End stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans. This led to the hypothesis that susceptibility alleles for ESRD have a higher frequency in West African than European gene pool. We performed a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and demonstrated a highly significant association between excess African ancestry and non-diabetic ESRD (LOD 5.70) but not diabetic ESRD (LOD 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% credible interval 0.39 -0.63) compared to African ancestry. Multiple common SNPs (allele frequency ranging from 0.2 to 0.6) in the gene that encodes non-muscle myosin heavy chain type II isoform A (MYH9) were associated with 2-4 times greater risk of non-diabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.End stage renal disease (ESRD) is the near-total loss of kidney function requiring treatment of 472,000 patients with dialysis or transplantation in the US 1 . Diabetes and hypertension are the two leading reported causes of treated ESRD in the U.S. accounting for 44% and 27% of incident cases respectively 1 . African Americans have consistently had a much higher rate of ESRD than European Americans in the US. In 2005, African-Americans had a 3.7 times higher age adjusted risk of ESRD. The risk ratio by assigned primary cause of ESRD was 3.8 for hypertension, 2.6 for diabetes, 2.3 for glomerulonephritis, 2.1 for the other causes of kidney disease 1 . While lower socioeconomic status and poorer access to health care explains some of this excess risk 2-4 , African Americans appear to have greater risk than European Americans after these factors are taken into account. Family studies show clustering of ESRD independent of hypertension and diabetes 5, 6 with one large study shows stronger aggregation in African Americans 6 . Studies attempting to detect susceptibility genes for ESRD and other complex diseases are challenging due to the late age of onset, causing difficulty in collecting multiply-affected families, and because linkage analysis has suggested that there are no genes of high penetrance (>4-fold increased risk) in populations of European descent, the focus of most published studies 7, 8 . For these reasons, ESRD is an excellent phenotype for whole genome association analysis, an approach with enhanced power to detect common variants of modest penetrance, and with the further advantage that unrelated individuals can be studied.We performed a scan for ESRD genes using a particular type of whole genome association analysis, termed admixture mapping or mapping by admixture linkage disequilibrium (MALD) Linda NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 9-11 . Admixture mapping is particularly suitable for finding genetic risk alleles that differ in frequency between populations which we hypothesized might be the case for ESRD.The...

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Abstract. Although atherosclerotic cardiovascular disease (AS-CVD) risk in end-stage renal disease (ESRD) is 5 to 30 times that of the general population, few data exist comparing AS-CVD risk factors among new dialysis patients to the general population. This cross-sectional study of 1041 dialysis patients describes the prevalence of ASCVD risk factors at the beginning of ESRD compared with estimates of ASCVD risk factors in the adult US population derived from the Third National Health and Nutrition Examination (NHANES III). CHOICE Study participants had a high prevalence of diabetes (54%), hypertension (96%), left ventricular hypertrophy by electrocardiogram (EKG) criteria (22%), low physical activity (80%), hypertriglyceridemia (36%), and low HDL cholesterol (33%). CHOICE participants were more likely to be older, black, and male than NHANES III participants. After adjustment for age, race, gender, and ASCVD (defined as myocardial infarction, revascularization procedure, stroke, carotid endarterectomy, and amputation in CHOICE; and as myocardial infarction and stroke in NHANES III), the prevalence of diabetes, hypertension, left ventricular hypertrophy by EKG, low physical activity, low HDL cholesterol, and hypertriglyceridemia were still more common in CHOICE participants. Smoking, obesity, hypercholesterolemia, and high LDL cholesterol, however, were less common in CHOICE than NHANES III participants. The projected 5-yr ASCVD risk based on the Framingham Risk Equation among those older than 40 yr without ASCVD was higher in CHOICE Study participants (13%) than in the NHANES III participants (6%). In summary, many ASCVD risk factors are more prevalent in ESRD than in the general population and may explain some, but probably not all, of the increased ASCVD risk in ESRD.Atherosclerotic cardiovascular disease (ASCVD) accounts for approximately half of deaths in end-stage renal disease (ESRD) and contributes to the extraordinarily high total annual mortality of 23% observed in such patients (1). The incidence of myocardial infarction (MI) and stroke in the dialysis population is 5-to 15-fold higher in ESRD (2), and cardiovascular mortality is 10-to 30-fold higher (3) than that seen in the general population (4 -6), This increased risk is only partially explained by a high prevalence of ASCVD (2,4,7-9) and traditional ASCVD risk factors (10) at the initiation of dialysis (3,11,12).The Special Report from the National Kidney Foundation Task Force on Cardiovascular Disease (13) called for further studies of ASCVD and its risk factors in ESRD patients. Most previous studies of ASCVD risk factors have investigated prevalent . Such studies may underestimate the presence and effect of risk factors because those with the highest degree of ASCVD risk tend to die sooner and are not included in a prevalent study population (i.e., survival bias), an effect diminished but not eliminated by cross-sectional studies of incident dialysis patients.Relatively few nationally representative studies (4,9,18 -20) have described select...

Arteriovenous fistulae (AVF) have advantages over arteriovenous grafts (AVG) and central venous catheters (CVC), but whether AVF are associated independently with better survival is unclear. Recent studies showing such a survival benefit did not include early access experience or account for changes in access type over time and did not include data on some important confounders. Reported here are survival rates stratified by the type of access in use up to 3 yr after initiation of hemodialysis among 616 incident patients who were enrolled in the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study. A total of 1084 accesses (185 AVF, 296 AVG, 603 CVC) were used for a total of 1381 person-years. At initiation, 409 (66%) patients were using a CVC, 122 (20%) were using an AVG, and 85 (14%) were using an AVF. After 6 mo, 34% were using a CVC, 40% were using an AVG, and 26% were using an AVF. Annual mortality rates were 11.7% for AVF, 14.2% for AVG, and 16.1% for CVC. Adjusted relative hazards (RH) of death compared with AVF were 1.5 (95% confidence interval, 1.0 to 2.2) for CVC and 1.2 (0.8 to 1.8) for AVG. The increased hazards associated with CVC, as compared with AVF, were stronger in men (n ‫؍‬ 334; RH ‫؍‬ 2.0; P ‫؍‬ 0.01) than women (n ‫؍‬ 282; RH ‫؍‬ 1.0 for CVC; P ‫؍‬ 0.92). These results strongly support existing clinical practice guidelines and suggest that the use of venous catheters should be minimized to reduce the frequency of access complications and to improve patient survival, especially among male hemodialysis patients.

Late evaluation of patients with chronic renal failure by a nephrologist is associated with greater burden and severity of comorbid disease, black ethnicity, lack of health insurance, and shorter duration of survival.

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Background Residual kidney function (RKF) is associated with improved survival in peritoneal dialysis patients but its role in hemodialysis patients is less well known. Urine output may provide an estimate of RKF. The aim of our study was to determine the association of urine output with mortality, quality of life (QOL) and inflammation in incident hemodialysis patients. Study Design Nationally representative prospective cohort study Setting & Participants 734 incident hemodialysis participants treated in 81 clinics; enrollment, 1995-1998, follow-up until December 2004. Predictor Urine output, defined as producing at least 250 mL (1 cup) of urine daily, ascertained by questionnaires at baseline and year 1. Outcomes & Measurements Primary outcomes were all-cause and cardiovascular (CVD) mortality, analyzed using Cox regression adjusted for demographic, clinical and treatment characteristics. Secondary outcomes were QOL, inflammation (CRP and interleukin-6 [IL-6] levels) and erythropoietin (EPO) requirements. Results 617/734 (84%) participants reported urine output at baseline and 163/579 (28%) at year 1. Baseline urine output was not associated with survival. Urine output at year 1, indicating preserved RKF, was independently associated with lower all-cause mortality (Hazard Ratio [HR], 0.70; 95% Confidence Interval [CI], 0.52-0.93; p=0.02) and a trend towards lower CVD mortality (HR, 0.69; 95% CI, 0.45-1.05; p=0.09). Participants with urine output at baseline reported better QOL and had lower CRP (p=0.02) and IL-6 (p=0.03) levels. Importantly, EPO dose was 12,000 units/week lower in those with urine output at year 1 compared with those without (p=0.001). Limitations Urine volume was measured in only a subset of patients (42%) but was in agreement with self-report (p<0.001). Conclusions RKF in hemodialysis patients is associated with better survival and QOL, lower inflammation and significantly less EPO use. RKF should be monitored routinely in hemodialysis patients. Development of methods to assess and preserve RKF is important and may improve dialysis care.

Elevated bone mineral parameters have been associated with mortality in dialysis patients. There are conflicting data about calcium, parathyroid hormone (PTH), and mortality and few data about changes in bone mineral parameters over time. We conducted a prospective cohort study of 1007 incident hemodialysis and peritoneal dialysis patients. We examined longitudinal changes in bone mineral parameters and whether their associations with mortality were independent of time on dialysis, inflammation, and comorbidity. Serum calcium, phosphate, and calcium-phosphate product (CaP) increased in these patients between baseline and 6 months (P<0.001) and then remained stable. Serum PTH decreased over the first year (P<0.001). In Cox proportional hazards models adjusting for inflammation, comorbidity, and other confounders, the highest quartile of phosphate was associated with a hazard ratio (HR) of 1.57 (1.07-2.30) using both baseline and time-dependent values. The highest quartiles of calcium, CaP, and PTH were associated with mortality in time-dependent models but not in those using baseline values. The lowest quartile of PTH was associated with an HR of 0.65 (0.44-0.98) in the time-dependent model with 6-month lag analysis. We conclude that high levels of phosphate both at baseline and over follow-up are associated with mortality in incident dialysis patients. High levels of calcium, CaP, and PTH are associated with mortality immediately preceding an event. Promising new interventions need to be rigorously tested in clinical trials for their ability to achieve normalization of bone mineral parameters and reduce deaths of dialysis patients.