Risk Of End-stage Renal Disease In Patients Research Articles

Polymorphisms in NADPH oxidase CYBA gene modify the risk of ESRD in patients with chronic glomerulonephritis

End-stage renal disease (ESRD) was defined as start of renal replacement therapy or death due to kidney disease. However, death due to acute kidney injury was not included. It typically occurs when chronic renal failure progresses to a point where the kidneys are permanently functioning at less than 10% of their capacity. Oxidative stress (OS) plays a crucial role in ESRD. Nicotinamide adenine dinucleotide phosphate (NADPH) is one of the most important enzymes during oxidative stress. Cytochrome b light chain (CYBA), encoded by a polymorphic gene, which is a critical component of the nicotinamide adenine dinucleotide (NADH)/NADPH oxidase system and plays an important role in electron transport and superoxide anion production, is located on chromosome band 16q24 and has six exons spanning almost 7.76 kb of genomic DNA. CYBA gene polymorphisms can influence the activity of NADPH oxidase. To evaluate the association between CYBA gene polymorphisms and ESRD, we genotyped five CYBA polymorphisms using TaqMan allelic discrimination assay on DNA samples from 306 healthy controls and 332 patients with ESRD. Our results suggested that rs1049255 polymorphism of CYBA modified the risk of ESRD (p = 0.019; OR = 0.625; 95%CI = 0.424–0.921). GG genotype and G allele might be a protective factor against the risk of ESRD, especially in patients with chronic glomerulonephritis.

The risk for end-stage renal disease is increased after burn

ObjectiveAcute kidney injury (AKI) commonly complicates burn. Recently, AKI has been suggested to be causally related to chronic end-stage renal disease (ESRD), but controversial data also exist. Our aim was to study the risk of ESRD after burn in a nationwide analysis. MethodsAll burn patients undergoing hospitalization between 1998 and 2011 were identified from the National Hospital Discharge Register, and the data were linked with the Finnish Registry for Kidney Diseases, which includes all individuals receiving chronic renal replacement therapy (RRT) in Finland. ResultsAltogether 41,179 adults were treated at hospitals for burns in Finland between 1998 and 2011. Of these, 86 had a diagnosis of AKI related to the burn. Forty-three burn survivors had ESRD and RRT initiated related to or after the burn. The overall risk for ESRD after burn was increased (standardized incidence ratio, SIR, 2.40, 95% CI 1.73–3.23) compared with the Finnish population. Standardized incidence ratio was 3.11 (95% CI 1.66–5.32) in women and 1.89 (95% CI 1.27–2.69) in men. Of these 43 patients, 38 had a specific non-burn-related diagnosis of ESRD identified in the registry, and ESRD was deemed unlikely to be directly related to the burn. In five patients, the diagnosis of ESRD was unknown cause of renal failure, and causality of the burn with ESRD was evaluated as plausible. ConclusionIn conclusion, a significantly increased risk of ESRD was recorded after a severe burn. Our results do not support increased incidence of ESRD solely as a consequence of AKI due to burn, but burn may increase the risk of ESRD in patients with pre-existing chronic kidney disease.

Nonadherence of Oral Antihyperglycemic Medication Will Increase Risk of End-Stage Renal Disease.

Poor glycemic control is related to an increased risk of end-stage renal disease (ESRD). This study investigated the association between medication adherence and the risk of ESRD in patients with newly diagnosed diabetes mellitus.In this population-based cohort study, we used the Taiwan National Health Insurance Research Database (NHIRD) to identify 559,864 patients with newly diagnosed or treated diabetes mellitus who were ages from 20 to 85 years between 2001 and 2008. We identified 1695 patients with ESRD during the study period. The mean follow-up time of the patients with ESRD was 5.7 years. Time-dependent Cox proportional hazards regression was performed to estimate the hazard ratios for ESRD among the patients with newly diagnosed diabetes mellitus.After adjustment for various covariates, nonadherence to oral antihyperglycemic medication (OAM) was associated with a higher risk of ESRD compared with adherence to OAM (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.01–1.23). The effects of nonadherence to OAM on the risk of ESRD were significant for patients without hypertension, without gout, without chronic kidney disease, undergoing OAM polytherapy, and undergoing metformin polytherapy (HR [95% CIs], 1.18 [1.00–1.39], 1.13 [1.02–1.26], 1.17 [1.03–1.33], 1.22 [1.08–1.38], and 1.13 [1.02–1.25], respectively).In conclusion, nonadherence to OAM therapy is associated with ESRD. Adherence to medication therapy can prevent the progressive loss of renal function and ESRD for patients with diabetes.

Hemodialysis Is Associated With Increased Peripheral Artery Occlusive Disease Risk Among Patients With End-Stage Renal Disease: A Nationwide Population-Based Cohort Study.

To investigate the effect of different dialysis modalities on the incidence of peripheral artery occlusive disease (PAOD) among patients with end-stage renal disease (ESRD) in a large population-based cohort study.The cohort study included 26,927 ESRD patients who underwent hemodialysis (17,737 patients, hemodialysis [HD] cohort) or peritoneal dialysis (PD, 9190 patients, PD cohort), and 107,588 matched controls between 2000 and 2010. A Cox proportional hazards model was to evaluate the risk of PAOD in the ESRD underwent HD or PD.Based on a mean follow-up period of 2.92, 3.64, and 4.91 years in the PD, HD, and control cohorts, respectively, the incidences of PAOD were 18.1% and 8.10% higher in the HD and PD cohorts, respectively, compared with the control cohort (log-rank test P < 0.001). The patients who underwent HD or PD exhibited a higher risk of PAOD compared with the control cohort regardless of age, sex, and presence or absence of comorbidities. In addition, the incidence of PAOD in the PD cohort and the propensity score-matched HD cohort were 12.4 and 20.7 per 1000 person-years, respectively, with a hazard ratio of 1.92 (95% confidence interval = 1.62–2.28) in HD patients, compared with the PD cohort.This nationwide population-based cohort study suggested a significantly increased risk of PAOD among ESRD patients. Moreover, the PD patients have a lower risk of developing PAOD compared with the HD cohort, indicating the beneficial roles of PD in reducing PAOD risk in ESRD patients.

FP330INCREASED RISK OF END-STAGE RENAL DISEASE IN PATIENTS WITH RENAL CELL CARCINOMA: A 12-YEAR NATIONWIDE FOLLOW-UP STUDY

FP330INCREASED RISK OF END-STAGE RENAL DISEASE IN PATIENTS WITH RENAL CELL CARCINOMA: A 12-YEAR NATIONWIDE FOLLOW-UP STUDY

Incidence of end stage renal disease among type 1 diabetes: a nationwide cohort study in Taiwan.

The aim of our study was to estimate the risk of end-stage renal disease (ESRD) in type 1 diabetes mellitus (T1DM) in Taiwanese people; in addition, our goal was to determine how the age, year, and sex at registration of T1DM affects the risk. Population-based cohort study. A nationwide cohort study of 7203 Taiwanese patients with T1DM registered in 1999 to 2010 was followed up until ESRD, death, or the end of follow-up on December 31, 2010. Annual age-, sex-, and calendar year-specific incidence rates of ESRD of the general population were used to calculate the standardized incidence ratio (SIR) of ESRD in relation to T1DM. The SIR of ESRD for male and female patients with T1DM was significantly increased at 25.85 (95% CI 23.40-28.29) and 28.08 (95% 25.45-30.71), respectively; the peak was at age 15 to 29 years for both genders. The cumulative incidence of ESRD was similar in male and female patients but was significantly higher in patients≥ 30 years old than in patients<30 years old (10.25% vs. 3.57%, P<0.001). Patients aged <15 years had a significantly lower risk of ESRD as compared to those aged 15 to 29 years; patients aged 30 to 44 (adjusted HR, 1.491) and 45 to 60 years (adjusted HR, 2.111) showed significantly increased hazards. Our data also demonstrated a lower risk of ESRD in patients who were registered in later years than in earlier years. The risk of ESRD is substantially increased in T1DM in the ethnic Chinese population. The continuously declining risk of ESRD in T1DM may advocate the use of a multidisciplinary chronic kidney disease care system in Taiwan.

Hepatic and pancreatic resection in patients with end-stage renal disease: a propensity analysis

BackgroundHepatic and pancreatic surgery is rarely performed in patients with end-stage renal disease (ESRD). The present authors used a national clinical database to characterize outcomes and perioperative risk in ESRD patients who require hepatic or pancreatic resection. MethodsThe 2005–2011 National Surgical Quality Improvement Program database was queried for all patients undergoing hepatic or pancreatic resection. Patients were classified by the presence or absence of ESRD. The independent effects of ESRD on outcomes were assessed after propensity score adjustment and multivariable logistic regression. ResultsOf the 27 376 patients submitted to hepatic or pancreatic procedures identified in the database, 101 patients were found to have preoperative ESRD. Patients with ESRD experienced perioperative mortality at a rate similar to that in those without ESRD (5.0% versus 2.3%; P = 0.08). After risk adjustment, the presence of ESRD was associated with three-fold higher odds of postoperative sepsis (adjusted odds ratio: 2.98, P = 0.014), but no significant differences in mortality or major complication rates. ConclusionsHepatic and pancreatic resections can be performed safely in selected patients with ESRD. These patients may have an increased risk for the development of postoperative sepsis. Further study is needed to characterize modifiable risk factors that impact outcomes in patients with ESRD who require hepatic or pancreatic resection.

Increased risk of end-stage renal disease in patients with renal cell carcinoma: a 12-year nationwide follow-up study.

The effect of renal cell carcinoma (RCC) on the risk for end-stage renal disease (ESRD) has not been confirmed. The present population-based study used the claims data from the Taiwan National Health Institutes from 1998 to 2010 to compare the risk for ESRD in patients with and without RCC.The study cohort consisted of 2940 patients who had newly diagnosed with RCC but no history of ESRD; the control cohort consisted of 23,520 matched patients without RCC. Cox proportional hazard regressions were performed to compute ESRD risk after adjusting for possible confounding factors. Kaplan–Meier analysis and the log-rank test were also used to compare patients and controls.A total of 119 patients in the RCC group (incidence rate: 119/2940; 4.05%) and 160 patients in the control group (incidence rate: 160/23,520; 0.68%) were diagnosed with ESRD during the follow-up period. After adjusting for potential confounders, the RCC group had an ESRD hazard ratio (HR) of 5.63 [95% confidence interval (CI): 4.37–7.24] relative to the control group. In addition, among patients with RCC, females (adjusted HR: 6.95, 95% CI: 4.82–10.1) had a higher risk for ESRD than males (adjusted HR: 4.79, 95% CI: 3.37–6.82). Finally, there were significant joint effects of chronic kidney disease and diabetes on increasing the risk of ESRD in patients with and without RCC (P < 0.01). The limitations of this study include the retrospective design and the inability to assess methods of treatment and measure the aggressiveness of RCC.Our data indicates that RCC is an independent risk factor for ESRD, especially in females.

Added value of soluble tumor necrosis factor-α receptor 1 as a biomarker of ESRD risk in patients with type 1 diabetes.

Recent studies have suggested that circulating levels of the tumor necrosis factor-α receptor 1 (sTNFαR1) may be a useful predictor for the risk of end-stage renal disease (ESRD) in patients with diabetes. However, its potential utility as a biomarker has not been formally quantified. Circulating levels of sTNFαR1 were assessed in 429 patients with type 1 diabetes and overt nephropathy from the Finnish Diabetic Nephropathy (FinnDiane) cohort study. Predictors of incident ESRD over a median of 9.4 years of follow-up were determined by Cox regression and Fine-Gray competing risk analyses. The added value of sTNFαR1 was estimated via time-dependent receiver operating characteristic curves, net reclassification index (NRI), and integrated discrimination improvement (IDI) for survival data. A total of 130 individuals developed ESRD (28%; ESRD incidence rate of 3.4% per year). In cause-specific modeling, after adjusting for baseline renal status, predictors of increased incidence of ESRD in patients with overt nephropathy were an elevated HbA1c, shorter duration of diabetes, and circulating levels of sTNFαR1. Notably, sTNFαR1 outperformed estimated glomerular filtration rate in terms of R(2). Circulating levels of the sTNFαR1 also remained associated with ESRD after adjusting for the competing risk of death. A prediction model including sTNFαR1 (as a -0.5 fractional polynomial) was superior to a model without it, as demonstrated by better global fit, an increment of R(2), the C index, and area under the curve. Estimates of IDI and NRI(>0) were 0.22 (95% CI 0.16-0.28; P < 0.0001) and 0.98 (0.78-1.23; P < 0.0001), respectively. The median increment in the risk score after including sTNFαR1 in the prediction model was 0.18 (0.12-0.30; P < 0.0001). Circulating levels of sTNFαR1 are independently associated with the cumulative incidence of ESRD. This association is both significant and biologically plausible and appears to provide added value as a biomarker, based on the absolute values of NRI and IDI.

The relationship between secondary hyperparathyroidism and thyroid cancer in end stage renal disease: A population based cohort study

ObjectivesWe conducted a retrospective cohort study to investigate the risk of cancer in end stage renal disease (ESRD) patients with secondary hyperparathyroidism (HPT). Patients and methodsThis study investigated the elevated overall cancer risk in ESRD patients with secondary HPT in Taiwan. We used a population-based retrospective cohort consisting of original claims data of 1million beneficiaries randomly sampled from the Taiwan National Health Insurance Research Database (NHIRD). We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer in the ESRD with secondary HPT and comparison cohorts, using the Cox proportional hazards regression model. ResultsWe observed that ESRD patients with secondary HPT exhibited a 10.1-fold increased risk of thyroid cancer than did ESRD patients without this parathyroid complication, after adjusting for comorbidities (95% confidence interval=1.12–91.0). ConclusionThese phenomena indicate that ESRD patients with secondary HPT are at greater risk of thyroid cancer. Physicians should be alert for occult thyroid cancer in ESRD patients with secondary HPT.

Associations of GSTM1*0 and GSTA1*Agenotypes with the risk of cardiovascular death among hemodialyses patients

BackgroundThe presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients.MethodsTotal of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier.ResultsGSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1*A/*A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1*0/GSTA1*A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1*B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1*B/*B genotype.ConclusionsCombined GSTM1*0/GSTA1*A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention.

Cardiovascular disease in end-stage renal disease

The number of end-stage renal disease (ESRD) patients is progressively growing with more than 60,000 ESRD patients on renal replacement therapy in Korea. The mortality risk in ESRD patients is approximately 10 to 20-fold higher compared to the general population, which is mainly attributed to prevalent cardiovascular disease in these patients. However, the risk factors for cardiovascular disease in ESRD patients are different from the general population, and useful biomarkers for predicting cardiovascular mortality are not completely defined. The nationwide multicenter Clinical Research Center (CRC) for ESRD program was initiated in Korea not only to elucidate the incidence and prevalence of cardiovascular disease in ESRD patients but also to identify potential risk factors including various biomarkers for cardiovascular disease. A prospective cohort of 864 incident hemodialysis patients, from 34 dialysis centers of the CRC for ESRD in Korea, was followed up for 36 months, and the clinical outcome of these patients was reviewed. This article presents the recent data from the CRC for ESRD program, and, in addition, brief reviews on key risk factors and potential biomarkers for cardiovascular disease in ESRD patients.

Sailing between Scylla and Charybdis: oral long-term anticoagulation in dialysis patients

End-stage renal disease (ESRD) patients exhibit an increased risk of bleeding compared with non-chronic kidney disease (CKD) patients due to uraemic platelet dysfunction, altered vessel architecture and other factors. This renders any long-term oral anticoagulation potentially difficult. While there is little doubt that ESRD patients with recurrent thromboembolism or a mechanical cardiac valve should receive vitamin K antagonists (coumarins), the use of coumarins in ESRD patients with atrial fibrillation is a matter of debate. In non-CKD patients, current guidelines strongly recommend the use of oral anticoagulants for stroke prophylaxis in atrial fibrillation if certain risk factors are present (CHA2DS2-VASc score). This recommendation is often extrapolated to patients with advanced CKD or ESRD but data supporting this practice are weak to absent. Besides an increased bleeding risk in ESRD patients, coumarins will also accelerate cardiovascular calcification and are potent risk factors for the development of calcific uraemic arteriolopathy (calciphylaxis). Novel coumarin alternatives such as direct thrombin inhibitors are promising but none is currently approved for use in ESRD patients. Whether interventional treatment strategies such as atrial appendage occlusion are safe and effective options in advanced CKD is also as yet unresolved. This review attempts to balance the potential risks and benefits of coumarin usage in ESRD patients and to give the best possible recommendations for everyday patient care.

Determinants and survival implications of low bone mineral density in end-stage renal disease patients

Reduced bone mineral density (BMD) is common in end-stage renal disease (ESRD) patients and predicts outcomes. The chronic kidney disease-mineral bone disorder contributes to low BMD in ESRD; however, the impact of classical risk factors for osteoporosis in the general population, such as body weight and fat mass, remains less well defined in ESRD subjects. BMD, body composition (dual-energy X-ray absorptiometry), nutritional status (subjective global assessment), hand grip strength and multiple biomarkers were investigated in 361 patients (218 males; 60.4%) starting on dialysis. The relations between BMD, body composition and biomarkers were analyzed at baseline, and the impact of BMD on mortality was analyzed prospectively. In univariate analysis, T-score correlated with fat mass (r = 0.308, p<0.001), lean body mass (r = 0.278, p<0.001), leptin (r = 0.124, p = 0.028) as well as the anabolic marker insulin-like growth factor-1 (IGF-1; r = 0.301, p<0.001), and its binding proteins IGFBP-1 (r = -0.342, p<0.001) and IGFBP-3 (0.231, p<0.001). BMD T-score was independently associated with age, total fat mass, intact parathyroid hormone and presence of wasting. During 5 years of follow-up, 87 deaths were recorded. Each unit of increase of T-score was associated with decreased all-cause mortality, which persisted after multivariate adjustment (hazard ratio = 0.824, 95% confidence interval, 0.681-0.996). BMD is associated with body composition, especially total fat mass, nutritional status and mortality risk in ESRD patients.

Meta‐analysis of the relationship between ACE I/D gene polymorphism and end‐stage renal disease in patients with diabetic nephropathy

Diabetic nephropathy (DN) is the major cause for end-stage renal disease (ESRD) and the pathogenesis for DN developing into ESRD is not clear at present. Results from published studies on the relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and ESRD risk in DN patients are still conflicting. This meta-analysis was performed to evaluate the association between ACE I/D gene polymorphism and ESRD risk in DN patients. Association studies were identified from the databases of PubMed, Embase and Cochrane Library on 1 October 2011, and eligible investigations were identified and synthesized using the meta-analysis method. Results were expressed using odds ratios (OR) for dichotomous data and 95% confidence intervals (CI) were also calculated. Twelve studies reporting the relation between ACE I/D gene polymorphism and ESRD risk in DN patients were identified. In overall populations, there was a notable association between D allele or DD genotype and ESRD susceptibility (D: OR = 1.32, 95% CI: 1.11-1.56, P = 0.002; DD: OR = 1.67, 95% CI: 1.25-2.21, P = 0.0004). In the sub-group analysis according to ethnicity, D allele or DD genotype was associated with ESRD risk in Asians. In Caucasians, the association of DD genotype with ESRD risk was observed, but the D allele was not. Furthermore, ACE I/D gene polymorphism was associated with ESRD risk in patients with DN due to diabetes mellitus type 2, but the association was not found for patients with DN due to diabetes mellitus type-1. Our results indicate that D allele or DD homozygous is associated with the ESRD susceptibility in DN patients. However, more investigations are required to further this association.

Role of non‐HLA genetic variants in end‐stage renal disease

Cytokines and intercellular adhesion molecule (ICAM) play a crucial role in the pathogenesis of primary kidney disease and progression to end-stage renal disease (ESRD). Cytokine secretion is reported to be dependent on the single nucleotide polymorphisms located in the cytokine genes. The role of different polymorphisms in cytokines and ICAM genes as probable susceptibility factors for ESRD has been explored in the present study. The study was conducted on 258 ESRD patients and on ethnically matched 569 controls. Individuals were genotyped for interleukin (IL)-6 (G174C), IL-4 (C590T), tumor necrosis factor-alpha (TNF-alpha) (-G308A and -G238A) and ICAM-1 (A469G) gene polymorphisms using standard polymerase chain reaction-restriction fragment length polymorphism-based method. We observed significant difference in the genotype frequencies of the TNF-alpha-308AA [P = 0.001; odds ratios (OR) = 7.61, 95% confidence intervals (CI) = 2.1-27.9] and TNF-alpha-238AA (P = 0.001; OR = 5.8, 95% CI = 2.2-15.1). Furthermore, C allele of IL-6 -G174C and G allele of ICAM-1 A469G were significantly different in ESRD patients when compared with controls (P = 0.0001; OR = 5.5, 95% CI = 3.9-7.7 and P < 0.0001; OR = 3.8, 95% CI = 3.1-4.7). For the IL-4 C590T polymorphism, although the homozygous mutant genotype (TT) was not found to be significantly associated with ESRD, a statistically significant association with T allele (P = 0.008) was observed. Furthermore, combined analysis showed a higher risk in ESRD patients with high IL-4- and low IL-6-producing genotypes, low IL-4- and low IL-6-producing genotypes and high-producing genotype of TNF-alpha (308 and 238) with the increased risk of 6.47-, 3.7- and 3.3-fold, respectively. Our results suggest that IL-6, IL-4, TNF-alpha and ICAM gene polymorphisms are implicated in ESRD.

Antiplatelet Medications in Hemodialysis Patients

Patients with end stage renal disease (ESRD) are often prescribed antiplatelet medications. However, these patients are also at increased risk of bleeding compared with the general population, and an aim was made to quantify this risk with antiplatelet agents. A systematic review of the literature (Medline, EMBASE, Cochrane CENTRAL and Google Scholar databases) was done to determine the bleeding risk in ESRD patients prescribed antiplatelet therapy. The secondary outcome was the effect on access thrombosis. All case series, cohort studies and clinical trials were considered if they included ten or more ESRD patients, assessed bleeding risk with antiplatelet agents, and lasted for more than 3 mo. Sixteen studies, including 40,676 patients, were identified that met predefined inclusion criteria. Due to study heterogeneity and weaknesses in methodology, bleeding rates were not pooled across studies. However, the bleeding risk appears to be increased for hemodialysis patients treated with combination antiplatelet therapy. The results are mixed for studies using a single antiplatelet agent. Antiplatelet agents appear to be effective in preventing shunt and central venous catheter thrombosis, but not for preventing thrombosis of arteriovenous grafts. The risks and benefits of antiplatelet agents in ESRD patients remain poorly defined. Until a clinical trial addresses this in the dialysis population, individual risk stratification taking into account the increased risk of bleeding should be considered before initiating antiplatelet agents, especially in combination therapy.

Measuring risk in end-stage renal disease: Is N-terminal pro brain natriuretic peptide a useful marker?

Natriuretic peptides are important in the maintenance of body volume homeostasis. There has been interest in utilizing the levels of these peptides to diagnose and prognosticate cardiovascular disease. In end-stage renal disease, the diagnostic utility of these peptides is limited. Madsen et al. report that levels of N-terminal pro brain natriuretic peptide (NT-proBNP) levels offer important information on the risk of mortality in patients undergoing hemodialysis.

Association of interleukin (IL)-4 intron-3 and IL-6 −174 G/C gene polymorphism with susceptibility to end-stage renal disease

Earlier studies suggest that end-stage renal disease (ESRD) is associated with inflammatory state and have become a major cause of morbidity and mortality worldwide. This study speculated the role of interleukins (IL)-2, -4, and -6 cytokines gene polymorphism with risk of susceptibility to ESRD. Polymorphism in IL-2 (-330 T/G, polymerase chain reaction [PCR]-restriction fragment length polymorphism), IL-4 (intron-3, variable number of tandem repeat, variable number tandem repeats analysis), and IL-6 (-174 G/C, amplification refractory mutation system, i.e. ARMS-PCR) were genotyped in 193 ESRD patients and 180 controls. Significant difference was observed in genotype frequencies of IL-4 and IL-6 between ESRD patients and control group (p<0.001 and p=0.032, respectively). Patients had higher frequency of homozygous B2B2 genotype (IL-4) than controls (62.7% vs 46.7) and GG genotype of IL-6 (73.1% vs 60.6%). The genotypic frequencies of IL-2 were comparable in patients and controls (p=0.102). Significant association of IL-4 was also observed in patients with glomerulonephritis (p=0.001). Combination of low IL-4 and high IL-6 genotypes were significantly associated with ESRD showing the highest risk, i.e. >threefolds risk (odds ratio=3.48, 95%CI=1.88-6.42; p < 0.001) among the four possible combinations taking high IL-4 and low IL-6 as reference. Our study suggests that polymorphism in IL-4 and IL-6 may be associated with susceptibility to ESRD. Further, combined analysis implicated a higher risk in ESRD patients with low IL-4 and high IL-6 producing genotypes. This study provided the basis for defined anti-inflammatory approaches to limit renal disease progression.

Nocturnal hemodialysis is associated with restoration of impaired endothelial progenitor cell biology in end-stage renal disease

Cardiovascular disease is the principal cause of death in end-stage renal disease (ESRD) patients. Endothelial progenitor cells (EPCs) play a critical role in vascular repair, and improving EPC biology represents a novel therapeutic target. Three groups of age- and gender-matched patients were studied: 1) 10 healthy control, 2) 12 conventional hemodialysis (CHD) patients, and 3) 10 nocturnal hemodialysis (NHD) patients. EPC number and migratory function were assessed. Left ventricular mass index (LVMI) was derived, and correlations between EPC biology, uremic clearance, and LVMI were made. Compared with controls, EPC number and function were markedly impaired in CHD patients [(3.48 +/- 1.2 vs. 0.86 +/- 0.20%/50,000 cells, P < 0.05) and (18.8 +/- 2.64 vs. 3.75 +/- 0.34 cells/high-power field, P < 0.05), respectively]. In contrast, EPC number and function were normal in NHD patients [(3.48 +/- 1.17 vs. 3.83 +/- 0.77%/50,000 cells) and (18.8 +/- 2.6 vs. 22.2 +/- 2.4 cells/high-power field), respectively]. Among ESRD patients, EPC number and function inversely correlated with predialysis urea concentration (r = -0.40; r = -0.57), LVMI (r = -0.41; -0.46) and systolic BP (r = -0.58; r = -0.44). We demonstrate that NHD is associated with restoration of abnormal EPC biology in ESRD. Given the increasing importance of EPCs in the repair and restoration of cardiovascular function, these data have important clinical implications for vascular risk in ESRD patients.