Treatment For End-stage Renal Disease Research Articles

Hepatitis C virus infection in end-stage renal disease and kidney transplantation.

Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on renal replacement therapy and after kidney transplantation (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for bloodborne infections because of prolonged vascular access and the potential for exposure to infected patients and contaminated equipment. Evaluation of HCV-positive/ESRD and HCV-positive/KT patients is warranted to determine the stage of disease and the appropriateness of antiviral therapy, despite such treatment is challenging especially due to tolerability issues. Antiviral treatment with interferon (IFN) is contraindicated after transplantation due to the risk of rejection, and therefore, treatment is recommended before KT. Newer treatment strategies of direct-acting antiviral agents in combination are revolutionizing HCV therapy, as a result of encouraging outcomes streaming from recent studies which report increased sustained viral response, low or no resistance, and good safety profiles, including preservation of renal function. KT has been demonstrated to yield better outcomes with respect to remaining on HD although survival after KT is penalized by the presence of HCV infection with respect to HCV-negative transplant recipients. Therefore, an appropriate, comprehensive, easily applicable set of clinical practice management guidelines is necessary in both ESRD and KT patients with HCV infection and HCV-related liver disease.

Risk factors for perioperative complications in hand-assisted laparoscopic donor nephrectomy.

Living donor kidney transplant is the preferred treatment for end-stage renal disease; however, the shortage of kidney donors remains a big problem. One of the major reasons for the shortage of living donors is the risk of potentially serious surgical complications of a procedure in which the donor has no personal medical benefit. Therefore it is important to understand the risk factors for perioperative complications associated with donor nephrectomy. Hand-assisted laparoscopic donor nephrectomy is the preferred approach for kidney procurement in many medical centers. This review gives an overview of the risk factors in donor nephrectomy and more specifically in hand-assisted laparoscopic donor nephrectomy.

Impact of mammalian target of rapamycin inhibition by everolimus on peripheral blood αβ and γδ T lymphocytes in renal transplant recipients (TRAN1P.875)

Abstract The kidney is an essential organ necessary for the human body to discharge harmful toxins and is imperative for filtering blood. According to the Centers for Disease Control and Prevention, kidney disease is the eighth leading cause of death in the United States. Diabetes and hypertension are two major factors that influence kidney function, which can consequently lead to end-stage renal disease. The primary method of treatment for end-stage renal disease is kidney transplantation, which requires a regimen of immunosuppressant drugs to prevent allograft rejection. Previously, our lab has shown that administration of the immunosuppressant drug, sirolimus a mammalian target of rapamycin inhibitor, also known as mTOR, impairs skin homeostasis and wound repair. To further understand the mechanism behind this adverse effect of mTOR suppression, we examined renal transplant recipients who were administered the sirolimus derivative everolimus. The number and activation of αβ and γδ T cells in the blood of patients administered everolimus were compared to a control group of patients not administered everolimus. Several of these T cell populations, including Vγ9Vδ2 T cells, have been previously displayed to home to sites of tissue damage to improve wound repair. This data explores which T lymphocyte populations require mTOR to maximize function in transplant recipients with implications in tissue repair and graft rejection.

A systematic review and meta-analysis of the influence of peritoneal dialysis catheter type on complication rate and catheter survival

Peritoneal dialysis (PD) is an effective treatment for end-stage renal disease. There are several configurations of PD catheter design that may impact catheter function, such as the shape of the intraperitoneal segment, the number of cuffs, and the subcutaneous configuration. This review and meta-analysis was carried out to determine whether there is a clinical advantage for one of the catheter types or configurations. Comprehensive searches were conducted in MEDLINE, Embase, and CENTRAL (the Cochrane Library 2012, issue 10). The methodology was in accordance with the Cochrane Handbook for Interventional Systematic Reviews and written based on the PRISMA statement. The initial search yielded 682 hits from which 13 randomized controlled trials were identified. Outcomes of interest were as follows: catheter survival, drainage dysfunction, migration, leakage, exit-site infections, peritonitis, and catheter removal. Comparing straight vs. swan neck and single vs. double-cuffed catheters, no differences were found when results were pooled. Comparison of straight vs. coiled-tip catheters demonstrated that survival was significantly different in favor of straight catheters (hazard ratio 2.05; confidence interval 1.10-3.79, P=0.02). For surgically inserted catheters, the removal rate and survival at 1 year after insertion were significantly in favor of straight catheters. Our meta-analysis clearly demonstrates benefits for catheters with a straight intraperitoneal segment.

Analysis of 1,500 Kidney Transplantations at Sungkyunkwan University

Background: The most effective treatment for end-stage renal disease is kidney transplantation, and the number of kidney transplantations has shown a rapid increase. The aim of this study was to determine graft survival and functional outcome of 1,500 kidney transplant cases in a single center. We also investigated the factors affecting graft failure after kidney transplantation. Methods: We retrospectively reviewed the clinical data of 1,500 pairs of donors and subsequent recipients who underwent kidney transplantation in Samsung Medical Center, from February 1995 to January 2012. Results: The mean follow-up period was 2,241.5±1,609.4 days. There were 851 (56.7%) male recipients; 62 (4.1%) recipients were younger than 19 years old. Eleven (0.7%) cases were ABO blood group incompatible kidney transplant. A total of 531 (35%) deceased and 969 (65%) living donors were included. Among them, 191 (12.7%) recipients were experienced in graft failure. The most common cause of graft loss was chronic allograft nephropathy. One-year, 5-year, 10-year, and 15-year graft survival were 97.3%, 92.8%, 81.6%, and 75.1% (85.2% for living, 75.4% for deceased donor), respectively. Higher incidence of graft failure was observed in recipients who received deceased donor kidneys or experienced a rejection episode. Conclusions: In our experience, overall 10-year graft survival after kidney transplantation was 81.6%. This report demonstrated that the type of donor (living or deceased) and history of allograft rejection are the only significant factors affecting graft survival.

Commentary to ‘Does bladder augmentation negatively affect renal transplant outcome in PUV patients?’

The authors present data on their experience with bladder augmentation in children undergoing transplantation for posterior urethral valves. Most of their augmented patients (10/12) were with a ureter. They found a higher incidence of urinary tract infections(UTIs) in the augmented group, but graft function and survival were similar. The presence of vesicoureteral reflux was the major risk factor in both groups. Even though this is one of the larger series of patients with posterior urethral valves undergoing transplantation, the numbers are still too small to determine if bladder augmentation is a confounding factor and if vesicoureteral reflux is not the main factor responsible for the increased incidence of UTIs. Does bladder augmentation negatively affect renal transplant outcome in posterior urethral valve patients?Journal of Pediatric UrologyVol. 10Issue 5PreviewAlthough renal transplant (RT) is a safe and effective treatment for end-stage renal disease, the outcome of RT has been mixed for posterior urethral valve (PUV) patients. In addition, some PUV patients need an augmentation cystoplasty (AC), which may negatively affect their RT outcome. The aim of this study is to compare RT outcome between PUV children with and without AC. Full-Text PDF

Immunosuppression Regimen and the Risk of Acute Rejection in HIV-Infected Kidney Transplant Recipients

Kidney transplantation (KT) is the treatment for end-stage renal disease in appropriate HIV-positive individuals. However, acute rejection (AR) rates are over twice those of HIV-negative recipients. To better understand optimal immunosuppression for HIV-positive KT recipients, we studied associations between immunosuppression regimen, AR at 1 year, and survival in 516 HIV-positive and 93,027 HIV-negative adult kidney-only recipients using Scientific Registry of Transplant Recipients data from 2003 to 2011. Consistent with previous reports, HIV-positive patients had twofold higher risk of AR (adjusted relative risk [aRR], 1.77; 95% confidence interval [CI], 1.45-2.2; P<0.001) than their HIV-negative counterparts as well as a higher risk of graft loss (adjusted hazard ratio, 1.51; 95% CI, 1.18-1.94; P=0.001), but these differences were not seen among patients receiving antithymocyte globulin (ATG) induction (aRR for AR, 1.16; 95% CI, 0.41-3.35, P=0.77; adjusted hazard ratio for graft loss, 1.54; 95% CI, 0.73-3.25; P=0.26). Furthermore, HIV-positive patients receiving ATG induction had a 2.6-fold lower risk of AR (aRR, 0.39; 95% CI, 0.18-0.87; P=0.02) than those receiving no antibody induction. Conversely, HIV-positive patients receiving sirolimus-based therapy had a 2.2-fold higher risk of AR (aRR, 2.15; 95% CI, 1.20-3.86; P=0.01) than those receiving calcineurin inhibitor-based regimens. These findings support a role for ATG induction, and caution against the use of sirolimus-based maintenance therapy, in HIV-positive individuals undergoing KT.

Does bladder augmentation negatively affect renal transplant outcome in posterior urethral valve patients?

ObjectiveAlthough renal transplant (RT) is a safe and effective treatment for end-stage renal disease, the outcome of RT has been mixed for posterior urethral valve (PUV) patients. In addition, some PUV patients need an augmentation cystoplasty (AC), which may negatively affect their RT outcome. The aim of this study is to compare RT outcome between PUV children with and without AC. Materials and methodsBetween 1985 and 2012 a total of 309 children received 369 RTs at our institution. Among these patients, 36 were had classified as having PUV. Of these, 12 underwent an AC before RT (AC group) and 24 did not (controls). Data, including age at transplant, allograft source, urological complications, urinary tract infection (UTI) incidence, the presence of vesicoureteral reflux (VUR), and patient and graft survival, were compared between groups. ResultsMean age at RT and mean follow-up were 7.6 versus 7.9 years and 8.9 versus 7.9 years in the AC group and in the control group, respectively (not significant [NS]). Allografts were from living donors in 50% of the AC group and in 41.6% of the controls (NS). The rate of UTI was 0.02 UTI/patient/year and 0.004 UTI/patient/year in the AC and control group, respectively (p = 0.001). Of the nine patients with UTI in the augmented group, five (55.5%) had VUR, while 5/8 (62.5%) patients in the control group with UTI had VUR. All patients with VUR in either group had UTIs previously. Of the five AC patients with more than three UTIs, two (40%) were non-compliant with clean intermittent catheterization (CIC), and UTI incidence was not associated with either a Mitrofanoff conduit or the urethra being used for CIC. Graft function at the end of study was 87.8 ± 40.5 ml/min/m2 in the AC group and 88.17 ± 28.20 ml/min/m2 in the control group (NS). The 10-year graft survival rate was 100% in AC group and 84.8% in controls. Two patients in the AC group lost their grafts (mean follow-up 13.3 ± 0.8 years) and five in the control group (mean follow-up 7.1 ± 4.7 years). ConclusionsBladder augmentation does not negatively affect renal outcome in PUV patients undergoing transplantation. However, recurrent UTIs are more frequent in transplanted PUV patients with an AC than in those without AC, and they are generally related to non-compliance with CIC or the presence of VUR but, mostly, they will not result in impaired graft function.

Recovery of Chronic Dialysis Hypotension After Kidney Transplantation: A Case Report

Chronic dialysis hypotension is described as low systolic blood pressure (<100 mmHg) during interdialytic period. The presence of low predialysis systolic blood pressure, typically <110 mmHg, is signifi cantly associated with increased mortality. Kidney transplantation is the preferred model of renal replacement therapy in the treatment of end-stage renal disease (ESRD) as it improves quality of life and survival. In this article, a long-term hemodialysis (HD) patient with chronic hypotension improved after kidney transplantation is presented. A 39-year-old male patient received a deceased donor kidney transplant. The patient was on HD for 23 years. The patient had suffered from chronic persistent hypotension for the last 8 years. Blood pressure was 70/50 mmHg before dialysis and 60/40 mmHg after dialysis. In the post-transplant period, blood pressure was maintained above 110/70 mmHg by intermittent infusion of dopamine. Hypotension was improved after 24 days and dopamine was discontinued. Various etiologies may cause chronic hypotension in patients receiving long-term HD treatment. Kidney transplantation may improve survival and quality of life by correcting hypotension in these patients. Therefore kidney transplantation should not be avoided as renal replacement therapy in ESRD patients with hypotension.

Quality of Life of Older Patients Undergoing Renal Transplantation: Finding the Right Immunosuppressive Treatment

Kidney transplantation is currently the best treatment for end-stage renal disease, both in terms of mortality benefit and quality of life (QOL). Elderly patients are a rapidly growing subset of the kidney transplant waiting list. While it is clear that elderly individuals have a mortality benefit from kidney transplant, it is less clear how to make sure these individuals benefit from optimal QOL following transplant. Several studies demonstrate superiority of some immunosuppressive regimens over others in the QOL domain. Tacrolimus has been shown to be associated with better QOL than cyclosporine (ciclosporin), as has corticosteroid-free immunosuppressive regimens. Similarly, patients on drug regimens, which tend to lessen the side effects, report better QOL. However, these studies are observational or cross-sectional and not focused exclusively on the elderly patient. More studies are needed to determine optimal immunosuppression regimens for elderly individuals. Additionally, further studies on determinants of QOL in elderly kidney transplant recipients are also needed.

Psychopathological aspects of kidney transplantation: Efficacy of a multidisciplinary team.

Renal transplantation is a well established treatment for end-stage renal disease, allowing most patients to return to a satisfactory quality of life. Studies have identified many problems that may affect adaptation to the transplanted condition and post-operative compliance. The psychological implications of transplantation have important consequences even on strictly physical aspects. Organ transplantation is very challenging for the patient and acts as an intense stressor stimulus to which the patient reacts with neurotransmitter and endocrine-metabolic changes. Transplantation can result in a psychosomatic crisis that requires the patient to mobilize all bio-psycho-social resources during the process of adaptation to the new foreign organ which may result in an alteration in self-representation and identity, with possible psychopathologic repercussions. These reactions are feasible in mental disorders, e.g., post-traumatic stress disorder, adjustment disorder, and psychosomatic disorders. In organ transplantation, the fruitful collaboration between professionals with diverse scientific expertise, calls for both a guarantee for mental health and greater effectiveness in challenging treatments for a viable association between patients, family members and doctors. Integrated and multidisciplinary care should include uniform criteria and procedures for standard assessments, for patient autonomy, adherence to therapy, new coping strategies and the adoption of more appropriate lifestyles.

Starting with PD Enables Diversity of Later Treatments

Background: Various reasons for “Peritoneal Dialysis (PD) First” rather than hemodialysis (HD) have been presented, such as better preservation of residual renal function (RRF), longer survival, and lower incidence of hospitalization. In spite of these advantages for “PD First”, in Japan as well as in the United States the annual rate of patients receiving PD has been reduced to less than 10%. One of the major reasons against selecting PD is that a large proportion of PD patients are transferred from PD to HD in less than 5 years. Our “PD First” policy is based on the diversity of modalities available after discontinuing PD therapy. The purpose of this study was to examine the follow-up of patients who selected “PD First” as the initial treatment of end-stage renal disease (EDRD) between April 1997 and December 2010. Methods: Sex, age, primary underlying diseases and selection of modalities were collected retrospectively. Results: A total of 377 (59.2 ± 8.3 years old; female/male: 255/122) patients were introduced to PD therapy as “PD First.” Patients who were very old, with cardiovascular problems, senile dementia, and neoplasms that were forced to select PD were excluded. One hundred and sixty patients started HD as complementary dialysis therapy and then continued with PD + HD in combination until transfer to HD, transplantation or home HD. Among them, 10 patients received transplants and 22 patients were transferred to home HD. One hundred and twenty eight patients were switched from PD to HD for various reasons. Overall patients’ survival after 5 and 10 years was 84.8% and 55.8%, respectively. Conclusion: Our data shows a diversity of modalities for selection after discontinuing PD therapy alone, as well as providing a rationale to support PD as the initial renal replacement modality for end-stage renal disease patients.

Mesenchymal Conversion of Mesothelial Cells Is a Key Event in the Pathophysiology of the Peritoneum during Peritoneal Dialysis.

Peritoneal dialysis (PD) is a therapeutic option for the treatment of end-stage renal disease and is based on the use of the peritoneum as a semipermeable membrane for the exchange of toxic solutes and water. Long-term exposure of the peritoneal membrane to hyperosmotic PD fluids causes inflammation, loss of the mesothelial cells monolayer, fibrosis, vasculopathy, and angiogenesis, which may lead to peritoneal functional decline. Peritonitis may further exacerbate the injury of the peritoneal membrane. In parallel with these peritoneal alterations, mesothelial cells undergo an epithelial to mesenchymal transition (EMT), which has been associated with peritoneal deterioration. Factors contributing to the bioincompatibility of classical PD fluids include the high content of glucose/glucose degradation products (GDPs) and their acidic pH. New generation low-GDPs-neutral pH fluids have improved biocompatibility resulting in better preservation of the peritoneum. However, standard glucose-based fluids are still needed, as biocompatible solutions are expensive for many potential users. An alternative approach to preserve the peritoneal membrane, complementary to the efforts to improve fluid biocompatibility, is the use of pharmacological agents protecting the mesothelium. This paper provides a comprehensive review of recent advances that point to the EMT of mesothelial cells as a potential therapeutic target to preserve membrane function.

Place de l’AMP-activated protein kinase dans le préconditionnement ischémique rénal

Kidney transplantation represents the best treatment of end-stage renal disease. In addition to the degree of human leukocyte antigen matching, long-term graft survival is influenced by the quality of the graft before its transplantation. Quality criteria include the level of ischemic damage caused by the transplantation per se. Renal ischemic preconditioning (IP) consists of different approaches to prevent ischemia/reperfusion (I/R) damage induced by the interruption and recovery of renal circulation, as observed during transplantation. Distinct animal models show promising results regarding the efficiency of PCI to preserve kidney structure and function in I/R conditions. Characterizing the cellular cascades involved in I/R led to the identification of putative targets of renal IP, including the adenosine monophosphate-activated protein kinase (AMPK). AMPK is a ubiquitous energy sensor, which has been implicated in the maintenance of epithelial cell polarization under energy deprivation. Among others, the anti-diabetic drug, metformin, is a potent activator of AMPK. Here, we summarize the in vitro and in vivo data about the role of AMPK in renal IP. Defining the pharmacological conditions of IP would help to improve the quality of the renal graft before its transplantation, thereby increasing its long-term survival.

Does community-wide chronic kidney disease management improve patient outcomes?

The number of patients starting renal replacement therapy (RRT) is increasing in England, as it is worldwide. Improvements in the management of chronic kidney disease (CKD) across communities to alter this trend are a public health priority. We have prospectively studied changes in the incidence and modality of treatment for end-stage renal disease following the introduction of a CKD management programme in the West Midlands region of England. Nephrology service to approximately 700 000 adult population of mixed ethnicity in urban and suburban areas, many with social deprivation. The programme was introduced in stages between 2003 and 2006 and comprised primary care education and financial incentives, personal clinical reports written directly to patients following every consultation, routine laboratory estimated glomerular filtration rate (eGFR) reporting, eGFR graph surveillance to identify and monitor patients at risk, multidisciplinary pre-RRT care and conservative care. Prevalent patients: 10 552 with CKD and 8509 without CKD with diabetes. access to nephrology care, trends in RRT incidence and starting modality, place of death without RRT. Incident count was adjusted for changes in the local adult population recorded in national censuses. Ninety-one per cent of patients aged ≥75 years with incident CKD stage 5 were known to a nephrologist. The population-adjusted incident RRT rate peaked in 2005 and then declined; the proportion starting with transplant, peritoneal dialysis or haemodialysis by arterio-venous fistula increased to 63% by 2012 (P = 0.001 versus 2005). Fifty-two per cent of patients receiving planned conservative care without dialysis died out of hospital. Following the introduction of a community-wide systematic CKD management programme, the population-adjusted incidence of RRT reduced, modality of initiation of RRT improved and a majority of patients receiving planned conservative care without dialysis died out of hospital.

Adverse effects of systemic glucose absorption with peritoneal dialysis

Treatment of end-stage renal disease with peritoneal dialysis is associated with an obligatory absorption of carbohydrates with both glucose and icodextrin-based dialysate. In this review, we examine the evidence linking this obligatory absorption with adverse systemic effects. Systemic glucose absorption is associated with worse glycemic control; this can be ameliorated with glucose-sparing peritoneal dialysis regimens. The studies examining the benefit of glucose-sparing regimens on dyslipidemia are inconsistent and the magnitude of benefit is potentially small. There are no studies demonstrating any improvement in clinically meaningful patient outcomes with glucose-sparing regimens. Although it is conceivable that the obligatory carbohydrate absorption with peritoneal dialysis increases systemic cardiovascular risk, this premise has not been systematically or rigorously examined to date, there are no robust biomarkers to measure the risk, modification of which may favorably improve outcomes, and whether glucose-sparing peritoneal dialysis regimens will lower the putative risk is currently unknown. Hence, there is a compelling need to bridge our gap in understanding the role of systemic glucose absorption with peritoneal dialysis on the health of individuals undergoing peritoneal dialysis.

The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study.

BackgroundWhile much has been learned about the epidemiology and treatment of end-stage renal disease (ESRD) in the last 30 years, chronic kidney disease (CKD) before the end-stage has been less investigated. Not enough is known about factors associated with CKD progression and complications, as well as its transition to ESRD. We designed the CKD-renal epidemiology and information network (REIN) cohort to provide a research platform to address these key questions and to assess clinical practices and costs in patients with moderate or advanced CKD.MethodsA total of 46 clinic sites and 4 renal care networks participate in the cohort. A stratified selection of clinic sites yields a sample that represents a diversity of settings, e.g. geographic region, and public versus for-profit and non-for-profit private clinics. In each site, 60–90 patients with CKD are enrolled at a routine clinic visit during a 12-month enrolment phase: 3600 total, including 1800 with Stage 3 and 1800 with Stage 4 CKD. Follow-up will continue for 5 years, including after initiation of renal replacement therapy. Data will be collected from medical records at inclusion and at yearly intervals, as well as from self-administered patient questionnaires and provider-level questionnaires. Patients will also be interviewed at baseline, and at 1, 3 and 5 years. Healthcare costs will also be determined. Blood and urine samples will be collected and stored for future studies on all patients at enrolment and at study end, and at 1 and 3 years in a subsample of 1200.ConclusionsThe CKD-REIN cohort will serve to improve our understanding of the biological, clinical and healthcare system determinants associated with CKD progression and adverse outcomes as well as of international variations in collaboration with the CKD Outcome and Practice Pattern Study (CKDopps). It will foster CKD epidemiology and outcomes research and provide evidence to improve the health and quality of life of patients with CKD and the performances of the healthcare system in this field.

Pretransplant peritoneal dialysis relative to hemodialysis improves long-term survival of kidney transplant patients: a single-center observational study

Kidney transplantation is the best option for the treatment of end-stage renal disease in terms of survival and quality of life. These results can be influenced by the pretransplant dialysis modality. The aim of this study was to evaluate whether the pretransplantation dialysis modality influences patient and allograft survival beyond 10 years and examine the potential risk factors associated with the outcomes. We conducted an observational, retrospective, single-center clinical study that included 236 patients [118 undergoing peritoneal dialysis (PD) and 118 undergoing hemodialysis (HD)] who proceeded to transplantation during the period December 1990-2002. Donor and recipient data were collected from our hospital's clinical registries. The follow-up period extended to the patient's death, the loss of the allograft, or loss to follow-up. The end date of the study was set at March 2012. In the multivariate analysis, the long-term patient survival rate was higher for the PD group than for the HD group [HR = 2.62 (1.01-6.8); p = 0.04]; however, the allograft survival rate was not significantly different between the two groups [HR = 0.68 (0.41-1.10); p = 0.12]. Pretransplantation dialysis modality is associated with long-term patient survival, with outcomes favoring peritoneal dialysis over hemodialysis. However, the pretransplant dialysis modality does not influence long-term graft loss risk.

Novel Role of NOD2 in Mediating Ca 2+ Signaling

Although hyperhomocysteinemia (hHcys) has been recognized as an important independent risk factor in the progression of end-stage renal disease and in the development of cardiovascular complications related to end-stage renal disease, the mechanisms triggering the pathogenic actions of hHcys are not yet fully understood. The present study was designed to investigate the contribution of nucleotide-binding oligomerization domain containing 2 (NOD2), an intracellular innate immunity mediator, to the development of glomerulosclerosis in hHcys. Our results showed that NOD2 deficiency ameliorated renal injury in mice with hHcys. We further discovered the novel role of NOD2 in mediating Ca 2+ signaling and found that homocysteine-induced NOD2 expression enhanced transient receptor potential cation channel 6 (TRPC6) expression and TRPC6-mediated calcium influx and currents, leading to intracellular Ca 2+ release, ultimately resulting in podocyte cytoskeleton rearrangement and apoptosis. Moreover, we found that nephrin expression was downregulated dependently by NOD2, and overexpression of nephrin attenuated homocysteine-induced TRPC6 expression in podocytes. The results add evidence to support the essential role of nephrin in mediating NOD2-induced TRPC6 expression in hHcys. In conclusion, our results for the first time establish a previously unknown function of NOD2 for the regulation of TRPC6 channels, suggesting that TRPC6-dependent Ca 2+ signaling is one of the critical signal transduction pathways that links innate immunity mediator NOD2 to podocyte injury. Pharmacological targeting of NOD2 signaling pathways at multiple levels may help design a new approach to develop therapeutic strategies for treatment of hHcys-associated end-stage renal disease.

End-stage renal disease: unmet treatment needs across the globe

BackgroundChronic kidney disease (CKD) is a major health and economic burden globally. This progressive disease is treatable by dialysis and kidney transplantation when the kidneys reach CKD stage 5 or end-stage renal disease (ESRD), but these two interventions are very expensive and often unavailable in low-resource settings. The aim of this study is to provide a country-level comparison of dialysis rates, transplantation rates, and untreated CKD stage 5 in order to identify countries and regions with large disparities and unmet treatment need for ESRD. MethodsWe used a negative binomial Bayesian meta-regression tool to analyse data collected from systematic literature reviews and national renal replacement registries in order to estimate incidence and prevalence of ESRD on dialysis, ESRD with kidney transplantation, and untreated ESRD for 187 countries by year, age, and sex. We then assessed ratios of treated to untreated ESRD to identify countries with extreme unmet need for kidney disease treatment. FindingsBoth dialysis and kidney transplantation rates have increased considerably since 1990, but there are still significant disparities both within and across countries. Globally in 2010, the proportion of CKD stage 5 and ESRD patients who received dialysis or had kidney transplantation was only 58·9% (95% CI 55·6–61·0), ranging from less than 2% in most of sub-Saharan Africa to over 70% in high-income North America, high-income Asia Pacific, and east Asia. InterpretationThese estimates are a crucial factor to help to inform public health policy decisions and the nephrology community, especially in countries previously lacking such estimates. There is an urgent need for better monitoring and data collection of CKD stage 5 in order to better prepare health systems for ESRD treatment needs. FundingBill & Melinda Gates Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.