International Journal of Nephrology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Proteasome Activators, PA28α and PA28β, Govern Development of Microvascular Injury in Diabetic Nephropathy and Retinopathy Tue, 18 Oct 2016 14:55:23 +0000 Diabetic nephropathy (DN) and diabetic retinopathy (DR) are major complications of type 1 and type 2 diabetes. DN and DR are mainly caused by injury to the perivascular supporting cells, the mesangial cells within the glomerulus, and the pericytes in the retina. The genes and molecular mechanisms predisposing retinal and glomerular pericytes to diabetic injury are poorly characterized. In this study, the genetic deletion of proteasome activator genes, PA28α and PA28β genes, protected the diabetic mice in the experimental STZ-induced diabetes model against renal injury and retinal microvascular injury and prolonged their survival compared with wild type STZ diabetic mice. The improved wellbeing and reduced renal damage was associated with diminished expression of Osteopontin (OPN) and Monocyte Chemoattractant Protein-1 (MCP-1) in the glomeruli of STZ-injected PA28α/PA28β double knockout (Pa28αβDKO) mice and also in cultured mesangial cells and retinal pericytes isolated from Pa28αβDKO mice that were grown in high glucose. The mesangial PA28-mediated expression of OPN under high glucose conditions was suppressed by peptides capable of inhibiting the binding of PA28 to the 20S proteasome. Collectively, our findings demonstrate that diabetic hyperglycemia promotes PA28-mediated alteration of proteasome activity in vulnerable perivascular cells resulting in microvascular injury and development of DN and DR. Saeed Yadranji Aghdam and Ali Mahmoudpour Copyright © 2016 Saeed Yadranji Aghdam and Ali Mahmoudpour. All rights reserved. Psychosocial Factors in End-Stage Kidney Disease Patients at a Tertiary Hospital in Australia Tue, 11 Oct 2016 08:59:17 +0000 Aim. This study seeks to review the psychosocial factors affecting patients with end-stage kidney disease (ESKD) from a tertiary hospital in Australia. Methods. We audited patients with ESKD, referred to social work services from January 2012 to December 2014. All patients underwent psychosocial assessments by one, full-time renal social worker. Patient demographics, cumulative social issues, and subsequent interventions were recorded directly into a database. Results. Of the 244 patients referred, the majority were >60 years (58.6%), male (60.7%), born in Australia (62.3%), on haemodialysis (51.6%), and reliant on government financial assistance (88%). Adjustment issues (41%), financial concerns (38.5%), domestic assistance (35.2%), and treatment nonadherence (21.3%) were the predominant reasons for social work consultation. Younger age, referral prior to start of dialysis, and unemployment were significant independent predictors of increased risk of adjustment issues (, <0.001, and =0.018, resp.). Independent risk factors for treatment nonadherence included age and financial and employment status (, 0.052, and 0.008, resp.). Conclusion. Psychosocial and demographic factors were associated with treatment nonadherence and adjustment difficulties. Additional social work support and counselling, in addition to financial assistance from government and nongovernment agencies, may help to improve adjustment to the diagnosis and treatment plans as patients approach ESKD. Charan Bale, Alexandra Douglas, Dev Jegatheesan, Linh Pham, Sonny Huynh, Atul Mulay, and Dwarakanathan Ranganathan Copyright © 2016 Charan Bale et al. All rights reserved. Is Anticoagulation Discontinuation Achievable with Citrate Dialysate during HDF Sessions? Mon, 10 Oct 2016 10:49:10 +0000 Citrate dialysate has been developed for few years to replace acetate and HCl concentrates. In Online Postdilution Hemodiafiltration (OL-POST-HDF), several issues are remaining concerning the possibility of stopping anticoagulation during sessions and the side effects of citrate solutions on calcium metabolism. This 1-year monocentric retrospective study included all patients exposed to citrate in OL-POST-HDF with nadroparin decrease for more than one month. Clotting events, serum calcium, PTH, hemoglobin, CRP, depuration parameters, and treatments administrated were recorded for analysis. 27 patients experienced nadroparin decrease and 5 did not receive nadroparin at the end of the study. Nadroparin decrease and withdrawal were both associated with more clotting events whereas the use of vitamin K antagonists was protective. No significant metabolic side effects were observed. Citrate dialysate does not allow anticoagulation discontinuation or decrease but has no significant side effects on mineral bone metabolism or erythropoiesis. Thibault Dolley-Hitze, Emmanuel Oger, Didier Hamel, Marie-Laure Lombart, and Isabelle Hermès Copyright © 2016 Thibault Dolley-Hitze et al. All rights reserved. Dialysate White Blood Cell Change after Initial Antibiotic Treatment Represented the Patterns of Response in Peritoneal Dialysis-Related Peritonitis Tue, 30 Aug 2016 11:32:52 +0000 Background. Patients with peritoneal dialysis-related peritonitis usually have different responses to initial antibiotic treatment. This study aimed to explore the patterns of response by using the changes of dialysate white blood cell count on the first five days of the initial antibiotic treatment. Materials and Methods. A retrospective cohort study was conducted. All peritoneal dialysis-related peritonitis episodes from January 2014 to December 2015 were reviewed. We categorized the patterns of antibiotic response into 3 groups: early response, delayed response, and failure group. The changes of dialysate white blood cell count for each pattern were determined by multilevel regression analysis. Results. There were 644 episodes in 455 patients: 378 (58.7%) of early response, 122 (18.9%) of delayed response, and 144 (22.3%) of failure episodes. The patterns of early, delayed, and failure groups were represented by the average rate reduction per day of dialysate WBC of 68.4%, 34.0%, and 14.2%, respectively ( value < 0.001 for all comparisons). Conclusion. Three patterns, which were categorized by types of responses, have variable rates of WBC declining. Clinicians should focus on the delayed response and failure patterns in order to make a decision whether to continue medical therapies or to aggressively remove the peritoneal catheter. Pichaya Tantiyavarong, Opas Traitanon, Piyatida Chuengsaman, Jayanton Patumanond, and Adis Tasanarong Copyright © 2016 Pichaya Tantiyavarong et al. All rights reserved. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis Tue, 23 Aug 2016 14:22:36 +0000 The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies. Rose M. Ayoob and Andrew L. Schwaderer Copyright © 2016 Rose M. Ayoob and Andrew L. Schwaderer. All rights reserved. Impact of Pediatric Chronic Dialysis on Long-Term Patient Outcome: Single Center Study Mon, 15 Aug 2016 12:08:11 +0000 Objective. Owing to a shortage of kidney donors in Israel, children with end-stage renal disease (ESRD) may stay on maintenance dialysis for a considerable time, placing them at a significant risk. The aim of this study was to understand the causes of mortality. Study Design. Clinical data were collected retrospectively from the files of children on chronic dialysis (>3 months) during the years 1995–2013 at a single pediatric medical center. Results. 110 patients were enrolled in the study. Mean age was  yrs. (range: 1 month–24 yrs). Forty-five children (42) had dysplastic kidneys and 19 (17.5) had focal segmental glomerulosclerosis. Twenty-five (22.7) received peritoneal dialysis, 59 (53.6) hemodialysis, and 6 (23.6) both modalities sequentially. Median dialysis duration was 1.46 years (range: 0.25–17.54 years). Mean follow-up was  yrs. Seventy-nine patients (71.8) underwent successful transplantation, 10 (11.2) had graft failure, and 8 (7.3) continued dialysis without transplantation. Twelve patients (10.9) died: 8 of dialysis-associated complications and 4 of their primary illness. The 5-year survival rate was 84: 90 for patients older than 5 years and 61 for younger patients. Conclusions. Chronic dialysis is a suitable temporary option for children awaiting renal transplantation. Although overall long-term survival rate is high, very young children are at high risk for life-threatening dialysis-associated complications. Daniella Levy Erez, Irit Krause, Amit Dagan, Roxana Cleper, Yafa Falush, and Miriam Davidovits Copyright © 2016 Daniella Levy Erez et al. All rights reserved. Prevalence and Risk Factors of Lower Limb Amputation in Patients with End-Stage Renal Failure on Dialysis: A Systematic Review Wed, 27 Jul 2016 12:56:39 +0000 Background. Renal dialysis has recently been recognised as a risk factor for lower limb amputation (LLA). However, exact rates and associated risk factors for the LLA are incompletely understood. Aim. Prevalence and risk factors of LLA in end-stage renal failure (ESRF) subjects on renal dialysis were investigated from the existing literature. Methods. Published data on the subject were derived from MEDLINE, PubMed, and Google Scholar search of English language literature from January 1, 1980, to July 31, 2015, using designated key words. Results. Seventy studies were identified out of which 6 full-text published studies were included in this systematic review of which 5 included patients on haemodialysis alone and one included patients on both haemodialysis and peritoneal dialysis. The reported findings on prevalence of amputation in the renal failure on dialysis cohort ranged from 1.7% to 13.4%. Five out of the six studies identified diabetes as the leading risk factor for amputation in subjects with ESRF on renal dialysis. Other risk factors identified were high haemoglobin A1c, elevated c-reactive protein, and low serum albumin. Conclusions. This review demonstrates high rate of LLA in ESRF patients receiving dialysis therapy. It has also identified diabetes and markers of inflammation as risk factors of amputation in ESRF subjects on dialysis. Rajit A. Gilhotra, Beverly T. Rodrigues, Venkat N. Vangaveti, and Usman H. Malabu Copyright © 2016 Rajit A. Gilhotra et al. All rights reserved. Effects of Therapy on Urine Neutrophil Gelatinase-Associated Lipocalin in Nondiabetic Glomerular Diseases with Proteinuria Mon, 25 Jul 2016 10:17:17 +0000 Urine neutrophil gelatinase-associated lipocalin (NGAL) is widely used as a biomarker for acute kidney injury. Cross-sectional studies have shown that NGAL may be elevated in glomerular diseases, but there is limited information on the value of NGAL in predicting treatment response or on the changes of NGAL levels after therapy. We prospectively evaluated the effects of therapy on NGAL in nondiabetic glomerular diseases. Urine NGAL was collected at biopsy and follow-up at 12 months. At baseline, NGAL in glomerular disease patients () correlated with proteinuria, but not with glomerular filtration rate (GFR). After therapy with renin-angiotensin blockers and/or immune modulating agents, change of NGAL correlated with change of proteinuria, but not with change of GFR. NGAL at baseline was not different between patients in complete remission (CR) at follow-up compared to those not in remission (NR). Compared to baseline, NGAL at follow-up decreased in CR (), but not in NR. Change of NGAL was greater in CR than NR. In conclusion, the change of urine NGAL correlated with the change of proteinuria. Baseline NGAL was not a predictor of complete remission. Future studies will be necessary to determine the role of NGAL as a predictor of long term outcome in proteinuric glomerular diseases. Amnuay Sirisopha, Somlak Vanavanan, Anchalee Chittamma, Bunyong Phakdeekitcharoen, Ammarin Thakkinstian, Amornpan Lertrit, Nuankanya Sathirapongsasuti, and Chagriya Kitiyakara Copyright © 2016 Amnuay Sirisopha et al. All rights reserved. Prevalence of Hypercalcaemia in a Renal Transplant Population: A Single Centre Study Thu, 14 Jul 2016 14:13:08 +0000 Introduction. Postrenal transplant bone disease is a significant problem. Factors influencing postrenal transplant bone status include high dose acute and low dose long-term steroid use, persistent hypercalcaemia, and graft failure. In this study, we aimed to determine the prevalence of hypercalcaemia and to evaluate the risk factors for postrenal transplant hypercalcaemia in long-term renal transplant patients at our centre. Methods. This is a biochemical audit in which we studied renal transplant recipients from the Central Northern Adelaide Renal Transplant Services, South Australia. Inclusion criteria include kidney transplant patients with functioning graft since 1971 and at least 3 months after transplantation at the time of analysis. Hypercalcaemia was defined as persistently elevated serum corrected calcium greater than or equal to 2.56 mmol/L for three consecutive months. Results. 679 renal transplant recipients with a functioning graft were studied and 101 were hypercalcaemic between March 2011 and June 2011 (15%). 60% of the hypercalcaemic patients were male and 40% were female, with chronic glomerulonephritis (39%) being the commonest cause of their end stage kidney disease (ESKD). Prevalence was similar in those that had haemodialysis and peritoneal dialysis pretransplantation. Hypercalcaemia in the renal transplant population was not secondary to suboptimal allograft function but secondary to pretransplantation hyperparathyroidism with persistent high parathyroid hormone (PTH) levels after transplantation. Conclusion. There is a high prevalence of hypercalcaemia (15%) in renal transplant recipients. The predominant cause for hypercalcaemia is pretransplantation hyperparathyroidism. The magnitude of pretransplantation hyperparathyroidism is the major determinant for long-term parathyroid function rather than graft function or pretransplantation duration on dialysis or mode of dialysis. Tony Amin, P. Toby Coates, Jeffrey Barbara, Paul Hakendorf, and Nazmul Karim Copyright © 2016 Tony Amin et al. All rights reserved. Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin β Wed, 13 Jul 2016 13:18:48 +0000 Meprin metalloproteases play a role in the pathology of ischemia/reperfusion- (IR-) induced renal injury. The endoplasmic reticulum-associated protein, osteosarcoma-9 (OS-9), has been shown to interact with the carboxyl-terminal tail of meprin β. More importantly, OS-9 interacts with the hypoxia inducible factor-1α (HIF-1α) and the prolyl-hydroxylase, proteins which mediate the cell’s response to hypoxia. To determine if OS-9 is a meprin substrate, kidney proteins from meprin αβ knockout mice (αβKO) (which lack endogenous meprins) and purified human OS-9 were incubated with activated forms of meprin A and meprin B, and Western blot analysis was used to evaluate proteolytic processing of OS-9. Fragmentation of OS-9 was observed in reactions with meprin B, but not meprin A. To determine whether meprin B cleaves OS-9 in vivo, wild-type (WT) and meprin αβKO mice were subjected to IR-induced renal injury. Fragmentation of OS-9 was observed in kidney proteins from WT mice subjected to IR, but not in meprin αβKO counterparts. Transfection of kidney cells (MDCK and HEK293) with meprin β cDNA prevented accumulation of OS-9 following exposure to the hypoxia mimic, CoCl2. These data suggest that meprin β interaction with OS-9 plays a role in the hypoxia response associated with IR-induced renal injury. Barry Lee Martin, Sabena Michelle Conley, Regine Simone Harris, Corshe Devon Stanley, Jean-Marie Vianney Niyitegeka, and Elimelda Moige Ongeri Copyright © 2016 Barry Lee Martin et al. All rights reserved. Long-Term Follow-Up Evaluation of Renal Function in Patients with Chronic Kidney Disease Undergoing Cardiac Surgery Thu, 30 Jun 2016 07:17:41 +0000 Background. Acute kidney injury (AKI) is a common complication of cardiac surgery but its long-term consequences, in patients with chronic kidney disease (CKD), are not known. Methods. We compared the long-term prognoses of CKD patients who developed () and did not develop () AKI during the period of hospitalization after undergoing coronary artery bypass graft (CABG). Fifty-eight patients who survived ( years old, 72% males, 83% Whites, 52% diabetics, baseline GFR:  mL/min) were followed up for months and treated for secondary prevention of events. Results. There were 6 deaths, 4 in the AKI+ and 2 in the AKI− group (Log-rank = 0.218), two attributed to CV causes. At the end of the study, renal function was similar in the two groups. One AKI− patient was started on dialysis. Only 4 patients had an increase in serum creatinine ≥ 0.5 mg/dL during follow-up. Conclusion. CKD patients developing AKI that survived the early perioperative period of coronary intervention present good renal and nonrenal long-term prognosis, compared to patients who did not develop AKI. Eduesley Santana-Santos, Felipe Kenji Oshiro Kamei, Tarcísia Karoline do Nascimento, Anas Abou Ismail, Jurema da Silva Herbas Palomo, Marcia Cristina da Silva Magro, Fátima Gil Ferreira, Larissa Bertacchini de Oliveira, Adriano Rogério Baldacin Rodrigues, and José Jayme Galvão de Lima Copyright © 2016 Eduesley Santana-Santos et al. All rights reserved. Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine Causality Thu, 19 May 2016 08:58:51 +0000 It has been previously reported that a higher erythropoiesis stimulating agent (ESA) dose in hemodialysis patients is associated with adverse outcomes including mortality; however the causal relationship between ESA and mortality is still hotly debated. We hypothesize ESA dose indeed exhibits a direct linear relationship with mortality in models of association implementing the use of a marginal structural model (MSM), which controls for time-varying confounding and examines causality in the ESA dose-mortality relationship. We conducted a retrospective cohort study of 128 598 adult hemodialysis patients over a 5-year follow-up period to evaluate the association between weekly ESA (epoetin-α) dose and mortality risk. A MSM was used to account for baseline and time-varying covariates especially laboratory measures including hemoglobin level and markers of malnutrition-inflammation status. There was a dose-dependent positive association between weekly epoetin-α doses ≥18 000 U/week and mortality risk. Compared to ESA dose of <6 000 U/week, adjusted odds ratios (95% confidence interval) were 1.02 (0.94–1.10), 1.08 (1.00–1.18), 1.17 (1.06–1.28), 1.27 (1.15–1.41), and 1.52 (1.37–1.69) for ESA dose of 6 000 to <12 000, 12 000 to <18 000, 18 000 to <24 000, 24 000 to <30 000, and ≥30 000 U/week, respectively. High ESA dose may be causally associated with excessive mortality, which is supportive of guidelines which advocate for conservative management of ESA dosing regimen in hemodialysis patients. Elani Streja, Jongha Park, Ting-Yan Chan, Janet Lee, Melissa Soohoo, Connie M. Rhee, Onyebuchi A. Arah, and Kamyar Kalantar-Zadeh Copyright © 2016 Elani Streja et al. All rights reserved. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy Mon, 16 May 2016 13:04:59 +0000 Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. Temesgen Fiseha and Zemenu Tamir Copyright © 2016 Temesgen Fiseha and Zemenu Tamir. All rights reserved. Single Nucleotide Polymorphisms in Pediatric Idiopathic Nephrotic Syndrome Mon, 09 May 2016 12:48:50 +0000 Polymorphic variants in several molecules involved in the glomerular function and drug metabolism have been implicated in the pathophysiology of pediatric idiopathic nephrotic syndrome (INS), but the results remain inconsistent. We analyzed the association of eleven allelic variants in eight genes (angiopoietin-like 4 (ANGPTL4), glypican 5 (GPC5), interleukin-13 (IL-13), macrophage migration inhibitory factor (MIF), neural nitric oxide synthetase (nNOS), multidrug resistance-1 (MDR1), glucocorticoid-induced transcript-1 (GLCCI1), and nuclear receptor subfamily-3 (NR3C1)) in 100 INS patients followed up till adulthood. We genotyped variants using PCR and direct sequencing and evaluated estimated haplotypes of MDR1 variants. The analysis revealed few differences in SNP genotype frequencies between patients and controls, or in clinical parameters among the patients. Genotype distribution of MDR1 SNPs rs1236, rs2677, and rs3435 showed significant () association with different medication regimes (glucocorticoids only versus glucocorticoids plus additional immunosuppressives). Some marginal association was detected between ANGPTL4, GPC5, GLCCI1, and NR3C1 variants and different medication regimes, number of relapses, and age of onset. Conclusion. While MDR1 variant genotype distribution associated with different medication regimes, the other analyzed gene variants showed only little or marginal clinical relevance in INS. Maija Suvanto, Timo Jahnukainen, Marjo Kestilä, and Hannu Jalanko Copyright © 2016 Maija Suvanto et al. All rights reserved. Population Based Trends in the Incidence of Hospital Admission for the Diagnosis of Hepatorenal Syndrome: 1998–2011 Wed, 06 Apr 2016 08:13:01 +0000 Background and Objectives. Hepatorenal syndrome carries a high risk of mortality. Understanding the incidence and mortality trends in hepatorenal syndrome will help inform future studies regarding the safety and efficacy of potential therapeutic interventions. Design and Methods. We conducted a retrospective cohort study using the Nationwide Inpatient Sample. We identified hospitalizations from January 1998–June 2011 with a primary diagnosis of hepatorenal syndrome. To characterize the incidence trends in monthly hepatorenal syndrome hospitalizations, we fit a piecewise linear model with a change point at January 2008. We examined hospital and patient characteristics before and after the change point. Results. Hospital admissions with a diagnosis of hepatorenal syndrome increased markedly between September of 2007 and March of 2008. Comparing patients who were admitted with a diagnosis of hepatorenal syndrome prior to 2008 with those after 2008, we found that length of stay increased while the mortality of patients admitted for hepatorenal syndrome decreased. Conclusion. The revision of the diagnostic criteria for hepatorenal syndrome may have contributed to the increase in the incidence of admissions for hepatorenal syndrome. However, the changes in the principles of hepatorenal syndrome management may have also contributed to the increase in incidence and lower mortality. Manish Suneja, Fan Tang, Joseph E. Cavanaugh, Linnea A. Polgreen, and Philip M. Polgreen Copyright © 2016 Manish Suneja et al. All rights reserved. Matrix Metalloproteinases and Subclinical Atherosclerosis in Chronic Kidney Disease: A Systematic Review Wed, 02 Mar 2016 13:16:33 +0000 Background. Cardiovascular disease (CVD) remains a significant problem in Chronic Kidney Disease (CKD). Subclinical atherosclerosis identified by noninvasive methods could improve CVD risk prediction in CKD but these methods are often unavailable. We therefore systematically reviewed whether circulating levels of Matrix Metalloproteinases (MMPs) and tissue inhibitors (TIMPs) are associated with subclinical atherosclerosis in CKD, as this would support their use as biomarkers or pharmacologic targets. Methods. All major electronic databases were systematically searched from inception until May 2015 using appropriate terms. Studies involving CKD patients with data on circulating MMPs levels and atherosclerosis were considered and subjected to quality assessment. Results. Overall, 16 studies were identified for qualitative synthesis and 9 studies were included in quantitative synthesis. MMP-2 and TIMP-1 were most frequently studied while most studies assessed carotid Intima-Media Thickness (cIMT) as a measure of subclinical atherosclerosis. Only MMP-2 demonstrated a consistent positive association with cIMT. Considerable variability in cIMT measurement methodology and poor plaque assessment was found. Conclusions. Although MMPs demonstrate great potential as biomarkers of subclinical atherosclerosis, they are understudied in CKD and not enough data existed for meta-analysis. Larger studies involving several MMPs, with more homogenized approaches in determining the atherosclerotic burden in CKD, are needed. Andreas Kousios, Panayiotis Kouis, and Andrie G. Panayiotou Copyright © 2016 Andreas Kousios et al. All rights reserved. Renal Damage Frequency in Patients with Solitary Kidney and Factors That Affect Progression Thu, 10 Dec 2015 13:43:14 +0000 Background. The aim of this study is to assess renal damage incidence in patients with solitary kidney and to detect factors associated with progression. Methods. Medical records of 75 patients with solitary kidney were investigated retrospectively and divided into two groups: unilateral nephrectomy (group 1) and unilateral renal agenesis/dysplasia (group 2). According to the presence of kidney damage, each group was divided into two subgroups: group 1a/b and group 2a/b. Results. Patients in group 1 were older than those in group 2 (). 34 patients who comprise group 1a had smaller kidney size () and higher uric acid levels () than those in group 1b at presentation. Uric acid levels at first and last visit were associated with renal damage progression (, 0.019). 18 patients who comprise group 2a were compared with those in group 2b in terms of presence of DM (), HT (), baseline proteinuria (), and uric acid () levels and group 2a showed higher rates for each. Progression was more common in patients with DM (), HT (), higher initial and final visit proteinuria (, for both), and higher baseline uric acid levels (). Conclusions. The majority of patients with solitary kidney showed renal damage at presentation. Increased uric acid level is a risk factor for renal damage and progression. For early diagnosis of renal damage and reducing the risk of progression, patients should be referred to a nephrologist as early as possible. T. Basturk, Y. Koc, Z. Ucar, T. Sakaci, E. Ahbap, E. Kara, F. Bayraktar, M. Sevinc, T. Sahutoglu, A. Kayalar, A. Sinangil, C. Akgol, and A. Unsal Copyright © 2015 T. Basturk et al. All rights reserved. Results in Assisted Peritoneal Dialysis: A Ten-Year Experience Tue, 27 Oct 2015 12:38:47 +0000 Background/Aims. Peritoneal dialysis is a successful renal replacement therapy (RRT) for old and dependent patients. We evaluated the clinical outcomes of an assisted peritoneal dialysis (aPD) program developed in a Portuguese center. Methods. Retrospective study based on 200 adult incident patients admitted during ten years to a PD program. We included all 17 patients who were under aPD and analysed various parameters, including complications with the technique, hospitalizations, and patient and technique survival. Results. The global peritonitis rate was lower in helped than in nonhelped patients: 0.4 versus 0.59 episodes/patient/year. The global hospitalization rate was higher in helped than in nonhelped patients: 0.67 versus 0.45 episodes/patient/year (). Technique survival in helped patients versus nonhelped patients was 92.3%, 92.3%, 83.1%, and 72.7% versus 91.9%, 81.7%, and 72.1%, and 68.3%, at 1, 2, 3, and 4 years, respectively (), and patient survival in helped patients versus nonhelped patients was 93.3%, 93.3%, 93.3%, and 74.7% versus 95.9% 93.7%, 89%, and 82% at 1, 2, 3, and 4 years, respectively (). Conclusions. aPD offers an opportune, reliable, and effective home care alternative for patients with no other RRT options. Sara Querido, Patrícia Quadros Branco, Elisabete Costa, Sara Pereira, Maria Augusta Gaspar, and José Diogo Barata Copyright © 2015 Sara Querido et al. All rights reserved. Cost-Utility Analysis of Mycophenolate Mofetil versus Azathioprine Based Regimens for Maintenance Therapy of Proliferative Lupus Nephritis Tue, 27 Oct 2015 11:51:47 +0000 Background/Aims. We aimed to examine the cost-effectiveness of mycophenolate mofetil (MMF) and azathioprine (AZA) as maintenance therapy for patients with Class III and Class IV lupus nephritis (LN), from a United States (US) perspective. Methods. Using a Markov model, we conducted a cost-utility analysis from a societal perspective over a lifetime horizon. The modeled population comprised patients with proliferative LN who received maintenance therapy with MMF (2 gm/day) versus AZA (150 mg/day) for 3 years. Risk estimates of clinical events were based on a Cochrane meta-analysis while costs and utilities were retrieved from other published sources. Outcome measures included costs, quality-adjusted life-years (QALY), incremental cost-effectiveness ratios (ICER), and net monetary benefit. Results. The base-case model showed that, compared with AZA strategy, the ICER for MMF was $2,630,592/QALY at 3 years. Over the patients’ lifetime, however, the ICER of MMF compared to AZA was $6,454/QALY. Overall, the ICER results from various sensitivity and subgroup analyses did not alter the conclusions of the model simulation. Conclusions. In the short term, an AZA-based regimen confers greater value than MMF for the maintenance therapy of proliferative LN. From a lifelong perspective, however, MMF is cost-effective compared to AZA. Robert Nee, Ian Rivera, Dustin J. Little, Christina M. Yuan, and Kevin C. Abbott Copyright © 2015 Robert Nee et al. All rights reserved. The Effects of Simvastatin on Proteinuria and Renal Function in Patients with Chronic Kidney Disease Mon, 12 Oct 2015 07:22:56 +0000 Current data suggests that statins might have beneficial effects on renal outcomes. Beneficial effects of statin treatment on renal progression in advanced chronic kidney disease (CKD) are obviously controversial. In a retrospective, controlled study, the authors have evaluated the effects of 53-week treatment with simvastatin, versus no treatment on proteinuria and renal function among 51 patients with CKD stages III-IV. By the end of the 53-week treatment, urine protein excretion decreased from 0.96 (IQR 0.54, 2.9) to 0.48 (IQR 0.18, 0.79) g/g creatinine () in patients treated with simvastatin in addition to ACEI and ARBs, while no change was observed among the untreated patients. Moreover, a significantly greater decrease in urine protein excretion was observed in the simvastatin group as compared with the untreated group. The mean changes of serum creatinine and eGFR did not significantly differ in both groups. A significantly greater decrease in total cholesterol and LDL-cholesterol was found in the simvastatin group than in the untreated group. In summary, apart from lipid lowering among CKD patients, ingesting simvastatin was associated with a decrease in proteinuria. These statin effects may become important for supportive therapy in renal damage in the future. Bancha Satirapoj, Anan Promrattanakun, Ouppatham Supasyndh, and Panbuppa Choovichian Copyright © 2015 Bancha Satirapoj et al. All rights reserved. Glycaemic Control Impact on Renal Endpoints in Diabetic Patients on Haemodialysis Sun, 20 Sep 2015 11:19:53 +0000 Objective. To identify the number of haemodialysis patients with diabetes in a large NHS Trust, their current glycaemic control, and the impact on other renal specific outcomes. Design. Retrospective, observational, cross-sectional study. Methods. Data was collected from an electronic patient management system. Glycaemic control was assessed from HbA1c results that were then further adjusted for albumin (Alb) and haemoglobin (Hb). Interdialytic weight gains were analysed from weights recorded before and after dialysis, 2 weeks before and after the most recent HbA1c date. Amputations were identified from electronic records. Results. 39% of patients had poor glycaemic control (HbA1c > 8%). Adjusted HbA1c resulted in a greater number of patients with poor control (55%). Significant correlations were found with interdialytic weight gains (, ), predialysis sodium (, ), and predialysis bicarbonate (, ). Trends were observed with albumin and C-reactive protein. Patients with diabetes had more amputations (24 versus 2). Conclusion. Large number of diabetic patients on haemdialysis have poor glycaemic control. This may lead to higher interdialytic weight gains, larger sodium and bicarbonate shifts, increased number of amputations, and possibly increased inflammation and decreased nutritional status. Comprehensive guidelines and more accurate long-term tests for glycaemic control are needed. Danielle Creme and Kieran McCafferty Copyright © 2015 Danielle Creme and Kieran McCafferty. All rights reserved. A Study to Inform the Design of a National Multicentre Randomised Controlled Trial to Evaluate If Reducing Serum Phosphate to Normal Levels Improves Clinical Outcomes including Mortality, Cardiovascular Events, Bone Pain, or Fracture in Patients on Dialysis Sun, 23 Aug 2015 11:43:26 +0000 Background. Retrospective, observational studies link high phosphate with mortality in dialysis patients. This generates research hypotheses but does not establish “cause-and-effect.” A large randomised controlled trial (RCT) of about 3000 patients randomised 50 : 50 to lower or higher phosphate ranges is required to answer the key question: does reducing phosphate levels improve clinical outcomes? Whether such a trial is technically possible is unknown; therefore, a study is necessary to inform the design and conduct of a future, definitive trial. Methodology. Dual centre prospective parallel group study: 100 dialysis patients randomized to lower (phosphate target 0.8 to 1.4 mmol/L) or higher range group (1.8 to 2.4 mmol/L). Non-calcium-containing phosphate binders and questionnaires will be used to achieve target phosphate. Primary endpoint: percentage successfully titrated to required range and percentage maintained in these groups over the maintenance period. Secondary endpoints: consent rate, drop-out rates, and cardiovascular events. Discussion. This study will inform design of a large definitive trial of the effect of phosphate on mortality and cardiovascular events in dialysis patients. If phosphate lowering improves outcomes, we would be reassured of the validity of this clinical practice. If, on the other hand, there is no improvement, a reassessment of resource allocation to therapies proven to improve outcomes will result. Trial Registration Number. This trial is registered with ISRCTN registration number ISRCTN24741445. Ramya Bhargava, Philip A. Kalra, Paul Brenchley, Helen Hurst, and Alastair Hutchison Copyright © 2015 Ramya Bhargava et al. All rights reserved. Morphological Retrospective Study of Peritoneal Biopsies from Patients with Encapsulating Peritoneal Sclerosis: Underestimated Role of Adipocytes as New Fibroblasts Lineage? Wed, 19 Aug 2015 14:16:13 +0000 Background. Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). Besides the endothelial-to-mesenchymal transition (EMT), recently peritoneal adipocytes emerged as a potential source of fibrosis. We performed immunohistochemistry to approach EMT and to localize peritoneal adipocytes in peritoneal biopsies from PD-related EPS patients. Material and Methods. We investigated tissue expression of podoplanin, cytokeratin AE1/AE3 (mesothelium), calretinin (adipocytes), alpha-smooth muscle actin [α-SMA] (mesenchymal cells), interstitial mononuclear cell inflammation, and neoangiogenesis (CD3, CD4, CD8, CD20, CD68, and CD31 immunostainings, resp.). Results. Three patients (1 man/2 women; 17, 64, and 39 years old, resp.) developed EPS after 21, 90, and 164 months of PD therapy. In patients with EPS, we observed (1) loss of AE1/AE3 cytokeratin+ mesothelial cells without any evidence of migration into the interstitium, (2) disappearance of adipose tissue, (3) diffuse infiltration of calretinin+ cells in the areas of submesothelial fibrosis with a huge number of α-SMA and calretinin+ fusiform cells, and (4) increased vascular density. Conclusion. We report that the involvement of EMT in peritoneal fibrosis is difficult to demonstrate and that the calretinin+ adipocytes might be an underestimated component and a new source of myofibroblasts in peritoneal remodeling during PD-related EPS. Monika Tooulou, Pieter Demetter, Anwar Hamade, Caroline Keyzer, Joëlle L. Nortier, and Agnieszka A. Pozdzik Copyright © 2015 Monika Tooulou et al. All rights reserved. High (≥6.5) Spontaneous and Persistent Urinary pH Is Protective of Renal Function at Baseline and during Disease Course in Idiopathic Membranous Nephropathy Thu, 30 Jul 2015 17:06:20 +0000 Metabolic acidosis correction in advanced renal failure slows renal function decline attributed to tubulointerstitial damage (TID) reduction. No study evaluated if spontaneous baseline high urinary pH (UpH) is renoprotective in patients with normal renal function and without metabolic acidosis. The study tested this hypothesis in idiopathic membranous nephropathy (IMN). Eighty-five patients (follow-up 81 ± 54 months) measured UpH, serum creatinine, eGFR, protein/creatinine ratio, fractional excretion of albumin, IgG, α1-microglobulin, and urinary N-acetyl-β-D-glucosaminidase (β-NAG)/creatinine ratio. Twenty-eight patients (33%) had UpH ≥ 6.5 and 57 (67%) pH < 6.5; high versus low UpH patients had significantly lower values of the tubulointerstitial damage (TID) markers FE α1m and β-NAG and significantly better baseline renal function. These differences persisted over time in a subset of 38 patients with 5 measurements along 53 ± 26 months. In 29 patients with nephrotic syndrome (NS) treated with supportive therapy (follow-up: 80 ± 52 months) renal function was stable in 10 high and significantly worse in 19 low UpH patients. Steroids + cyclophosphamide treatment in 35 NS patients masks the renoprotection of high UpH. Conclusions. In IMN high and persistent UpH is associated with reduction of the proteinuric markers of tubulointerstitial damage and baseline better renal function in all patients and in NS patients treated only with supportive therapy during disease course. The factors associated with high pH-dependent renoprotection were lower values of TID markers, eGFR ≥ 60 mL/min, BP < 140/90 mmHg, and age < 55 years. Claudio Bazzi, Elena Tagliabue, Sara Raimondi, Virginia Rizza, Daniela Casellato, and Masaomi Nangaku Copyright © 2015 Claudio Bazzi et al. All rights reserved. Clinical Use of Diuretics in Heart Failure, Cirrhosis, and Nephrotic Syndrome Wed, 29 Jul 2015 15:37:01 +0000 Diuretics play significant role in pharmacology and treatment options in medicine. This paper aims to review and evaluate the clinical use of diuretics in conditions that lead to fluid overload in the body such as cardiac failure, cirrhosis, and nephrotic syndrome. To know the principles of treatment it is essential to understand the underlying pathophysiological mechanisms that cause the need of diuresis in the human body. Various classes of diuretics exist, each having a unique mode of action. A systemic approach for management is recommended based on the current guidelines, starting from thiazides and proceeding to loop diuretics. The first condition for discussion in the paper is cardiac failure. Treatment of ascites in liver cirrhosis with spironolactone as the primary agent is highlighted with further therapeutic options. Lastly, management choices for nephrotic syndrome are discussed and recommended beginning from basic sodium restriction to combined diuretic therapies. Major side effects are discussed. Ahmed Hassaan Qavi, Rida Kamal, and Robert W. Schrier Copyright © 2015 Ahmed Hassaan Qavi et al. All rights reserved. Hyperuricemia: An Early Marker for Severity of Illness in Sepsis Wed, 29 Jul 2015 10:39:53 +0000 Background. Uric acid can acutely activate various inflammatory transcription factors. Since high levels of oxyradicals and lower antioxidant levels in septic patients are believed to result in multiorgan failure, uric acid levels could be used as a marker of oxidative stress and poor prognosis in patients with sepsis. Design. We conducted a prospective cohort study on Medical Intensive Care Unit (MICU) patients and hypothesized that elevated uric acid in patients with sepsis is predictive of greater morbidity. The primary end point was the correlation between hyperuricemia and the morbidity rate. Secondary end points were Acute Kidney Injury (AKI), mortality, Acute Respiratory Distress Syndrome (ARDS), and duration of stay. Results. We enrolled 144 patients. 54 (37.5%) had the primary end point of hyperuricemia. The overall morbidity rate was 85.2%. The probability of having hyperuricemia along with AKI was 68.5% and without AKI was 31.5%. Meanwhile the probability of having a uric acid value <7 mg/dL along with AKI was 18.9% and without AKI was 81.1% ( value < 0.0001). Conclusion. We report that elevated uric acid levels on arrival to the MICU in patients with sepsis are associated with poor prognosis. These patients are at an increased risk for AKI and ARDS. Sana R. Akbar, Dustin M. Long, Kashif Hussain, Ahmad Alhajhusain, Umair S. Ahmed, Hafiz I. Iqbal, Ailia W. Ali, Rachel Leonard, and Cheryl Dalton Copyright © 2015 Sana R. Akbar et al. All rights reserved. High Prevalence of Cardiovascular Disease in End-Stage Kidney Disease Patients Ongoing Hemodialysis in Peru: Why Should We Care About It? Wed, 29 Jul 2015 09:07:03 +0000 Purpose. To determine clinical, biochemical, and pharmacological characteristics as well as cardiovascular disease prevalence and its associated factors among end-stage kidney disease patients receiving hemodialysis in the main hemodialysis center in Lima, Peru. Methods. This cross-sectional study included 103 patients. Clinical charts were reviewed and an echocardiogram was performed to determine prevalence of cardiovascular disease, defined as the presence of systolic/diastolic dysfunction, coronary heart disease, ventricular dysrhythmias, cerebrovascular disease, and/or peripheral vascular disease. Associations between cardiovascular disease and clinical, biochemical, and dialysis factors were sought using prevalence ratio. A robust Poisson regression model was used to quantify possible associations. Results. Cardiovascular disease prevalence was 81.6%, mainly due to diastolic dysfunction. It was significantly associated with age older than 50 years, metabolic syndrome, C-reactive protein levels, effective blood flow ≤ 300 mL/min, severe anemia, and absence of mild anemia. However, in the regression analysis only age older than 50 years, effective blood flow ≤ 300 mL/min, and absence of mild anemia were associated. Conclusions. Cardiovascular disease prevalence is high in patients receiving hemodialysis in the main center in Lima. Diastolic dysfunction, age, specific hemoglobin levels, and effective blood flow may play an important role. Katia Bravo-Jaimes, Alvaro Whittembury, and Vilma Santivañez Copyright © 2015 Katia Bravo-Jaimes et al. All rights reserved. Prognosis of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis: A Prospective Cohort Study Wed, 22 Jul 2015 13:18:09 +0000 Background/Aims. Acute kidney injury is a common problem for patients with cirrhosis and is associated with poor survival. We aimed to examine the association between type of acute kidney injury and 90-day mortality. Methods. Prospective cohort study at a major US liver transplant center. A nephrologist’s review of the urinary sediment was used in conjunction with the 2007 Ascites Club Criteria to stratify acute kidney injury into four groups: prerenal azotemia, hepatorenal syndrome, acute tubular necrosis, or other. Results. 120 participants with cirrhosis and acute kidney injury were analyzed. Ninety-day mortality was 14/40 (35%) with prerenal azotemia, 20/35 (57%) with hepatorenal syndrome, 21/36 (58%) with acute tubular necrosis, and 1/9 (11%) with other ( overall). Mortality was the same in hepatorenal syndrome compared to acute tubular necrosis (). Mortality was lower in prerenal azotemia compared to hepatorenal syndrome () and acute tubular necrosis (). Ten participants (22%) were reclassified from hepatorenal syndrome to acute tubular necrosis because of granular casts on urinary sediment. Conclusions. Hepatorenal syndrome and acute tubular necrosis result in similar 90-day mortality. Review of urinary sediment may add important diagnostic information to this population. Multicenter studies are needed to validate these findings and better guide management. Andrew S. Allegretti, Guillermo Ortiz, Julia Wenger, Joseph J. Deferio, Joshua Wibecan, Sahir Kalim, Hector Tamez, Raymond T. Chung, S. Ananth Karumanchi, and Ravi I. Thadhani Copyright © 2015 Andrew S. Allegretti et al. All rights reserved. Hydration Status Is Associated with Aortic Stiffness, but Not with Peripheral Arterial Stiffness, in Chronically Hemodialysed Patients Wed, 17 Jun 2015 13:45:02 +0000 Background. Adequate fluid management could be essential to minimize high arterial stiffness observed in chronically hemodialyzed patients (CHP). Aim. To determine the association between body fluid status and central and peripheral arterial stiffness levels. Methods. Arterial stiffness was assessed in 65 CHP by measuring the pulse wave velocity (PWV) in a central arterial pathway (carotid-femoral) and in a peripheral pathway (carotid-brachial). A blood pressure-independent regional arterial stiffness index was calculated using PWV. Volume status was assessed by whole-body multiple-frequency bioimpedance. Patients were first observed as an entire group and then divided into three different fluid status-related groups: normal, overhydration, and dehydration groups. Results. Only carotid-femoral stiffness was positively associated () with the hydration status evaluated through extracellular/intracellular fluid, extracellular/Total Body Fluid, and absolute and relative overhydration. Conclusion. Volume status and overload are associated with central, but not peripheral, arterial stiffness levels with independence of the blood pressure level, in CHP. Daniel Bia, Cintia Galli, Rodolfo Valtuille, Yanina Zócalo, Sandra A. Wray, Ricardo L. Armentano, and Edmundo I. Cabrera Fischer Copyright © 2015 Daniel Bia et al. All rights reserved. The Clinical Efficacy and Safety of Ertapenem for the Treatment of Complicated Urinary Tract Infections Caused by ESBL-Producing Bacteria in Children Wed, 27 May 2015 11:23:27 +0000 Background. Urinary tract infections (UTIs) are common and important clinical problem in childhood, and extended-spectrum-beta-lactamase- (ESBL-) producing organisms are the leading cause of healthcare-related UTIs. In this study, we aimed to evaluate the clinical efficacy and safety of ertapenem therapy in children with complicated UTIs caused by ESBL-producing organisms. Methods. Seventy-seven children with complicated UTIs caused by ESBL-producing organisms were included in this retrospective study, and all had been treated with ertapenem between January 2013 and June 2014. Results. Sixty-one (79%) females and sixteen (21%) males with a mean ± standard deviation (SD) age of months (range 3–204, median 72 months) were enrolled in this study. Escherichia coli (E. coli) (; 87%) was the most common bacterial cause of the UTIs followed by Klebsiella pneumoniae (K. pneumoniae) (; 11.7%) and Enterobacter cloacae (E. cloacae) (; 1.3%). The mean duration of the ertapenem therapy was days (range 4–11). No serious drug-related clinical or laboratory adverse effects were observed, and the ertapenem therapy was found to be safe and well tolerated in the children in our study. Conclusion. Ertapenem is a newer carbapenem with the advantage of once-daily dosing and is highly effective for treating UTIs caused by ESBL-producing microorganisms. Ayse Karaaslan, Eda Kepenekli Kadayifci, Serkan Atici, Gulsen Akkoc, Nurhayat Yakut, Sevliya Öcal Demir, Ahmet Soysal, and Mustafa Bakir Copyright © 2015 Ayse Karaaslan et al. All rights reserved.