End-stage Renal Disease Therapy Research Articles

Improvement of Kidney Failure With Fetal Kidney Precursor Cell Transplantation

Current therapies for end-stage renal disease have severe limitations. Dialysis is only a temporary treatment and does not restore kidney function. Transplantation is limited by donor organ shortage and immune-related problems. Here, we show that the transplantation of fetal kidney precursor cells reconstitutes kidney tissues, reduces uremic symptoms, and provides life-saving metabolic support in kidney failure animal models. Kidney failure was surgically induced by resecting kidneys, leaving approximately 1/6 of the total kidney mass (5/6 nephrectomy). Fetal kidney precursor cells were isolated from metanephroi of E17.5 rat fetuses using collagenase/dispase digestion. Five weeks after the nephrectomy procedure, isolated fetal kidney precursor cells were transplanted under the kidney capsule of rats using fibrin gel matrix. Six and ten weeks after transplantation, animals were analyzed biochemically and the grafts were retrieved for histological analyses. Five weeks after the nephrectomy, glomerular hypertrophy, and increased blood urea nitrogen and serum creatinine levels were observed. The cell transplantation into the kidneys of kidney failure-induced rats resulted in kidney tissue reconstitution and the transplanted cells were observed in the reconstitution region of the kidneys as evidenced by the presence of fluorescently labeled cells. In addition, biochemical parameters from serum and urine samples showed improved kidney functions compared with non-treated group without severe immune response after ten weeks. Transplanting fetal kidney precursor cells showed the potential for the partial augmentation of kidney structure and function in the treatment of kidney failure.

Overview of Peritoneal Dialysis in Latin America

Latin America is a heterogeneous region comprised of 20 countries, former colonies of European countries, in which Latin-derived languages are spoken. According to the Latin American Society of Nephrology and Hypertension/Sociedad Latino Americana de Nefrologia e Hipertensión (SLANH), the acceptance rate for renal replacement therapy is 103 new patients per million population. In Latin America, hemodialysis is the predominant form of replacement therapy for end-stage renal disease; however, some countries employ peritoneal dialysis (PD) in 30% or more patients. In particular, Mexico is the country with the largest PD utilization in the world, and furthermore, it is estimated that approximately 25% of the world's PD population may be found Latin America. Data concerning clinical practice and long-term outcome of PD in Latin America are scarce, although regional registries are increasing in number and quality. In this review article, we present an overview of the situation of PD in several countries of Latin America, based on the registry of the SLANH, national registries, and personal communication with PD experts from different countries.

Rapport REIN 2005 — Synthèse

In 2005, 6,021 patients with end-stage renal disease living in fourteen regions covering 45 millions inhabitants (73% of the French population), started renal replacement therapy (dialysis or preemptive graft): median age was 70 years; 3% had a preemptive graft. The overall crude annual incidence rate of renal replacement therapy for end-stage renal disease was 139 per million population (pmp) in thirteen regions that met exhaustivity, with significant differences in sex and age-adjusted incidence across regions (92 to 171 pmh). At initiation, 48% of the patients had at least one cardiovascular disease and 36% diabetes (89% Type 2 non-insulin-dependent diabetes). On December 31, 2005, 21,813 patients living in these fourteen regions were on dialysis: median age was 69 years. The overall crude prevalence rate of dialysis was 539 pmp in thirteen regions. On December 31, 2005, 19,491 patients were living with a functioning graft : median age was 53 years. The overall crude prevalence rate for these patients was 390 pmp in thirteen regions. The overall crude prevalence rate of renal replacement therapy for end-stage renal disease was 929 pmp in thirteen regions, with significant differences in age-adjusted prevalence across regions (732 to 1009 pmh). In the 2002-05 cohort of 11,632 incident patients, the overall one-year survival rate was 82%, 72% at 2 years and 62% at 3 years. Survival decreased with age, but remained above 50% at 2 years in patients older than 75 at RRT initiation. Among the 5,902 new patients starting dialysis in 2005 in the 14 regions, 7% had a BMI lower than 18,5 kg/m 2 and 16% a BMI higher than 30. At initiation, 63% had an haemoglobin value lower than 11g/l and 9% an albumin value lower than 25 g/l. The first haemodialysis was started in emergency in 30% of the patients and with a catheter in 46%. On December 31, 2005, 8% treated in the dialysis units of the fourteen regions received peritoneal dialysis, of which 35% were treated with automated peritoneal dialysis. 94% of the patients on haemodialysis had 3 sessions per week, with a median duration of 4 hours. In 2005, 1,911 patients received a renal graft. On December 31, 2005, 4,634 patients were on the waiting list for a renal graft in the transplantation centres of the 14 regions.

Survival Analysis of Korean End-Stage Renal Disease Patients According to Renal Replacement Therapy in a Single Center

This study was to investigate clinical characteristics and any differential trends in survival among renal replacement therapy (hemodialysis [HD], peritoneal dialysis [PD], and kidney transplantation [KT]) in Korean end-stage renal disease (ESRD) population. We tried to analyze retrospectively the survival rate adjusted by risk factors and the relative risk stratified by key risk factors among 447 ESRD patients who began dialysis or had a kidney transplant at Ajou University Hospital from 1994 to 2004. In adjusted Cox survival curves, the KT patients had the best survival rate, and the HD patients had better survival than PD patients. The consistent trends in different subgroups stratified by age and diabetes were as following: 1) The risk of death for PD and HD was not proportional over time, 2) The relative risk of PD was similar or lower than that of HD for the first 12 months, but it became higher at later period. The significant predictors for mortality were age (over 55 yr), presence of diabetes, cerebrovascular accident at ESRD onset, and more than one time of hospitalization caused by malnutrition. Further large-scaled, multicenter-based comparative study is needed in Korean ESRD patients and more meticulous attention is required in high-risk patients.

Effect of Early Nephrology Referral on the Initiation of Hemodialysis and Survival in Patients With Chronic Kidney Disease and Cardiovascular Diseases

The timing of referral to nephrologists is highly variable in patients with chronic kidney disease (CKD). The impact of early referral on the timing of hemodialysis (HD) and mortality in the patients with CKD and cardiovascular diseases (CVD) was evaluated in this present study. A total of 366 patients with CKD and CVD began HD at the National Cardiovascular Center between 1983 and 2003, and survival was followed until 2005. The times between the first evaluation by a nephrologist and the date of the first HD were categorized as late (LR <6 months) or early (ER > or =6 months) referral. Patients were classified into the ER (n=194) and LR (n=172) groups. Clinical data and renal function were not different. In the LR group, the renal function declined more rapidly and the duration between the first visit to the hospital and the first HD was shorter than the ER group. The survival rate after the initiation of HD was better in the ER group. Age, pre end-stage renal disease therapy and cardiac function had a significant impact on survival. Early nephrology referral is important and necessary for for patients with CKD and CVD in terms of a better renal prognosis and survival.

Prevention of cardiovascular events in end-stage renal disease: Results of a randomized trial of fosinopril and implications for future studies

Cardiovascular events (CVEs) are the leading cause of death in chronic hemodialysis patients. Results of trials in non-end-stage renal disease (ESRD) patients cannot be extrapolated to patients with ESRD. It is critical to test cardiovascular therapies in these high-risk patients who are usually excluded from major cardiovascular trials. The study objective was to evaluate the effect of fosinopril on CVEs in patients with ESRD. Eligible patients were randomized to fosinopril 5 mg titrated to 20 mg daily (n=196) or placebo (n=201) plus conventional therapy for 24 months. The primary end point was combined fatal and nonfatal first major CVEs (cardiovascular death, resuscitated death, nonfatal stroke, heart failure, myocardial infarction, or revascularization). No significant benefit for fosinopril was observed in the intent to treat analysis (n=397) after adjusting for independent predictors of CVEs (RR=0.93, 95% confidence interval (CI) 0.68-1.26, P=0.35). The per protocol secondary supportive analysis (n=380) found a trend towards benefit for fosinopril (adjusted RR=0.79 (95% CI 0.59-1.1, P=0.099)). In the patients who were hypertensive at baseline, systolic and diastolic blood pressures were significantly decreased in the fosinopril as compared to the placebo group. After adjustment for risk factors, trends were observed suggesting fosinopril may be associated with a lower risk of CVEs. These trends may have become statistically significant had the sample size been larger, and these findings warrant further study.

The Enigma of Hypertensive ESRD: Observations on Incidence and Trends in 18 European, Canadian, and Asian-Pacific Populations, 1998 to 2002

Despite improved treatment of hypertension and decreasing rates of stroke and coronary heart disease, the reported incidence of hypertensive end-stage renal disease (ESRD) increased during the 1990s. However, bias, particularly from variations in acceptance into ESRD treatment (ascertainment) and diagnosis (classification), has been a major source of error when comparing ESRD incidences or estimating trends. Age-standardized rates were calculated in persons aged 30 to 44, 45 to 64, and 65 to 74 years for 15 countries or regions (separately for the Europid and non-Europid populations of Canada, Australia, and New Zealand), and temporal trends were estimated by means of Poisson regression. For 10 countries or regions, population-based estimates of mean systolic blood pressures and prevalences of hypertension were extracted from published sources. Hypertensive ESRD, comprising ESRD attributed to essential hypertension or renal artery occlusion, was least common in Finland, non-Aboriginal Australians, and non-Polynesian New Zealanders; intermediate in most European and Canadian populations; and most common in Aboriginal Australians and New Zealand Maori and Pacific Island people. Rates correlated with the incidence of all other nondiabetic ESRD, but not with diabetic ESRD or community rates of hypertension. Between 1998 and 2002, hypertensive ESRD did not increase in Northwestern Europe or non-Aboriginal Canadians, although it did so in Australia. Despite the likelihood of classification bias, the probability remains of significant variation in incidence of hypertensive ESRD within the group of Europid populations. These between-population differences are not explained by community rates of hypertension or ascertainment bias.

Factors Influencing Route of Administration for Epoetin Treatment Among Hemodialysis Patients in the United States

Published clinical guidelines advocate subcutaneous (SC) administration for epoetin therapy, although this is practiced among only 7% of all hemodialysis patients. Despite this disparity, few studies have examined factors associated with route of epoetin administration in hemodialysis patients. Data from the Centers for Medicare & Medicaid Services End-Stage Renal Disease Clinical Performance Measures Project were used to identify 13,854 patients receiving hemodialysis in 3,069 dialysis facilities from October to December in 1999 and 2000. Unadjusted associations were examined by using t-test and chi-square test. Adjusted associations were estimated by using generalized estimating equations to control for clustering of patients within the same dialysis facility. In the United States, use of the SC route of epoetin administration varies widely across the country. After adjusting for patient sociodemographics and comorbidities, the greatest rates of SC therapy are found in the Midwest and West, in providers not affiliated with chains, and in hospital-based and not-for-profit freestanding units. Previous exposure to SC administration (as a predialysis or peritoneal dialysis patient) predicted subsequent SC use, for-profit and large chains were significantly less likely to use SC administration, and increased use of injectable drugs overall (to maximize income) was associated with less SC use. In addition to regional variation in SC use, study findings indicate that physician decision making for epoetin administration route is influenced primarily by type of ownership and financial incentives. Adherence to published clinical guidelines was not a consistent predictor of SC use. Given the similar effectiveness, but significantly decreased dose associated with SC epoetin, these findings suggest an enormous opportunity for cost savings for the Medicare program.

Plasma Cell-Rich Rejection Processes in Renal Transplantation: Morphology and Prognostic Relevance

Renal transplantation is the most effective therapy in end-stage renal disease. The prognosis of transplant survival is still determined by rejection. Morphologically, this involves interstitial rejection with potential development of vascular rejection (VR) and/or glomerular rejection processes, designated as transplant glomerulopathy (TGP). The cellular infiltrates are usually dominated by lymphocytes and macrophages in differing quantity, characterizing the severity of the rejection processes. In 14% of the renal transplant biopsies and explants in our investigation (n = 399) plasma cells (PR) predominate in the cellular infiltrate. To determine whether the enrichment of PR has an impact on graft function or could even constitute an independent parameter for transplant survival, we analyzed 109 cases of transplanted patients matched for AR and CR and divided them into those rich and those nonrich in PR. In the group rich in PR, PR comprised 30% of all infiltrates in comparison to 5% in the group non-rich in PR. VR and TGP appeared significantly more often in PR-rich rejections (P = 0.0044). The group rich in PR had a significantly more adverse prognosis (P = 0.0024), especially if PR enrichment was observed in the chronic rejection processes (P = 0.0148). In the Cox proportional hazard model the occurrence of VR was the only independent factor. In itself, plasma-cell enrichment is not a prognostic marker, but it is an indicator of a more adverse outcome because it is often accompanied by the appearance or subsequent development of VR +/- TGP. The detection of PR-rich rejection processes should therefore encourage the clinician to intensify the immunosuppressive schedule.

We-P11:20 Impact of aortic valve calcification in cardiac death for Japanese type 2 diabetic patients during end-stage renal disease therapy

The presence of small dense low-density lipoprotein (sdLDL) is closely associated with an increased risk of developing coronary artery disease. The Trp64Arg polymorphism of the β3-adrenergic receptor (β3-AR) gene is a genetic marker for obesity-related traits. However, any possible association between this polymorphism and sdLDL profiles is unclear. The objective of this study is to investigate the effects of the polymorphism of the β3-AR gene on LDL particle size and sdLDL in a rural Japanese population. Among 277 subjects, body mass index, blood pressure, fasting serum insulin levels, and insulin resistance index (fasting glucose × fasting insulin/405) were determined. The polymorphism of the β3-AR gene was assessed by polymerase chain reaction–restriction fragment length polymorphism using buccal samples. Low-density lipoprotein particle size and sdLDL were measured with the electrophoretic separation of lipoproteins on the LipoPrint System (Quantimetrix, Redondo Beach, CA). The frequency of the β3-AR allele was 0.19. In Arg carriers (Trp/Arg or Arg/Arg), the mean value of LDL particle size was smaller than that of non-Arg carriers (Trp/Trp) (P < .05). The area percentage of sdLDL was higher in Arg carriers (P < .05) than in non-Arg carriers. A multiple regression analysis showed that the area percentage of sdLDL was correlated with the polymorphism of the β3-AR gene (P < .05), independently of age, sex, body mass index, smoking, and insulin resistance index. The present findings suggest that the β3-AR gene polymorphism plays a role in the genetic predisposition to increased sdLDL, independently of insulin resistance.

Establishment of renal stem/progenitor-like cell line from S3 segment of proximal tubules in adult rat kidney

Significant attention has been directed to the biologic and therapeutic capabilities of stem cells. However, it is still unknown whether stem/progenitor cells exist in adult kidney. We attempted to isolate and establish of an epithelial cell capable of growth from a single cell, which may indicate a potential for self renewal as stem/progenitor cell population. We dissected various segments of nephron from an adult Sprague-Dawley rat kidney. Each segment was cultured separately. Outgrowing cells were harvested and replated after limiting dilution so that each well contained a single cell. Cell colonies were observed only in the wells contained S3 segment-derived cells. One of cell lines most potent to grow was designated as rKS56. rKS56 cells showed cobblestone appearance and they were positive for pan-cytokeratin and vimentin by immunnocytechemistry. Reverse transcription-polymerse chain reaction (RT-PCR) study revealed rKS56 expressed both immature cell markers such as Pax-2, Wnt-4, and WT-1 and mature tubular cell markers like aquaporin-1 and chloride channel. rKS56 cells grew exponentially and could be maintained over 300 days without transformation. In different culture conditions, rKS56 cells differentiated into mature tubular cells like proximal or distal tubular cells defined by aquaporin-1 and -2 expression and responsiveness to parathyroid hormone or vasopressin. Engrafted to kidney in rat ischemic reperfusion model, rKS56 cells labeled with dioctadecyl tetramethylindocarbocyanine perchlorate (DiI) replaced in injured tubules in part at 7 days after implantation. These results suggest rKS56 possess characteristic of self-renewal, multiplasticity, and direct contribution to tissue repair and this step will potentially contribute to the development of novel therapies for end-stage renal disease (ESRD).

Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients

Standard therapy for chronic hepatitis C (HCV) is pegylated interferon in combination with ribavirin. There is limited experience with either drug in dialysis [end stage renal disease (ESRD)]. Six haemodialysis patients, four with HCV genotype 1, one with genotype 4 and one genotype 2 were treated with pegylated interferon-alfa-2b (n = 4) and pegylated interferon-alfa-2a (n = 2) for 24-48 weeks according to genotype with a dose of 50 or 135 mug/week respectively. All patients were given reduced ribavirin doses, initially 200-400 mg/day. Ribavirin trough plasma concentrations were measured with a HPLC method previously developed for earlier treatment studies, aiming at a target concentration of 10-15 micromol/L. Interferon related side-effects were common, in one patient peg-alfa-2b was permanently reduced to 50 mug every 9-10 days with improvement in tolerance. Average ribavirin dose was 170-300 mg/day. Ribavirin-induced anaemia was treated with high doses of erythropoietin and low doses of iron. Blood-transfusions were not needed. All patients became HCV-RNA-PCR negative during treatment which was completed or nearly completed in four patients. One patient terminated therapy prematurely due to pronounced interferon related side-effects and another died of myocardial infarction probably not related to therapy. Three patients have remained HCV-RNA negative with extended follow-up, two of whom have had a successful kidney transplant. Pegylated interferons are likely to become a valuable addition for HCV therapy in ESRD and are possible to combine with ribavirin. However the pharmacokinetics and tolerability of both peg-alfa-2a and 2b need to be studied more closely in prospective studies before definite dosing recommendations can be made.

The renal epidemiology and information network (REIN): a new registry for end-stage renal disease in France

The French Renal Epidemiology and Information Network (REIN) registry began in 2002 to provide a tool for public health decision support, evaluation and research related to renal replacement therapies (RRT) for end-stage renal disease (ESRD). It relies on a network of nephrologists, epidemiologists, patients and public health representatives, coordinated regionally and nationally. Continuous registration covers all dialysis and transplanted patients. In 2003, 2070 patients started RRT, 7854 were on dialysis and 7294 lived with a functioning graft in seven regions (with a population of 16.5 million people). The overall crude annual incidence rate of RRT for ESRD was 123 per million population (p.m.p.) with significant differences in age-adjusted rates across regions, from 84 [95% confidence interval (CI): 74-94] to 155 [138-172] p.m.p. The principal causes of ESRD were hypertension (21%) and diabetic (20%) nephropathies. Initial treatment for ESRD was peritoneal dialysis for 15% of patients and a pre-emptive graft for 3%. The one-year survival rate was 81% [79-83] in the cohort of 2002-2003 incident patients. As of December 31, 2003, the overall crude prevalence was 898 [884-913] p.m.p, with 5% of patients receiving peritoneal dialysis, 47% on haemodialysis and 48% with a functioning graft. The experience in these seven regions over these two years clearly shows the feasibility of the REIN registry, which is progressively expanding to cover the entire country.

ESRD patients in 2004: global overview of patient numbers, treatment modalities and associated trends

Since the beginning of maintenance therapy for endstage renal disease (ESRD) through dialysis or transplantation, the number of patients treated for terminal kidney failure worldwide has continued to grow at a rate that is far in excess of the growth rate of the general population. By 2001, more than 1 million patients were reported worldwide to receive dialysis treatment alone, with the numbers growing at an annual global average rate of 7% [1,2]. The main factors contributing to the continued growth are the universal ageing of populations, multi-morbidity, higher life-expectancy of treated ESRD patients and increasing access of a generally younger patient population to treatment in countries in which access had previously been limited [3–6]. Solutions targeting the prevention or reversal of renal disease receive widespread attention, but have as yet failed to significantly change the development of global patient numbers. A superior and financially viable alternative to dialysis or allograft transplantation for chronic renal failure is not foreseen for the near or even mid-term future [6–9]. In order to facilitate effective future planning by healthcare authorities, reliable and up-to-date information on ESRD patient numbers, development trends, treatment modalities and treatment outcomes are indispensable. An increasing number of national and international renal registries have provided valuable demographic and epidemiologic information on renal patients since the first report of the European Dialysis and Transplant Association (EDTA) was published in 1965 [6,10–17]. These reports provide a base for comparison between specified patient populations and an understanding of treatment practices and policies and their implications for the well-being of those undergoing treatment for ESRD. The conclusions that can be drawn from such considerations provide knowledge of value to both medical communities and policy makers throughout the world. Even at a national level, data collection and analysis requires extensive resources to enable fast and reliable reporting of the most recent numbers. The collection of records reflecting the situation in a large group of countries presents additional challenges that render timely reporting a difficult target to achieve. A multicountry European database is organized by the ERA/ EDTA, and now consolidates renal replacement information from different renal registries collecting patient data of 27 countries [16]. An alternative approach to reporting international ESRD-relevant data is pursued in the Dialysis Outcomes and Practice Patterns Study (DOPPS). This was initiated in 2002 as an observational study and presently collects information on haemodialysis (HD) practice patterns and their associated outcomes from 12 countries in Europe, North America and Asia [15]. Fresenius Medical Care, the largest dialysis care company worldwide, follows two different and separate approaches, one addressing practice patterns and outcomes in its clinics (e.g. the European Clinical Database, EuClid), and the other using its extensive international network for retrieving and comparing reliable and contemporary ESRD demographic information from 122 countries [2,18]. This article supplies an extract of the latter for use and reference by renal care specialists and healthcare administrative bodies. In addition, trends observed in association with patient demographic data are specified and discussed.

Thrombotic microangiopathy in United States long-term dialysis patients

The incidence, risk factors, recurrence rates and prognosis of thrombotic microangiopathy (TMA) among long-term dialysis patients in the United States have not been previously described in a national population. 272 024 Medicare primary patients in the United States Renal Data System (USRDS) initiated on end-stage renal disease (ESRD) therapy between 1 April 1995 and 31 December 1999 with Medicare as primary payer were analysed in a retrospective cohort study of USRDS of TMA. Cox regression was used to calculate adjusted hazard ratios (AHR) for risk of TMA and risk of death after TMA. The incidence of TMA in the first year of dialysis was 0.5% overall. Among patients with renal failure due to haemolytic uraemic syndrome (HUS), the incidence of TMA was highest in the first year of dialysis (HUS, 11.3% first year, 4.5% per year thereafter), while among patients without HUS the incidence of TMA was much lower and more constant over time (0.3% per year). In Cox regression analysis, independent risk factors for TMA were renal failure due to HUS (adjusted hazard ratio (AHR) 179, 95% CI 95-338), paediatric age (<or=18 years vs older, AHR 2.59, 95% CI 1.48-4.55), female gender (AHR 1.99, 95% CI 1.43-2.78), and systemic lupus erythematosus (SLE, AHR 3.66, 95% CI 1.49-8.51). One-year survival after TMA was poor at 58% (AHR for mortality 2.04, 95% CI 1.23-3.38). TMA is an uncommon cause of hospitalization after dialysis, but does recur in patients with HUS at a substantial rate. Younger age and SLE were risk factors for new onset TMA, which was associated with poor survival. Vigilant monitoring of select patients with HUS-related ESRD and higher-risk patients with SLE is warranted in the dialysis population.

Patient education and access of ESRD patients to renal replacement therapies beyond in-center hemodialysis

Nephrologists report that patients' choice should play an important role in the selection of renal replacement therapy (RRT) for end-stage renal disease (ESRD). In the United States, kidney transplant rates remain low and <10% of patients utilize home dialysis therapies. This study examined the effect of pre-ESRD processes on the selection of RRT among incident ESRD patients. Using surveys, data were collected for all patients admitted to 229 dialysis units in ESRD Network 18 between April 1, 2002 and May 31, 2002. A total of 1365 patients began chronic dialysis and 1193 facility (87%) and 428 patient (31%) surveys were returned. Substantial proportions of patients were unaware of their kidney disease (36%) or were not seeing a nephrologist (36%) until <4 months before first dialysis. The presentation of treatment options was delayed (48% either after or < 1 month before the first dialysis). The majority of ESRD patients were not presented with chronic peritoneal dialysis, home hemodialysis, or renal transplantation as options (66%, 88%, and 74%, respectively). Using multivariate analyses, variables significantly associated with selection of chronic peritoneal dialysis as dialysis modality were the probability of chronic peritoneal dialysis being presented as a treatment option and the time spent on patient education. An incomplete presentation of treatment options is an important reason for under-utilization of home dialysis therapies and probably delays access to transplantation. Improvements in and reimbursement for pre-ESRD education could provide an equal and timely access for all medically suitable patients to various RRTs.

Proteomic analysis of renal diseases: unraveling the pathophysiology and biomarker discovery

Current biomedical applications of proteomics have been conducted with four main objectives: to better understand the normal biology and physiology of cells, microorganisms, tissues and organs; to explore the pathogenic mechanisms and better understand the pathophysiology of medical diseases; to identify novel biomarkers for early disease detection, prediction and prognosis; and to define new therapeutic targets, drugs and vaccines. This review focuses predominantly on proteomic applications to unravel the pathophysiology and to define novel biomarkers for various renal diseases (i.e., glomerular diseases, tubulointerstitial diseases, renal vascular disorders and renal cancers). In addition, proteomic evaluations of renal transplantation and renal replacement therapy (for acute renal failure and end-stage renal disease) are summarized. Personal opinion, future perspectives and information resources for the field of renal and urinary proteomics are provided.

Diabetic end‐stage renal disease in the indigenous population of the Commonwealth of the Northern Mariana Islands

The number of cases of treated end-stage renal disease (ESRD) attributable to type 2 diabetes and survival after the onset of renal replacement therapy was examined in the Commonwealth of the Northern Mariana Islands (CNMI). All Chamorros and Carolinians to receive renal replacement therapy for ESRD between January 1982 and December 2002 were identified. Changes in survival over time were examined by dividing the study into three equal periods. Of 180 new cases of ESRD, 137 (76%; 101 Chamorros, 36 Carolinians) were attributed to diabetes. Ninety-nine subjects, 80% of whom had diabetic ESRD, began renal replacement therapy in the last 7 years of the study compared with 81 (72% with diabetic ESRD) in the previous 14 years. All 137 of the diabetic subjects received haemodialysis. During the 21-year study period, 79 of the diabetic subjects receiving dialysis died. The median survival after the onset of haemodialysis was 37 months in the first time period (1982-1988), 47 months in the second period (1989-1995) and 67 months in the third period (1996-2002). The death rate in the first period was 4.3 times (95% CI, 2.1-8.9) as high and the second period was 2.9 times (95% CI, 1.5-5.8) as high as the most recent period, after adjustment for age, sex and ethnicity in a proportional-hazards analysis. The number of diabetic patients in CNMI who are receiving renal replacement therapy is rising rapidly. Considerable improvement in survival after the onset of haemodialysis has occurred over the past 21 years.

Renal replacement therapy for diabetic end-stage renal disease: Data from 10 registries in Europe (1991–2000)

There is concern about the rising prevalence of type 2 diabetes mellitus and of the resultant nephropathy. This study uses data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry to provide information on the epidemiology and outcome of renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetic nephropathy (DN). Data from the following 10 registries: Austria, French-speaking Belgium, Denmark, Finland, Greece, Norway, Scotland (UK), Catalonia (Spain), Sweden, and The Netherlands were combined. Average annual changes (%) were estimated by Poisson regression. Analyses of mortality were performed by Cox regression. An increase in patients with type 2 DN entering RRT has been observed (+11.9% annually, P < 0.05), while large differences in RRT incidence in this disease continue to exist between countries in Europe. There was a reduction in mortality during the first 2 years on dialysis therapy among patients with type 2 DN (AHR 0.96, 95%CI 0.94-0.97 annually). The mortality among transplant recipients decreased for both type 1 DN and nondiabetic ESRD (non DN) within the 1995-1998 cohort (type 1 DN: AHR 0.49, 95% CI 0.35-0.68; non DN: AHR 0.79, 95% CI 0.69-0.90) compared to the 1991-1994 cohort. This report has shown that during the last decade there has been a marked increase in the incidence of RRT for type 2 DN. Survival analysis showed that over the period 1991-1999 the mortality rates of all dialysis patients and of type 1 diabetic and nondiabetic renal transplant recipients have fallen.

Glycoprotein IIb/IIIa Inhibitors in Patients with End-Stage Renal Disease

To determine whether glycoprotein IIb/IIIa inhibitors (GPIs) are effective and safe as adjunctive therapy for percutaneous coronary intervention (PCI) in patients with end-stage renal disease (ESRD). MEDLINE (1966-June 2004), EMBASE (1980-June 2004), and International Pharmaceutical Abstracts (1970-June 2004) were searched, in addition to a manual bibliographic search. Even though GPIs have an established role as adjunctive therapy in PCI, little is known about their use in patients with ESRD. We found 3 reports describing experience with abciximab in this population. Based on the limited information from registries and a retrospective chart review, it is difficult to draw definitive conclusions about the utility of GPIs in ESRD. The decision to use abciximab in this population must be made on an individual case basis. Studies are needed to evaluate the benefit versus risk of GPI therapy in ESRD.