+CXCR5+ TFH cells were negatively correlated with the values of eGFR (, ) and the percentages of CD4+CXCR5+PD-1+ TFH cells were correlated positively with the levels of serum IL-21 (, ) and 24 h urinary protein (, ) in those patients. Also, the percentages of CD4+CXCR5+ICOS+ TFH cells were correlated positively with the levels of serum IL-21 (, ) and 24 h urinary protein (, ). Following standard therapies, the percentages of circulating CD4+CXCR5+, CD4+CXCR5+PD-1+, and CD4+CXCR5+ICOS+ TFH cells and the levels of serum IL-21 were significantly reduced, but the levels of serum IL-4 and IL-10 were increased (). Conclusions. A higher frequency of CD4+CXCR5+ TFH cells that existed in adult patients with MCD could be new target for intervention of MCD. Nan Zhang, Pingwei Zhao, Amrita Shrestha, Li Zhang, Zhihui Qu, Mingyuan Liu, Songling Zhang, and Yanfang Jiang Copyright © 2014 Nan Zhang et al. All rights reserved. Chinese Herbs Containing Aristolochic Acid Associated with Renal Failure and Urothelial Carcinoma: A Review from Epidemiologic Observations to Causal Inference Wed, 27 Aug 2014 05:59:04 +0000 Herbal remedies containing aristolochic acid (AA) have been designated to be a strong carcinogen. This review summarizes major epidemiologic evidence to argue for the causal association between AA exposure and urothelial carcinoma as well as nephropathy. The exposure scenarios include the following: Belgian women taking slimming pills containing single material Guang Fang Ji, consumptions of mixtures of Chinese herbal products in the general population and patients with chronic renal failure in Taiwan, occupational exposure in Chinese herbalists, and food contamination in farming villages in valleys of the Danube River. Such an association is corroborated by detecting specific DNA adducts in the tumor tissue removed from affected patients. Preventive actions of banning such use and education to the healthcare professionals and public are necessary for the safety of herbal remedies. Hsiao-Yu Yang, Pau-Chung Chen, and Jung-Der Wang Copyright © 2014 Hsiao-Yu Yang et al. All rights reserved. Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention Thu, 14 Aug 2014 13:23:35 +0000 It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24–72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. Michele Andreucci, Teresa Faga, Antonio Pisani, Massimo Sabbatini, and Ashour Michael Copyright © 2014 Michele Andreucci et al. All rights reserved. Long-Term Outcomes after Dialysis-Requiring Acute Kidney Injury Tue, 12 Aug 2014 11:06:40 +0000 AKI-dialysis patients had a higher incidence of long-term ESRD and mortality than the patients without AKI. The patients who recovered from dialysis were associated with a lower incidence of long-term ESRD and mortality than in the patients who still required dialysis. Vin-Cent Wu, Chih-Chung Shiao, Chia-Hsuin Chang, Tao-Min Huang, Chun-Fu Lai, Meng-Chun Lin, Wen-Chih Chiang, Tzong-Shinn Chu, Kwan-Dun Wu, Wen-Je Ko, Cheng-Yi Wang, Shuo-Meng Wang, and Likwang Chen Copyright © 2014 Vin-Cent Wu et al. All rights reserved. Hypervolemia for Hypertension Pathophysiology: A Population-Based Study Mon, 11 Aug 2014 07:10:38 +0000 Objectives. Hypertension and hypervolemia relationship was proven among renal disease, although it is not known in normal population. Present study determines the fluid distribution defects in relation to blood pressure. Material and Methods. In a population-based survey in Turkey demographics, height, weight, blood pressure, urine analysis, and serum creatinine measurements were recorded. Bioimpedance measured with the Body Composition Monitor. Results. Total 2034 population of 71.6% male, mean age 47 ± 12.6 (18–89) years, systolic blood pressure (SBP) 134.7 ± 20, diastolic blood pressure 77.9 ± 11.6 mmHg. Body mass index (BMI) was 28.5 ± 4.5 (15.8–50.6) kg/m2; overhydration was 0.05 ± 1.05 L. There was a correlation between extracellular water (ECW)/height and SBP (r = 0.21, P < 0.001). Receiver operating characteristic (ROC) curve with the performance of 0.60 (P < 0.001) that showed cut-off value of ECW/height was 10.06 L/m, with the 69% sensitivity and 45% specificity for SBP: 140 mmHg values. Risk factors for high SBP were increase of ECW/Height, age, BMI and presence of diabetes. ECW/height, SBP, and fat tissue index (FTI) increased in BMI categories (low, normal, and obese) and in diabetics. SBP and FTI were lower in smokers. Conclusions. High blood pressure may be accompanied by increased extracellular volume indices. In the future volume status assessment could be of use in evaluating the effectiveness of pharmacological intervention in the treatment of hypertension. Ender Hür, Melih Özişik, Cihan Ural, Gürsel Yildiz, Kemal Mağden, Sennur Budak Köse, Füruzan Köktürk, Çağatay Büyükuysal, İbrahim Yildirim, Gültekin Süleymanlar, Kenan Ateş, and Soner Duman Copyright © 2014 Ender Hür et al. All rights reserved. Dialysis Complications in AKI Patients Treated with Extended Daily Dialysis: Is the Duration of Therapy Important? Mon, 11 Aug 2014 07:06:22 +0000 This trial aimed to compare the dialysis complications occurring during different durations of extended daily dialysis (EDD) sessions in critically ill AKI patients. We included patients older than 18 years with AKI associated with sepsis admitted to the intensive care unit and using noradrenaline dose ranging from 0.3 to 0.7 μg/kg/min. Patients were divided into two groups randomly: in G1, 6 h sessions were performed and, in G2, 10 h sessions were performed. Seventy-five patients were treated with 195 EDD sessions for 18 consecutive months. The prevalence of hypotension, filter clotting, hypokalaemia, and hypophosphataemia was 82.6, 25.3, 20, and 10.6%, respectively. G1 and G2 were similar in male predominance and SOFA. There was no significant difference between the two groups in hypotension, filter clotting, hypokalaemia, and hypophosphataemia. However, the group treated with sessions of 10 hours showed higher refractory to clinical measures for hypotension and dialysis sessions were interrupted more often. Metabolic control and fluid balance were similar between G1 and G2. In conclusion, intradialysis hypotension was common in AKI patients treated with EDD. There was no difference in the prevalence of dialysis complications in patients undergoing different durations of EDD. Bianca Ballarin Albino, André Luis Balbi, and Daniela Ponce Copyright © 2014 Bianca Ballarin Albino et al. All rights reserved. A Modified Single Mini-Incision Complete Urinary Tract Exenteration for Urothelial Carcinoma in Dialysis Patients Mon, 11 Aug 2014 00:00:00 +0000 Objective. To present our experience with single mini-incision complete urinary tract exenteration (CUTE) for female dialysis patients suffering from urothelial carcinoma (UC). Patients and Methods. Institutional review board approval was obtained. From 2005 through 2012, 14 female dialysis patients with UC underwent single mini-incision CUTE, in combination with radical hysterectomy and bilateral salpingo-oophorectomy. All were placed in the modified dorsal lithotomy position without repositioning. An infraumbilical midline mini-incision was made. Bilateral nephroureterectomy was first performed entirely extraperitoneally, followed by radical cystectomy with removal of the uterus and ovaries transperitoneally. Results. All procedures were done successfully without major complications. The median operative time was 242.5 minutes, and estimated blood loss was 500 mL. The median time to oral intake was 2 postoperative days; the median hospital stay was 11 days. Ten patients remained cancer-free at a median follow-up of 46.5 months; six patients were confirmed as having preoperatively undetectable UC or renal cell carcinoma, even after reviewing preoperative computed tomography. Conclusions. This modified technique provides a time-saving complete urinary tract extirpation to eliminate preoperatively undetectable malignancy, reduce metachronous recurrences, and avert perioperative complications associated with pneumoperitoneum and repositioning. Good cancer control and early convalescence can mutually be achieved in experienced hands. I-Hsuan Chen, Jen-Tai Lin, Jeng-Yu Tsai, Tony Wu, and Chia-Cheng Yu Copyright © 2014 I-Hsuan Chen et al. All rights reserved. Nomogram Predicting Renal Insufficiency after Nephroureterectomy for Upper Tract Urothelial Carcinoma in the Chinese Population: Exclusion of Ineligible Candidates for Adjuvant Chemotherapy Sun, 10 Aug 2014 08:15:01 +0000 Objectives. To report the decline of renal function after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC) patients and to develop a nomogram to predict ineligibility for cisplatin-based adjuvant chemotherapy (AC). Methods. We retrospectively analyzed 606 consecutive Chinese UTUC patients treated by RNU from 2000 to 2010. We chose an eGFR of 60 and 45 ml/min/1.73 m2 as cut-offs for full-dose and reduced-dose AC eligibility. Results. Median eGFR for all patients before and after surgery was 64 and 49 ml/min/1.73 m2 (). The proportion of patients ineligible to receive full-dose and reduced-dose AC changed from 42% to 74% and from 20% to 38.1%. Older age (OR = 1.007), preoperative eGFR (OR = 0.993), absence of hydronephrosis (OR = 0.801), smaller tumor size (OR = 0.962), and tumor without multifocality (OR = 0.876) were predictive for ineligibility for full-dose AC. Preoperative eGFR (OR = 0.991), absence of hydronephrosis (OR = 0.881), tumor located in renal pelvis (OR = 1.164), and smaller tumor size (OR = 0.969) could predict ineligibility for reduced-dose AC. The c-index of the two models was 0.757 and 0.836. Postoperative renal function was not associated with worse survival. Conclusions. Older age, lower preoperative eGFR, smaller tumor size, tumor located in renal pelvis, and absence of hydronephrosis or multifocality were predictors of postoperative renal insufficiency. Dong Fang, Qifu Zhang, Xuesong Li, Cheng Qian, Gengyan Xiong, Lei Zhang, Xiaopeng Chen, Xiaoyu Zhang, Wei Yu, Zhisong He, and Liqun Zhou Copyright © 2014 Dong Fang et al. All rights reserved. Upper Tract Urothelial Carcinomas in Patients with Chronic Kidney Disease: Relationship with Diagnostic Challenge Thu, 07 Aug 2014 09:38:03 +0000 Chronic kidney disease and upper tract urothelial carcinomas display a bidirectional relationship. Review of the literature indicates that early diagnosis and correct localization of upper tract urothelial carcinomas in dialysis patients and kidney transplant recipients are important but problematic. Urine cytology and cystoscopy have limited sensitivity for the diagnosis of upper tract urothelial carcinomas in dialysis patients. Enhanced computed tomography and magnetic resonance imaging could prove useful for the detection and staging of upper tract urothelial carcinomas in dialysis patients. Renal ultrasound can detect hydronephrosis caused by upper tract urothelial carcinomas in kidney transplant recipients but cannot visualize the carcinomas themselves. High detection rates for upper tract urothelial carcinomas in kidney transplant recipients have recently been demonstrated using computed tomography urography, which appears to be a promising tool. To detect carcinomas in dialysis patients and kidney transplant recipients as early as possible, regular screening in asymptomatic patients and diagnostic work-up in symptomatic patients should be performed using a combination of urological and imaging methods. Careful assessment of subsequent recurrence within the contralateral upper urinary tract and the urinary bladder is necessary for dialysis patients and kidney transplant recipients with upper tract urothelial carcinomas. Li-Jen Wang, Shen-Yang Lee, Bin Tean Teh, Cheng-Keng Chuang, and Joëlle Nortier Copyright © 2014 Li-Jen Wang et al. All rights reserved. Extended Renal Outcomes with Use of Iodixanol versus Iohexol after Coronary Angiography Thu, 07 Aug 2014 07:19:36 +0000 The impact of isoosmolar versus low-osmolar contrast media (CM) administration on contrast-induced acute kidney injury (CI-AKI) and extended renal dysfunction (ERD) is unclear. We retrospectively examined incidences of CI-AKI and ERD in patients who received iodixanol (isoosmolar) versus iohexol (low-osmolar) during angiography for cardiac indications. Of 713 patients, 560 (cohort A), 190 (cohort B), and 172 (cohort C) had serum creatinine monitored at 3 days, 30 days, and 6 months after angiography, respectively. 18% of cohort A developed CI-AKI, which was more common with iodixanol than iohexol (22% versus 13%, ). However, patients given iodixanol were older with lower baseline estimated glomerular filtration rates (eGFR). On multivariate analysis, independent associations with higher CI-AKI risk include age >65 years, female gender, cardiac failure, ST-elevation myocardial infarction, intra-aortic balloon pump, and critical illness, but not CM type, higher CM load, or  mL/min/1.73 m2. 32% of cohort B and 34% of cohort C had ERD at 30 days and 6 months, while 44% and 41% of subcohorts had ERD at 90 days and 1 year, respectively. CI-AKI, but not CM type, was associated with medium- and longer-term ERD, with 3-fold higher risk. Advanced age, emergent cardiac conditions, and critical illness are stronger predictors of CI-AKI, compared with CM-related factors. CI-AKI predicts longer-term ERD. Horng-Ruey Chua, Mark Horrigan, Elizabeth Mcintosh, and Rinaldo Bellomo Copyright © 2014 Horng-Ruey Chua et al. All rights reserved. Pathophysiology of Cisplatin-Induced Acute Kidney Injury Wed, 06 Aug 2014 09:31:22 +0000 Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality. Abdullah Ozkok and Charles L. Edelstein Copyright © 2014 Abdullah Ozkok and Charles L. Edelstein. All rights reserved. Anticancer Drug 2-Methoxyestradiol Protects against Renal Ischemia/Reperfusion Injury by Reducing Inflammatory Cytokines Expression Wed, 06 Aug 2014 06:47:42 +0000 Background. Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure and allograft dysfunction in kidney transplantation. ROS/inflammatory cytokines are involved in I/R injury. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, inhibits inflammatory cytokine expression and is an antiangiogenic and antitumor agent. We investigated the inhibitory effect of 2ME2 on renal I/R injury and possible molecular actions. Methods. BALB/c mice were intraperitoneally injected with 2ME2 (10 or 20 mg/kg) or vehicle 12 h before and immediately after renal I/R experiments. The kidney weight, renal function, tubular damages, and apoptotic response were examined 24 h after I/R injury. The expression of mRNA of interleukin-1β, tumor necrosis factor- (TNF) α, caspase-3, hypoxia inducible factor- (HIF) 1α, and proapoptotic Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) in kidney tissue was determined using RT-PCR, while the expression of nuclear factor κB (NF-κB), BCL-2, and BCL-xL, activated caspase-9, and HIF-1α was determined using immunoblotting. In vitro, we determined the effect of 2ME2 on reactive oxygen species (ROS) production and cell viability in antimycin-A-treated renal mesangial (RMC) and tubular (NRK52E) cells. Results. Serum creatinine and blood urea nitrogen were significantly higher in mice with renal I/R injury than in sham control and in I/R+2ME2-treated mice. Survival in I/R+2ME2-treated mice was higher than in I/R mice. Histological examination showed that 2ME2 attenuated tubular damage in I/R mice, which was associated with lower expression TNF-α, IL-1β, caspase-9, HIF-1α, and BNIP3 mRNA in kidney tissue. Western blotting showed that 2ME2 treatment substantially decreased the expression of activated caspase-9, NF-κB, and HIF-1α but increased the antiapoptotic proteins BCL-2 and BCL-xL in kidney of I/R injury. In vitro, 2MR2 decreased ROS production and increased cell viability in antimycin-A-treated RMC and NRK52E cells. Conclusions. 2ME2 reduces renal I/R injury in mice because it inhibits the expression of ROS and proinflammatory cytokines and induces antiapoptotic proteins. Ying-Yin Chen, Ching-Hua Yeh, Edmund Cheung So, Ding-Ping Sun, Li-Yun Wang, and Chung-Hsi Hsing Copyright © 2014 Ying-Yin Chen et al. All rights reserved. Metabolic Acidosis and Strong Ion Gap in Critically Ill Patients with Acute Kidney Injury Tue, 05 Aug 2014 12:15:45 +0000 Purpose. To determine the influence of physicochemical parameters on survival in metabolic acidosis (MA) and acute kidney injury (AKI) patients. Materials and Methods. Seventy-eight MA patients were collected and assigned to AKI or non-AKI group. We analyzed the physiochemical parameters on survival at 24 h, 72 h, 1 week, 1 month, and 3 months after AKI. Results. Mortality rate was higher in the AKI group. AKI group had higher anion gap (AG), strong ion gap (SIG), and apparent strong ion difference (SIDa) values than non-AKI group. SIG value was higher in the AKI survivors than nonsurvivors and this value was correlated serum creatinine, phosphate, albumin, and chloride levels. SIG and serum albumin are negatively correlated with Acute Physiology and Chronic Health Evaluation IV scores. AG was associated with mortality at 1 and 3 months post-AKI, whereas SIG value was associated with mortality at 24 h, 72 h, 1 week, 1 month, and 3 months post-AKI. Conclusions. Whether high or low SIG values correlate with mortality in MA patients with AKI depends on its correlation with serum creatinine, chloride, albumin, and phosphate (P) levels. AG predicts short-term mortality and SIG value predicts both short- and long-term mortality among MA patients with AKI. Cai-Mei Zheng, Wen-Chih Liu, Jing-Quan Zheng, Min-Tser Liao, Wen-Ya Ma, Kuo-Chin Hung, Chien-Lin Lu, Chia-Chao Wu, and Kuo-Cheng Lu Copyright © 2014 Cai-Mei Zheng et al. All rights reserved. Citrate Anticoagulation for CRRT in Children: Comparison with Heparin Sun, 03 Aug 2014 07:18:25 +0000 Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (). 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I) of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin. Sara Nicole Fernández, Maria José Santiago, Jesús López-Herce, Miriam García, Jimena Del Castillo, Andrés José Alcaraz, and Jose María Bellón Copyright © 2014 Sara Nicole Fernández et al. All rights reserved. Randomized Controlled Trial of Strain-Specific Probiotic Formulation (Renadyl) in Dialysis Patients Thu, 24 Jul 2014 00:00:00 +0000 Background. Primary goal of this randomized, double-blind, placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins. Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress. Methods. Two 2-month treatment periods separated by 2-month washout and crossover, with physical examinations, venous blood testing, and quality of life questionnaires completed at each visit. Data were analyzed with SAS V9.2. Results. 22 subjects (79%) completed the study. Observed trends were as follows (none reaching statistical significance): decline in WBC count , and reductions in levels of C-reactive protein , and total indoxyl glucuronide , . No statistically significant changes were observed in other uremic toxin levels or measures of QOL. Conclusions. Renadyl appeared to be safe to administer to ESRD patients on hemodialysis. Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease. Efficacy could not be confirmed definitively, primarily due to small sample size and low statistical power—further studies are warranted. Ranganathan Natarajan, Bohdan Pechenyak, Usha Vyas, Pari Ranganathan, Alan Weinberg, Peter Liang, Mary C. Mallappallil, Allen J. Norin, Eli A. Friedman, and Subodh J. Saggi Copyright © 2014 Ranganathan Natarajan et al. All rights reserved. Frequency of TGF-β and IFN-γ Genotype as Risk Factors for Acute Kidney Injury and Death in Intensive Care Unit Patients Wed, 23 Jul 2014 10:57:21 +0000 Genetic variations in TGF-β and IFN-γ may interfere with proinflammatory cytokine production and, consequently, may be involved with inflammatory diseases, as acute kidney injury (AKI). We considered that genetic polymorphisms of these cytokines may have a crucial role in the outcome of critically ill patients. To investigate whether the genetic polymorphisms of rs1800470 (codon 10 T/C), rs1800471 (codon 25 C/G) from the TGF-β, and rs2430561 (+874 T/A) from IFN-γ may be a risk factor for ICU patients to the development of AKI and/or death. In a prospective nested case-control study, were included 139 ICU patients who developed AKI, 164 ICU patients without AKI, and 244 healthy individuals. We observed a higher frequency to T/A genotype for IFN-γ (intermediate producer phenotype) and higher frequency of TT GG and TC GG genotype (high producer) for TGF-β polymorphism in overall population. However, these polymorphisms have not been shown as a predictor of risk for AKI and death. We found an increased prevalence of high and intermediate producer phenotypes from TGF-β and IFN-γ, respectively, in patients in ICU setting. However, the studied genetic polymorphism of the TGF-β and IFN-γ was not associated as a risk factor for AKI or death in our population. Caren Cristina Grabulosa, Marcelo Costa Batista, Miguel Cendoroglo, Beata Marie Redublo Quinto, Roberto Narciso, Julio Cesar Monte, Marcelino Durão, Luiz Vicente Rizzo, Oscar Fernando Pavão Santos, and Maria Aparecida Dalboni Copyright © 2014 Caren Cristina Grabulosa et al. All rights reserved. Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy Mon, 21 Jul 2014 11:51:30 +0000 Background. Tissue transglutaminase (TG2), a cross-linking enzyme, modulates deposition of extracellular matrix protein in renal fibrosis. This study aimed to examine TG2 and its cross-link product ε(γ-glutamyl)-lysine in the Fisher-Lewis rat renal transplantation (RTx) model of chronic allograft nephropathy (CAN). Materials and Methods. Left renal grafts from male Fisher and Lewis were transplanted into Lewis rats, generating allografts and isografts, respectively. Blood pressure, renal function, and proteinuria were monitored for up to 52 weeks. At termination, CAN was assessed in the renal tissue by light and electron microscopy, TG2 and ε(γ-glutamyl)-lysine by immunofluorescence, and the urinary ε(γ-glutamyl)-lysine by high performance liquid chromatography. Results. Compared to the isograft, the allografts were hypertensive, proteinuric, and uraemic and developed CAN. Extracellular TG2 (glomerulus: versus , ; interstitium: versus , ), ε(γ-glutamyl)-lysine (glomerulus: versus , ; interstitium: versus , ), TG2 enzyme activity ( versus  nmol/h/mg protein, ), TG2 mRNA (20-fold rise), and urinary ε(γ-glutamyl)-lysine ( nmol/24 h versus  nmol/24 h, ) levels were significantly elevated in the allografts and showed a positive linear correlation with tubulointerstitial fibrosis. Conclusion. CAN was associated with upregulation of renal TG2 pathway, which has a potential for pharmacological intervention. The elevated urinary ε(γ-glutamyl)-lysine, measured for the first time in RTx, is a potential biomarker of CAN. Badri Shrestha, Imran Butt, Michelle Da Silva, Armando Sanchez-Lara, Bart Wagner, Andrew Raftery, Timothy Johnson, and John Haylor Copyright © 2014 Badri Shrestha et al. All rights reserved. Hypoxia-Pretreated Human MSCs Attenuate Acute Kidney Injury through Enhanced Angiogenic and Antioxidative Capacities Wed, 16 Jul 2014 00:00:00 +0000 Hypoxia preconditioning has been confirmed as an effective strategy to enhance the therapeutic potentials of mesenchymal stem cells (MSCs), such as for myocardial ischemia. However, whether hypoxia preconditioning would produce beneficial effects on MSC-based renal repair has not been demonstrated. In the study, we aimed to determine the feasibility and efficacy of hypoxia preconditioning to enhance MSC-based therapy of acute kidney injury (AKI). MSCs were isolated from human adipose tissues. The paracrine effects of MSCs under normoxia and hypoxia were determined in vitro. Rats of AKI were induced by kidney I/R surgery and randomly divided into three groups: I/R control receiving PBS injection; MSC group receiving normal MSC injection; hypoMSC group receiving hypoxia-preconditioned MSC injection. It was demonstrated in vitro that paracrine effects of MSCs were significantly enhanced, especially angiogenic factors. Dihydroethidium (DHE) staining showed that antioxidative activities of MSCs were significantly enhanced by hypoxia stimulation. Vascularization, apoptosis, and histological injury were all significantly improved in hypoMSC injected group compared with that in control and MSC injected groups. Finally, the renal function was also significantly improved in hypoMSC injected group compared with that in the other two groups as assessed by the serum creatinine and BUN levels. Wenbo Zhang, Lirui Liu, Yanhong Huo, Yonghong Yang, and Yaping Wang Copyright © 2014 Wenbo Zhang et al. All rights reserved. Could Pyelonephritic Scarring Be Prevented by Anti-Inflammatory Treatment? An Experimental Model of Acute Pyelonephritis Thu, 03 Jul 2014 07:05:14 +0000 Objectives. This study aimed to demonstrate if the addition of anti-inflammatory treatment to antibiotic therapy shows any superiority to the treatment with antibiotic only. Methods. Forty-nine Wistar rats were divided into 7 groups. Pyelonephritis was performed by E. coli injection to upper pole of kidneys except control group. Group 2 was not treated. Ceftriaxone, ketoprofen, “ceftriaxone + ketoprofen,” methylprednisolone, and “ceftriaxone + methylprednisolone” were given in the groups. The technetium-99m-dimercaptosuccinic acid scintigraphies were performed in 3rd day to detect pyelonephritis and 10th week to detect renal scarring. All kidneys were also histopathologically evaluated. Results. When 3rd day and 10th week scintigraphies were compared, initial 2.00 ± 0.30 point pyelonephritis score resulted in 0.71 ± 0.36 renal scar score in “ceftriaxone + ketoprofen” group (). Initial 2.00 ± 0.43 point pyelonephritis score resulted in 0.86 ± 0.26 renal scar score in “ceftriaxone + methylprednisolone” group (). Renal scar score was declined in “ceftriaxone + ketoprofen” group and “ceftriaxone + methylprednisolone” group compared with no-treatment group on 10th week of the study (, ). On histopathological evaluation, it was seen that renal scar prevalence and expansion declined significantly in “ceftriaxone + ketoprofen and ceftriaxone + methylprednisolone” (, ). Conclusion. It was evidenced that ceftriaxone treatment in combination with ketoprofen or methylprednisolone declined scar formation in scintigraphic and histopathologic examinations of the kidneys. Elif Bahat Özdoğan, Tuğba Özdemir, Seçil Arslansoyu Çamlar, Mustafa İmamoğlu, Ümit Çobanoğlu, Bircan Sönmez, İlknur Tosun, and İsmail Doğan Copyright © 2014 Elif Bahat Özdoğan et al. All rights reserved. Emerging Urinary Markers of Renal Injury in Obstructive Nephropathy Wed, 02 Jul 2014 12:17:44 +0000 The effects of obstruction on renal function are the consequence of many factors that profoundly alter all components of glomerular function. Besides the acute effects on glomerular filtration rate and tubule function, a chronic obstruction induces tubular and interstitial injury that results from the activation of different pathways. The progression of tubulointerstitial injury leads to chronic renal damage characterized by tubular atrophy, inflammatory cell infiltration, and interstitial fibrosis. Obstructive nephropathy is an evolving disease in which the renal damage continues even after relief of the obstruction. In particular, it has been demonstrated that the time of relief is the most important factor in predicting long-term renal function deterioration. In this setting, the EGF/MCP-1 ratio, urinary NGAL, and urinary KIM-1 are useful early biomarkers of progressive renal damage and could have a potential role in predicting the long-term renal outcome. This minireview summarizes the role of these emerging urinary biomarkers of obstructive nephropathy based on the current understanding of the pathophysiology of renal injury. Giuseppe Lucarelli, Vito Mancini, Vanessa Galleggiante, Monica Rutigliano, Antonio Vavallo, Michele Battaglia, and Pasquale Ditonno Copyright © 2014 Giuseppe Lucarelli et al. All rights reserved. Impact of Gentamicin Coadministration along with High Fructose Feeding on Progression of Renal Failure and Metabolic Syndrome in Sprague-Dawley Rats Mon, 23 Jun 2014 05:46:01 +0000 The current study evaluates the impact of high fructose feeding in rat model of gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180–200 g were randomized into four groups; (C) received standard rodents chow with free access to ad libitum drinking water for 8 weeks and was considered as control, (F) received standard rodents chow with free access to drinking water supplemented with 20% (W/V) fructose for the same abovementioned period, (FG) was fed as group F and was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally during the last 20 days of the feeding period, and (G) was given gentamicin as above and fed as group C. Renal function was assessed at the end of the treatment period through measuring serum creatinine, uric acid and albumin, creatinine clearance, absolute and fractional excretion of both sodium and potassium, twenty-four-hour urinary excretion of albumin, and renal histology. For metabolic syndrome assessment, fasting plasma glucose and insulin were measured and oral glucose tolerance test was performed throughout the treatment period. Results showed that gentamicin enhances progression of fructose induced metabolic syndrome. On the other hand, fructose pretreatment before gentamicin injection produced a comparable degree of renal dysfunction to those which were given fructose-free water but the picture of nephrotoxicity was somewhat altered as it was characterized by higher extent of glomerular congestion and protein urea. Overall, more vigilance is required when nephrotoxic drugs are prescribed for patients with fructose induced metabolic syndrome. Zaid O. Ibraheem, Rusliza Basir, Ahmad Kh. Aljobory, Omar E. Ibrahim, Ajwad Alsumaidaee, and Mun Fee Yam Copyright © 2014 Zaid O. Ibraheem et al. All rights reserved. Acute Superoxide Radical Scavenging Reduces Blood Pressure but Does Not Influence Kidney Function in Hypertensive Rats with Postischemic Kidney Injury Sun, 22 Jun 2014 07:19:45 +0000 Acute kidney injury (AKI) is associated with significant morbidity and mortality in hypertensive surroundings. We investigated superoxide radical molecules influence on systemic haemodynamic and kidney function in spontaneously hypertensive rats (SHR) with induced postischemic AKI. Experiment was performed in anesthetized adult male SHR. The right kidney was removed, and left renal artery was subjected to ischemia by clamping for 40 minutes. The treated group received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5 minutes before, during, and 175 minutes after the period of reperfusion, while the control AKI group received the vehicle via the same route. All parameters were measured 24 h after renal reperfusion. TEMPOL treatment significantly decreased mean arterial pressure and total peripheral resistance compared to AKI control. It also increased cardiac output and catalase activity . Lipid peroxidation and renal vascular resistance were decreased in TEMPOL . Plasma creatinine and kidney morphological parameters were unchanged among TEMPOL treated and control groups. Our study shows that superoxide radicals participate in haemodynamic control, but acute superoxide scavenging is ineffective in glomerular and tubular improvement, probably due to hypertension-induced strong endothelial dysfunction which neutralizes beneficial effects of scavenging. Zoran Miloradović, Milan Ivanov, Nevena Mihailović-Stanojević, Jelica Grujić Milanović, Đurđica Jovović, Una-Jovana Vajić, and Jasmina Marković-Lipkovski Copyright © 2014 Zoran Miloradović et al. All rights reserved. Increased Upper and Lower Tract Urothelial Carcinoma in Patients with End-Stage Renal Disease: A Nationwide Cohort Study in Taiwan during 1997–2008 Mon, 16 Jun 2014 08:08:01 +0000 Background. Urothelial cancer (UC) is the leading cancer of patients with end-stage renal disease (ESRD) in Taiwan. The aims of this study were to explore the time trends of UC incidences and propose possible etiologic factors. Methods. Abstracting from the National Health Insurance Research Database (NHIRD), there were 90,477 newly diagnosed cases of ESRD between 1997 and 2008 covering the patients aged 40–85. Among them, 2,708 had developed UC after diagnosis of ESRD. The CIR40–85 (cumulative incidence rate) of upper tract UC (UTUC) and lower tract UC (LTUC) were calculated for ESRD patients and general population, as well as SIR40–85 (standardized incidence ratio) for comparison. Results. Female ESRD patients were found to have 9–18 times of elevated risks of UC, while those of males were increased up to 4–14 times. The time trends of CIR40–84 and SIR40–84 of UTUC in females appear to decline after calendar year 2000. These trends may be related to AA associated herbal products after 1998. Conclusions. Patients with ESRD are at increased risks for both LTUC and UTUC in Taiwan. We hypothesize that the time trends associate with the consumption of aristolochic acid in Chinese herbal products (female predominant). Shuo-Meng Wang, Ming-Nan Lai, Pau-Chung Chen, Yeong-Shiau Pu, Ming-Kuen Lai, Jing-Shiang Hwang, and Jung-Der Wang Copyright © 2014 Shuo-Meng Wang et al. All rights reserved. Caffeic Acid Phenethyl Ester Protects against Amphotericin B Induced Nephrotoxicity in Rat Model Mon, 16 Jun 2014 07:37:15 +0000 The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on amphotericin B induced nephrotoxicity in rat models. Male Wistar-Albino rats were randomly divided into four groups: (I) control group (), (II) CAPE group () which received 10 μmol/kg CAPE intraperitoneally (i.p.), (III) amphotericin B group () which received one dose of 50 mg/kg amphotericin B, and (IV) amphotericin B plus CAPE group () which received 10 μmol/kg CAPE i.p. and one dose of 50 mg/kg amphotericin B. The left kidney was evaluated histopathologically for nephrotoxicity. Levels of malondialdehyde (MDA), nitric oxide (NO), enzyme activities including catalase (CAT), and superoxide dismutase (SOD) were measured in the right kidney. Histopathological damage was prominent in the amphotericin B group compared to controls, and the severity of damage was lowered by CAPE administration. The activity of SOD, MDA, and NO levels increased and catalase activity decreased in the amphotericin B group compared to the control group (, , , and , resp.). Amphotericin B plus CAPE treatment caused a significant decrease in MDA, NO levels, and SOD activity (, , and , resp.) and caused an increase in CAT activity compared with amphotericin B treatment alone (). CAPE treatment seems to be an effective adjuvant agent for the prevention of amphotericin B nephrotoxicity in rat models. Atila Altuntaş, H. Ramazan Yılmaz, Ayşegül Altuntaş, Efkan Uz, Murat Demir, Alparslan Gökçimen, Oğuzhan Aksu, Dilek Şenol Bayram, and Mehmet Tuğrul Sezer Copyright © 2014 Atila Altuntaş et al. All rights reserved. Atrial Natriuretic Peptide and Renal Dopaminergic System: A Positive Friendly Relationship? Thu, 12 Jun 2014 10:41:54 +0000 Sodium metabolism by the kidney is accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Renal dopamine plays a central role in this interactive network. The natriuretic hormones, such as the atrial natriuretic peptide, mediate some of their effects by affecting the renal dopaminergic system. Renal dopaminergic tonus can be modulated at different steps of dopamine metabolism (synthesis, uptake, release, catabolism, and receptor sensitization) which can be regulated by the atrial natriuretic peptide. At tubular level, dopamine and atrial natriuretic peptide act together in a concerted manner to promote sodium excretion, especially through the overinhibition of Na+, K+-ATPase activity. In this way, different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome or hypertension, are associated with impaired action of renal dopamine and/or atrial natriuretic peptide, or as a result of impaired interaction between these two natriuretic systems. The aim of this review is to update and comment on the most recent evidences demonstrating how the renal dopaminergic system interacts with atrial natriuretic peptide to control renal physiology and blood pressure through different regulatory pathways. Marcelo Roberto Choi, Natalia Lucía Rukavina Mikusic, Nicolás Martín Kouyoumdzian, María Cecilia Kravetz, and Belisario Enrique Fernández Copyright © 2014 Marcelo Roberto Choi et al. All rights reserved. Emerging Biomarkers and Metabolomics for Assessing Toxic Nephropathy and Acute Kidney Injury (AKI) in Neonatology Wed, 11 Jun 2014 09:19:23 +0000 Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called “omics” allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS), proton nuclear magnetic resonance (1H NMR), and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods. M. Mussap, A. Noto, V. Fanos, and J. N. Van Den Anker Copyright © 2014 M. Mussap et al. All rights reserved. Stem Cell-Based Cell Therapy for Glomerulonephritis Mon, 09 Jun 2014 07:29:30 +0000 Glomerulonephritis (GN), characterized by immune-mediated inflammatory changes in the glomerular, is a common cause of end stage renal disease. Therapeutic options for glomerulonephritis applicable to all cases mainly include symptomatic treatment and strategies to delay progression. In the attempt to yield innovative interventions fostering the limited capability of regeneration of renal tissue after injury and the uncontrolled pathological process by current treatments, stem cell-based therapy has emerged as novel therapy for its ability to inhibit inflammation and promote regeneration. Many basic and clinical studies have been performed that support the ability of various stem cell populations to ameliorate glomerular injury and improve renal function. However, there is a long way before putting stem cell-based therapy into clinical practice. In the present article, we aim to review works performed with respect to the use of stem cell of different origins in GN, and to discuss the potential mechanism of therapeutic effect and the challenges for clinical application of stem cells. Meiling Jin, Yuansheng Xie, Qinggang Li, and Xiangmei Chen Copyright © 2014 Meiling Jin et al. All rights reserved. Side Effects of Radiographic Contrast Media Mon, 02 Jun 2014 07:03:47 +0000 Michele Andreucci Copyright © 2014 Michele Andreucci. All rights reserved. Novel Biomarkers for Contrast-Induced Acute Kidney Injury Thu, 29 May 2014 16:12:32 +0000 Biomarkers of acute kidney injury (AKI) may be classified in 2 groups: (1) those representing changes in renal function (e.g., serum creatinine or cystatin C and urine flow rate) and (2) those reflecting kidney damage (e.g., kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18, etc.). According to these 2 fundamental criteria, 4 subgroups have been proposed: (1) no marker change; (2) damage alone; (3) functional change alone; and (4) combined damage and functional change. Therefore, a new category of patients with “subclinical AKI” (that is, an increase in damage markers alone without simultaneous loss of kidney function) has been identified. This condition has been associated with higher risk of adverse outcomes (including renal replacement therapy and mortality) at followup. The ability to measure these physiological variables may lead to identification of patients at risk for AKI and early diagnosis of AKI and may lead to variables, which may inform therapeutic decisions. Carlo Briguori, Cristina Quintavalle, Elvira Donnarumma, and Gerolama Condorelli Copyright © 2014 Carlo Briguori et al. All rights reserved. Olmesartan Attenuates Tacrolimus-Induced Biochemical and Ultrastructural Changes in Rat Kidney Tissue Wed, 28 May 2014 10:46:23 +0000 Tacrolimus, a calcineurin inhibitor, is clinically used as an immunosuppressive agent in organ transplantation, but its use is limited due to its marked nephrotoxicity. The present study investigated the effect of olmesartan (angiotensin receptor blocker) on tacrolimus-induced nephrotoxicity in rats. A total of 24 rats were divided into four groups, which included control, tacrolimus, tacrolimus + olmesartan, and olmesartan groups. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. Tacrolimus significantly increased BUN and creatinine level. Treatment with olmesartan reversed tacrolimus-induced changes in the biochemical markers (BUN and creatinine) of nephrotoxicity. Tacrolimus significantly decreased GSH level and catalase activity while increasing MDA level. Olmesartan also attenuated the effects of tacrolimus on MDA, GSH, and catalase. In tacrolimus group histological examination showed marked changes in renal tubule, mitochondria, and podocyte processes. Histopathological and ultrastructural studies showed that treatment with olmesartan prevented tacrolimus-induced renal damage. These results suggest that olmesartan has protective effects on tacrolimus-induced nephrotoxicity, implying that RAS might be playing role in tacrolimus-induced nephrotoxicity. Naif O. Al-Harbi, Faisal Imam, Mohammed M. Al-Harbi, Muzaffar Iqbal, Ahmed Nadeem, Mohammed M. Sayed-Ahmed, Ali D. Alabidy, and Ali F. Almukhallafi Copyright © 2014 Naif O. Al-Harbi et al. All rights reserved. Biological Pathways and Potential Targets for Prevention and Therapy of Chronic Allograft Nephropathy Tue, 27 May 2014 06:20:28 +0000 Renal transplantation (RT) is the best option for patients with end-stage renal disease, but the half-life is limited to a decade due to progressive deterioration of renal function and transplant failure from chronic allograft nephropathy (CAN), which is the leading cause of transplant loss. Extensive research has been done to understand the pathogenesis, the biological pathways of fibrogenesis, and potential therapeutic targets for the prevention and treatment of CAN. Despite the advancements in the immunosuppressive agents and patient care, CAN continues to remain an unresolved problem in renal transplantation. The aim of this paper is to undertake a comprehensive review of the literature on the pathogenesis, biological pathways of RT fibrogenesis, and potential therapeutic targets for the prevention and therapy of CAN. Badri Man Shrestha and John Haylor Copyright © 2014 Badri Man Shrestha and John Haylor. All rights reserved. Value of Plasmatic Membrane Attack Complex as a Marker of Severity in Acute Kidney Injury Sun, 25 May 2014 10:41:44 +0000 The aim of this study was to determine if complement pathway is activated in AKI; for this purpose, we measured, through ELISA sandwich, the terminal lytic fraction of the complement system, called membrane attack complex (C5b-C9), in AKI patients compared with patients with similar clinical conditions but normal renal function. Our data showed that complement system is activated in AKI. Plasmatic MAC concentrations were significantly higher in AKI patients than in those with normal renal function; this difference is maintained independently of the AKI etiology and is proportional to the severity of AKI, measured by ADQI classification. In addition, we found that plasmatic MAC concentrations were significantly higher in patients who did not recover renal function at time of hospitalization discharge, in patients who died during the acute process, and in patients who need renal replacement therapy during hospitalization, but in this last group, the differences did not reach statistical significance. In conclusion, plasmatic MAC concentration seems valuable as a marker of AKI severity. Eva Rodríguez, Marta Riera, Clara Barrios, and Julio Pascual Copyright © 2014 Eva Rodríguez et al. All rights reserved. Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers Mon, 19 May 2014 08:53:05 +0000 Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups () were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κβ, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF-β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL. José Sereno, Sara Nunes, Paulo Rodrigues-Santos, Helena Vala, Petronila Rocha-Pereira, João Fernandes, Alice Santos-Silva, Frederico Teixeira, and Flávio Reis Copyright © 2014 José Sereno et al. All rights reserved. Circulating Endothelial Cells and Chronic Kidney Disease Sun, 18 May 2014 07:05:06 +0000 Endothelial dysfunction may play a crucial role in initiation of the pathogenesis of vascular disease and atherosclerosis. The identification and quantification of circulating endothelial cells (CEC) have been developed as a novel marker of endothelial function. We describe, in great detail, mechanisms of endothelial dysfunction and CEC detachment. We also review the relationship between numbers of CEC and disease severity and response to treatment. In addition, we describe the possible clinical use of CEC in chronic kidney disease (CKD) and kidney transplantation. In summary, CEC have been developed as a novel approach to assess the endothelial damage. Measurement of the CEC level would provide an important diagnostic and prognostic value on the endothelium status and the long-term outcome of vascular dysfunction. Kunying Zhang, Fang Yin, and Lin Lin Copyright © 2014 Kunying Zhang et al. All rights reserved. NGS Nominated CELA1, HSPG2, and KCNK5 as Candidate Genes for Predisposition to Balkan Endemic Nephropathy Thu, 15 May 2014 15:15:18 +0000 Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients’ groups, we nominated 3 genes with possible deleterious/damaging variants—CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN. D. Toncheva, M. Mihailova-Hristova, R. Vazharova, R. Staneva, S. Karachanak, P. Dimitrov, V. Simeonov, S. Ivanov, L. Balabanski, D. Serbezov, M. Malinov, V. Stefanovic, R. Čukuranović, M. Polenakovic, L. Jankovic-Velickovic, V. Djordjevic, T. Jevtovic-Stoimenov, D. Plaseska-Karanfilska, A. Galabov, V. Djonov, and I. Dimova Copyright © 2014 D. Toncheva et al. All rights reserved. Heart Failure in Patients with Chronic Kidney Disease: A Systematic Integrative Review Thu, 15 May 2014 12:00:23 +0000 Introduction. Heart failure (HF) is highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) and is strongly associated with mortality in these patients. However, the treatment of HF in this population is largely unclear. Study Design. We conducted a systematic integrative review of the literature to assess the current evidence of HF treatment in CKD patients, searching electronic databases in April 2014. Synthesis used narrative methods. Setting and Population. We focused on adults with a primary diagnosis of CKD and HF. Selection Criteria for Studies. We included studies of any design, quantitative or qualitative. Interventions. HF treatment was defined as any formal means taken to improve the symptoms of HF and/or the heart structure and function abnormalities. Outcomes. Measures of all kinds were considered of interest. Results. Of 1,439 results returned by database searches, 79 articles met inclusion criteria. A further 23 relevant articles were identified by hand searching. Conclusions. Control of fluid overload, the use of beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and optimization of dialysis appear to be the most important methods to treat HF in CKD and ESRD patients. Aldosterone antagonists and digitalis glycosides may additionally be considered; however, their use is associated with significant risks. The role of anemia correction, control of CKD-mineral and bone disorder, and cardiac resynchronization therapy are also discussed. Liviu Segall, Ionut Nistor, and Adrian Covic Copyright © 2014 Liviu Segall et al. All rights reserved. Side Effects of Radiographic Contrast Media: Pathogenesis, Risk Factors, and Prevention Sun, 11 May 2014 13:39:34 +0000 Radiocontrast media (RCM) are medical drugs used to improve the visibility of internal organs and structures in X-ray based imaging techniques. They may have side effects ranging from itching to a life-threatening emergency, known as contrast-induced nephropathy (CIN). We define CIN as acute renal failure occurring within 24–72 hrs of exposure to RCM that cannot be attributed to other causes. It usually occurs in patients with preexisting renal impairment and diabetes. The mechanisms underlying CIN include reduction in medullary blood flow leading to hypoxia and direct tubule cell damage and the formation of reactive oxygen species. Identification of patients at high risk for CIN is important. We have reviewed the risk factors and procedures for prevention, providing a long list of references enabling readers a deep evaluation of them both. The first rule to follow in patients at risk of CIN undergoing radiographic procedure is monitoring renal function by measuring serum creatinine and calculating the eGFR before and once daily for 5 days after the procedure. It is advised to discontinue potentially nephrotoxic medications, to choose radiocontrast media at lowest dosage, and to encourage oral or intravenous hydration. In high-risk patients N-acetylcysteine may also be given. Michele Andreucci, Richard Solomon, and Adis Tasanarong Copyright © 2014 Michele Andreucci et al. All rights reserved. Independent Value of Cardiac Troponin T and Left Ventricular Global Longitudinal Strain in Predicting All-Cause Mortality among Stable Hemodialysis Patients with Preserved Left Ventricular Ejection Fraction Wed, 07 May 2014 08:24:43 +0000 Using a speckle-tracking echocardiography (STE), we recently demonstrated that a left ventricular (LV) global longitudinal strain (GLS) ≥ −15% and the serum cardiac troponin T (cTnT) concentration are associated with mortality in stable hemodialysis patients with preserved LV ejection fraction (LVEF). In this study, we explored the relationship between cTnT and echocardiographic parameters and evaluated whether the prognostic value provided by cTnT is independent of a GLS ≥ −15% and vice versa. Eighty-eight stable hemodialysis patients with preserved LVEF were followed for 31 months. STE studies and measurements of cTnT were performed at baseline. CTnT concentration had a modest correlation with GLS (; ) but had a weak or nonsignificant correlation with other echocardiographic parameters. Adjusting for clinical parameters, hazard ratios for each increase of 0.01 ng/mL in cTnT, and a GLS ≥ −15% on mortality were 1.13 () and 3.09 () without significant interaction between cTnT and GLS ≥ −15%. In addition, an increased cTnT concentration, a GLS ≥ −15%, or their combination showed significant additional predictive value for mortality when included in models consisting of clinical parameters. Therefore, both cTnT and a GLS ≥ −15% are independent predictors of mortality and are useful for risk stratification. Junne-Ming Sung, Chi-Ting Su, Yu-Tzu Chang, Yu-Ru Su, Wei-Chuan Tsai, Saprina P. H. Wang, Chun-Shin Yang, Liang-Miin Tsai, Jyh-Hong Chen, and Yen-Wen Liu Copyright © 2014 Junne-Ming Sung et al. All rights reserved. Habitual Coffee Consumption Enhances Attention and Vigilance in Hemodialysis Patients Mon, 05 May 2014 14:10:14 +0000 Objective. Coffee drinking is the main source of caffeine intake among adult population in the western world. It has been reported that low to moderate caffeine intake has beneficial effect on alertness and cognitive functions in healthy subjects. The aim of this study is to evaluate the impact of habitual coffee consumption on cognitive function in hemodialysis patients. Methods. In a cross-sectional study, 86 patients from a single-dialysis centre underwent assessment by the Montreal Cognitive Assessment tool and evaluation for symptoms of fatigue, mood, and sleep disorders by well-validated questionnaires. The habitual coffee use and the average daily caffeine intake were estimated by participants’ response to a dietary questionnaire. Results. Sixty-seven subjects (78%) consumed black coffee daily, mostly in low to moderate dose. Cognitive impairment was found in three-quarters of tested patients. Normal mental performance was more often in habitual coffee users (25% versus 16%). Regular coffee drinkers achieved higher mean scores on all tested cognitive domains, but a significant positive correlation was found only for items that measure attention and concentration (). Conclusions. Moderate caffeine intake by habitual coffee consumption could have beneficial impact on cognitive function in hemodialysis patients due to selective enhancement of attention and vigilance. Petar M. Nikić, Branislav R. Andrić, Biljana B. Stojimirović, Jasna Trbojevic-Stanković, and Zoran Bukumirić Copyright © 2014 Petar M. Nikić et al. All rights reserved. Elastase and Cathepsin G from Primed Leukocytes Cleave Vascular Endothelial Cadherin in Hemodialysis Patients Sun, 04 May 2014 08:17:57 +0000 Aims. To test the hypothesis that primed PMNLs in blood of chronic kidney disease patients release the active form of elastase and cathepsin G causing degradation of vital proteins and promote tissue damage. Methods. RT-PCR, immunocytochemical staining, immunoblotting, and FACS analyses were used to study these enzymes in hemodialysis patients (HD) versus healthy normal controls (NC). Using PMNLs and endothelial cells cocultivation system we measure the effect of HD PMNLs on the endothelial VE-cadherin, an essential protein for maintaining endothelial integrity. Results. Levels of elastase and cathepsin G were reduced in PMNLs of HD patients, while mRNA enzymes levels were not different. Elevated levels of the active form of these enzymes were found in blood of HD patients compared to NC.HD plasma had higher levels of soluble VE-cadherin present in three molecular forms: whole 140 kDa molecule and two fragments of 100 and 40 kDa. Cocultivation studies showed that primed PMNLs cleave the endothelial cadherin, resulting in a 100 kDa fragment. Conclusions. Elastase and cathepsin G are elevated in the plasma of HD patients, originating from primed PMNLs. In these patients, chronic elevation of these enzymes contributes to cleavage of VE-cadherin and possible disruption of endothelial integrity. Meital Cohen-Mazor, Rafi Mazor, Batya Kristal, and Shifra Sela Copyright © 2014 Meital Cohen-Mazor et al. All rights reserved. Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media? Wed, 30 Apr 2014 00:00:00 +0000 The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. Michele Mussap and Giampaolo Merlini Copyright © 2014 Michele Mussap and Giampaolo Merlini. All rights reserved. Posttransplant Allosensitization in Low Immunological Risk Kidney and Kidney-Pancreas Graft Recipients Tue, 15 Apr 2014 14:03:55 +0000 Introduction. Posttransplantation allosensitization prevalence and effect on kidney grafts outcomes remain unsettled. Methods. Between 2007 and 2012, 408 patients received a primary kidney graft (with 68 patients also receiving a pancreas graft) after a negative cytotoxic crossmatch. All patients had a pretransplant negative anti-HLA screening and 0% panel reactive antibodies. We analyzed retrospectively the results of anti-HLA antibodies screening by Luminex assay, performed between 6 and 24 months after transplant, and searched for the risk factors for antibody positivity and its impact on kidney graft outcomes. Results. Anti-HLA antibodies prevalence at 6 months was 17.4%. Previous steroid-insensitive acute rejection was the only risk factor for both anti-HLA classes detected antibodies. Antithymocyte globulin induction was also a risk factor for anti-HLA-I antibodies. Antibody positivity status was associated with reduced graft function at 12 months and graft survival at 5 years (91.5% versus 96.4%, ). In multivariable Cox analysis, delayed graft function (HR = 6.1, ), HLA mismatches 3 (HR = 10.2, ), and antibody positivity for anti-HLA class II (HR = 5.1, ) or class I/II (HR = 13.8, ) were independent predictors of graft loss. Conclusions. Allosensitization against HLA class after transplant was associated with adverse kidney graft outcomes. A screening protocol seems advisable within the first year in low immunological risk patients. Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Manuela Almeida, Sofia Pedroso, Fátima Freitas, Idalina Beirão, António Castro Henriques, and António Cabrita Copyright © 2014 Jorge Malheiro et al. All rights reserved. Mechanisms of Contrast-Induced Nephropathy Reduction for Saline (NaCl) and Sodium Bicarbonate (NaHCO3) Tue, 15 Apr 2014 00:00:00 +0000 Nephropathy following contrast media (CM) exposure is reduced by administration before, during, and after the contrast procedure of either isotonic sodium chloride solution (Saline) or isotonic sodium bicarbonate solution (IsoBicarb). The reasons for this reduction are not well established for either sodium salt; probable mechanisms are discussed in this paper. For Saline, the mechanism for the decrease in CIN is likely related primarily to the increased tubular flow rates produced by volume expansion and therefore a decreased concentration of the filtered CM during transit through the kidney tubules. Furthermore, increased tubular flow rates produce a slight increase in tubular pH resulting from a fixed acid excretion in an increased tubular volume. The mechanism for the decreased CIN associated with sodium bicarbonate includes the same mechanisms listed for Saline in addition to a renal pH effect. Increased filtered bicarbonate anion raises both tubular pH and tubular bicarbonate anion levels toward blood physiologic levels, thus providing increased buffer for reactive oxygen species (ROS) formed in the tubules as a result of exposure to CM in renal tubular fluid. W. Patrick Burgess and Phillip J. Walker Copyright © 2014 W. Patrick Burgess and Phillip J. Walker. All rights reserved. Urokinase Gene 3′-UTR T/C Polymorphism Is Associated with Malignancy and ESRD in Idiopathic Membranous Nephropathy Mon, 14 Apr 2014 12:14:55 +0000 Idiopathic membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults, and 25% of MN patients proceed to ESRD. Urokinase plasminogen activator (uPA) may play an important role in reducing renal fibrosis. This study was conducted to clarify the relationship between uPA gene polymorphisms and clinical manifestations of MN. We recruited 91 biopsy-diagnosed MN patients and 105 healthy subjects. Genotyping of uPA gene 3′-UTR T/C polymorphism was performed by polymerase chain reaction methods. The genotype distribution had no effect on the development of MN. Thirteen patients (15.9%; ) acquired malignancies and seventeen (20.7%; ) patients progressed to ESRD with the C/C genotype, but no patients with the T/C genotype did. In conclusion, we demonstrated that the presence of the uPA gene 3′-UTR C/C genotype was associated with ESRD as well as acquired malignancies in MN patients. These findings should prompt specific considerations for the treatment of MN patients to maintain a balance between treating disease entities and protecting the immune system from cancers. Cheng-Hsu Chen, Shih-Yin Chen, Kuo-Hsiung Shu, Mei-Chin Wen, Chi-Hung Cheng, Ming-Ju Wu, Tung-Min Yu, Ya-Wen Chuang, and Fuu-Jen Tsai Copyright © 2014 Cheng-Hsu Chen et al. All rights reserved. Prophylaxis of Contrast-Induced Nephrotoxicity Thu, 10 Apr 2014 14:01:10 +0000 Contrast-induced nephrotoxicity (CIN) is a form of acute kidney injury that follows intravascular contrast media exposure. CIN may be preventable because its risk factors are well established and the timing of renal insult is commonly known in advance. However, contrast-induced nephrotoxicity is still the third leading cause of iatrogenic renal failure. This important complication accounts up to 10% of acute renal failure cases in hospitalized patients and it is associated with increased short- and long-term morbidity and mortality. Prolonged hospitalization follows and overall increases healthcare resource utilization. This paper will discuss the various prophylactic procedures tested in clinical trials. Ulla Ludwig and Frieder Keller Copyright © 2014 Ulla Ludwig and Frieder Keller. All rights reserved. Effects of Single Pill-Based Combination Therapy of Amlodipine and Atorvastatin on Within-Visit Blood Pressure Variability and Parameters of Renal and Vascular Function in Hypertensive Patients with Chronic Kidney Disease Tue, 08 Apr 2014 00:00:00 +0000 Both strict blood pressure (BP) control and improvements in BP profile such as BP variability are important for suppression of renal deterioration and cardiovascular complication in hypertension and chronic kidney disease (CKD). In the present study, we examined the beneficial effects of the single pill-based combination therapy of amlodipine and atorvastatin on achievement of the target BP and clinic BP profile, as well as markers of vascular and renal damages in twenty hypertensive CKD patients. The combination therapy with amlodipine and atorvastatin for 16 weeks significantly decreased clinic BP, and achievement of target BP control was attained in an average of 45% after the combination therapy in spite of the presence of no achievement at baseline. In addition, the combination therapy significantly decreased the within-visit BP variability. With respect to the effects on renal damage markers, combination therapy with amlodipine and atorvastatin for 16 weeks significantly decreased albuminuria (urine albumin-to-creatinine ratio, versus  mg/g-Cr, ) without decline in estimated glomerular filtration rate. Concerning parameters of vascular function, the combination therapy significantly improved both brachial-ankle pulse wave velocity (baPWV) and central systolic BP (cSBP) (baPWV, versus  cm/s, ; cSBP, versus  mmHg, ). Collectively, these results suggest that the combination therapy with amlodipine and atorvastatin may exert additional beneficial effects on renal and vascular damages as well as BP profile in addition to BP lowering in hypertension with CKD. Kengo Azushima, Kazushi Uneda, Kouichi Tamura, Hiromichi Wakui, Masato Ohsawa, Ryu Kobayashi, Toru Dejima, Tomohiko Kanaoka, Akinobu Maeda, Yoshiyuki Toya, and Satoshi Umemura Copyright © 2014 Kengo Azushima et al. All rights reserved. Is Contrast Medium Osmolality a Causal Factor for Contrast-Induced Nephropathy? Mon, 31 Mar 2014 14:33:47 +0000 The exact pathophysiology of contrast-induced nephropathy (CIN) is not fully clarified, yet the osmotic characteristics of contrast media (CM) have been a significant focus in many investigations of CIN. Osmotic effects of CM specific to the kidney include transient decreases in blood flow, filtration fraction, and glomerular filtration rate. Potentially significant secondary effects include an osmotically induced diuresis with a concomitant dehydrating effect. Clinical experiences that have compared the occurrence of CIN between the various classes of CM based on osmolality have suggested a much less than anticipated advantage, if any, with a lower osmolality. Recent animal experiments actually suggest that induction of a mild osmotic diuresis in association with iso-osmolar agents tends to offset potentially deleterious renal effects of high viscosity-mediated intratubular CM stagnation. Andreas M. Bucher, Carlo N. De Cecco, U. Joseph Schoepf, Felix G. Meinel, Aleksander W. Krazinski, James V. Spearman, Andrew D. McQuiston, Rui Wang, Judith Bucher, Thomas J. Vogl, and Richard W. Katzberg Copyright © 2014 Andreas M. Bucher et al. All rights reserved. Targeting Spleen Tyrosine Kinase-Bruton’s Tyrosine Kinase Axis for Immunologically Mediated Glomerulonephritis Sun, 30 Mar 2014 07:32:01 +0000 The importance of B-cell activation and immune complex-mediated Fc-receptor activation in the pathogenesis of immunologically mediated glomerulonephritis has long been recognized. The two nonreceptor tyrosine kinases, spleen tyrosine kinase (Syk) and Bruton’s tyrosine kinase (Btk), are primarily expressed by hematopoietic cells, and participate in B-cell-receptor- and Fc-receptor-mediated activation. Pharmacological inhibitors of Syk or Btk are undergoing preclinical development and clinical trials for several immune diseases; and Syk inhibitors have been shown to reduce disease activity in rheumatoid arthritis patients. However, the clinical therapeutic efficacies of these inhibitors in glomerulonephritis have not been evaluated. Herein, we review recent studies of Syk and Btk inhibitors in several experimental primary and secondary glomerulonephritis models. These inhibitors suppressed development of glomerular injury, and also ameliorated established kidney disease. Thus, targeting Syk and Btk signaling pathways is a potential therapeutic strategy for glomerulonephritis, and further evaluation is recommended. Jin-Shuen Chen, Li-Chien Chang, Shyh-Jer Huang, and Chao-Wen Cheng Copyright © 2014 Jin-Shuen Chen et al. All rights reserved. Nonpharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury Wed, 26 Mar 2014 07:14:04 +0000 Contrast-induced AKI (CI-AKI) has been one of the leading causes for hospital-acquired AKI and is associated with independent risk for adverse clinical outcomes including morbidity and mortality. The aim of this review is to provide a brief summary of the studies that focus on nonpharmacological strategies to prevent CI-AKI, including routine identification of at-risk patients, use of appropriate hydration regimens, withdrawal of nephrotoxic drugs, selection of low-osmolar contrast media or isoosmolar contrast media, and using the minimum volume of contrast media as possible. There is no need to schedule dialysis in relation to injection of contrast media or injection of contrast agent in relation to dialysis program. Hemodialysis cannot protect the poorly functioning kidney against CI-AKI. Paweena Susantitaphong and Somchai Eiam-Ong Copyright © 2014 Paweena Susantitaphong and Somchai Eiam-Ong. All rights reserved. Association between Circulating Endothelial Cells and Carotid Atherosclerosis in Patients Receiving Maintenance Hemodialysis Thu, 20 Mar 2014 00:00:00 +0000 Accelerated atherosclerosis is the major cause of mortality in maintenance hemodialysis (MHD) patients, and endothelial injury associated with MHD might contribute strongly to pathogenesis. The current study was designed to explore possible associations between circulating endothelial cells (CECs) and intima-media thickness of common carotid artery (CCA-IMT) as an indicator of carotid atherosclerosis. Sixty-two MHD patients and 26 age- and sex-matched healthy volunteers were recruited. The number of CECs was determined in peripheral blood using multiparametric flow cytometry. CCA-IMT and presence of plaques in the common carotid arteries were assessed with ultrasound. Laboratory tests results and the demographics were recorded. The finding indicated that numbers of CECs were higher in patients before hemodialysis (predialysis) compared with numbers in controls (P = 0.045). CCA-IMT was also significantly higher in patients than in controls (P < 0.01). A positive relationship was observed between predialysis CECs numbers and CCA-IMT (P < 0.01) in MHD patients. In multiple linear regression analysis, the relationship between the predialysis CECs level and CCA-IMT remained the same even if adjusting for confounding effects. Accordingly, the investigation indicates that the CECs level is positively associated with CCA-IMT in our hemodialysis patients. CECs might be an important marker to the severity of carotid atherosclerosis in MHD patients. Zhang Kun-ying, Liu Hui-lan, Duan Xiao-feng, and Li Guo-gang Copyright © 2014 Zhang Kun-ying et al. All rights reserved. Molecular Mechanisms of Renal Cellular Nephrotoxicity due to Radiocontrast Media Tue, 18 Mar 2014 11:43:14 +0000 Modern iodinated radiocontrast media are all based on the triiodinated benzene ring with various chemical modifications having been made over the last few decades in order to reduce their toxicity. However, CIN remains a problem especially in patients with pre-existing renal failure. In vitro studies have demonstrated that all RCM are cytotoxic. RCM administration in vivo may lead to a decrease in renal medullary oxygenation leading to the generation of reactive oxygen species that may cause harmful effects to renal tissue. In addition, endothelin and adenosine release and decreased nitric oxide levels may worsen the hypoxic milieu. In vitro cell culture studies together with sparse in vivo rat model data have shown that important cell signalling pathways are affected by RCM. In particular, the prosurvival and proproliferative kinases Akt and ERK1/2 have been shown to be dephosphorylated (deactivated), whilst proinflammatory/cell death molecules such as the p38 and JNK kinases and the transcription factor NF-κB may be activated by RCM, accompanied by activation of apoptotic mediators such as caspases. Increasing our knowledge of the mechanisms of RCM action may help to develop future therapies for CIN. Ashour Michael, Teresa Faga, Antonio Pisani, Eleonora Riccio, Placido Bramanti, Massimo Sabbatini, Michele Navarra, and Michele Andreucci Copyright © 2014 Ashour Michael et al. All rights reserved. Resistance to Erythropoiesis-Stimulating Agents Is Associated with Arterial Microcalcification in Early Hemodialysis Patients Mon, 17 Mar 2014 12:04:54 +0000 The aim of this study was to evaluate the relationship between arterial microcalcification (AMiC) and erythropoiesis-stimulating agents (ESA) hyporesponsiveness in hemodialysis patients. The presence of AMiC was confirmed by pathologic examination of von Kossa-stained arterial specimens acquired during vascular access surgery. We assessed the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram body weight divided by the hemoglobin level. AMiC was detected in 33 (40.2%) of 82 patients. Patients with diabetes had a higher incidence of AMiC than patients without diabetes. The serum levels of albumin and cholesterol were higher in patients without AMiC than in patients with AMiC. The serum levels of intact parathyroid hormone were lower in patients with AMiC than in patients without AMiC. The serum levels of phosphate and calcium-phosphorus product did not differ between the two groups. The mean EHRI value was higher in patients with AMiC than in patients without AMiC. In multivariate analyses, ESA hyporesponsiveness and diabetes showed a significant association with AMiC. In conclusion, ESA hyporesponsiveness may be a clinical relevant parameters related to AMiC in hemodialysis patients. Hye Sung Won, Su Jin Choi, Yu Seon Yun, Ok-Ran Shin, Yoon Ho Ko, Young Soo Kim, Sun Ae Yoon, and Young Ok Kim Copyright © 2014 Hye Sung Won et al. All rights reserved. Contrast-Induced Acute Kidney Injury: Definition, Epidemiology, and Outcome Mon, 10 Mar 2014 16:25:05 +0000 Contrast-induced acute kidney injury (CI-AKI) is commonly defined as a decline in kidney function occurring in a narrow time window after administration of iodinated contrast material. The incidence of AKI after contrast material administration greatly depends on the specific definition and cutoff values used. Although self-limiting in most cases, postcontrast AKI carries a risk of more permanent renal insufficiency, dialysis, and death. The risk of AKI from contrast material, in particular when administered intravenously for contrast-enhanced CT, has been exaggerated by older, noncontrolled studies due to background fluctuations in renal function. More recent evidence from controlled studies suggests that the risk is likely nonexistent in patients with normal renal function, but there may be a risk in patients with renal insufficiency. However, even in this patient population, the risk of CI-AKI is probably much smaller than traditionally assumed. Since volume expansion is the only preventive strategy with a convincing evidence base, liberal hydration should be encouraged to further minimize the risk. The benefits of the diagnostic information gained from contrast-enhanced examinations will still need to be balanced with the potential risk of CI-AKI for the individual patient and clinical scenario. Felix G. Meinel, Carlo N. De Cecco, U. Joseph Schoepf, and Richard Katzberg Copyright © 2014 Felix G. Meinel et al. All rights reserved. Pharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury Wed, 26 Feb 2014 08:13:02 +0000 Contrast-induced acute kidney injury (CI-AKI) is the most common iatrogenic cause of acute kidney injury after intravenous contrast media administration. In general, the incidence of CI-AKI is low in patients with normal renal function. However, the rate is remarkably elevated in patients with preexisting chronic kidney disease, diabetes mellitus, old age, high volume of contrast agent, congestive heart failure, hypotension, anemia, use of nephrotoxic drug, and volume depletion. Consequently, CI-AKI particularly in high risk patients contributes to extended hospitalizations and increases long-term morbidity and mortality. The pathogenesis of CI-AKI involves at least three mechanisms; contrast agents induce renal vasoconstriction, increase of oxygen free radicals through oxidative stress, and direct tubular toxicity. Several strategies to prevent CI-AKI have been evaluated in experimental studies and clinical trials. At present, intravascular volume expansion with either isotonic saline or sodium bicarbonate solutions has provided more consistent positive results and was recommended in the prevention of CI-AKI. However, the proportion of patients with risk still develops CI-AKI. This review critically evaluated the current evidence for pharmacological strategies to prevent CI-AKI in patients with a risk of developing CI-AKI. Pattharawin Pattharanitima and Adis Tasanarong Copyright © 2014 Pattharawin Pattharanitima and Adis Tasanarong. All rights reserved. Contrast Media Viscosity versus Osmolality in Kidney Injury: Lessons from Animal Studies Sun, 23 Feb 2014 00:00:00 +0000 Iodinated contrast media (CM) can induce acute kidney injury (AKI). CM share common iodine-related cytotoxic features but differ considerably with regard to osmolality and viscosity. Meta-analyses of clinical trials generally failed to reveal renal safety differences of modern CM with regard to these physicochemical properties. While most trials’ reliance on serum creatinine as outcome measure contributes to this lack of clinical evidence, it largely relies on the nature of prospective clinical trials: effective prophylaxis by ample hydration must be employed. In everyday life, patients are often not well hydrated; here we lack clinical data. However, preclinical studies that directly measured glomerular filtration rate, intrarenal perfusion and oxygenation, and various markers of AKI have shown that the viscosity of CM is of vast importance. In the renal tubules, CM become enriched, as water is reabsorbed, but CM are not. In consequence, tubular fluid viscosity increases exponentially. This hinders glomerular filtration and tubular flow and, thereby, prolongs intrarenal retention of cytotoxic CM. Renal cells become injured, which triggers hypoperfusion and hypoxia, finally leading to AKI. Comparisons between modern CM reveal that moderately elevated osmolality has a renoprotective effect, in particular, in the dehydrated state, because it prevents excessive tubular fluid viscosity. Erdmann Seeliger, Diana C. Lenhard, and Pontus B. Persson Copyright © 2014 Erdmann Seeliger et al. All rights reserved. Hemodynamic and Tubular Changes Induced by Contrast Media Tue, 11 Feb 2014 09:09:53 +0000 The incidence of acute kidney injury induced by contrast media (CI-AKI) is the third cause of AKI in hospitalized patients. Contrast media cause relevant alterations both in renal hemodynamics and in renal tubular cell function that lead to CI-AKI. The vasoconstriction of intrarenal vasculature is the main hemodynamic change induced by contrast media; the vasoconstriction is accompanied by a cascade of events leading to ischemia and reduction of glomerular filtration rate. Cytotoxicity of contrast media causes apoptosis of tubular cells with consequent formation of casts and worsening of ischemia. There is an interplay between the negative effects of contrast media on renal hemodynamics and on tubular cell function that leads to activation of renin-angiotensin system and increased production of reactive oxygen species (ROS) within the kidney. Production of ROS intensifies cellular hypoxia through endothelial dysfunction and alteration of mechanisms regulating tubular cells transport. The physiochemical characteristics of contrast media play a critical role in the incidence of CI-AKI. Guidelines suggest the use of either isoosmolar or low-osmolar contrast media rather than high-osmolar contrast media particularly in patients at increased risk of CI-AKI. Older age, presence of atherosclerosis, congestive heart failure, chronic renal disease, nephrotoxic drugs, and diuretics may multiply the risk of CI-AKI. Antonella Caiazza, Luigi Russo, Massimo Sabbatini, and Domenico Russo Copyright © 2014 Antonella Caiazza et al. All rights reserved. Tumour Markers and Kidney Function: A Systematic Review Thu, 06 Feb 2014 16:29:48 +0000 Tumour markers represent useful tools in diagnosis and clinical management of patients with cancer, because they are easy to use, minimally invasive, and easily measured in either blood or urine. Unfortunately, such an ideal marker, as yet, does not exist. Different pathological states may increase the level of a tumour marker in the absence of any neoplasia. Alternatively, low levels of tumour markers could be also found in the presence of neoplasias. We aimed at reviewing studies currently available in the literature examining the association between tumour markers and different renal impairment conditions. Each tumour marker was found to be differently influenced by these criteria; additionally we revealed in many cases a lack of available published data. Giuseppe Coppolino, Davide Bolignano, Laura Rivoli, Giuseppe Mazza, Piera Presta, and Giorgio Fuiano Copyright © 2014 Giuseppe Coppolino et al. All rights reserved. ACE-I/ARB Therapy prior to Contrast Exposure: What Should the Clinician Do? Wed, 29 Jan 2014 00:00:00 +0000 Contrast-induced nephropathy (CIN) is now one of the three leading causes of acute kidney injury in the world. A lot is known about the risk factors of CIN, yet it remains a major cause of morbidity, end stage renal disease, prolonged hospital stay, and increased costs as well as a high mortality. Many patients undergoing contrast-based radiological investigations are treated with angiotensin converting inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) for their cardiac and renal benefits and their known mortality benefits. However, controversy exists among clinicians as to whether ACE-Is and ARBs should be continued or discontinued prior to contrast media exposure. In this paper we review the current evidence on ACE-I/ARB therapy for patients undergoing procedures involving use of contrast media and provide recommendations as to whether these drugs should be continued or held prior to contrast exposure. Robert Kalyesubula, Peace Bagasha, and Mark A. Perazella Copyright © 2014 Robert Kalyesubula et al. All rights reserved. The Association of Long-Functioning Hemodialysis Vascular Access with Prevalence of Left Ventricular Hypertrophy in Kidney Transplant Recipients Tue, 28 Jan 2014 13:44:56 +0000 Left ventricular hypertrophy (LVH) is frequently observed in chronic dialysis patients and is also highly prevalent in kidney transplant recipients. This study evaluates the impact of long-functioning hemodialysis vascular access on LVH in single center cohort of kidney transplant recipients. 162 patients at 8.7 ± 1.8 years after kidney transplantation were enrolled. Echocardiography, carotid ultrasound, and assessment of pulse wave velocity were performed. LVH was defined based on left ventricular mass (LVM) indexed for body surface area (BSA) and height2.7. There were 67 patients with and 95 without patent vascular access. Both study groups were comparable with respect to gender, age, duration of dialysis therapy, and time after transplantation, kidney graft function, and cardiovascular comorbidities. Patients with patent vascular access were characterized by significantly elevated LVM and significantly greater percentage of LVH, based on LVMI/BSA (66.7 versus 48.4%, ). OR for LVH in patients with patent vascular access was 2.39 (1.19–4.76), . Regression analyses confirmed an independent contribution of patent vascular access to higher LVM and increased prevalence of LVH. We concluded that long-lasting patent hemodialysis vascular access after kidney transplantation is associated with the increased prevalence of LVH in kidney transplant recipients. Aureliusz Kolonko, Agata Kujawa-Szewieczek, Magdalena Szotowska, Piotr Kuczera, Jerzy Chudek, and Andrzej Więcek Copyright © 2014 Aureliusz Kolonko et al. All rights reserved. Contrast Media: Are There Differences in Nephrotoxicity among Contrast Media? Wed, 22 Jan 2014 12:04:45 +0000 Iodinated contrast agents are usually classified based upon their osmolality—high, low, and isosmolar. Iodinated contrast agents are also nephrotoxic in some but not all patients resulting in loss of glomerular filtration rate. Over the past 30 years, nephrotoxicity has been linked to osmolality although the precise mechanism underlying such a link has been elusive. Improvements in our understanding of the pathogenesis of nephrotoxicity and prospective randomized clinical trials have attempted to further explore the relationship between osmolality and nephrotoxicity. In this review, the basis for our current understanding that there are little if any differences in nephrotoxic potential between low and isosmolar contrast media will be detailed using data from clinical studies. Richard Solomon Copyright © 2014 Richard Solomon. All rights reserved. Heterogeneous Downregulation of Angiotensin II AT1-A and AT1-B Receptors in Arterioles in STZ-Induced Diabetic Rat Kidneys Tue, 21 Jan 2014 13:05:09 +0000 Introduction. The renin granulation of kidney arterioles is enhanced in diabetes despite the fact that the level of angiotensin II in the diabetic kidney is elevated. Therefore, the number of angiotensin II AT1-A and AT1-B receptors in afferent and efferent arteriole’s renin-positive and renin-negative smooth muscle cells (SMC) was estimated. Method. Immunohistochemistry at the electron microscopic level was combined with 3D stereological sampling techniques. Results. In diabetes the enhanced downregulation of AT1-B receptors in the renin-positive than in the renin-negative SMCs in both arterioles was resulted: the significant difference in the number of AT1 (AT1-A + AT1-B) receptors between the two types of SMCs in the normal rats was further increased in diabetes and in contrast with the significant difference observed between the afferent and efferent arterioles in the normal animals, there was no such difference in diabetes. Conclusions. The enhanced downregulation of the AT1-B receptors in the renin-negative SMCs in the efferent arterioles demonstrates that the regulation of the glomerular filtration rate by the pre- and postglomerular arterioles is changed in diabetes. The enhanced downregulation of the AT1-B receptors in the renin-positive SMCs in the arterioles may result in an enhanced level of renin granulation in the arterioles. Zsolt Razga, Gabor Kovacs, Nikolett Bódi, Petra Talapka, and Jens Randel Nyengaard Copyright © 2014 Zsolt Razga et al. All rights reserved. Serum and Urinary NGAL in Septic Newborns Tue, 21 Jan 2014 11:50:40 +0000 Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a potentially new and highly specific/sensitive marker of acute kidney injury (AKI). The aim of this study was to assess the impact of inflammation on serum and urine NGAL in newborns that were treated due to infection. We determined serum and urine NGAL concentrations in 73 infants (51 with sepsis; 22 with severe sepsis) admitted to the Intensive Care Unit in the first month of life, for three consecutive days during the course of treatment for infection. 29 neonates without infection served as the control group. Septic patients, in particular, severe sepsis patients, had increased serum and urinary NGAL levels in the three subsequent days of observation. Five septic patients who developed AKI had elevated serum and urinary NGAL values to a similar extent as septic neonates without AKI. A strong correlation was found between the concentration of serum and urinary NGAL and inflammatory markers, such as CRP and procalcitonin. Serum and urinary NGAL levels were also significantly associated with NTISS (neonatal therapeutic intervention scoring system) values. We conclude that increased serum and urinary NGAL values are not solely a marker of AKI, and more accurately reflect the severity of inflammatory status. Mike Smertka, Jolanta Wroblewska, Anna Suchojad, Malgorzata Majcherczyk, Danuta Jadamus-Niebroj, Teresa Owsianka-Podlesny, Aniceta Brzozowska, and Iwona Maruniak-Chudek Copyright © 2014 Mike Smertka et al. All rights reserved. Role of Reactive Oxygen Species in Pathogenesis of Radiocontrast-Induced Nephropathy Sun, 29 Dec 2013 13:10:52 +0000 In vitro and in vivo studies have demonstrated enhanced hypoxia and formation of reactive oxygen species (ROS) in the kidney following the administration of iodinated contrast media, which play a relevant role in the development of contrast media-induced nephropathy. Many studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetylcysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy, are prone to enhanced renal parenchymal hypoxia and ROS formation. In this review, the association of renal hypoxia and ROS-mediated injury is outlined. Generated during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular and vascular endothelial injury and might further intensify renal parenchymal hypoxia by virtue of endothelial dysfunction and dysregulation of tubular transport. Preventive strategies conceivably should include inhibition of ROS generation or ROS scavenging. Antonio Pisani, Eleonora Riccio, Michele Andreucci, Teresa Faga, Michael Ashour, Antonella Di Nuzzi, Aldo Mancini, and Massimo Sabbatini Copyright © 2013 Antonio Pisani et al. All rights reserved. A Glimpse of the Pathogenetic Mechanisms of Wnt/β-Catenin Signaling in Diabetic Nephropathy Wed, 25 Dec 2013 11:00:06 +0000 The Wnt family of proteins belongs to a group of secreted lipid-modified glycoproteins with highly conserved cysteine residues. Prior results indicate that Wnt/β-catenin signaling plays a prominent role in cell differentiation, adhesion, survival, and apoptosis and is involved in organ development, tumorigenesis, and tissue fibrosis, among other functions. Accumulating evidence has suggested that Wnt/β-catenin exhibits a pivotal function in the progression of diabetic nephropathy (DN). In this review, we focused on discussing the dual role of Wnt/β-catenin in apoptosis and epithelial mesenchymal transition (EMT) formation of mesangial cells. Moreover, we also elucidated the effect of Wnt/β-catenin in podocyte dysfunction, tubular EMT formation, and renal fibrosis under DN conditions. In addition, the molecular mechanisms involved in this process are introduced. This information provides a novel molecular target of Wnt/β-catenin for the protection of kidney damage and in delay of the progression of DN. Li Xiao, Ming Wang, Shikun Yang, Fuyou Liu, and Lin Sun Copyright © 2013 Li Xiao et al. All rights reserved. Efficacy of Triptolide for Children with Moderately Severe Henoch-Schönlein Purpura Nephritis Presenting with Nephrotic Range Proteinuria: A Prospective and Controlled Study in China Wed, 18 Dec 2013 09:39:56 +0000 Objective. To observe the clinical efficacy of the Chinese herb, Triptolide, in children with moderately severe Henoch-Schönlein purpura nephritis (HSPN). Methods. From January 2007 to December 2011, 56 HSPN children manifested by nephrotic range proteinuria with normal kidney function and 50% crescents or sclerosing lesions on biopsy were hospitalized in the Children’s Hospital of Zhejiang University School of Medicine. They were divided into two groups: the treatment group (; Triptolide at a dosage of 1 mg/kg·d, combined with prednisone at a dosage of 2 mg/kg·d, within a course of medium-to-long-term therapy of 6 to 9 months) and the control group (; prednisone alone, with the same procedure). Results. Short-term remission was observed in 95% of patients from treatment group and in 72% of patients from control group, respectively. There was a significant difference between both groups (, ) for short-term effects. Meanwhile, no significant difference, as proteinuria, hematuria, hypertension, and decreased eGFR, was observed between the two groups in long-term followup (, ). The Kaplan-Meier plot analysis also revealed no significant difference (, ). Conclusion. Triptolide is effective in relieving short-term symptoms for moderately severe HSPN children, though its long-term effects need to be observed further. Li Wu, Jianhua Mao, Xia Jin, Haidong Fu, Huijun Shen, Jingjing Wang, Aimin Liu, Qiang Shu, and Lizhong Du Copyright © 2013 Li Wu et al. All rights reserved. N-Acetylcysteine Prevents Hypertension via Regulation of the ADMA-DDAH Pathway in Young Spontaneously Hypertensive Rats Tue, 17 Dec 2013 13:43:45 +0000 Asymmetric dimethylarginine (ADMA) reduces nitric oxide (NO), thus causing hypertension. ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH), which can be inhibited by oxidative stress. N-Acetylcysteine (NAC), an antioxidant, can facilitate glutathione (GSH) synthesis. We aimed to determine whether NAC can prevent hypertension by regulating the ADMA-DDAH pathway in spontaneously hypertensive rats (SHR). Rats aged 4 weeks were assigned into 3 groups (/group): control Wistar Kyoto rats (WKY), SHR, and SHR receiving 2% NAC in drinking water. All rats were sacrificed at 12 weeks of age. SHR had higher blood pressure than WKY, whereas NAC-treated animals did not. SHR had elevated plasma ADMA levels, which was prevented by NAC therapy. SHR had lower renal DDAH activity than WKY, whereas NAC-treated animals did not. Renal superoxide production was higher in SHR than in WKY, whereas NAC therapy prevented it. NAC therapy was also associated with higher GSH-to-oxidized GSH ratio in SHR kidneys. Moreover, NAC reduced oxidative stress damage in SHR. The observed antihypertensive effects of NAC in young SHR might be due to restoration of DDAH activity to reduce ADMA, leading to attenuation of oxidative stress. Our findings highlight the impact of NAC on the development of hypertension by regulating ADMA-DDAH pathway. Nai-Chia Fan, Chih-Min Tsai, Chien-Ning Hsu, Li-Tung Huang, and You-Lin Tain Copyright © 2013 Nai-Chia Fan et al. All rights reserved. Impact of Mannose-Binding Lectin Deficiency on Radiocontrast-Induced Renal Dysfunction Tue, 10 Dec 2013 13:09:44 +0000 Contrast-induced nephropathy (CIN) is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL), a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R) injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN. Michael Osthoff and Marten Trendelenburg Copyright © 2013 Michael Osthoff and Marten Trendelenburg. All rights reserved. Why Is Diabetes Mellitus a Risk Factor for Contrast-Induced Nephropathy? Thu, 21 Nov 2013 13:55:44 +0000 Contrast-induced nephropathy (CIN) remains a leading cause of iatrogenic acute kidney injury, as the usage of contrast media for imaging and intravascular intervention keeps expanding. Diabetes is an important predisposing factor for CIN, particularly in patients with renal functional impairment. Renal hypoxia, combined with the generation of reactive oxygen species, plays a central role in the pathogenesis of CIN, and the diabetic kidney is particularly susceptible to intensified hypoxic and oxidative stress following the administration of contrast media. The pathophysiology of this vulnerability is complex and involves various mechanisms, including a priori enhanced tubular transport activity, oxygen consumption, and the generation of reactive oxygen species. The regulation of vascular tone and peritubular blood flow may also be altered, particularly due to defective nitrovasodilation, enhanced endothelin production, and a particular hyperresponsiveness to adenosine-related vasoconstriction. In addition, micro- and macrovascular diseases and chronic tubulointerstitial changes further compromise regional oxygen delivery, and renal antioxidant capacity might be hampered. A better understanding of these mechanisms and their control in the diabetic patient may initiate novel strategies in the prevention of contrast nephropathy in these susceptible patients. Samuel N. Heyman, Christian Rosenberger, Seymour Rosen, and Mogher Khamaisi Copyright © 2013 Samuel N. Heyman et al. All rights reserved. Dual Inhibiting Senescence and Epithelial-to-Mesenchymal Transition by Erythropoietin Preserve Tubular Epithelial Cell Regeneration and Ameliorate Renal Fibrosis in Unilateral Ureteral Obstruction Tue, 19 Nov 2013 14:54:40 +0000 This study aims to investigate the renoprotective effect of recombinant human erythropoietin (rhEPO) treatment could preserve tubular epithelial cell regeneration and ameliorate renal fibrosis by dual inhibition of stress-induced senescence and EMT in unilateral ureteric obstruction (UUO) mouse model. UUO or sham-operated mice were randomly assigned to receive rhEPO or vehicle treatment and were sacrificed on days 3, 7, and 14. Kidney specimens were fixed for histopathological and immunohistochemical study. The expression of S100A4, TGF-β1, BMP-7, Smad2/3, Smad1/5/8, and was determined by western blot and real-time RT-PCR. Vehicle treated UUO mice had increased tubular atrophy and interstitial fibrosis within 3 to 14 days. An increase in TGF-β1, Smad2/3, S100A4, and expression and a decrease in BMP-7 and Smad1/5/8 expression were observed in the obstructed kidneys. was positively correlated with TGF-β1/Smad2/3 and negatively correlated with BMP-7/Smad1/5/8 in UUO mice. rhEPO treatment significantly suppressed the upregulation of TGF-β, Smad2/3, S100A4, and and preserved the downregulation of BMP-7 and Smad1/5/8, resulting in markedly reduced TA/IF compared to the vehicle treated mice. The renoprotective effects of rhEPO could ameliorate renal TA/IF by modulating senescence and EMT which could be a part of therapeutic option in patients with chronic kidney disease. Adis Tasanarong, Supranee Kongkham, and Sookkasem Khositseth Copyright © 2013 Adis Tasanarong et al. All rights reserved. Role of Intracellular Ca2+ and Na+/Ca2+ Exchanger in the Pathogenesis of Contrast-Induced Acute Kidney Injury Mon, 18 Nov 2013 09:38:24 +0000 The precise mechanisms underlying contrast-induced acute kidney injury (CI-AKI) are not well understood. Intracellular Ca2+ overload is considered to be a key factor in CI-AKI. Voltage-dependent Ca2+ channel (VDC) and Na+/Ca2+ exchanger (NCX) system are the main pathways of intracellular Ca2+ overload in pathological conditions. Here, we review the potential underlying mechanisms involved in CI-AKI and discuss the role of NCX-mediated intracellular Ca2+ overload in the contrast media-induced renal tubular cell injury and renal hemodynamic disorder. Dingping Yang and Dingwei Yang Copyright © 2013 Dingping Yang and Dingwei Yang. All rights reserved. Tumor Necrosis Factor Receptor 2: Its Contribution to Acute Cellular Rejection and Clear Cell Renal Carcinoma Sun, 17 Nov 2013 09:28:52 +0000 Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein and one of the two receptors that orchestrate the complex biological functions of tumor necrosis factor (TNF, also designed TNF-α). Accumulating experimental evidence suggests that TNFR2 plays an important role in renal disorders associated with acute cellular rejection and clear cell renal carcinoma but its exact role in these settings is still not completely understood. This papers reviews the factors that may mediate TNFR2 induction in acute cellular rejection and clear cell renal carcinoma and its contribution to these conditions and discusses its therapeutic implications. A greater understanding of the function of TNFR2 may lead to the development of new anti-TNF drugs. Jun Wang and Rafia S. Al-Lamki Copyright © 2013 Jun Wang and Rafia S. Al-Lamki. All rights reserved. Comparison of a Bayesian Network with a Logistic Regression Model to Forecast IgA Nephropathy Sun, 17 Nov 2013 07:59:47 +0000 Models are increasingly used in clinical practice to improve the accuracy of diagnosis. The aim of our work was to compare a Bayesian network to logistic regression to forecast IgA nephropathy (IgAN) from simple clinical and biological criteria. Retrospectively, we pooled the results of all biopsies performed by nephrologists in a specialist clinical facility between 2002 and 2009. Two groups were constituted at random. The first subgroup was used to determine the parameters of the models adjusted to data by logistic regression or Bayesian network, and the second was used to compare the performances of the models using receiver operating characteristics (ROC) curves. IgAN was found (on pathology) in 44 patients. Areas under the ROC curves provided by both methods were highly significant but not different from each other. Based on the highest Youden indices, sensitivity reached (100% versus 67%) and specificity (73% versus 95%) using the Bayesian network and logistic regression, respectively. A Bayesian network is at least as efficient as logistic regression to estimate the probability of a patient suffering IgAN, using simple clinical and biological data obtained during consultation. Michel Ducher, Emilie Kalbacher, François Combarnous, Jérome Finaz de Vilaine, Brigitte McGregor, Denis Fouque, and Jean Pierre Fauvel Copyright © 2013 Michel Ducher et al. All rights reserved. Hippuric Acid as a Significant Regulator of Supersaturation in Calcium Oxalate Lithiasis: The Physiological Evidence Thu, 07 Nov 2013 14:16:11 +0000 At present, the clinical significance of existing physicochemical and biological evidence and especially the results we have obtained from our previous in vitro experiments have been analyzed, and we have come to the conclusion that hippuric acid (C6H5CONHCH2COOH) is a very active solvent of Calcium Oxalate (CaOX) in physiological solutions. Two types of experiments have been discussed: clinical laboratory analysis on the urine excretion of hippuric acid (HA) in patients with CaOX lithiasis and detailed measurements of the kinetics of the dissolution of CaOX calculi in artificial urine, containing various concentrations of HA. It turns out that the most probable value of the HA concentration in the control group is approximately ten times higher than the corresponding value in the group of the stone-formers. Our in vitro analytical measurements demonstrate even a possibility to dissolve CaOX stones in human urine, in which increased concentration of HA have been established. A conclusion can be that drowning out HA is a significant regulator of CaOX supersaturation and thus a regulation of CaOX stone formation in human urine. Discussions have arisen to use increased concentration of HA in urine both as a solubilizator of CaOX stones in the urinary tract and on the purpose of a prolonged metaphylactic treatment. Stoyanka S. Atanassova and Ivan S. Gutzow Copyright © 2013 Stoyanka S. Atanassova and Ivan S. Gutzow. All rights reserved. Angiopoietin-Like 3 Induces Podocyte F-Actin Rearrangement through Integrin /FAK/PI3K Pathway-Mediated Rac1 Activation Tue, 05 Nov 2013 11:47:17 +0000 Glomerular podocytes are highly differentiated cells whose foot processes, which are mainly maintained by the architecture of actin filaments, have a unique morphology. A rearrangement of F-actin in podocytes causes changes in their motility that involve foot process effacement and proteinuria in glomerular diseases. Members of the Rho family small GTPases, especially RhoA, Rac1, and Cdc42, are key molecules in the regulation of actin cytoskeleton rearrangement. Our previous study showed that angiopoietin-like 3 (Angptl3) can increase the motility of podocytes in vitro. In this study, we found that recombinant Angptl3 treatment, together with the activation of Rac1, could cause F-actin rearrangement in podocytes. We also found that these effects could be blocked by an integrin inhibitor, implicating integrin as the Angptl3 receptor in its effects on actin cytoskeleton rearrangement. In addition, we studied the molecular pathway for this process. Our results showed that in podocytes, Angptl3 could induce actin filament rearrangement, mainly in lamellipodia formation, and that this process was mediated by integrin -mediated FAK and PI3K phosphorylation and Rac1 activation. Our results might provide a new explanation for the effect of Angptl3 on increasing podocyte motility. Yi Lin, Jia Rao, Xi-liang Zha, and Hong Xu Copyright © 2013 Yi Lin et al. All rights reserved. Mycobacterium tuberculosis Infection following Kidney Transplantation Tue, 08 Oct 2013 13:52:23 +0000 Introduction and Aims. Post-transplant tuberculosis (TB) is a problem in successful long-term outcome of renal transplantation recipients. Our objective was to describe the pattern and risk factors of TB infection and the prognosis in our transplant recipients. Patients and Methods. This study was a retrospective review of the records of 491 renal transplant recipients in our hospital during the period from January 1986 to December 2009. The demographic data, transplant characteristics, clinical manifestations, diagnostic criteria, treatment protocol, and long-term outcome of this cohort of patients were analyzed. Results. 16 patients (3,2%) developed post-transplant TB with a mean age of 32,5 ± 12,7 (range: 13–60) years and a mean post-transplant period of 36,6months (range: 12,3 months–15,9 years). The forms of the diseases were pulmonary in 10/16 (62,6%), disseminated in 3/16 (18,7%), and extrapulmonary in 3/16 (18,7%). Graft dysfunction was observed in 7 cases (43,7%) with tissue-proof acute rejection in 3 cases and loss of the graft in 4 cases. Hepatotoxicity developed in 3 patients (18,7%) during treatment. Recurrences were observed in 4 cases after early stop of treatment. Two patients (12.5%) died. Conclusion. Extra pulmonary and disseminated tuberculosis were observed in third of our patients. More than 9months of treatment may be necessary to prevent recurrence. Karima Boubaker, Tahar Gargah, Ezzedine Abderrahim, Taieb Ben Abdallah, and Adel Kheder Copyright © 2013 Karima Boubaker et al. All rights reserved. Organic Anion Transporter 5 Renal Expression and Urinary Excretion in Rats with Vascular Calcification Wed, 02 Oct 2013 15:00:47 +0000 It has been described renal damage in rats with vascular calcification. The organic anion transporter 5 (Oat5) is only expressed in kidney, and its urinary excretion was proposed as potential early biomarker of renal injury. The aim of this study was to evaluate the Oat5 renal expression and its urinary excretion in an experimental model of vascular calcification in comparison with traditional markers of renal injury. Vascular calcification was obtained by the administration of an overdose of vitamin D3 (300,000 IU/kg, b.w., i.m.) to male Wistar rats. Oat5 urinary abundance was evaluated by Western blotting. Traditional markers of renal injury, such as creatinine and urea plasma levels, urinary protein levels, and urinary alkaline phosphatase (AP) activity, were determined using commercial kits. Histology was assessed by hematoxylin/eosin staining. Oat5 renal expression was evaluated by Western blotting and by immunohistochemistry. An increased expression of Oat5 in renal homogenates, in apical membranes, and in its urinary excretion was observed in rats with vascular calcification. The traditional parameters used to evaluate renal function were not modified, with the exception of histology. It is possible to postulate the urinary excretion of Oat5 as a potential noninvasive biomarker of renal injury associated with vascular calcification. María Herminia Hazelhoff, Romina Paula Bulacio, and Adriana Mónica Torres Copyright © 2013 María Herminia Hazelhoff et al. All rights reserved. Nephrolithiasis: Molecular Mechanism of Renal Stone Formation and the Critical Role Played by Modulators Sat, 14 Sep 2013 08:40:42 +0000 Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person’s ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation. Kanu Priya Aggarwal, Shifa Narula, Monica Kakkar, and Chanderdeep Tandon Copyright © 2013 Kanu Priya Aggarwal et al. All rights reserved. Low Serum Concentration of Obestatin as a Predictor of Mortality in Maintenance Hemodialysis Patients Thu, 12 Sep 2013 08:22:56 +0000 Obestatin, a proposed anorexigenic gut hormone, has been shown to have a number of beneficial cardiotropic effects in experimental studies. We hypothesized that obestatin alteration in hemodialysis patients may link to clinical outcomes. This cross-sectional study with prospective followup for almost 4 years was performed on 94 prevalent hemodialysis patients. Obestatin, leptin, proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6, and various nutritional markers were measured. Patients with low obestatin levels, defined as a level less than median, had a worse all-cause mortality and cardiovascular mortality. The crude all-cause (HR 2.23, 95% CI 1.17 to 4.24) and cardiovascular mortality hazard ratios (HR 4.03, 95% CI 1.27 to 12.76) in these patients continued to be significant after adjustment for various confounders for all-cause mortality. Across the four obestatin-TNF-α categories, the group with low obestatin and high TNF-α (above median level) exhibited a worse outcome in both all-cause mortality and cardiovascular mortality. Clinical characteristics of patients in low obestatin high TNF-α group did not differ from other obestatin-TNF-α categorized groups. In summary, low serum obestatin concentration is an independent predictor of mortality in prevalent hemodialysis patients. Novel interactions were observed between obestatin and TNF-α, which were associated with mortality risk, especially those due to cardiovascular causes. Ilia Beberashvili, Inna Sinuani, Ada Azar, Hadas Kadoshi, Gregory Shapiro, Leonid Feldman, Judith Sandbank, and Zhan Averbukh Copyright © 2013 Ilia Beberashvili et al. All rights reserved. “Zebrafishing” for Novel Genes Relevant to the Glomerular Filtration Barrier Wed, 11 Sep 2013 11:44:47 +0000 Data for genes relevant to glomerular filtration barrier function or proteinuria is continually increasing in an era of microarrays, genome-wide association studies, and quantitative trait locus analysis. Researchers are limited by published literature searches to select the most relevant genes to investigate. High-throughput cell cultures and other in vitro systems ultimately need to demonstrate proof in an in vivo model. Generating mammalian models for the genes of interest is costly and time intensive, and yields only a small number of test subjects. These models also have many pitfalls such as possible embryonic mortality and failure to generate phenotypes or generate nonkidney specific phenotypes. Here we describe an in vivo zebrafish model as a simple vertebrate screening system to identify genes relevant to glomerular filtration barrier function. Using our technology, we are able to screen entirely novel genes in 4–6 weeks in hundreds of live test subjects at a fraction of the cost of a mammalian model. Our system produces consistent and reliable evidence for gene relevance in glomerular kidney disease; the results then provide merit for further analysis in mammalian models. Nils Hanke, Lynne Staggs, Patricia Schroder, Jennifer Litteral, Susanne Fleig, Jessica Kaufeld, Cornelius Pauli, Hermann Haller, and Mario Schiffer Copyright © 2013 Nils Hanke et al. All rights reserved. What Is the Role of Apelin regarding Cardiovascular Risk and Progression of Renal Disease in Type 2 Diabetic Patients with Diabetic Nephropathy? Mon, 09 Sep 2013 13:40:10 +0000 Aims. To evaluate the association of different apelin levels with cardiovascular mortality, hospitalization, renal function, and cardiovascular risk factors in type 2 diabetic patients with mild to moderate CKD. Methods. An observational, prospective study involving 150 patients divided into groups according to baseline apelin levels:  pg/mL, 2 = 98–328 pg/mL, and  pg/mL. Baseline characteristics were analyzed and compared. Multivariate Cox regression was used to find out predictors of cardiovascular mortality, and multivariate logistic regression was used to find out predictors of hospitalization and disease progression. Simple linear regressions and Pearson correlations were used to investigate correlations between apelin and renal disease and cardiovascular risk factors. Results. Patients’ survival at 83 months in groups 1, 2, and 3 was 39%, 40%, and 71.2%, respectively (). Apelin, age, and eGFR were independent predictors of mortality, and apelin, creatinine, eGFR, resistin, and visfatin were independent predictors of hospitalization. Apelin levels were negatively correlated with cardiovascular risk factors and positively correlated with eGFR. Patients with lower apelin levels were more likely to start a depurative technique. Conclusions. Apelin levels might have a significant clinical use as a marker/predictor of cardiovascular mortality and hospitalization or even as a therapeutic agent for CKD patients with cardiovascular disease. Ana Paula Silva, André Fragoso, Claudia Silva, Carla Viegas, Nelson Tavares, Patrícia Guilherme, Nélio Santos, Fátima Rato, Ana Camacho, Cidália Cavaco, Victor Pereira, Marilia Faísca, João Ataíde, Ilídio Jesus, and Pedro Neves Copyright © 2013 Ana Paula Silva et al. All rights reserved. Different Impact of Pretransplant Anti-HLA Antibodies Detected by Luminex in Highly Sensitized Renal Transplanted Patients Thu, 05 Sep 2013 08:40:57 +0000 It is well know that anti-HLA antibodies are an important obstacle in kidney transplantation. Our aim was to study the clinical impact of pretransplant donor specific anti-HLA antibodies (HLA-DSA), in highly sensitized (HS) patients. We analyzed retrospectively the day-of-transplant sera by Luminex Single Antigen Assay (LSA) in HS patients, and the results were correlated with episodes of humoral and cellular rejection as well as with graft and patient survival. All HS subjects received the same induction therapy and rejection episodes were biopsy proven. Thirteen patients (56.5%) preformed HLA-DSA, and we observed higher incidence of acute rejection in aforementioned patients than in the pre-transplant negatives DSA recipients (77% versus 30%, ). The one-year graft survival was significantly reduced in positive pre-transplant HLA-DSA patients (60% versus 100%, Breslow). The positive predicted value of HLA-DSA in relation to rejection reached 100% if patients lost their previous graft in the first year after transplant. Among anti-HLA antibodies present in patients before transplant, HLA-DSA were significantly associated with high risk of acute humoral and cellular rejection and reduced graft survival in posttransplant outcome. The negative impact of these antibodies was even higher when patients suffered an early loss of the previous transplant. Isabel Pérez-Flores, Jose Luis Santiago, Natividad Calvo-Romero, Alberto Barrientos-Guzmán, and Ana Isabel Sánchez-Fructuoso Copyright © 2013 Isabel Pérez-Flores et al. All rights reserved. Urinary IgG and α2-Macroglobulin Are Powerful Predictors of Outcome and Responsiveness to Steroids and Cyclophosphamide in Idiopathic Focal Segmental Glomerulosclerosis with Nephrotic Syndrome Wed, 04 Sep 2013 15:24:46 +0000 Objective. To assess whether high-molecular-weight proteins excretion predicts outcome and therapy-responsiveness in patients with FSGS and nephrotic syndrome. Research Design and Methods. Thirty-eight patients measured at biopsy fractional excretion of IgG (FEIgG) and urinary α2-macroglobulin/creatinine ratio (α2m/C). Low and high risk groups were defined by cutoffs assessed by ROC analysis. In all patients first-line therapy was with steroids alone or in combination with cyclophosphamide. Results. α2m/C and FEIgG were correlated with segmental sclerosis (; ). Twenty-three patients (61%) entered Remission and 9 (24%) progressed to ESRD. Comparing low and high risk groups, by univariate analysis remission was predicted by FEIgG (77% versus 25%, ) and α2m/C (81% versus 17%, ) and ESRD at best by FEIgG (0% versus 75%, ) and α2m/C (4% versus 67%, ). By multivariate analysis FEIgG was the only independent predictor of remission and α2m/C the most powerful predictor of ESRD. Low and high risk groups of FEIgG and α2m/C in combination had very high predictive value of sustained remission and ESRD in response to therapy. Conclusions. FEIgG and α2m/C are powerful predictors of outcome and responsiveness to steroids and cyclophosphamide; their predictive value, if validated in prospective studies, may be useful in clinical practice suggesting first-line alternative treatments in high risk patients. Claudio Bazzi, Virginia Rizza, Daniela Casellato, Gilda Stivali, Gregorio Rachele, Pietro Napodano, Maurizio Gallieni, and Giuseppe D'Amico Copyright © 2013 Claudio Bazzi et al. All rights reserved. Role of the eNOS-NO System in Regulating the Antiproteinuric Effects of VEGF Receptor 2 Inhibition in Diabetes Thu, 22 Aug 2013 08:45:46 +0000 Subtle perturbations in intraglomerular VEGF/VEGFR-2 signaling or in the influencing microenvironment can profoundly affect renal function, resulting in the apparently paradoxical observation that VEGF blockade attenuates proteinuria development in experimental diabetes despite exerting the opposite effect under other circumstances. In the present study, we sought to explore the role of eNOS-NO activity in regulating the differential response to VEGF blockade in the diabetic and nondiabetic settings. In a rodent model of accelerated renal injury, the transgenic (mRen-2)27 (Ren-2) rat, VEGFR-2 inhibition with the small molecule vandetanib resulted in an increase in urine protein excretion preceding a subsequent rise in systolic blood pressure. When compared to their normoglycaemic counterparts, diabetic Ren-2 rats exhibited an increase in the renal expression of eNOS and in urinary excretion of nitric oxide (NO) metabolites. In contrast to the heavy proteinuria observed with vandetanib in nondiabetic TGR(mRen-2)27 rats, VEGFR-2 inhibition reduced urine protein excretion in diabetic animals, despite a comparable magnitude of histological injury. However, proteinuria was markedly increased by concomitant treatment of diabetic Ren-2 rats with vandetanib and the nitric oxide synthase inhibitor L-NAME. These observations highlight the pivotal role that the eNOS-NO system plays in regulating the biologic response to VEGF within the glomerulus. Andrew Advani, Kim A. Connelly, Suzanne L. Advani, Kerri Thai, Yuan Zhang, Darren J. Kelly, and Richard E. Gilbert Copyright © 2013 Andrew Advani et al. All rights reserved. Which Vitamin D in CKD-MBD? The Time of Burning Questions Wed, 07 Aug 2013 13:46:24 +0000 Vitamin D is a common treatment against secondary hyperparathyroidism in renal patients. However, the rationale for the prescription of vitamin D sterols in chronic kidney disease (CKD) is rapidly increasing due to the coexistence of growing expectancies close to unsatisfactory evidences, such as (1) the lack of randomized controlled trials (RCTs) proving the superiority of any vitamin D sterol against placebo on patients centered outcomes, (2) the scanty clinical data on head to head comparisons between the multiple vitamin D sterols currently available, (3) the absence of RCTs confirming the crescent expectations on nutritional vitamin D pleiotropic effects even in CKD patients, (4) the promising effects of vitamin D receptors activators (VDRA) against proteinuria and myocardial hypertrophy in diabetic CKD cohorts, and (5) the conflicting data on the impact on mortality of VDRA versus calcimimetic centered regimens to control CKD-MBD. The present review arguments these issues focusing on the opened questions that nephrologists should consider dealing with the prescription of nutritional vitamin D or VDRA and with the choice of a VDRA versus a calcimimetic based regimen in CKD-MBD patients. Andrea Galassi, Antonio Bellasi, Sara Auricchio, Sergio Papagni, and Mario Cozzolino Copyright © 2013 Andrea Galassi et al. All rights reserved. Cardiovascular and Renal Effects of Bromocriptine in Diabetic Patients with Stage 4 Chronic Kidney Disease Sun, 04 Aug 2013 10:35:41 +0000 Objective. The objective of this study was to investigate the effect of bromocriptine (BEC) on left ventricular mass index (LVMI) and residual renal function (RRF) in chronic kidney disease (CKD) patients with type 2 diabetes (T2D). Research Design and Methods. A 6-month double-blind randomized controlled trial was conducted in 28 patients with T2D and stage 4 CKD with increased LVMI. Fourteen patients received BEC (2.5 mg, initially 1 tablet with subsequent increase to three times a day) and 14 received a placebo (PBO; initially 1 tablet with subsequent increase to three times a day). Cardiovascular changes were assessed by monitoring 24 h ambulatory blood pressure, two-dimensional-guided M-mode echocardiography, and N-terminal brain natriuretic peptide (NT-proBNP) plasma levels. RRF was evaluated by creatinine clearance and cystatin-C plasma levels. Results. Both BEC and PBO groups decreased blood pressure—but the effect was more pronounced in the BEC group. Average 24 h, diurnal and nocturnal blood pressures, and circadian profile showed improved values compared to the PBO group; LVMI decreased by 14% in BEC and increased by 8% in PBO group. NT-proBNP decreased in BEC ( to  pg/mL) and increased in PBO ( to  pg/mL). Creatinine clearance did not change in the BEC group and decreased in the PBO group. Conclusions. BEC resulted in a decrease on blood pressure and LVMI. BEC also prevented the progression of CKD while maintaining the creatinine clearance unchanged. Oliva Mejía-Rodríguez, Jorge E. Herrera-Abarca, Guillermo Ceballos-Reyes, Marcela Avila-Diaz, Carmen Prado-Uribe, Francisco Belio-Caro, Antonio Salinas-González, Helios Vega-Gomez, Cleto Alvarez-Aguilar, Bengt Lindholm, Elvia García-López, and Ramón Paniagua Copyright © 2013 Oliva Mejía-Rodríguez et al. All rights reserved. Dietary Intake as a Link between Obesity, Systemic Inflammation, and the Assumption of Multiple Cardiovascular and Antidiabetic Drugs in Renal Transplant Recipients Tue, 30 Jul 2013 12:34:18 +0000 We evaluated dietary intake and nutritional-inflammation status in ninety-six renal transplant recipients, years after transplantation. Patients were classified as normoweight (NW), overweight (OW), and obese (OB), if their body mass index was between 18.5 and 24.9, 25.0 and 29.9, and ≥30 kg/m2, respectively. Food composition tables were used to estimate nutrient intakes. The values obtained were compared with those recommended in current nutritional guidelines. 52% of the patients were NW, 29% were OW, and 19% were OB. Total energy, fat, and dietary n-6 PUFAs intake was higher in OB than in NW. IL-6 and hs-CRP were higher in OB than in NW. The prevalence of multidrug regimen was higher in OB. In all patients, total energy, protein, saturated fatty acids, and sodium intake were higher than guideline recommendations. On the contrary, the intake of unsaturated and n-6 and n-3 polyunsaturated fatty acids and fiber was lower than recommended. In conclusion, the prevalence of obesity was high in our patients, and it was associated with inflammation and the assumption of multiple cardiovascular and antidiabetic drugs. Dietary intake did not meet nutritional recommendations in all patients, especially in obese ones, highlighting the need of a long-term nutritional support in renal transplant recipients. Bruna Guida, Mauro Cataldi, Immacolata Daniela Maresca, Roberta Germanò, Rossella Trio, Anna Maria Nastasi, Stefano Federico, Andrea Memoli, Luca Apicella, Bruno Memoli, and Massimo Sabbatini Copyright © 2013 Bruna Guida et al. All rights reserved. Clinical Benefits of an Adherence Monitoring Program in the Management of Secondary Hyperparathyroidism with Cinacalcet: Results of a Prospective Randomized Controlled Study Thu, 18 Jul 2013 11:51:31 +0000 Background/Aims. One of the causes of uncontrolled secondary hyperparathyroidism (sHPT) is patient’s poor drug adherence. We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet. Methods. Prospective, randomized, controlled, multicenter, open-label study. Fifty hemodialysis patients on a stable dose of cinacalcet were randomized to an integrated care approach (IC) or usual care approach (UC). In the IC group, cinacalcet adherence was monitored using an electronic system. Results were discussed with the patients in motivational interviews, and drug prescription adapted accordingly. In the UC group, drug adherence was monitored, but results were not available. Results. At six months, 84% of patients in the IC group achieved recommended iPTH targets versus 55% in the UC group (). The mean cinacalcet taking adherence improved by 10.8% in the IC group and declined by 5.3% in the UC group (). Concomitantly, the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group (). Conclusions. The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet. Valentina Forni Ogna, Menno Pruijm, Carole Zweiacker, Grégoire Wuerzner, Eric Tousset, and Michel Burnier Copyright © 2013 Valentina Forni Ogna et al. All rights reserved. Concerted Action of ANP and Dopamine D1-Receptor to Regulate Sodium Homeostasis in Nephrotic Syndrome Mon, 15 Jul 2013 11:17:34 +0000 The edema formation in nephrotic syndrome (NS) is associated with a blunted response to atrial natriuretic peptide (ANP). The natriuretic effects of ANP have been related to renal dopamine D1-receptors (D1R). We examined the interaction between ANP and renal D1R in rats with puromycin aminonucleoside-induced NS (PAN-NS). Urinary sodium, cyclic guanosine monophosphate (cGMP) excretion, and D1R protein expression and localization in renal tubules were evaluated in PAN-NS and control rats before and during volume expansion (VE). The effects of zaprinast (phosphodiesterase type 5 inhibitor), alone or in combination with Sch-23390 (D1R antagonist), were examined in both groups. The increased natriuresis and urinary cGMP excretion evoked by acute VE were blunted in PAN-NS despite increased levels of circulating ANP. This was accompanied in PAN-NS by a marked decrease of D1R expression in the renal tubules. Infusion of zaprinast in PAN-NS resulted in increased urinary excretion of cGMP and sodium to similar levels of control rats and increased expression of D1R in the plasma membrane of renal tubular cells. Combined administration of Sch-23390 and zaprinast prevented natriuresis and increased cGMP excretion induced by zaprinast alone. We conclude that D1R may play a major role in the ANP resistance observed in PAN-NS. Cátia Fernandes-Cerqueira, Benedita Sampaio-Maia, Janete Quelhas-Santos, Mónica Moreira-Rodrigues, Liliana Simões-Silva, Ana M. Blazquez-Medela, C. Martinez-Salgado, Jose M. Lopez-Novoa, and Manuel Pestana Copyright © 2013 Cátia Fernandes-Cerqueira et al. All rights reserved. Factors Affecting Graft Survival among Patients Receiving Kidneys from Live Donors: A Single-Center Experience Wed, 26 Jun 2013 11:34:31 +0000 Introduction. The aim of this report is to study the graft and patient survival in a large cohort of recipients with an analysis of factors that may affect the final outcomes. Methods. Between March 1976 and March 2008, 1967 consecutive live-donor renal transplants were carried out. Various variables that may have an impact on patients and/or graft survival were studied in two steps. Initially, a univariate analysis was carried out. Thereafter, significant variables were embedded in a stepwise regression analysis. Results. The overall graft survival was 86.7% and 65.5%, at 5 and 10 years, respectively. The projected half-life for grafts was 17.5 years and for patients was 22 years. Five factors had an independent negative impact on graft survival: donor's age, genetic considerations, the type of primary immunosuppression, number of acute rejection episodes, and total steroid dose during the first 3 months after transplantation. Conclusions. Despite refinements in tissue matching techniques and improvements in immunosuppression protocols, an important proportion of grafts is still lost following living donor kidney transplantation, presumably due to chronic allograft nephropathy. Mohamed A. Ghoneim, Mohamed A. Bakr, Ayman F. Refaie, Ahmed I. Akl, Ahmed A. Shokeir, Ahmed B. Shehab El-Dein, Hesham M. Ammar, Amani M. Ismail, Hussein A. Sheashaa, and Mahmoud A. El-Baz Copyright © 2013 Mohamed A. Ghoneim et al. All rights reserved. Reproducibility of NMR Analysis of Urine Samples: Impact of Sample Preparation, Storage Conditions, and Animal Health Status Sun, 23 Jun 2013 09:01:54 +0000 Introduction. Spectroscopic analysis of urine samples from laboratory animals can be used to predict the efficacy and side effects of drugs. This employs methods combining 1H NMR spectroscopy with quantification of biomarkers or with multivariate data analysis. The most critical steps in data evaluation are analytical reproducibility of NMR data (collection, storage, and processing) and the health status of the animals, which may influence urine pH and osmolarity. Methods. We treated rats with a solvent, a diuretic, or a nephrotoxicant and collected urine samples. Samples were titrated to pH 3 to 9, or salt concentrations increased up to 20-fold. The effects of storage conditions and freeze-thaw cycles were monitored. Selected metabolites and multivariate data analysis were evaluated after 1H NMR spectroscopy. Results. We showed that variation of pH from 3 to 9 and increases in osmolarity up to 6-fold had no effect on the quantification of the metabolites or on multivariate data analysis. Storage led to changes after 14 days at 4°C or after 12 months at −20°C, independent of sample composition. Multiple freeze-thaw cycles did not affect data analysis. Conclusion. Reproducibility of NMR measurements is not dependent on sample composition under physiological or pathological conditions. Christina Schreier, Werner Kremer, Fritz Huber, Sindy Neumann, Philipp Pagel, Kai Lienemann, and Sabine Pestel Copyright © 2013 Christina Schreier et al. All rights reserved. Impact of Cardiovascular Organ Damage on Cortical Renal Perfusion in Patients with Chronic Renal Failure Tue, 18 Jun 2013 16:11:57 +0000 Introduction. Properly preserved renal perfusion is the basic determinant of oxygenation, vitality, nutrition, and organ function and its structure. Perfusion disorders are functional changes and are ahead of the appearance of biochemical markers of organ damage. The aim of this study was to evaluate a relationship between the renal cortex perfusion and markers of cardiovascular organ damage in patients with stable chronic renal failure (CKD). Methods. Seventeen patients (2 F; 15 M; age ) with stable CKD at 2–4 stages and hypertension or signs of heart failure were enrolled in this study. Blood tests with an estimation of renal and cardiac functions, echocardiographic parameters, intima-media thickness (IMT), renal resistance index (RRI), and total (TPI), proximal (PPI), and distal (DPI) renal cortical perfusion intensity measurements were collected. Results. DPI was significantly lower than PPI. TPI significantly correlated with age, Cys, CKD-EPI (cystatin), and IMT, whereas DPI significantly depended on Cystain, CKD-EPI (cystatin; cystatin-creatinine), IMT, NT-proBNP, and troponin I. In multiple stepwise regression analysis model only CKD-EPI (cystatin) independently influenced DPI. Conclusions. Cardiovascular and kidney damage significantly influences renal cortical perfusion. Ultrasound measurement of renal perfusion could be a sensitive method for early investigation of cardiovascular and renal injuries. Arkadiusz Lubas, Robert Ryczek, Grzegorz Kade, Jerzy Smoszna, and Stanisław Niemczyk Copyright © 2013 Arkadiusz Lubas et al. All rights reserved. Dexamethasone Inhibits Podocyte Apoptosis by Stabilizing the PI3K/Akt Signal Pathway Wed, 24 Apr 2013 10:00:43 +0000 Corticosteroids like dexamethasone (DEX) are well-established treatments for the glomerular disease that sustain renal function, at least in part, by protecting podocytes from apoptotic death. In this study, we found that PAN causes abnormal expression of the PI3K-binding protein CD2AP, reducing PI3K/Akt signaling and promoting podocyte apoptosis. In contrast, DEX restores CD2AP-PI3K-Akt-GSK3β signaling, which promotes the activity of antiapoptotic proteins and inhibits the activity of proapoptotic proteins. In addition, we also found that CD2AP was aberrantly colocalized with p85. Normal CD2AP mRNA expression and subcellular protein distribution were maintained in the PAN + DEX group, and DEX coapplication also reduced CD2AP-p85 colocalization. PAN evoked a concentration-dependent decrease in p-Akt and p-GSK3β expressions, with p-Akt expression reaching a nadir at 15 min and p-GSK3β expression at 30 min. DEX treatment induced a concentration-dependent reversal of PAN-induced p-Akt and p-GSK3β downregulation. The PI3K inhibitor LY294002 blocked p-Akt and p-GSK3β expressions in podocytes. Cells treated with PAN exhibited a significantly higher apoptosis rate than untreated or vehicle-treated cells. Furthermore, LY294002 exacerbated PAN-induced apoptosis. DEX cotreatment caused a significant concentration-dependent decrease in PAN-induced apoptosis. These results strongly suggest that DEX protects podocytes by stabilizing the expression and subcellular distribution of CD2AP and by maintaining the expression of phosphor-activated Akt and GSK3β. Yu-Shengyou and Yu Li Copyright © 2013 Yu-Shengyou and Yu Li. All rights reserved. Function of the p38MAPK-HSP27 Pathway in Rat Lung Injury Induced by Acute Ischemic Kidney Injury Wed, 27 Mar 2013 08:49:01 +0000 This study aims to observe the changes and the function of p38MAPK-HSP27 signaling pathways in acute lung injury (ALI) induced by acute ischemic kidney injury in rats. Wistar rats were randomly divided into Group A (control group), Group B (acute kidney injury group), and Group C (acute kidney injury +SB203580). The concentration of protein in BALF, neutrophil counts, PI, W/D; the concentration of TNF-α, IL-6, and IL-1β in plasma and BALF; and the concentrations of MDA and NO in the lung tissue started to increase 2 h after the experiment in Group B, which showed a significant difference compared with those in Groups A and C. The expressions of p-p38MAPK and p-HSP27 in the lung tissue began to increase 2 h after the experiment in Group B, which was different from those in Groups A and C. A significant increase was observed in the F-actin expression in Group B than that in Group A. In Group B, the correlation of cytokine TNF-α, IL-6, and p-p38MAPK in BALF was positive. Acute kidney injury (AKI) induced by bilateral renal arteriovenous clamp closure could activate p38MAPK-HSP27 signaling pathways and induce lung injury, which blocks the p38MAPK-HSP27 signal pathway to reduce the risk of lung injury. Tao Ma, Xiao Wei Liu, and Zhi Liu Copyright © 2013 Tao Ma et al. All rights reserved. Meta-Analysis: The Efficacy and Safety of Paricalcitol for the Treatment of Secondary Hyperparathyroidism and Proteinuria in Chronic Kidney Disease Thu, 27 Dec 2012 11:22:02 +0000 Introduction. Previous studies have demonstrated the safety and efficacy of using Paricalcitol for the treatment of secondary hyperparathyroidism (SHPT) in patients on dialysis. The aim of the current meta-analysis was to assess the safety and efficacy of Paricalcitol for the management of SHPT in patients with chronic kidney disease (CKD) not yet on dialysis. A secondary aim was to determine if sufficient data was available to assess the effect of Paricalcitol for the management of proteinuria. Methods. A meta-analysis was conducted using the Cochrane Collaboration’s RevMan 4.2 software. Results. Paricalcitol is effective in lowering PTH in patients with CKD not yet on dialysis and is also effective in lowering proteinuria in diabetic CKD patients. However, we uncovered a safety signal identifying an elevated calcium phosphate product and a trend towards the development of hypercalcemia. A phosphate elevation was not demonstrated because the target used in the clinical studies was a  mg/dl, a value appropriate for dialysis patients and not CKD patients. Conclusion. Although Paricalcitol is effective in lowering PTH, we advise caution in the use of any active Vitamin D analogues in patients with CKD because of the potential risk of exacerbating vascular calcification. Tianzhao Han, Gong Rong, Dayong Quan, Ying Shu, Zhu Liang, Ninglan She, Manli Liu, Bing Yang, Gong Cheng, Yongman Lv, and Leonard Stern Copyright © 2013 Tianzhao Han et al. All rights reserved. miRNA589 Regulates Epithelial-Mesenchymal Transition in Human Peritoneal Mesothelial Cells Wed, 03 Oct 2012 10:15:19 +0000 Background. microRNA (miRNA, miR) are thought to interact with multiple mRNAs which are involved in the EMT process. But the role of miRNAs in peritoneal fibrosis has remained unknown. Objective. To determine if miRNA589 regulates the EMT induced by TGFβ1 in human peritoneal mesothelial cell line (HMrSV5 cells). Methods. 1. Level of miR589 was detected in both human peritoneal mesothelial cells (HPMCs) isolated from continuous ambulatory peritoneal dialysis (CAPD) patients’ effluent and HMrSV5 cells treated with or without TGFβ1. 2. HMrSV5 cells were divided into three groups: control group, TGFβ1 group, and pre-miR-589+TGFβ1 group. The level of miRNA589 was determined by realtime PCR. The expressions of ZO-1, vimentin, and E-cadherin in HPMCs were detected, respectively. Results. Decreased level of miRNA589 was obtained in either HPMCs of long-term CAPD patients or HMrSV5 cells treated with TGFβ1. In vitro, TGFβ1 led to upregulation of vimentin and downregulation of ZO-1 as well as E-cadherin in HMrSV5 cells, which suggested EMT, was induced. The changes were accompanied with notably decreased level of miRNA589 in HMrSV5 cells treated with TGFβ1. Overexpression of miRNA589 by transfection with pre-miRNA589 partially reversed these EMT changes. Conclusion. miRNA589 mediates TGFβ1 induced EMT in human peritoneal mesothelial cells. Ke Zhang, Hao Zhang, Xun Zhou, Wen-bin Tang, Li Xiao, Ying-hong Liu, Hong Liu, You-ming Peng, Lin Sun, and Fu-you Liu Copyright © 2012 Ke Zhang et al. All rights reserved. Urinary TWEAK Level as a Marker of Lupus Nephritis Activity in 46 Cases Wed, 06 Jun 2012 10:43:26 +0000 Objective. This study is designed to observe the urinary tumor necrosis factor-like weak inducer of apoptosis (TWEAK) levels in patients with lupus nephritis (LN) and to identify new biomarker of lupus nephritis activity. Methods. Study subjects were 46 cases of patients with LN (including 34 of active cases) who underwent routine renal biopsy. Activity and chronicity indexes of LN were assessed using pathological criteria proposed by Hill et al. in 2000. Urinary TWEAK (uTWEAK) level and Monocyte chemoattractant protein-1 (MCP-1) level were detected by ELISA. Results. Urinary TWEAK level was significantly higher in active LN group than in non-active LN group. Correlation analysis showed that urinary TWEAK levels were significantly correlated with activity index (𝑟=0.825, 𝑃<0.01), glomerular activity index (𝑟=0.754, 𝑃<0.01), and tubulointerstitial qualitative activity index (𝑟=0.751, 𝑃<0.01), while not significant correlated with chronicity Index (𝑃>0.05). The association between urinary TWEAK levels and urinary MCP-1 levels were significant in active LN group (𝑟=0.809, 𝑃<0.01) but not significant in non-active LN group (𝑃>0.05). Conclusions. uWEAK levels were correlated with all active indexes of LN, suggesting its potential role as novel biomarker of active lupus nephritis. Zhu Xuejing, Tan Jiazhen, Li Jun, Xu Xiangqing, Yuan Shuguang, and Liu Fuyou Copyright © 2012 Zhu Xuejing et al. All rights reserved. Pathophysiology of the Peritoneal Membrane during Peritoneal Dialysis: The Role of Hyaluronan Mon, 12 Dec 2011 08:13:06 +0000 During peritoneal dialysis (PD), constant exposure of mesothelial cells to bioincompatible PD solutions results in the denudation of the mesothelial monolayer and impairment of mesothelial cell function. Hyaluronan, a major component of extracellular matrices, is synthesized by mesothelial cells and contributes to remesothelialization, maintenance of cell phenotype, and tissue remodeling and provides structural support to the peritoneal membrane. Chronic peritoneal inflammation is observed in long-term PD patients and is associated with increased hyaluronan synthesis. During inflammation, depolymerization of hyaluronan may occur with the generation of hyaluronan fragments. In contrast to native hyaluronan which offers a protective role to the peritoneum, hyaluronan fragments exacerbate inflammatory and fibrotic processes and therefore assist in the destruction of the tissue. This paper will discuss the contribution of mesothelial cells to peritoneal membrane alterations that are induced by PD and the putative role of hyaluronan in these processes. Susan Yung and Tak Mao Chan Copyright © 2011 Susan Yung and Tak Mao Chan. All rights reserved. Explanting Is an Ex Vivo Model of Renal Epithelial-Mesenchymal Transition Thu, 24 Nov 2011 14:13:45 +0000 Recognised by their de novo expression of alpha-smooth muscle actin (SMA), recruitment of myofibroblasts is key to the pathogenesis of fibrosis in chronic kidney disease. Increasingly, we realise that epithelial-mesenchymal transition (EMT) may be an important source of these cells. In this study we describe a novel model of renal EMT. Rat kidney explants were finely diced on gelatin-coated Petri dishes and cultured in serum-supplemented media. Morphology and immunocytochemistry were used to identify mesenchymal (vimentin+, α-smooth muscle actin (SMA)+, desmin+), epithelial (cytokeratin+), and endothelial (RECA+) cells at various time points. Cell outgrowths were all epithelial in origin (cytokeratin+) at day 3. By day 10, 50 ± 12% (mean ± SE) of cytokeratin+ cells double-labelled for SMA, indicating EMT. Lectin staining established a proximal tubule origin. By day 17, cultures consisted only of myofibroblasts (SMA+/cytokeratin−). Explanting is a reproducible ex vivo model of EMT. The ability to modify this change in phenotype provides a useful tool to study the regulation and mechanisms of renal tubulointerstitial fibrosis. Catherine E. Winbanks, Ian A. Darby, Kristen J. Kelynack, Dodie Pouniotis, Gavin J. Becker, and Tim D. Hewitson Copyright © 2011 Catherine E. Winbanks et al. All rights reserved. Contribution of Large Pig for Renal Ischemia-Reperfusion and Transplantation Studies: The Preclinical Model Thu, 03 Mar 2011 18:16:23 +0000 Animal experimentation is necessary to characterize human diseases and design adequate therapeutic interventions. In renal transplantation research, the limited number of in vitro models involves a crucial role for in vivo models and particularly for the porcine model. Pig and human kidneys are anatomically similar (characterized by multilobular structure in contrast to rodent and dog kidneys unilobular). The human proximity of porcine physiology and immune systems provides a basic knowledge of graft recovery and inflammatory physiopathology through in vivo studies. In addition, pig large body size allows surgical procedures similar to humans, repeated collections of peripheral blood or renal biopsies making pigs ideal for medical training and for the assessment of preclinical technologies. However, its size is also its main drawback implying expensive housing. Nevertheless, pig models are relevant alternatives to primate models, offering promising perspectives with developments of transgenic modulation and marginal donor models facilitating data extrapolation to human conditions. S. Giraud, F. Favreau, N. Chatauret, R. Thuillier, S. Maiga, and T. Hauet Copyright © 2011 S. Giraud et al. All rights reserved. High-Sensitivity C-Reactive Protein: An Independent Risk Factor for Left Ventricular Hypertrophy in Patients with Lupus Nephritis Sun, 07 Nov 2010 08:49:05 +0000 Objective. To determine the prevalence of left ventricular hypertrophy (LVH) and its associated risk factors in lupus nephritis (LN) patients. Methods. 287 LN patients (age: 38.54 ± 13.31, 262 female) were recruited. Echocardiography and serum high-sensitivity C-reactive protein (hs-CRP) were measured. Their relationship was evaluated by univariate correlation analysis and multivariate regression analysis. Results. The prevalence of LVH in this cohort was 21.25% (𝑛=61). Serum hs-CRP level was significantly elevated in patients with LVH compared to those without (8.03 (3.22–30.95) versus 3.93 (1.48–9.48) mg/L, 𝑃<.01), and correlated with left ventricular mass index (LVMI) (𝑟=0.314, 𝑃=.001). Multivariate regression analysis further confirmed that hs-CRP was an independent risk factor (𝛽=0.338, 𝑃=.002) for LVH in patients with LN. Conclusions. Our findings demonstrated that serum hs-CRP level is independently correlated with LVMI and suggested that measurement of hs-CRP may provide important clinical information to investigate LVH in LN patients. Beili Shi, Zhaohui Ni, Hong Cai, Minfang Zhang, Shan Mou, Qin Wang, Liou Cao, Zanzhe Yu, Yucheng Yan, and Jiaqi Qian Copyright © 2010 Beili Shi et al. All rights reserved. Oral Microencapsulated Live Saccharomyces cerevisiae Cells for Use in Renal Failure Uremia: Preparation and In Vivo Analysis Tue, 27 Jul 2010 08:17:32 +0000 Orally administrable alginate-poly-L-lysine-alginate (APA) microcapsules containing live yeast cells was investigated for use in renal failure. At all times, yeast cells remain inside the microcapsules, which are then excreted in the stool. During their gastrointestinal passage, small molecules, like urea, diffuse into the yeast microcapsules where they are hydrolyzed. Orally administrating these microcapsules to uremic rats was found to decrease urea concentrations from  mmol/L to  mmol/L over a treatment period of eight weeks. After stopping the treatment, the urea concentrations increased back to uremic levels of  mmol/L. The analysis of creatinine concentrations averaged  mol/L,  mol/L, and  mol/L for the normal-control, uremic-control and uremic-treatment groups, respectively. While creatinine concentrations for both uremic-control and uremic-treatment groups did not differ among each other (), they were, however, significantly higher than those of the normal control group (). Uric acid concentrations averaged  mol/L,  mol/L, and  mol/L for the normal-control, uremic-control and uremic-treatment groups, respectively. There were no significant differences in both calcium and phosphate concentrations among all three groups (). The microbial populations of five tested types of bacteria were not substantially altered by the presence of the yeast APA encapsulated yeast (). Razek Coussa, Christopher Martoni, Jasmine Bhathena, Aleksandra Malgorzata Urbanska, and Satya Prakash Copyright © 2010 Razek Coussa et al. All rights reserved. Decrease of Klotho in the Kidney of Streptozotocin-Induced Diabetic Rats Sun, 27 Jun 2010 16:07:34 +0000 The klotho gene is expressed in a limited number of tissues, most notably in distal convoluted tubules in the kidney and choroid plexus in the brain. A previous study suggested that Klotho increases resistance to oxidative stress. However, changes of Klotho expression in high glucose-induced oxidative stress remain unclear. In the present study, we used streptozotocin-induced diabetic rats (STZ rats) to examine the effects of insulin, phloridzin or antioxidant, tiron on diabetic nephropathy. Both insulin and phloridzin reversed the lower Klotho expression levels in kidneys of STZ rats by the correction of hyperglycemia. Also, renal functions were improved by these treatments. In addition to the improvement of renal functions, the decrease of Klotho expression in kidney of STZ rats was also reversed by tiron without changing blood glucose levels. The reduction of oxidative stress induced by high glucose can be considered for this action of tiron. This view was further confirmed in vitro using high glucose-exposed Madin-Darby canine kidney (MDCK) epithelial cells. Thus, we suggest that decrease of oxidative stress is not only responsible for the improvement of renal function but also for the recovery of Klotho expression in kidney of STZ rats. Meng-Fu Cheng, Li-Jen Chen, and Juei-Tang Cheng Copyright © 2010 Meng-Fu Cheng et al. All rights reserved. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury Mon, 14 Jun 2010 11:15:02 +0000 This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes) during regeneration of S3 tubules of outer stripe of outer medulla (OSOM). Groups of experimental animals () were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo--deoxyuridine (BrdU) and Proliferating Cell Nuclear Antigen (PCNA) labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM) positive interstitial cells increased transiently (18–72 hours) in the vicinity of altered tubules. We have also localized a small population of -Smooth Muscle Actin (SMA)-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis. David Vansthertem, Annabel Gossiaux, Anne-Emilie Declèves, Nathalie Caron, Denis Nonclercq, Alexandre Legrand, and Gérard Toubeau Copyright © 2010 David Vansthertem et al. All rights reserved. Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells Wed, 05 May 2010 12:29:12 +0000 Erythropoietin (EPO) exerts (renal) tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs) from oxidative stress and if so which pathways are involved. EPO (epoetin delta) could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR) since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1), aquaporin-1 (AQP-1), and B-cell CLL/lymphoma 2 (Bcl-2) have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPPIV), and cytoglobin (Cygb) to play a role in this process. Annelies De Beuf, Xiang-hua Hou, Patrick C. D'Haese, and Anja Verhulst Copyright © 2010 Annelies De Beuf et al. All rights reserved. Expression of VE-Cadherin in Peritubular Endothelial Cells during Acute Rejection after Human Renal Transplantation Thu, 26 Jul 2007 00:00:00 +0000 Genes involved in acute rejection (AR) after organ transplantation remain to be further elucidated. In a previous work we have demonstrated the under-expression of VE-Cadherin by endothelial cells (EC) in AR following murine and human heart transplantation. Serial sections from 15 human kidney Banff-graded transplant biopsies were examined for the presence of VE-Cadherin and CD34 staining by immunohistochemistry (no AR (n=5), AR grade IA (n=5), or AR grade IIA (n=5)). Quantification of peritubular EC staining were evaluated and results were expressed by the percentage of stained cells per surface analysed. There was no difference in CD34 staining between the 3 groups. VE-Cadherin expression was significantly reduced in AR Grade IIA when compared to no AR (P=.01) and to AR grade IA (P=.02). This study demonstrates a reduced VE-Cadherin expression by EC in AR after renal transplantation. The down-regulation of VE-Cadherin may strongly participate in human AR. Ana Roussoulières, Brigitte McGregor, Lara Chalabreysse, Catherine Cerutti, Jeanne-Luce Garnier, Pascale Boissonnat, Olivier Bastien, Jean-Yves Scoazec, Françoise Thivolet-Bejui, Laurent Sebbag, and John L. McGregor Copyright © 2007 Ana Roussoulières et al. All rights reserved.