Advances in Nephrology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Planar Cell Polarity Pathway in Kidney Development and Function Wed, 25 Feb 2015 13:10:19 +0000 The evolutionarily conserved planar cell polarity (PCP) signaling pathway controls tissue polarity within the plane orthogonal to the apical-basal axis. PCP was originally discovered in Drosophila melanogaster where it is required for the establishment of a uniform pattern of cell structures and appendages. In vertebrates, including mammals, the PCP pathway has been adapted to control various morphogenetic processes that are critical for tissue and organ development. These include convergent extension (crucial for neural tube closure and cochlear duct development) and oriented cell division (needed for tubular elongation), ciliary tilting that enables directional fluid flow, and other processes. Recently, strong evidence has emerged to implicate the PCP pathway in vertebrate kidney development. In this review, we will describe the experimental data revealing the role of PCP signaling in nephrogenesis and kidney disease. Brittany Rocque and Elena Torban Copyright © 2015 Brittany Rocque and Elena Torban. All rights reserved. Deleterious Effects of Increased Intra-Abdominal Pressure on Kidney Function Wed, 12 Nov 2014 08:06:24 +0000 Elevated intra-abdominal pressure (IAP) occurs in many clinical settings, including sepsis, severe acute pancreatitis, acute decompensated heart failure, hepatorenal syndrome, resuscitation with large volume, mechanical ventilation with high intrathoracic pressure, major burns, and acidosis. Although increased IAP affects several vital organs, the kidney is very susceptible to the adverse effects of elevated IAP. Kidney dysfunction is among the earliest physiological consequences of increased IAP. In the last two decades, laparoscopic surgery is rapidly replacing the open approach in many areas of surgery. Although it is superior at many aspects, laparoscopic surgery involves elevation of IAP, due to abdominal insufflation with carbonic dioxide (pneumoperitoneum). The latter has been shown to cause several deleterious effects where the most recognized one is impairment of kidney function as expressed by oliguria and reduced glomerular filtration rate (GFR) and renal blood flow (RBF). Despite much research in this field, the systemic physiologic consequences of elevated IAP of various etiologies and the mechanisms underlying its adverse effects on kidney excretory function and renal hemodynamics are not fully understood. The current review summarizes the reported adverse renal effects of increased IAP in edematous clinical settings and during laparoscopic surgery. In addition, it provides new insights into potential mechanisms underlying this phenomenon and therapeutic approaches to encounter renal complications of elevated IAP. Zaher Armaly and Zaid Abassi Copyright © 2014 Zaher Armaly and Zaid Abassi. All rights reserved. Moderately Decreased Dietary Salt Intake Suppresses the Progression of Renal Insufficiency in Rats with 5/6 Nephrectomy Mon, 10 Nov 2014 12:29:34 +0000 Aim. Up to now, an appropriate salt intake in renal insufficiency has not been clearly determined. We hypothesize that even a moderate decrease in salt intake may affect functional and morphologic response of the rat remnant kidney after 5/6 nephrectomy. Methods. Subtotal nephrectomy was performed in 77 inbred 12 week-old-female AVN Wistar rats. The two groups of rats were fed either a standard or a low salt diet. Median of salt intake was 14.6 and 10.4 mg/100 g/24 h in the two groups. Results. Ten weeks after ablation, the remnant kidney parenchyma wet weight was 0.66 ± 0.16 g/100 g of body weight and 0.56 ± 0.11 g/100 g of body weight () in rats with a standard and low salt diet, respectively. In these two groups, systolic blood pressure was 151 ± 29 versus 126 ± 21 mmHg (), serum creatinine levels were 164 ± 84 versus 106 ± 29 µmol/L (), proteinuria was 84 ± 37 versus 83 ± 40 mg/100 g/24 h (N.S.), and the glomerular injury score was 2.06 ± 0.49 versus 1.43 ± 0.62 (), respectively. Conclusion. Moderately decreased salt intake slowed down the development of ablation nephropathy in AVN inbred strain of rats. Jan Burkert, Anna Steklacova, Pavel Rossmann, Jaroslav Spatenka, Jan Opatrný, and Karel Matousovic Copyright © 2014 Jan Burkert et al. All rights reserved. Magnesium and Muscle Cramps in End Stage Renal Disease Patients on Chronic Hemodialysis Sun, 09 Nov 2014 11:12:18 +0000 We evaluated the frequency and severity of muscle cramps, and the effect of dialysate magnesium on muscle cramps in 62 stable ESRD patients on chronic hemodialysis. Each subject was surveyed twice within a 6-month period. A single nephrology fellow conducted all in-person surveys. During the first survey, the patients were dialyzed with dialysate magnesium of 0.75 meq/L (0.375 mmol/L). Prior to the second survey, the dialysate magnesium was increased to 1.0 meq/L (0.50 mmol/L). The severity of cramps was scored on a 1–10 scale, with 10 indicating maximal severity. The number of patients with muscle cramps was significantly lower with dialysate magnesium of 1.0 meq/L (0.50 mmol/L) (56% versus 77%, ). No significant difference was observed in interdialytic weight gain, intradialytic ultrafiltration, dry weight, or intradialytic hypotension. The mean ± SD severity score of muscle cramps decreased from to (). Seven of 31 (23%) patients in the group with low dialysate magnesium while 0/20 (0%) patients receiving high magnesium dialysate terminated hemodialysis early due to cramps (). Both the number of patients reporting muscle cramps and the severity score decreased with higher dialysate magnesium which contributed to better adherence to hemodialysis treatments. Patrick G. Lynch, Mersema Abate, Heesuck Suh, and Nand K. Wadhwa Copyright © 2014 Patrick G. Lynch et al. All rights reserved. Peritoneal Membrane Injury and Peritoneal Dialysis Sun, 02 Nov 2014 11:56:50 +0000 For patients with chronic renal failure, peritoneal dialysis (PD) is a common, life sustaining form of renal replacement therapy that is used worldwide. Exposure to nonbiocompatible dialysate, inflammation, and uremia induces longitudinal changes in the peritoneal membrane. Application of molecular biology techniques has led to advances in our understanding of the mechanism of injury of the peritoneal membrane. This understanding will allow for the development of strategies to preserve the peritoneal membrane structure and function. This may decrease the occurrence of PD technique failure and improve patient outcomes of morbidity and mortality. Shaan Chugh, Sultan Chaudhry, Timothy Ryan, and Peter J. Margetts Copyright © 2014 Shaan Chugh et al. All rights reserved. Incremental Hemodialysis Schedule in Patients with Higher Residual Renal Function at the Start of Dialysis Tue, 28 Oct 2014 11:49:32 +0000 We present an observational study to evaluate a progressive schedule of dose of dialysis, starting with 2 HD/week, when the renal clearance of urea was equal to or greater than 2,5 mL/min/1,73 m2 and the patient is in a stable clinical situation. From 2006 to 2011, 182 patients started hemodialysis in our center, of which 134 were included in the study. Residual renal function (RRF), Kt/V, eKru, nPCR, hemoglobin, weekly erythropoietin dose, and beta-2-microglobulin were determined at 6, 12, 18, 24, and 30 months after dialysis initiation. Seventy patients (52%) began with the progressive schedule of 2 HD/week and 64 (48%) patients began with the conventional thrice-weekly schedule (3 HD/week). The decline of RRF was lower in the group of 2 HD/week: 0,20 (0,02–0,53) versus 0,50 (0,14–1,08) mL/min/month (median and interquartile range, ). No relationship was found between the decline rate and the basal RRF. Survival analysis did not show differences between both groups. Our experience demonstrates that patients with higher residual renal function may require less than conventional 3 HD sessions per week at the start of dialysis. Twice-weekly hemodialysis schedule is safe and cost-effective and may have additional benefit in maintaining the residual renal function. Milagros Fernández Lucas, José Luis Teruel, Gloria Ruíz-Roso, Martha Díaz, Viviana Raoch, Fernando Caravaca, and Carlos Quereda Copyright © 2014 Milagros Fernández Lucas et al. All rights reserved. The Choice of the Iodinated Radiographic Contrast Media to Prevent Contrast-Induced Nephropathy Wed, 15 Oct 2014 09:44:42 +0000 In patients with preexisting renal impairment, particularly those who are diabetic, the iodinated radiographic contrast media may cause contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI), that is, an acute renal failure (ARF), usually nonoliguric and asymptomatic, occurring 24 to 72 hours after their intravascular injection in the absence of an alternative aetiology. Radiographic contrast media have different osmolalities and viscosities. They have also a different nephrotoxicity. In order to prevent CIN, the least nephrotoxic contrast media should be chosen, at the lowest dosage possible. Other prevention measures should include discontinuation of potentially nephrotoxic drugs, adequate hydration with i.v. infusion of either normal saline or bicarbonate solution, and eventually use of antioxidants, such as N-acetylcysteine, and statins. Michele Andreucci, Teresa Faga, Antonio Pisani, Massimo Sabbatini, Domenico Russo, and Ashour Michael Copyright © 2014 Michele Andreucci et al. All rights reserved. Comparison of Different Measures of Fat Mass and Their Association with Serum Cystatin C Levels Tue, 07 Oct 2014 14:03:59 +0000 Introduction. Cystatin C (CysC) is a glomerular filtration rate (GFR) marker affected by GFR and obesity. Because percentage body fat (%BF) distribution is affected by ethnicity, different measures of %BF may improve CysC prediction. This study aims to create multivariate models that predict serum CysC and determine which %BF metric gives the best prediction. Methods. Serum CysC was measured by nephelometric assay. We estimated %BF by considering weight, body mass index, waist-hip ratio, triceps skin fold, bioimpedance, and Deurenberg and Yap %BF equations. A base multivariate model for CysC was created with a %BF metric added in turn. The best model is considered by comparing values, , Akaike information criterion (AIC), and Bayesian information criterion (BIC). Results. There were 335 participants. Mean serum CysC and creatinine were 1.27 mg/L and 1.44 mg/dL, respectively. Variables for the base model were age, gender, ethnicity, creatinine, serum urea, c-reactive protein, log GFR, and serum albumin. %BF had a positive correlation with CysC. The best model for predicting CysC included bioimpedance-derived %BF (), with the highest (0.917) and the lowest AIC and BIC (−371, −323). Conclusion. Obesity is associated with CysC, and the best predictive model for CysC includes bioimpedance-derived %BF. Boon Wee Teo, Jonathan J. H. Soon, Qi Chun Toh, Hui Xu, Jialiang Li, and Evan J. C. Lee Copyright © 2014 Boon Wee Teo et al. All rights reserved. Preinterventional Cystatin C: A Highly Prognostic Marker for All-Cause Mortality after Coronarography Thu, 25 Sep 2014 09:15:21 +0000 Purpose. Glomerular filtration rate <60 mL/min/1.73 m2 is associated with increased all-cause mortality. Multiple studies have shown that serum cystatin C is more accurate than serum creatinine for detection of mild to moderate chronic kidney dysfunction. We examined the predictive value of the preinterventional cystatin C for all-cause mortality after contrast media exposition. Methods. The prognostic value of preinterventional cystatin C for all-cause mortality was retrospectively analysed in the prospective single-centre “Dialysis-versus-Diuresis” Trial (January 2001–July 2004). Associations during up to 1316 days of followup for all-cause mortality were assessed. The study population consisted of 373 patients (aged 35–89, mean 67 years, 16.4% female). Results. During followup, 65 deaths occurred. Multivariate cox regression confirmed the preinterventional CyC level to be an independent predictor of all-cause mortality (odds ratio 2.061, 95% confidence interval 1.054–4.031, ). Hazard rate ratio for all-cause mortality was increased in the third cystatin C quartile (>1.4 mg/L) compared with the lowest quartile (<1.1 mg/L), 4.12, 95% confidence interval 1.747–9.694 (), in the fourth cystatin C quartile (>1.6 mg/L) compared with the lowest quartile, 5.38, 95% confidence interval 2.329–12.427 (). Conclusions. Cystatin C is significantly associated with all-cause mortality after coronarography, regardless of the age, gender, and glomerular filtration rate. Florian Lüders, Nasser Malyar, Matthias Meyborg, and Holger Reinecke Copyright © 2014 Florian Lüders et al. All rights reserved. Fragility Fractures in Chronic Kidney Disease: Assessment and Pharmacologic Management Tue, 16 Sep 2014 11:36:28 +0000 Fractures are common in all stages of chronic kidney disease (CKD), and are associated with increased morbidity and mortality. Both CKD and osteoporosis often coexist as they both are strongly age associated. However, the management of fragility fractures in CKD poses many dilemmas. These include diagnosing the aetiology of fractures and choosing appropriate treatment. This paper reviews the current evidence for the assessment and pharmacologic management of fragility fractures in CKD. Mahesan Anpalahan, Sudharsan Venkatesan, and Aksharaa Anpalahan Copyright © 2014 Mahesan Anpalahan et al. All rights reserved. Chronic Kidney Disease: Evolution of Healthcare Costs and Resource Consumption from Predialysis to Dialysis in Piedmont Region, Italy Tue, 16 Sep 2014 09:33:46 +0000 This study aims at assessing the evolution in healthcare costs for chronic kidney disease (CKD) patients through the analysis of administrative databases of Piedmont region, Italy. This is a retrospective, observational study, for which patients undergoing at least one dialysis for CKD in the period of June 1, 2010–May 31, 2011 were selected. Two subpopulations were evaluated: patients incident-to-dialysis observed for the 12 months preceding dialysis entrance (PreD) and “established” dialysis patients (at least 120 dialyses/year) observed for 12 months (EstD). Overall, 1,059 PreD and 2,018 EstD patients were selected. The average yearly cost per PreD patient accounted for 11,123€ ± 15,095€ (75% hospitalizations, 17% drugs, and 8% diagnostic/therapeutic procedures). The average yearly cost per EstD patient accounted for 53,764€ ± 14,685€ (59% dialysis, 21% diagnostic/therapeutic procedures, 13% hospitalizations, and 6.7% drugs). Among EstD population, hemodialysis patients cost 56,049€ ± 13,473€ per year, whereas peritoneal dialysis patients cost 34,978€ ± 10,847€ per year. The significant difference in expenditure between predialysis and dialysis suggests that prevention, early diagnosis, and the consequent possible delay of dialysis entrance could lead to important savings for healthcare services, as well as a better global health status for patients. Daniela Paola Roggeri, Alessandro Roggeri, and Mario Salomone Copyright © 2014 Daniela Paola Roggeri et al. All rights reserved. Risk Factors of Arterial Damage Assessed by ABI and baPWV among Hemodialysis Patients in Macau Tue, 09 Sep 2014 08:38:15 +0000 Cardiovascular disease (CVD) is the leading cause of mortality and morbidity among patients with ESRD on chronic dialysis. Arterial damage is one of the characteristics of CVD. But the association between arterial damage and conventional risk factors for CVD has not yet been fully highlighted in chronic hemodialysis patients. Here we validate the clinical value of assessment of arterial damage by ABI and PWV in chronic hemodialysis patients in Macau. Mingxin Li, Jing Xin, Ding-Wei Kuang, Un-I Kuok, Chiu-Leong Li, Kin Cheung, and Weng-In Lio Copyright © 2014 Mingxin Li et al. All rights reserved. Calcium Carbonate versus Sevelamer Hydrochloride as Phosphate Binders after Long-Term Disease Progression in 5/6 Nephrectomized Rats Sun, 24 Aug 2014 07:56:52 +0000 Our aim was to compare the effects of calcium carbonate and sevelamer-HCl treatments on calcium-phosphate metabolism and renal function in 5/6 nephrectomized (NX) rats so that long-term disease progression preceded the treatment. After 15-week progression, calcium carbonate (3.0%), sevelamer-HCl (3.0%), or control diets (0.3% calcium) were given for 9 weeks. Subtotal nephrectomy reduced creatinine clearance (−40%), plasma calcidiol (−25%), and calcitriol (−70%) and increased phosphate (+37%), parathyroid hormone (PTH) (11-fold), and fibroblast growth factor-23 (FGF-23) (4-fold). In NX rats, calcium carbonate diet increased plasma (+20%) and urinary calcium (6-fold), reduced plasma phosphate (−50%) and calcidiol (−30%), decreased creatinine clearance (−35%) and FGF 23 (−85%), and suppressed PTH without influencing blood pH. In NX rats, sevelamer-HCl increased urinary calcium (4-fold) and decreased creatinine clearance (−45%), PTH (−75%), blood pH (by 0.20 units), plasma calcidiol (−40%), and calcitriol (−65%). Plasma phosphate and FGF-23 were unchanged. In conclusion, when initiated after long-term progression of experimental renal insufficiency, calcium carbonate diet reduced plasma phosphate and FGF-23 while sevelamer-HCl did not. The former induced hypercalcemia, the latter induced acidosis, while both treatments reduced vitamin D metabolites and deteriorated renal function. Thus, delayed initiation influences the effects of these phosphate binders in remnant kidney rats. Suvi Törmänen, Arttu Eräranta, Asko Riutta, Peeter Kööbi, Teemu Honkanen, Emmanouil Karavalakis, Onni Niemelä, Heikki Tokola, Heikki Ruskoaho, Jukka Mustonen, and Ilkka Pörsti Copyright © 2014 Suvi Törmänen et al. All rights reserved. Association between Severity of Anemia and 30-Day Readmission Rate: Archival Data of 847 Patients with Acute Decompensated Heart Failure Mon, 14 Jul 2014 13:35:27 +0000 Hospitals today are facing adjustments to reimbursements from excessive readmission rates. One of the most common and expensive causes of readmissions is exacerbation of a heart failure condition. The objective of this paper was to determine if there was an association between the presence of anemia in patients with acute decompensated heart failure and their readmission rate. Using archival data of 4 hospitals in the Miami area, a sample of 847 inpatients with a diagnostic related group (DRG) of HF at discharge was considered. There was a significant association between low hemoglobin values and a high rate of readmissions at 14 days and at 30 days in subjects with normal sodium and creatinine values. For subjects with low sodium and high creatinine values, a higher readmission rate was seen in men with low hemoglobin but not in women. These results support a prospective effort to measure the impact of anemia and its treatment on readmission rates. Jorge C. Busse, Tanya M. Cohn, Rosalina Butao, and Julie Lamoureux Copyright © 2014 Jorge C. Busse et al. All rights reserved. Rho-GTPase Signalling in the Pathogenesis of Nephrotic Syndrome Sun, 15 Jun 2014 06:25:11 +0000 Nephrotic syndrome (NS) is characterized by heavy proteinuria, hypoalbuminemia, and edema. The underlying causes of NS are diverse and are tied to inheritable and environmental factors. A common diagnostic marker for NS is effacement of podocyte foot processes. The formation and maintenance of foot processes are under the control of many signalling molecules including Rho-GTPases. Our knowledge of Rho-GTPases is based largely on the functions of three prototypic members: RhoA, Rac1, and Cdc42. In the event of podocyte injury, the rearrangement to the actin cytoskeleton is orchestrated largely by this family of proteins. The importance of maintaining proper actin dynamics in podocytes has led to much investigation as to how Rho-GTPases and their regulatory molecules form and maintain foot processes as a critical component of the kidney’s filtration barrier. Modern sequencing techniques have allowed for the identification of novel disease causing mutations in genes such as ARHGDIA, encoding Rho-GDIα. Continued use of whole exome sequencing has the potential to lead to the identification of new mutations in genes encoding Rho-GTPases or their regulatory proteins. Expanding our knowledge of the dynamic regulation of the actin network by Rho-GTPases in podocytes will pave the way for effective therapeutic options for NS patients. Richard Robins and Tomoko Takano Copyright © 2014 Richard Robins and Tomoko Takano. All rights reserved. Managing End-Stage Renal Disease in Older Patients: A Single Centre Experience with Renal Transplantation in the Elderly Tue, 25 Mar 2014 07:45:23 +0000 The increase of patients developing end-stage renal disease (ESRD) has occurred predominantly in the older adult population. As a consequence, the nephrologists will need to decide whom of these older patients are siutable for transplantation. There are very few absolute contraindications, such as active infection and recent malignancy, but there are many relative or potential contraindications in older patients. Worldwide, organs available for transplantation are limited. Some centers are reluctant to use organs from expanded criteria donors also in elderly recipients. This leads to long waiting lists and many older patients will die while they are waiting for an organ. It is vital that the patients who are accepted for renal transplantation are those who will derive most benefit, and correct selection of patients and donor organs is therefore of outmost importance. This paper describes the previous and planned research our research group has performed with focus on older renal transplant recipients with special emphasis on survival, basic immunosuppression, selection of organs, and health related quality of life. Karsten Midtvedt, Kjersti Lønning, and Kristian Heldal Copyright © 2014 Karsten Midtvedt et al. All rights reserved.