End-stage Renal Disease In Individuals Research Articles

Protocol for a systematic review of the application of the kidney failure risk equation and Oxford classification in estimating prognosis in IgA nephropathy

BackgroundIgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Outcomes are highly variable and predicting risk of disease progression at an individual level is challenging. Accurate risk stratification is important to identify individuals most likely to benefit from treatment. The Kidney Failure Risk Equation (KFRE) has been extensively validated in CKD populations and predicts the risk of ESRD at 2 and 5 years using non-invasive tests; however, its predictive performance in IgAN is unknown. The Oxford classification (OC) describes pathological features demonstrated on renal biopsy that are associated with adverse clinical outcomes that may also inform prognosis. The objective of this systematic review is to compare the KFRE with the OC in determining prognosis in IgAN.MethodsA systematic review will be conducted and reported in line with PRISMA guidelines (PRISMA-P checklist attached as Additional file 1). Inclusion criteria will be cohort studies that apply the KFRE or OC to determine the risk of CKD progression or ESRD in individuals with IgAN. Multiple databases will be searched in duplicate to identify relevant studies, which will be screened first by title, then by abstract and then by full-text analysis. Results will be collated for comparison. Risk of bias and confidence assessments will be conducted independently by two reviewers, with a third reviewer available if required.DiscussionIdentifying individuals at the highest risk of progression to ESRD is challenging in IgAN, due to the heterogeneity of clinical outcomes. Risk prediction tools have been developed to guide clinicians; however, it is imperative that these aids are accurate and reproducible. The OC is based on observations made by specialist renal pathologists and may be open to observer bias, therefore the utility of prediction models incorporating this classification may be diminished, particularly as in the future novel biomarkers may be incorporated into clinical practice.Systematic review registrationPROSPERO CRD42022364569

435-P: Remnant-C as an Independent Risk Factor for End-Stage Renal Disease in Patients with Type 2 Diabetes—A Nationwide Population-Based Cohort Study

Few studies have investigated the association between remnant-C and the progression of diabetic nephropathy. We aimed to evaluate the association between remnant-C and the risk of newly developed end-stage renal disease (ESRD) in patients with type 2 diabetes in a nationwide cohort of Korean adults. The risk of incident ESRD according to remnant-C levels was analyzed by Cox proportional hazard models. During the median follow-up period of 9 years, 11,615 individuals (1.4% of the total population) developed ESRD. The serum concentrations of remnant-C was associated with 7% higher risk of ESRD per every 10 mg/dL increase. In multivariable-adjusted analyses, participants in the upper quartile of remnant-C had a higher risk of ESRD, with hazard ratios of 1.15 (95% CI 1.09-1.22) in the second quartile, 1.26 (95% CI 1.20-1.33) in the third quartile, and 1.47 (95% CI 1.40-1.55) in the fourth quartile, compared with the lowest quartile. Furthermore, the magnitude of the increased risk for incident ESRD in individuals with higher remnant-C quartiles was significant in participants aged 50 years or older. These results suggest that remnant-C concentration is an independent risk factor for the development of ESRD in patients with type 2 diabetes. Disclosure E.Roh: None.

#4317 CLINICAL DIVERSITY OF STEROID-RESISTANT NEPHROTIC SYNDROME CAUSED BY TRPC6 MUTATIONS

Abstract Background and Aims Steroid-resistant nephrotic syndrome (SRNS) is a clinically and genetically heterogeneous disorder caused by either genetic or immunological factors or their combination. Approximately 30–40% of patients with SRNS make a fast progression to ESRD. SRNS represents the second leading cause of end-stage renal disease in individuals under the age of 25 years worldwide. More than 60 podocyte-related gene mutations have thus far been reported in monogenic SRNS. Recent studies indicate that almost 30% of patients with childhood-onset SRNS have monogenic causative variants in one of the 27 SRNS genes. Among these, a mutation in Transient Receptor Potential Canonical 6 (TRPC6) gene, encoding non-selective cation channel, accounts for 6% of familial SRNS and approximately 2% of sporadic cases. We recently detected eight patients with TRPC6 mutations in our SRNS cohort (n = 39, 21%) and found inter- and intra-familial heterogeneity of clinical phenotypes in terms of disease onset and progression. Method A total of 39 Japanese SRNS patients were studied according to the protocol approved by the institutional review board of each affiliation. Subjects who manifested SRNS at age one to 14-year-old with biopsy-proven FSGS were enrolled. A total of 39 SRNS patients, whose average onset of proteinuria at median age 4 (range 0.9 to 17 yr) and ESRD at median age 7 (49% of total n = 19, range 3.0 to 16.0 yr) were studied. Family history was found in 44% (n = 17), including 13 autosomal recessive, 3 dominant, and one X-linked transmission. Sixteen percent (n = 10) of the patients who underwent renal transplantation win no recurrence. Sequence analysis revealed the pathogenic variants in 62% (n = 24) of all cases. Library for whole-exome sequencing or targeted panel sequencing were prepared from genomic DNA by use of SureSelect Human All Exon V5 (Agilent) or a HaloPlex target enrichment system kit (Agilent Technologies), or Ampli-Seq (Thermo), Prepared samples were run on a HiSeq 2000, or MiSeq (Illumina), or Ion PGM (Thermo). The sequence reads with 101-bp paired-end reads and 7-bp index reads were mapped to the human reference sequence (hg19, GRCh38.p7). After filtering the superfluous begin variants, only variants that fulfill the “pathogenic” criteria of ACMG and/or ClinVar, Varsome were selected. Results Sequence analysis revealed the pathogenic variants in 62% (n = 24) of all cases. TRPC6 mutations were the most frequent cause of SRNS (n = 8), which was followed by NUP107 (n = 5), PLCE1 (n = 3), COL4A3 (n = 2), COL4A5 (n = 1), and others were identified in only single case. The eight TRPC6 mutations clustered into the two distinctive cytoplasmic domains; N-terminal ANK (Y173D, R175W, R175G) and C-terminal coiled-coil domain (p.E875V, p.867_868Del, p.S893N, p.R895C). The p.R895C is deposited as the pathogenic in ClinVar and may be a gain-of-function. The remaining 7 variants are of unknown functions: six have not yet been deposited in ClinVar, whereas one is VUS. Four patients were de novo occurrence, three followed the dominant transmission, and one arose from gonadal mosaicism. Two index patients exhibited SRNS in early childhood (< age 3), four manifested it in childhood (age 3–12), while the remaining two developed it in adolescence (age >12). In familial cases, for example, affected ones harboring R175W or p.E875V showed a remarkable discordant age onset and disease severity. Conclusion TRPC6 channelopathy was found to be the most frequent cause in our SRNS cohort, of which age onset ranges from age 0.9 to 17 year. Heterogeneity of disease severity may reflect that channel activity is regulated by the mode of action (gain- or loss-of-function), the combination of channel subunit assembly, and interaction with other modifying factors. Mutations in these TRPCs are associated with relatively common kidney diseases as well as other pathologies. Further expression studies will improve our mechanistic understanding of TRP channel pathology and may help the development of novel therapeutic targets.

Sexual dysfunction in patients with end-stage renal disease: A systematic review and meta-analysis

ABSTRACT Introduction Sexual dysfunction (SD) is an under-recognized clinical entity in both men and women with end-stage renal disease (ESRD). Studies on renal transplant recipients and dialysis patients report different prevalence rates and severity of SD among these groups. Moreover, the effect of renal transplantation on sexual function remains unknown. Objectives To explore the prevalence, severity, correlates, diagnostic approach and treatment modalities of sexual symptoms in patients with ESRD. Methods We performed a systematic review and meta-analysis assessing the prevalence of SD in ESRD individuals and evaluating the effect of renal transplantation on sexual function. Records were identified by searching PubMed, EMBASE, Scopus, and CENTRAL databases, as well as sources of grey literature. We conducted a random-effects meta-analysis of proportions (double arcsine transformation) to estimate the prevalence of SD in patients with ESRD. Multiple subgroup and sensitivity analyses, cumulative meta-analyses and univariate meta-regression analyses of important correlates were also performed. Results We included 94 studies with 10,320 ESRD male individuals and 47 studies with 3,490 ESRD female individuals. Overall, 7,253 males experienced erectile dysfunction (71%, 95% CI: 67% to 74%, I2= 92%). The pooled prevalence of erectile dysfunction was 59% (95% CI: 53% to 64%, I2= 92%) among renal transplant recipients, 79% (95% CI: 75% to 82%, I2= 86%) in hemodialysis patients and 71% (95% CI: 58% to 83%, I2= 86%) in peritoneal dialysis patients. On the contrary, 1,797 females experienced SD (74%, 95%CI: 67%-80%, I2=92%). The pooled prevalence of female SD was 63% (95%CI: 43%-81%, I2=92%) in renal transplant recipients, 80% (95%CI: 72%-87%, I2=91%) in hemodialysis patients and 67% (95%CI: 46%-84%, I2=90%) in peritoneal dialysis patients. In studies comparing erectile function before and after renal transplantation, renal transplant recipients reported an improvement in EF (RR: 2.53, 95%CI: 1.44 to 4.44, I2= 90%). The latter was also observed in women. Conclusions Sexual symptoms negatively affect the quality of life and warrant appropriate clinical attention, as they are an underdetermined and undertreated clinical entity in patients with ESRD. Renal transplantation seems to improve sexual function both in men and in women. Still, further studies on the field are mandatory. Disclosure Work supported by industry: no.

Prevalence of Erectile Dysfunction in Patients With End-Stage Renal Disease: A Systematic Review and Meta-Analysis

BackgroundErectile dysfunction (ED) is an under-recognized clinical entity in men with end-stage renal disease (ESRD), and studies on renal transplant recipients, patients on dialysis, and patients starting dialysis report different prevalence rates and severity of ED among these groups. AimTo determine the prevalence and severity of ED in patients with ESRD, assessed with the International Index of Erectile Function-15 and International Index of Erectile Function-5. MethodsWe performed a systematic review and meta-analysis of observational studies assessing the prevalence of ED in ESRD individuals. (PROSPERO ID: CRD42020182680). Records were identified by search in MEDLINE, Scopus, and CENTRAL databases and sources of gray literature until July 2020. We conducted a random-effects meta-analysis of proportions (double arcsine transformation). OutcomesWe included 94 studies with 110 patient group entries and a total of 10,320 ESRD male individuals with a mean age of 48.8 ± 14.25 years. ResultsOverall, 7,253 patients experienced ED. We estimated an overall pooled ED prevalence of 71% (95% CI: 67–74%, I2 = 92%). In the subgroup analyses, the pooled prevalence was 59% (95% CI: 53–64%, I2 = 92%) among renal transplant recipients, 79% (95% CI: 75–82%, I2 = 86%) in patients on hemodialysis, 71% (95% CI: 58–83%, I2 = 86%) in patients on peritoneal dialysis, and 82% (95% CI: 75–88%, I2 = 0%) in patients with ESRD starting dialysis. The prevalence of the severity of ED was also estimated. Further assessment of heterogeneity was conducted via sensitivity analysis, cumulative meta-analysis, and meta-regression of significant risk factors. Clinical translationDespite its high prevalence in patients with ESRD, ED constitutes an underestimated and taboo subject in this group. Therefore, arousing clinical concern among healthcare providers involved in ESRD management is more than necessary to screen and treat ED in patients receiving renal replacement therapy. Strengths & LimitationsWe estimated ED solely for ESRD, included the largest number of patients compared with previous studies and estimated ED prevalence as per severity and renal replacement therapy subgroups. Contrary, because we restricted our eligibility criteria to the International Index of Erectile Function, some studies assessing ED prevalence with other validated tools were not included in this meta-analysis. Moreover, the levels of heterogeneity among studies remained high after sensitivity and meta-regression analyses, and for some moderators, the results of the meta-regression might have been underpowered. ConclusionsED is highly prevalent in patients with ESRD irrespective of the type of renal replacement therapy, thereby warranting clinical attention.Pyrgidis N, Mykoniatis I, Nigdelis MP, et al. Prevalence of Erectile Dysfunction in Patients With End-Stage Renal Disease: A Systematic Review and Meta-Analysis. J Sex Med 2021;18:113–120.

Widening the lens to childhood: relevance and lifetime risk of kidney failure.

Lifetime risk of outcomes is emerging as a highly relevant health indicator, even in the context of low absolute risk of disease progression in short time frames. Evidence to support this concept for kidney failure is increasing, with growing emphasis on the long-term impact of risk factors occurring early in life. Proteinuria and stage of chronic kidney disease (CKD) are now established predictors of CKD progression in children, and youth with type 2 diabetes are emerging as a group at significant risk. Recent population-based studies have also examined the lifetime risk of end-stage renal disease in individuals with any childhood CKD. A recent study found that even in the absence of biomarkers of renal injury, childhood CKD can increase the lifetime risk of end-stage renal disease four-fold, and up to 10-fold in adults less than 40 years of age. Children with CKD are at high lifetime risk of kidney failure and require follow-up. Identifying children at highest lifetime risk through the use of biomarkers and risk equations, and determining the optimal duration and intensity of follow-up requires further research.

Association of Urinary Oxalate Excretion With the Risk of Chronic Kidney Disease Progression

Oxalate is a potentially toxic terminal metabolite that is eliminated primarily by the kidneys. Oxalate nephropathy is a well-known complication of rare genetic disorders and enteric hyperoxaluria, but oxalate has not been investigated as a potential contributor to more common forms of chronic kidney disease (CKD). To assess whether urinary oxalate excretion is a risk factor for more rapid progression of CKD toward kidney failure. This prospective cohort study assessed 3123 participants with stages 2 to 4 CKD who enrolled in the Chronic Renal Insufficiency Cohort study from June 1, 2003, to September 30, 2008. Data analysis was performed from October 24, 2017, to June 17, 2018. Twenty-four-hour urinary oxalate excretion. A 50% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD). This study included 3123 participants (mean [SD] age, 59.1 [10.6] years; 1414 [45.3%] female; 1423 [45.6%] white). Mean (SD) eGFR at the time of 24-hour urine collection was 42.9 (16.8) mL/min/1.73 m2. Median urinary excretion of oxalate was 18.6 mg/24 hours (interquartile range [IQR], 12.9-25.7 mg/24 hours) and was correlated inversely with eGFR (r = -0.13, P < .001) and positively with 24-hour proteinuria (r = 0.22, P < .001). During 22 318 person-years of follow-up, 752 individuals reached ESRD, and 940 individuals reached the composite end point of ESRD or 50% decline in eGFR (CKD progression). Higher oxalate excretion was independently associated with greater risks of both CKD progression and ESRD: compared with quintile 1 (oxalate excretion, <11.5 mg/24 hours) those in quintile 5 (oxalate excretion, ≥27.8 mg/24 hours) had a 33% higher risk of CKD progression (hazard ratio [HR], 1.33; 95% CI, 1.04-1.70) and a 45% higher risk of ESRD (HR, 1.45; 95% CI, 1.09-1.93). The association between oxalate excretion and CKD progression and ESRD was nonlinear and exhibited a threshold effect at quintiles 3 to 5 vs quintiles 1 and 2. Higher vs lower oxalate excretion (at the 40th percentile) was associated with a 32% higher risk of CKD progression (HR, 1.32; 95% CI, 1.13-1.53) and 37% higher risk of ESRD (HR, 1.37; 95% CI, 1.15-1.63). Results were similar when treating death as a competing event. Higher 24-hour urinary oxalate excretion may be a risk factor for CKD progression and ESRD in individuals with CKD stages 2 to 4.

Isotope-specific breath analysis to track the end-stage renal disease during hemodialysis

The underlying mechanisms towards the progression of end-stage renal disease (ESRD) in chronic kidney disease (CKD) are poorly understood and it still remains a major clinical stumbling block for early detection of CKD. Most patients with CKD pass through ESRD with the necessity of frequent hemodialysis (HD) treatment. At present, plasma urea and creatinine levels are examined in most CKD patients to monitor their health status after dialysis. But it is impossible to get immediate feedback on the patients’ health as the conventional tests involve the collection of blood samples, laboratory processing for a prolonged period of time and, finally, analysis of those samples. However, the test results are very important in deciding the treatment plan for those ESRD patients. Here, we show that the enzymatic activity of carbonic anhydrase in erythrocytes is distinctly altered in ESRD subjects under HD. This, in turn, leads to the isotopic enrichments of oxygen-18 (18O) and carbon-13 (13C) of CO2 during respiration in HD treatment. High-resolution cavity-enhanced absorption spectroscopic measurements show that 18O and 13C-isotopic fractionations of breath CO2 are correlated with Kt/V values, suggesting a novel unifying strategy for ESRD patients that can be used as an isotope-specific methodology for non-invasive assessment of dialysis adequacy and hence 12C18O16O and 13C16O16O could be used as novel markers for tracking the physiological parameters of ESRD individuals. Our findings suggest that the monitoring of 18O and 13C isotopes of breath CO2 may facilitate the proper management of advanced CKD patients. The primary advantage of this isotopic breath test is that it may reduce the valuable time lag between the completion of dialysis and obtaining the clinical report on the status of patients’ health.

Diabetes mellitus, superoxide dismutase and peroxisome proliferator activated receptor gamma polymorphisms modify the outcome of end-stage renal disease patients of Han Chinese origin.

Increased oxidative stress significantly modifies the outcome of patients with diabetes mellitus (DM) and end-stage renal disease (ESRD), and is counteracted by antioxidative capacity. We aimed to investigate whether antioxidant single nucleotide polymorphisms (SNPs) influence the outcome of ESRD individuals and the influences exerted by DM, which has not been tested before. We prospectively enrolled multi-centre ESRD patients of Han Chinese origin between 2002 and 2003, recording their antioxidant (superoxide dismutase [SOD2], glutathione peroxidase [GPX1]) and peroxisome proliferator activated receptor-γ (PPAR-γ) genotyping results, and stratified based on DM. They were followed up until 2008, with risk factors for mortality analyzed by Cox proportional hazard regression. We discovered that diabetic ESRD carriers of CC genotype of SOD2 exon 2 had an increased risk of mortality compared to non-diabetic ones with other genotypes (hazard ratio [HR] 4.04, P=0.04), while GPX1 SNPs had no influence. Interactions between SOD2 and PPAR-γ SNPs regarding the mortality influence were also detected (for SOD2 CC genotype x PPAR-γ exon 6 CT genotype, HR 3.19, P=0.008), suggesting the importance of considering a combination panel of SNPs on patient survival. This might be the largest study focusing on the relationship between antioxidant SNPs and the outcomes of diabetic ESRD patients of Han Chinese origin. More studies are needed to validate our findings.

Prognostic value of myocardial perfusion imaging and coronary artery calcium measurements in patients with end-stage renal disease.

Coronary artery disease (CAD) is highly prevalent in patients with end-stage renal disease (ESRD), owing to clustering of traditional and uremic-specific risk factors. However, in this population asymptomatic course of CAD is common and it has been reported that myocardial perfusion imaging (MPI) with single-photon emission tomography (SPET) has lower sensitivity. In the current study, we assessed the value of MPI gated-SPET and its combination with coronary artery calcium (CAC) score measurements in risk stratification of ESRD patients. MPI gated-SPET was performed with dual-headed SPET camera and CAC score measured by multi-detector computed tomography (MDCT) system.There were tested 77 ESRD individuals. During the follow-up study, cardiac events (CE) defined as cardiac death or nonfatal myocardial infarction (MI) or the necessity for coronary revascularization were recorded. Univariate and stepwise multivariable Cox proportional hazards-models were used to identify the predictors of CE. Eighteen CE were recorded during the follow-up. They were significantly associated with higher summed stress scores on MPI, higher percentage of ischaemic myocardium, higher occurrence of defects in multiple territories and higher CAC score (all with P<0.05). Univariate Cox proportional hazard-models showed that severe perfusion abnormalities as well as CAC score ≥1000 were significantly associated with cardiac events (P<0.0001, P=0.0056). In stepwise Cox proportional hazards-models considering age, gender, history of diabetes mellitus, post-stress left ventricular stunning, the degree of perfusion abnormality and CAC score, only severe perfusion abnormalities and CAC score ≥1000 were independent predictors of CE. There was no CE in patients with normal perfusion, normal function and zero CAC score. This study suggests that combined evaluation of MPI and CAC can predict the outcome in ESRD individuals, while severe perfusion abnormality on gated-SPET and high CAC score ≥1000 are predictors of future cardiac events.

Dietary Patterns and Risk of Death and Progression to ESRD in Individuals With CKD: A Cohort Study

Nutrition is linked strongly with health outcomes in chronic kidney disease (CKD). However, few studies have examined relationships between dietary patterns and health outcomes in persons with CKD. Observational cohort study. 3,972 participants with CKD (defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 or albumin-creatinine ratio ≥ 30 mg/g at baseline) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a prospective cohort study of 30,239 black and white adults at least 45 years of age. 5 empirically derived dietary patterns identified by factor analysis: "convenience" (Chinese and Mexican foods, pizza, and other mixed dishes), "plant-based" (fruits and vegetables), "sweets/fats" (sugary foods), "Southern" (fried foods, organ meats, and sweetened beverages), and "alcohol/salads" (alcohol, green-leafy vegetables, and salad dressing). All-cause mortality and end-stage renal disease (ESRD). 816 deaths and 141 ESRD events were observed over approximately 6 years of follow-up. There were no statistically significant associations of convenience, sweets/fats, or alcohol/salads pattern scores with all-cause mortality after multivariable adjustment. In Cox regression models adjusted for sociodemographic factors, energy intake, comorbid conditions, and baseline kidney function, higher plant-based pattern scores (indicating greater consistency with the pattern) were associated with lower risk of mortality (HR comparing fourth to first quartile, 0.77; 95% CI, 0.61-0.97), whereas higher Southern pattern scores were associated with greater risk of mortality (HR comparing fourth to first quartile, 1.51; 95% CI, 1.19-1.92). There were no associations of dietary patterns with incident ESRD in multivariable-adjusted models. Missing dietary pattern data, potential residual confounding from lifestyle factors. A Southern dietary pattern rich in processed and fried foods was associated independently with mortality in persons with CKD. In contrast, a diet rich in fruits and vegetables appeared to be protective.

Exploration of Insertion/Deletion Polymorphism of Angiotensin Converting Enzyme in Post-Transplant Diabetes Mellitus Individuals from an Asian Indian Population

This work intended to test the association of Angiotensin Converting Enzyme (ACE) gene insertion (I) and Deletion (D) polymorphism in the End Stage Renal Disease (ESRD) subjects who developed post-transplant diabetes mellitus (PTDM) on using immunosuppressive drugs from an Asian Indian population. ACE is known to play an important role in the adaptation and regulation of systemic and renal circulations through angiogenesis II formation and kinins metabolism. A total of 240 non-diabetic ESRD individuals were prospectively screened for PTDM after renal transplant and 42 (30%) patients developed PTDM, whereas remaining 98 (70%) patients were non-PTDM. Genomic DNA was isolated from all the subjects and genotyping was performed for I28005D polymorphism using PCR-based assay. Individuals with PTDM had a higher DD (33.3%) genotypes and D (0.51) allele compared to controls. There was a significant difference between the genotype and allele frequencies of the PTDM cases and controls [for D Vs I, χ2=0.0244; p=0.02, odds ratio=1.98 (95% CI: 1.09-3.63; DD+ID Vs II, χ2=0.0316; p=0.03, odds ratio=2.9 (95% CI: 1.07-7.8)]. From our results we conclude that ACE gene polymorphism has role and a conventional risk facto r in developing the disease in PTDM individuals from Asian Indian population.

Risk Factors for ESRD in Individuals With Preserved Estimated GFR With and Without Albuminuria: Results From the Kidney Early Evaluation Program (KEEP)

Given the increasing costs and poor outcomes of end-stage renal disease (ESRD), we sought to identify risk factors for ESRD in people with preserved estimated glomerular filtration rate (eGFR), with or without albuminuria, who were at high risk of ESRD. This cohort study included participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) with eGFR ≥ 60 mL/min/1.73 m(2) at baseline stratified by the presence or absence of albuminuria. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate eGFR. Urine was tested for albuminuria by semiquantitative dipstick. The outcome was the development of treated chronic kidney failure, defined as initiation of maintenance dialysis therapy or kidney transplantation, determined by linkage to the US Renal Data System. We used a Cox model with the Fine-Gray method to assess risk factors for treated chronic kidney failure while accounting for the competing risk of death. During a median follow-up of 4.8 years, 126 of 13,923 participants with albuminuria (16/10,000 patient-years) and 56 of 109,135 participants without albuminuria (1.1/10,000 patient-years) developed treated chronic kidney failure. Diabetes was a strong risk factor for developing treated chronic kidney failure in participants with and without albuminuria (adjusted HRs of 9.3 [95% CI, 5.7-15.3] and 7.8 [95% CI, 4.1-14.8], respectively). Black race, lower eGFR, and higher systolic blood pressure also were associated with higher adjusted risks of developing treated chronic kidney failure. In a diverse high-risk cohort of KEEP participants with preserved eGFR, we showed that diabetes, higher systolic blood pressure, lower eGFR, and black race were risk factors for developing treated chronic kidney failure irrespective of albuminuria status, although the absolute risk of kidney failure in participants without albuminuria was very low. Our findings support testing for kidney disease in high-risk populations, which often have otherwise unrecognized kidney disease.

IGF2 ApaI A/G Polymorphism Evaluated in ESRD Individuals as a Biomarker to Identify Patients with New Onset Diabetes Mellitus after Renal Transplant in Asian Indians

Insulin like growth factors2 (IGF2) regulates pancreatic β-cell renewal and apoptosis, which in turn plays a role in altering insulin activity and glucose homeostasis. Polymorphisms in IGF2 gene have been associated with altered levels of IGF2. Hence, ApaI polymorphism in exon 9 of IGF2 (rs#680) gene was assessed in patients with end stage renal disease (ESRD) to identify individuals at risk of developing new onset diabetes mellitus (NODM) in Asian Indians. Isolated DNA was used for PCR&RFLP based genotyping of IGF2 ApaI polymorphism which was carried out in 364 individuals these included 140 patients who had undergone renal transplant, 42 of which developed new onset diabetes mellitus after renal transplant and 224 healthy control volunteers. In the present study NODM or post transplant diabetes mellitus (PTDM) showed a significant association with G allele and AG genotype when compared with the Non-NODM ESRD patients after transplant (OR 2.081, 95% CI = 1.191 - 3.634, p = 0.01 and OR 3.188, 95% CI = 1.498 - 6.785, p = 0.002) ESRD patients with healthy controls also showed an association with G allele and AG genotype (OR 1.512, 95% CI = 1.060 - 2.155, p = 0.02 and OR 2.235, 95% CI = 1.453 - 3.438, p = 0.0002). IGF2 could be used as a biomarker to identify individuals at high risk of developing NODM, it would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals undergoing transplant. Present study shows the importance of IGF2 ApaI polymorphism in assessing the risk of NODM in ESRD individuals in Asian Indians with ESRD.

Comparison of microalbuminuria w ith hs-CRP and low density lipoprotein levels in nondiabetic, nonhypertensive myocardial infarction patients

Introduction:Microalbuminuria (MA), defined as urine albumin to urine creatinine ratio (UACR) of 30 to 300 mg/G of creatinine, is an established risk factor for cardiovascular morbidity and mortality and for end-stage renal disease in individuals with an adverse cardiovascular risk profile such as those with hypertension or/and diabetes mellitus.Materials and Methods:Thirty five patients were included in the study and equal number of age- and sex-matched controls were also included. 2 ml of venous blood was collected for hs-CRP determination and early morning mid stream urine sample was collected under strict aseptic precautions. The lipid profile was estimated in cobas autoanalyzer.Results:There was significant increase in levels of Low density lipoprotein (LDL) cholesterol, microalbumin, and hs-CRP (P< 0.001) in patients with myocardial infarction compared to healthy controls.Conclusion:Therefore, MA and hsCRP evaluation may have potential role in improving cardiovascular risk prediction, when used along with traditional lipid profiles.

Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis

Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis

Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis

Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown. We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes. We analysed data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75,306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21,237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2-1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) [vs 95 mL/min per 1·73 m(2)], HR 1·35; 95% CI 1·18-1·55; vs 1·33; 1·19-1·48 and at ACR 30 mg/g [vs 5 mg/g], 1·50; 1·35-1·65 vs 1·52; 1·38-1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts. Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes. US National Kidney Foundation.

Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m2 at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.

Increased risk of end-stage renal disease in individuals with coeliac disease

ObjectiveThe prevalence of end-stage renal disease (ESRD) is increasing worldwide. Although increased levels of coeliac disease (CD) autoantibodies are often seen in renal disease, the importance of biopsy-verified CD for...

People with epilepsy receiving renal replacement therapy with hemodialysis: Scientists recall progress and promise of translational research

Nowadays, we have observed that discoveries in medical sciences have rapidly accelerated and continue to expand. One of the reasons for these positive recent changes is due to the onset of translational research. The term translational research, which was recently incorporated in the dictionary of medical sciences, indicates the integration of the advancements in basic science with clinical trials, taking research from the “bench-to-bedside”. This perspective gives rise to a completely new approach to improving health care for people with chronic diseases. Following this line of thought, we currently know that this scientific convergence works very well in several fields, but can still be considered rare among nephrologists and neurologists. Evaluating the field of nephrology, the chronic renal failure, a progressive loss of kidney function that results in permanent kidney failure, is a worldwide public health problem. Furthermore, individuals in this condition need dialysis or a transplanted kidney. Even more problematic than these aspects, renal failure is associated with an increased risk of cardiovascular disease and sudden death. Now, looking through the prism of Neurology, we know that epilepsy is considered the most common serious neurological condition. Unfortunately, each year about one in a 1000 patients with chronic epilepsy will die suddenly, unexpectedly, and without explanation, even with post-mortem examination. Among neurologists around the world, this phenomenon is called sudden unexplained death in epilepsy (SUDEP). In the actual scenario, epilepsy is associated with a twoto three-fold increase in mortality compared to the general population, and SUDEP is the most important direct epilepsy-related cause of death. Thus, as these two chronic diseases are very common in the world and also a global public health problem, a new line of translational research would have great value in helping neurologists and nephrologists to investigate what would be the best strategy to be drawn if these two chronic diseases involve the same individual. From this perspective and mainly due lack of data in the world, our research group decided to investigate the possible relationship between seizure frequencies in patients with end-stage renal disease (ESRD) under regular dialysis program. Briefly, from 189 ESRD patients, 7 had suffered some type of convulsive seizure during dialytic program. At that time, we concluded that despite the occurrence of seizures is considered rare among ESRD individuals receiving dialysis, it should be apparent that a true convergence of clinical nephrology and neurology should always be part of this scenario. The next step for the researchers of our Institute of Nephrology was to verify the possible association between epilepsy and hence SUDEP in these individuals. Overall, we noted in all the cases evaluated (7 out of 209) that cardiovascular abnormalities and hence SUDEP is a rare event in ESRD people with epilepsy receiving dialysis. Although these data have to be interpreted with caution due to a small number of cases examined, we continue to believe that the flame of translational science among professionals directly involved with these patients must be permanently lit. In sum, it has been repeatedly and firmly established in medical literature that chronic diseases, epilepsy and chronic renal insufficiency in this particular case, have extraordinarily high mortality rates and dialysis people and individuals with epilepsy are at increased risk of sudden