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Background and Objectives: Metabolic acidosis may contribute to morbidity and disease progression in patients with chronic kidney disease (CKD). The ratio of dietary protein, the major source of nonvolatile acid, to dietary potassium, which is naturally bound to alkali precursors, can be used to estimate net endogenous acid production (NEAP). We tested the association between estimated NEAP and serum bicarbonate in patients with CKD., Design, Setting, Participants, & Measurements: NEAP was estimated among 462 African American adults with hypertensive CKD using published equations: NEAP (mEq/d) = -10.2 + 54.5 (protein [g/d]/potassium [mEq/d]). Dietary protein and potassium intake were estimated from 24-hour urinary excretion of urea nitrogen and potassium, respectively. All of the eligible measurements during follow-up were modeled using generalized linear regression clustered by participant and adjusted for demographics, 24-hour urinary sodium, kidney function, and selected medications., Results: Higher NEAP was associated with lower serum bicarbonate in a graded fashion (P trend < 0.001). Serum bicarbonate was 1.27 mEq/L lower among those in the highest compared with the lowest quartile of NEAP (P < 0.001). There was a greater difference in serum bicarbonate between the highest and lowest quartiles of NEAP among patients with stage 4/5 CKD (-2.43 mEq/L, P < 0.001) compared with those with stage 2/3 disease (-0.77 mEq/L, P = 0.01; P-interaction = 0.02)., Conclusions: Reducing NEAP, through reduction of dietary protein and increased intake of fruits and vegetables, may prevent metabolic acidosis in patients with CKD.

Polymorphisms in the MYH9 and adjacent APOL1 gene region demonstrate a strong association with non-diabetic kidney disease in African-Americans. However, it is not known to what extent these polymorphisms are present in other ethnic groups. To examine the association of genetic polymorphisms in this region with chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml/min/1.73 m(2)) in individuals of European ancestry, we examined rs4821480, an MYH9 single-nucleotide polymorphism (SNP) recently identified as associated with kidney disease in African-Americans, in 13 133 participants from the Framingham Heart Study (FHS) and Atherosclerosis Risk in Communities (ARIC) Study. In addition, we further interrogated the MYH9/APOL1 gene region using 282 SNPs for association with CKD using age-, sex- and center-adjusted models and performed a meta-analysis of the results from both studies. Because of prior data linking rs4821480 and kidney disease, we used a P-value of <0.05 to test the association with CKD. In the meta-analysis, rs4821480 (minor allele frequency 4.45 and 3.96% in FHS and ARIC, respectively) was associated with higher CKD prevalence in participants free of diabetes (odds ratio 1.44; 95% confidence interval 1.15-1.80; P = 0.001). No other SNPs achieved significance after adjusting for multiple testing. Results utilizing directly genotyped data confirmed the results of the primary analysis. Recently identified APOL1 risk variants were also directly genotyped, but did not account for the observed MYH9 signal. These data suggest that the MYH9 polymorphism rs4821480 is associated with an increased risk of non-diabetic CKD in individuals of European ancestry.

Background and Objectives: Stroke remains a leading cause of morbidity and mortality for patients on dialysis; however, its risk factors in this population and measures to prevent it are not well understood., Design, Setting, Participants, & Measurements: We investigated whether inflammation was associated with cerebrovascular events in a national US cohort of 1041 incident dialysis patients enrolled from October 1995 to June 1998 and followed until January 31, 2004. Incident cerebrovascular events were defined as nonfatal (hospitalized stroke, carotid endarterectomy) and fatal (stroke death) events after dialysis initiation. With Cox proportional hazards regression analysis accounting for the competing risk of nonstroke death, we assessed the independent event risk associated with baseline levels of multiple inflammatory markers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 (IL-6), matrix metalloproteinase-3 [MMP-3], and P-selectin) and hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) use, which may have pleiotropic inflammatory effects., Results: 165 patients experienced a cerebrovascular event during 3548 person-years of follow-up; overall incidence rate was 4.9/100 person-years. None of the inflammatory markers were associated with cerebrovascular event risk (adjusted hazard ratios [HRs] per log unit [95% confidence interval]: hsCRP, 0.97 [0.85 to 1.11]; IL-6, 1.04 [0.85 to 1.26]; MMP-3, 1.02 [0.70 to 1.48]; P-selectin, 0.98 [0.57 to 1.68]). Statin use was also not associated with significant risk of events in unadjusted (HR 1.07 [0.69 to 1.68]) or propensity-score adjusted analyses (HR 0.98 [0.61 to 1.56])., Conclusions: In conclusion, neither inflammatory markers nor statin use was associated with risk of cerebrovascular events. Further studies are needed to understand the pathophysiology and prevention of stroke in patients on dialysis.

Background/aims: P-selectin is released by activated platelets and endothelium contributing to inflammation and thrombosis. We evaluated the association between soluble P-selectin and atherosclerotic cardiovascular disease (ASCVD) in dialysis patients., Methods: We measured soluble P-selectin in serum from 824 incident dialysis patients. Using Cox proportional hazards models, we modeled the association of P-selectin levels with ASCVD events, cardiovascular mortality and sudden cardiac death., Results: After adjustment for demographics, comorbidity and traditional cardiovascular risk factors, higher P-selectin levels were associated with increased risk of ASCVD and cardiovascular mortality among males (p = 0.02 and p = 0.01, respectively), but not females (p = 0.52 and p = 0.31, respectively; p interaction = 0.003), over a median of 38.2 months. Higher P-selectin was associated with a greater risk of sudden cardiac death among males (p = 0.05). The associations between increasing P-selectin and cardiovascular mortality as well as sudden cardiac death in males persisted after adjustment for C-reactive protein, interleukin-6, serum albumin and platelet count (p = 0.01 and p = 0.03, respectively). The risk for sudden cardiac death was more than 3 times greater for males in the highest tertile of soluble P-selectin compared with the lowest tertile after adjustment (HR: 3.19; 95% CI: 1.18 - 8.62; p = 0.02)., Conclusion: P-selectin is associated with ASCVD, cardiovascular mortality and sudden cardiac death among male dialysis patients., (Copyright © 2011 S. Karger AG, Basel.)

Background: Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals., Methods: A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations., Results: Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10(-5), LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies., Conclusion: These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN., (Copyright © 2011 S. Karger AG, Basel.)

Objective: Race is a known risk factor for hypertension and cardiovascular disease in adults and influences blood pressure (BP) in children. We sought to determine if there are differences in clinical, laboratory, or echocardiographic characteristics among children with primary hypertension from different racial groups., Patients and Methods: Study participants were 184 children aged 3 to 20 years with a diagnosis of primary hypertension who were examined at 1 of 3 participating centers at the time of initial evaluation of elevated BP. Black children were categorized as African American (AA) and nonblack children as non-AA. Comparisons were made for the entire group and after stratification according to age (<13 or ≥ 13 years)., Results: Overall, children categorized as AA had a higher prevalence of overweight/obesity and left ventricular hypertrophy and had higher plasma renin activity than children who were categorized as non-AA. After age stratification, these differences remained only in the children younger than 13 years old; there were no differences in these findings among children aged 13 years or older. AA children who were aged 13 years or older, however, had higher BPs for both casual and ambulatory measurements. Specifically, they had higher casual diastolic BP, higher 24-hour diastolic BP, higher daytime systolic and diastolic BP, and higher BP loads at night and over a 24-hour period compared with non-AA children who were aged 13 years or older., Conclusions: These data indicate that black children with primary hypertension may be at increased cardiovascular risk compared with nonblack children with primary hypertension. However, the high prevalence of overweight/obesity and left ventricular hypertrophy in all youth with primary hypertension demonstrates the need for greater preventive and therapeutic efforts aimed at reducing cardiovascular risk in this vulnerable population.

Background: In the early highly active antiretroviral therapy (HAART) era, kidney dysfunction was strongly associated with death among HIV-infected individuals. We re-examined this association in the later HAART period to determine whether chronic kidney disease remains a predictor of death after HAART initiation., Methods: To evaluate the effect of kidney function at the time of HAART initiation on time to all-cause mortality, we evaluated 1415 HIV-infected women initiating HAART in the Women's Interagency HIV Study. Multivariable proportional hazards models with survival times calculated from HAART initiation to death were constructed; participants were censored at the time of the last available visit or December 31, 2006., Results: Chronic kidney disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m) at HAART initiation was associated with higher mortality risk adjusting for age, race, hepatitis C serostatus, AIDS history, and CD4 cell count (hazard ratio 2.23, 95% confidence interval: 1.45-3.43). Adjustment for hypertension and diabetes history attenuated this association (hazard ratio = 1.89, confidence interval: 0.94-3.80). Lower kidney function at HAART initiation was weakly associated with increased mortality risk in women with prior AIDS (hazard ratio = 1.09, confidence interval: 1.00-1.19, per 20% decrease in estimated glomerular filtration rate)., Conclusions: Kidney function at HAART initiation remains an independent predictor of death in HIV-infected individuals, especially in those with a history of AIDS. Our study emphasizes the necessity of monitoring kidney function in this population. Additional studies are needed to determine mechanisms underlying the increased mortality risk associated with chronic kidney disease in HIV-infected persons.

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 is 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 using questionnaires at baseline and year 1., Outcomes & Measurements: Primary outcomes were all-cause and cardiovascular mortality, analyzed using Cox regression adjusted for demographic, clinical, and treatment characteristics. Secondary outcomes were QOL, inflammation (C-reactive protein and interleukin 6 levels), and erythropoietin (EPO) requirements., Results: 617 of 734 (84%) participants reported urine output at baseline, and 163 of 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 (HR, 0.70; 95% CI, 0.52-0.93; P = 0.02) and a trend toward lower cardiovascular 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 C-reactive protein (P = 0.02) and interleukin 6 (P = 0.03) levels. Importantly, EPO dose was 12,000 U/wk 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 agreed 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. The development of methods to assess and preserve RKF is important and may improve dialysis care., (Copyright (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Anaemia worsens as kidney function declines. Both conditions are associated with increased mortality. Serum cystatin C is purportedly a more sensitive marker of kidney disease and a better predictor of mortality than serum creatinine. However, studies suggest that extrarenal factors also influence cystatin C levels., Methods: We determined whether estimates of glomerular filtration rate [estimated glomerular filtration rate (eGFR)] based on serum cystatin C alone or in combination with serum creatinine were superior to those based on serum creatinine in recognizing impaired kidney function in the setting of anaemia in a sub-sample of the Third National Health and Nutrition Examination Survey of the USA consisting of 6734 participants, 20 years or older., Results: The prevalence of moderate to severe kidney disease (eGFR 15-59 mL/min/1.73 m(2)) among anaemic persons was 15-16% when based on serum creatinine alone (eGFR(SCR)) or combined with cystatin C (eGFR(SCR) (+) (CYSC)); this estimate increased to nearly 25% when kidney function was estimated by cystatin C (eGFR(CYSC)). The adjusted odds ratios of kidney disease in anaemic versus non-anaemic persons were slightly higher with eGFR(CYSC) than eGFR(SCR) and eGFR(SCR) (+) (CYSC) in younger adults [odds ratio (OR) = 5.22, 95% confidence interval (CI): 2.23, 12.17], women (OR = 5.34, 95% CI: 2.36, 12.06) and those with elevated C-reactive protein (CRP) (OR = 7.36, 95% CI: 1.98-27.36)., Conclusions: Impaired kidney function was common in individuals with anaemia. Among anaemic individuals, the prevalence estimate for kidney disease was notably higher when kidney function was estimated by cystatin C alone compared with the estimations by serum creatinine alone or in combination with serum cystatin C. eGFR(CYSC) may be particularly helpful in identifying kidney disease in the setting of anaemia among younger persons, women and those with elevated CRP. Regardless of which renal biomarker is used, our study suggests that an evaluation for underlying kidney disease should be considered in the standard workup of anaemia.

There have been no studies in pediatric dialysis patients to evaluate the impact of higher estimated glomerular filtration rate (eGFR) at dialysis initiation on clinical outcomes. Baseline clinical and demographic information was collected for children aged 1-18 years undergoing incident dialysis from 1995-2002 within the United States Renal Data System. Baseline eGFRs calculated by the Schwartz formula were categorized as high (>15 ml/min/1.73 m(2)) or low (< or = 15 ml/min/1.73 m(2)). We determined predictors of eGFR at baseline, and associations between baseline eGFR and subsequent hospitalization for hypertension (HTN) or pulmonary edema (PE) in a longitudinal nonconcurrent pediatric end-stage renal disease (ESRD) cohort. Twenty percent of children had a high eGFR at initiation. Black children were less likely to initiate dialysis with a high eGFR [adjusted odds ratio (adjOR) 0.71, p < 0.001]. Girls were less likely to have a high eGFR at baseline (adjOR 0.71, p < 0.001). Children who received predialysis erythropoietin therapy were more likely to start dialysis with a high eGFR (adjOR 6.67, p < 0.001). Children with higher baseline eGFR were found to have a 21% decreased risk of hospitalization [adjusted hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.65-0.96, p = 0.02]. It is not known whether this clinical benefit will result in decreased mortality and complication rates from cardiovascular disease.

Objective: The goal was to determine patient-, provider-, and clinic-level predictors of unrecognized elevated blood pressure (BP) in children. We hypothesized that being of healthy weight, having a BP of <120/80 mmHg, and being seen by a less experienced provider would result in decreased recognition., Methods: A cross-sectional study of clinic visits for children 3 to 20 years of age at an urban, pediatric primary care practice between January 1, 2006, and June 30, 2006, was performed. Children with elevated systolic or diastolic BP (> or = 90th percentile or > or = 120/80 mmHg) were included. Recognition was defined as having any of the following documented: repeat BP measurement, elevated-BP/hypertension diagnosis, plan to recheck BP, or initiation of hypertension evaluation. Multivariate logistic regression analysis was used to identify characteristics associated with underrecognition., Results: Elevated BP occurred in 779 (39%) of 2000 visits. Of 726 cases included in the analysis, 87% were not recognized by providers. Patient-level predictors of underrecognition included systolic BP of <120 mmHg (odds ratio: 7.7 [95% confidence interval: 3.2-18.6]), diastolic BP of <80 mmHg (odds ratio: 2.4 [95% confidence interval: 1.1-5.0]), decreasing BMI z score, male gender, older age, lack of family history of cardiovascular disease, and negative medical history findings. Being seen by a nurse practitioner and being seen by a less-experienced provider also were significant predictors., Conclusions: Most BP elevations were not recognized by providers. Poor recognition was most influenced by the absence of obviously elevated BP, obesity, and family history of cardiovascular disease.

Purpose of Review: To provide a brief review of methods used in genetic epidemiology studies, an update of recent significant findings in genome-wide studies of kidney disease, and a discussion of the clinical implications of these findings., Recent Findings: Recent developments in genetic epidemiology methodologies, specifically the use of genome-wide panels of single nucleotide polymporphisms (SNPs) for association analyses, have yielded exciting insights into the underlying pathogenesis of chronic kidney disease and its progression. The two most notable and promising genetic discoveries are those of MYH9 and UMOD, both of which have been replicated in separate populations., Summary: Genomic studies have the potential to yield exciting new areas of biological research, potential targets for treatment, and ultimately markers of disease risk. This review addresses recent genetic studies and their implications in chronic kidney disease care.

Recent breakthroughs in genomics have led to a critical reappraisal of factors once thought to initiate common complex forms of kidney disease. The tenet that diabetes mellitus and hypertension routinely initiate kidney disease whenever blood glucose concentrations or systemic blood pressures reach critical levels for prolonged periods is falling from favor, although it remains important to control hypertension and hyperglycemia to slow nephropathy progression and to prevent cardiovascular disease. Many patients with systemic diseases that potentially may involve their kidneys never develop nephropathy. In addition, severe forms of several common kidney diseases cluster tightly in families. This article discusses the existence of differential nephropathy susceptibility based on an individual's genetic make-up, in the context of environmental exposures. Novel genetic analysis methods and recently identified major kidney disease susceptibility genes are discussed, including novel perspectives for categorizing complex forms of nephropathy based on the expanding spectrum of non-muscle myosin heavy chain 9 gene-associated disease. Genetic screening, gene-environment, and gene-gene interactions are also addressed.

Background: Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations., Methods: Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM., Results: Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies., Conclusions: The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

Background: Apolipoprotein E polymorphisms (APOE) have been associated with lowered glomerular filtration rate (GFR) and chronic kidney disease (CKD) with e2 allele conferring risk and e4 providing protection. However, few data are available in non-European ethnic groups or in a population-based cohort., Methods: The authors analyzed 5,583 individuals from the Third National Health and Nutrition Examination Survey (NHANES III) to determine association with estimated GFR by the Modification of Diet in Renal Disease (MDRD) equation and low-GFR cases. Low-GFR cases were defined as GFR <75 ml/min/1.73 m2; additionally, GFR was analyzed continuously., Results: In univariate analysis, the e4 allele was negatively associated with low-GFR cases in non-Hispanic whites, odds ratio (OR): 0.76, 95% confidence interval (CI): 0.60, 0.97. In whites, there was a significant association between increasing APOE score (indicating greater number of e2 alleles) and higher prevalence of low-GFR cases (OR: 1.21, 95%CI: 1.01, 1.45). Analysis of continuous GFR in whites found the e4 allele was associated with higher levels of continuous GFR (beta-coefficient: 2.57 ml/min/1.73 m2, 95%CI: 0.005, 5.14); in non-Hispanic blacks the e2 allele was associated with lower levels of continuous GFR (beta-coefficient: -3.73 ml/min/1.73 m2, 95%CI: -6.61, -0.84). APOE e2 and e4 alleles were rare and not associated with low-GFR cases or continuous GFR in Mexican Americans., Conclusion: In conclusion, the authors observed a weak association between the APOE e4 allele and low-GFR cases and continuous GFR in non-Hispanic whites, and the APOE e2 allele and continuous GFR in non-Hispanic blacks, but found no association with either measure of kidney function in Mexican Americans. Larger studies including multiethnic groups are needed to determine the significance of this association.

Background and Objectives: Peripheral vascular disease (PVD) is prevalent among dialysis patients, and many dialysis patients undergo PVD-related procedures. We aimed to examine the risk factors for and prognosis after such procedures in the dialysis setting., Design, Setting, Participants, & Measurements: In a national prospective cohort study of 1041 incident dialysis patients, we examined the factors that are associated with PVD procedures (lower extremity amputations and bypasses) after the start of dialysis. Adjusted risk for PVD procedures of various factors was estimated using multivariable Cox proportional hazards models. Incidence rates of subsequent cardiovascular events, infectious hospitalizations, PVD- and cardiovascular disease-related mortality, and all-cause mortality were compared for those with and without a PVD procedure., Results: Overall, 217 (21%) patients underwent a PVD procedure after the start of dialysis. For those without diabetes, only PVD history (relative hazard [RH] 2.9; 95% confidence interval [CI] 1.3 to 6.6) and increased fibrinogen (RH 1.2; 95% CI 1.0 to 1.5) predicted PVD procedures. For those with diabetes, increased serum phosphate (RH 1.2; 95% CI 1.1 to 1.4), along with decreased albumin, increased C-reactive protein and fibrinogen, and lower SBP, was associated with risk for PVD procedures. Of those who had a procedure compared with those who did not, 68 versus 30% experienced a subsequent cardiovascular event, 85 versus 66% an infectious hospitalization, 11 versus 2% a PVD-related death, and 81 versus 59% all-cause death (mean follow-up 3.0 yr)., Conclusions: Prognosis after PVD procedures is poor, and providers should be aware that risk factors for PVD procedures may differ by diabetes status.

Background: Stroke is the third most common cause of cardiovascular disease death in patients on dialysis therapy; however, characteristics of cerebrovascular disease, including clinical subtypes and subsequent consequences, have not been well described., Study Design: Prospective national cohort study, the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study., Settings & Participants: 1,041 incident dialysis patients treated in 81 clinics enrolled from October 1995 to July 1998, followed up until December 31, 2004., Predictor: Time from dialysis therapy initiation., Outcomes & Measurements: Cerebrovascular disease events were defined as nonfatal (hospitalized stroke and carotid endarterectomy) and fatal (stroke death) events after dialysis therapy initiation. Stroke subtypes were classified by using standardized criteria from the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) system. The incidence of cerebrovascular event subtypes was analyzed by using time-to-event analyses accounting for competing risk of death. Clinical outcomes after stroke were abstracted from medical records., Results: 165 participants experienced a cerebrovascular event with an overall incidence of 4.9 events/100 person-years. Ischemic stroke was the most common (76% of all 200 events), with cardioembolism subtype accounting for 28% of the 95 abstracted ischemic events. Median time from onset of symptoms to first stroke evaluation was 8.5 hours (25th and 75th percentiles, 1 and 42), with only 56% of patients successfully escaping death, nursing home, or skilled nursing facility., Limitations: Relatively small sample size limits power to determine risk factors., Conclusions: Cerebrovascular disease is common in dialysis patients, is identified late, and carries a significant risk of morbidity and mortality. Stroke etiologic subtypes on dialysis therapy are multifactorial, suggesting risk factors may change the longer one has end-stage renal disease. Additional studies are needed to address the poor prognosis through prevention, early identification, and treatment.

Deaths of participants and losses to follow-up pose challenges for defining outcomes in epidemiologic studies. The authors compared several definitions of incident chronic kidney disease (CKD) in terms of incidence, agreement, and risk factor associations. They used data from 14,873 participants in the community-based, multicenter, biracial Atherosclerosis Risk in Communities Study (1987-1999). The estimated glomerular filtration rate (eGFR) was based on serum creatinine at baseline and the 3- and 9-year follow-up visits. Hospitalizations were ascertained continuously. The authors compared 4 definitions of incident CKD: 1) low eGFR (<60 mL/minute/1.73 m(2)); 2) low and declining (> or =25%) eGFR; 3) an increase in serum creatinine (> or =0.4 mg/dL) at 3- or 9-year follow-ups; and 4) CKD-related hospitalization or death. From these definitions, they identified 1,086, 677, 457, and 163 cases, respectively. There was relatively good agreement among definitions 1-3, but definition 4 identified mostly different cases. Risk factor associations were consistent across definitions for hypertension and lipids. Diabetes showed weaker associations with definition 1 (incidence rate ratio = 1.5, 95% confidence interval: 1.2, 1.7) than with definition 4 (incidence rate ratio = 6.3, confidence interval: 4.4, 8.9). Associations with gender differed in direction and magnitude across definitions. Case definition can impact relative risk estimates for CKD risk factors.

Background: Clinical practice guidelines were established to improve the diagnosis and management of chronic kidney disease (CKD), but the extent, determinants, and cost implications of guideline adherence and variation in adherence have not been evaluated., Study Design: Cross-sectional survey., Settings & Participants: The questionnaire was sent (on paper or through the internet) to a nationally representative sample of 1,200 US primary care physicians and nephrologists., Predictor: Provider and patient characteristics., Outcomes & Measurements: Guideline adherence was assessed as present if physicians recommended at least 5 of 6 clinical tests prescribed by the National Kidney Foundation's Kidney Disease Outcomes and Quality Initiative guidelines for a hypothetical patient with newly identified CKD. We also assessed patterns and costs of additional nonrecommended tests for the initial clinical evaluation of CKD., Results: Of the 301 (86 family medicine, 89 internal medicine, and 126 nephrology) eligible physicians who responded to the survey (response rate, 32%), most practiced longer than 10 years (54%), were in nonacademic practices (76%), spent greater than 80% of their time performing clinical duties (77%), and correctly estimated kidney function (73%). Overall, 35% of participants were guideline adherent. Compared with nephrologists, internal medicine and family physicians had lower odds of adherence for all recommended testing (odds ratio, 0.6; 95% confidence interval, 0.3 to 1.1; and odds ratio, 0.3; 95% confidence interval, 0.1 to 0.6, respectively). Participants practicing longer than 10 years had lower odds of ordering all recommended testing compared with participants practicing fewer than 10 years (odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9). Eighty-five percent of participants recommended additional tests, which resulted in a 23% increased total per-patient cost of the clinical evaluation., Limitations: Recommendations for a hypothetical case scenario may differ from those of actual patients., Conclusions: Adherence to recommended clinical testing for the diagnosis and management of CKD was poor, and additional testing was associated with substantially increased cost of the clinical evaluation. Improved clarity, dissemination, and uptake of existing guidelines are needed to improve quality and decrease costs of care for patients with CKD.

Background: Increasing evidence supports a role for cell-mediated immunity in the pathogenesis of cardiovascular disease. Single-nucleotide polymorphisms (SNPs) in JAK3, STAT4, and STAT6 of the Janus kinase-signal transducer and activator of transcription (Jak-Stat) signal transduction pathway were examined for association with time to new cardiovascular events in incident dialysis patients from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Study., Study Design: Prospective cohort study., Setting & Participants: 764 white (n = 518) and black (n = 246) participants from 79 dialysis centers., Predictor: SNPs in JAK3, STAT4, and STAT6 selected using a pairwise approach to identify a maximally informative set of tag SNPs for populations of European and African descent., Outcomes & Measurements: Cox proportional hazards models were used to estimate unadjusted and multivariable-adjusted hazard ratios (HRs) for incident cardiovascular disease events after dialysis therapy initiation associated with each race-specific SNP., Results: 2 European tag SNPs (rs3212780 and rs3213409) in JAK3 were associated with new cardiovascular disease events in white patients with unadjusted HRs of 1.92 (P < 0.001) and 1.82 (P = 0.07), respectively. One dual-tag SNP (rs3212752) in JAK3 was associated with new cardiovascular events in white patients with an unadjusted HR of 2.09 (P < 0.001) and in black patients with an HR of 2.07 (P = 0.007). SNP rs3213409 codes for a valine to isoleucine change at amino acid 722, a potentially functional mutation. SNPs in STAT4 and STAT6 were not associated with cardiovascular events after the initiation of dialysis therapy., Limitations: This study does not provide direct evidence for the mechanism of increased risk. Replication in independent cohorts is necessary., Conclusions: Genetic polymorphisms in the Jak-Stat signaling pathway are associated with an increased risk of new cardiovascular events in incident dialysis patients.

The prevalence of obesity (body mass index (BMI) > or =30 kg/m(2)) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (rho = -0.042, P = 1.6x10(-7)). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = -3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = -4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI., Competing Interests: The authors have declared that no competing interests exist.

Women have less access to kidney transplantation than men, but the contributions of age and comorbidity to this disparity are largely unknown. We conducted a national cohort study of 563,197 patients with first-onset ESRD between 2000 and 2005. We used multivariate generalized linear models to evaluate both access to transplantation (ATT), defined as either registration for the deceased-donor waiting list or receiving a live-donor transplant, and survival benefit from transplantation, defined as the relative rate of survival after transplantation compared with the rate of survival on dialysis. We compared relative risks (RRs) between women and men, stratified by age categories and the presence of common comorbidities. Overall, women had 11% less ATT than men. When the model was stratified by age, 18- to 45-yr-old women had equivalent ATT to men (RR 1.01), but with increasing age, ATT for women declined dramatically, reaching a RR of 0.41 for those who were older than 75 yr, despite equivalent survival benefits from transplantation between men and women in all age subgroups. Furthermore, ATT for women with comorbidities was lower than that for men with the same comorbidities, again despite similar survival benefits from transplantation. This study suggests that there is no disparity in ATT for women in general but rather a marked disparity in ATT for older women and women with comorbidities. These disparities exist despite similar survival benefits from transplantation for men and women regardless of age or comorbidities.

Thiazides, recommended as first-line antihypertensive therapy, are associated with an increased risk of diabetes. Thiazides also lower serum potassium. To determine whether thiazide-induced diabetes is mediated by changes in potassium, we analyzed data from 3790 nondiabetic participants in the Systolic Hypertension in Elderly Program, a randomized clinical trial of isolated systolic hypertension in individuals aged >or=60 years treated with chlorthalidone or placebo. Incident diabetes was defined by self-report, antidiabetic medication use, fasting glucose >or=126 mg/dL, or random glucose >or=200 mg/dL. The mediating variable was change in serum potassium during year 1. Of the 459 incident cases of diabetes during follow-up, 42% occurred during year 1. In year 1, the unadjusted incidence rates of diabetes per 100 person-years were 6.1 and 3.0 in the chlorthalidone and placebo groups, respectively. In year 1, the adjusted diabetes risk (hazard ratio) with chlorthalidone was 2.07 (95% CI: 1.51 to 2.83; P<0.001). After adjustment for change in serum potassium, the risk was significantly reduced (hazard ratio: 1.54; 95% CI: 1.09 to 2.17; P=0.01); the extent of risk attenuation (41%; 95% CI: 34% to 49%) was consistent with a mediating effect. Each 0.5-mEq/L decrease in serum potassium was independently associated with a 45% higher adjusted diabetes risk (95% CI: 24% to 70%; P<0.001). After year 1, chlorthalidone use was not associated with increased diabetes risk. In conclusion, thiazide-induced diabetes occurs early after initiating treatment and appears to be mediated by changes in serum potassium. Potassium supplementation might prevent thiazide-induced diabetes. This hypothesis can and should be tested in a randomized trial.

Despite the frequency of cardiovascular death in dialysis patients, few studies have prospectively measured sudden cardiac death in these individuals. Here, we sought to determine the frequency of sudden cardiac death and its association with inflammation and other risk factors among the CHOICE (Choices for Healthy Outcomes In Caring for ESRD) cohort of 1,041 incident dialysis patients. Sudden cardiac death was defined as that occurring outside of the hospital with an underlying cardiac cause from death certificate data. Over a median 2.5 years of follow-up, 22% of all mortality in this cohort was due to sudden cardiac death. Using Cox proportional hazards, we found that the highest tertiles of high-sensitivity C-reactive protein and of IL-6 were each associated with twice the risk of sudden cardiac death compared to their lowest tertiles when adjusted for demographics, comorbidities and laboratory factors. A decrement in serum albumin was associated with a 1.35 times increased risk for sudden cardiac death in the highest compared to the lowest tertile. These findings were robust and consistent when accounting for competing risks of death from other causes. Hence, we found that sudden cardiac death is common among patients with end stage renal disease and that inflammation and malnutrition significantly increased its occurrence independent of traditional cardiovascular risk factors.

As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 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% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.

To characterize the distribution of blood pressure (BP), prevalence, and risk factors for hypertension in pediatric chronic kidney disease, we conducted a cross-sectional analysis of baseline BPs in 432 children (mean age 11 years; 60% male; mean glomerular filtration rate 44 mL/min per 1.73 m(2)) enrolled in the Chronic Kidney Disease in Children cohort study. BPs were obtained using an aneroid sphygmomanometer. Glomerular filtration rate was measured by iohexol disappearance. Elevated BP was defined as BP >or=90th percentile for age, gender, and height. Hypertension was defined as BP >or=95th percentile or as self-reported hypertension plus current treatment with antihypertensive medications. For systolic BP, 14% were hypertensive and 11% were prehypertensive (BP 90th to 95th percentile); 68% of subjects with elevated systolic BP were taking antihypertensive medications. For diastolic BP, 14% were hypertensive and 9% were prehypertensive; 53% of subjects with elevated diastolic BP were taking antihypertensive medications. Fifty-four percent of subjects had either systolic or diastolic BP >or=95th percentile or a history of hypertension plus current antihypertensive use. Characteristics associated with elevated BP included black race, shorter duration of chronic kidney disease, absence of antihypertensive medication use, and elevated serum potassium. Among subjects receiving antihypertensive treatment, uncontrolled BP was associated with male sex, shorter chronic kidney disease duration, and absence of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. Thirty-seven percent of children with chronic kidney disease had either elevated systolic or diastolic BP, and 39% of these were not receiving antihypertensives, indicating that hypertension in pediatric chronic kidney disease may be frequently under- or even untreated. Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may improve BP control in these patients.

Background: There has been controversy about the utility of new third-generation parathyroid hormone (PTH) assays measuring only 1-84 PTH, with few large studies comparing second- and third-generation PTH measurements in patients with ESRD., Methods: We measured 1-84 PTH ('biointact' or 'whole' PTH) and total PTH ('intact' PTH) in a national cohort of 515 incident dialysis patients from banked frozen EDTA plasma (median follow-up, 35 months) and examined the accuracy of estimating 1-84 PTH from total PTH and the associations of these levels with patient characteristics and mortality., Results: The 1-84 PTH and total PTH levels were closely correlated. Higher 1-84 PTH was associated with African-American race and higher serum phosphate and lower calcium levels. The percentage of total PTH represented by 1-84 PTH was, on average, 53%, but with a wide range (25-89%). Calculating 1-84 PTH from total PTH using a proposed standard conversion factor (54%) led to misclassification of 8% of the population compared with measured 1-84 PTH. In a multivariate Cox proportional hazards model for all-cause mortality, a 1-84 PTH value >160 pg/ml was associated with increased risk of mortality (HR = 1.62, 95% CI, 1.03-2.54) compared to a level of 80-160 pg/ml. Elevated total PTH, 7-84 PTH and the 1-84 PTH/7-84 PTH ratio were not significantly associated with mortality., Conclusions: The 1-84 PTH and total PTH are highly correlated. Elevated 1-84 PTH was significantly associated with increased mortality, whereas total PTH did not reach statistical significance. Thus, although in other respect they are similar, there may be utility in measuring 1-84 PTH for its associations with mortality.

Objective: Diabetic nephropathy, the most common cause of end-stage renal disease, aggregates in families and specific ethnic groups. Deconstructing diabetic nephropathy into intermediate, quantitative phenotypes may increase feasibility of detecting susceptibility loci by genetic screens. Glomerular filtration rate (GFR), which characterizes diabetic nephropathy, was employed as a quantitative trait in a preliminary whole-genome scan., Research Design and Methods: Estimated GFR (eGFR) was calculated for 882 diabetic sibpairs (mean age 57 years) of African-American (25.6% of total), American Indian (8.6%), European-American (14.2%), and Mexican-American (51.6%) descent enrolled in the initial phase of the Family Investigation of Nephropathy and Diabetes (FIND). A whole-genome scan was performed using 404 microsatellite markers (average spacing 9 cM) and model-free linkage analysis., Results: For all ethnicities combined, strong evidence for linkage was observed on chromosomes 1q43 (P = 3.6 x 10(-3)), 7q36.1 (P = 2.1 x 10(-4)), 8q13.3 (P = 4.6 x 10(-4)), and 18q23.3 (P = 2.7 x 10(-3)). Mexican-American families, who comprised the major ethnic subpopulation in FIND, contributed to linkage on chromosomes 1q43, 2p13.3, 7q36.1, 8q13.3, and 18q23.3, whereas African-American and American-Indian families displayed linkage peaks on chromosomes 11p15.1 and 15q22.3, respectively., Conclusions: We have demonstrated multiple chromosomal regions linked to eGFR in a multi-ethnic collection of families ascertained by a proband with diabetic nephropathy. Identification of genetic variants within these loci that are responsible for the linkage signals could lead to predictive tests or novel therapies for subsets of patients at risk for diabetic nephropathy.

Background and Objectives: This study investigated the effect of long-term storage at -70 degrees C on urinary albumin, protein, and creatinine measurements in the Family Investigation of Nephropathy and Diabetes, a multicenter study designed to identify genes for diabetic nephropathy., Design, Setting, Participants, & Measurements: Spot urine samples were collected at eight centers and shipped overnight on ice packs to a central laboratory. Samples were aliquotted and frozen at -70 degrees C for a median of 8 d before initial assay. As part of quality control procedures to determine interassay variability, 351 replicate samples were retrieved from storage at -70 degrees C after a median storage time between original and quality control analyses of 126 d (range 28 to 869 d). Freezer time was characterized as the difference in days between the initial assay and quality control assay. Percentage difference [(quality control - original/original) x 100%] between samples was regressed on storage time and adjusted for original value, age, race, gender, hypertension, and diabetes., Results: After adjustment, freezer time per 30 d was associated with small decreases in percentage difference of urinary albumin (0.25%, P = 0.02), total protein (0.23%, P = 0.02), and albumin-to-creatinine ratio (0.34%, P = 0.001). Urinary creatinine levels were not affected by freezer time (P = 0.25)., Conclusions: Measurements of urinary albumin, total protein, and albumin-to-creatinine ratio are minimally affected by storage at -70 degrees C for approximately 2.5 yr. Prolonged storage results in small decreases of urinary albumin and protein that do not substantially affect phenotype classification of overt renal disease.

The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers. Model-free linkage analyses, using a dichotomous definition for diabetic nephropathy in 397 sibling pairs, as well as the quantitative trait urinary albumin-to-creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the diabetic nephropathy trait was on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3. In ACR (883 diabetic sibling pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1, and 15q26.3. These results confirm regions of linkage to diabetic nephropathy on chromosomes 7q, 10p, and 18q from prior reports, making it important that genes underlying these peaks be evaluated for their contribution to nephropathy susceptibility. Large family collections consisting of multiple members with diabetes and advanced nephropathy are likely to accelerate the identification of genes causing diabetic nephropathy, a life-threatening complication of diabetes.

Although for most children the process of atherosclerosis is subclinical, dramatically accelerated atherosclerosis occurs in some pediatric disease states, with clinical coronary events occurring in childhood and very early adult life. As with most scientific statements about children and the future risk for cardiovascular disease, there are no randomized trials documenting the effects of risk reduction on hard clinical outcomes. A growing body of literature, however, identifies the importance of premature cardiovascular disease in the course of certain pediatric diagnoses and addresses the response to risk factor reduction. For this scientific statement, a panel of experts reviewed what is known about very premature cardiovascular disease in 8 high-risk pediatric diagnoses and, from the science base, developed practical recommendations for management of cardiovascular risk.

Although for most children the process of atherosclerosis is subclinical, dramatically accelerated atherosclerosis occurs in some pediatric disease states, with clinical coronary events occurring in childhood and very early adult life. As with most scientific statements about children and the future risk for cardiovascular disease, there are no randomized trials documenting the effects of risk reduction on hard clinical outcomes. A growing body of literature, however, identifies the importance of premature cardiovascular disease in the course of certain pediatric diagnoses and addresses the response to risk factor reduction. For this scientific statement, a panel of experts reviewed what is known about very premature cardiovascular disease in 8 high-risk pediatric diagnoses and, from the science base, developed practical recommendations for management of cardiovascular risk.

Background: Atherosclerotic cardiovascular disease (ASCVD) is increasing in incidence in persons with human immunodeficiency virus (HIV). It is not known whether the morbidity and mortality rate of ASCVD is similarly increasing among patients with HIV end-stage renal disease (ESRD), who are living longer since the initiation of newer therapeutic regimens in 1997., Methods: We conducted a population-based study of 8,312 HIV ESRD patients enrolled in the US Renal Data System from 1987 to 2001. We determined the incidence of fatal and nonfatal ASCVD events stratified by date of dialysis therapy initiation., Results: There were 3,112 HIV ESRD patients (77.9% men; mean age, 39.6 +/- 9.6 years) who initiated dialysis therapy before 1997 and 2,371 patients (71.5% men; mean age, 41.3 +/- 9.7 years) who initiated dialysis therapy after 1997. Cumulative incidences of ASCVD for those initiating dialysis therapy before 1997 compared with after 1997 were 10.6% versus 13.5% at 12 months, 18.8% versus 27.6% at 24 months, 26.2% versus 42.4% at 36 months, and 33.7% versus 65.9% at 48 months (P < 0.0001 by log rank). Those who initiated dialysis therapy after 1997 had a greater risk for developing ASCVD (adjusted hazard ratio, 1.57; 95% confidence interval, 1.29 to 1.92) than those who initiated dialysis therapy before 1997 after adjusting for demographics and ASCVD risk factors., Conclusion: There is an increased risk for ASCVD in patients with HIV who initiated dialysis therapy after 1997. This may reflect the long-term complications of multidrug regimens, as well as improved survival from these regimens leading to prolonged exposure to ASCVD risk factors.

It is unknown whether patient-physician discussion about live kidney transplantation (LT) among African Americans (AA) is affected by preferences, knowledge and family discussions regarding LT. We recruited 182 AA dialysis patients and their families and assessed the relation of preferences, knowledge and family discussions regarding LT to the occurrence of patient-physician discussion using multivariable logistic regression. Most patients (76%) desired a transplant, and most patients (93%), spouses (91%) and children (88%) had knowledge of LT. Nearly half of the families discussed transplantation. Only 68% of patients and less than half of their spouses (41%) and children (31%) had discussed transplantation with physicians. Patient-physician discussion was more common among patients: whose spouses acknowledged their interest in transplantation (adjusted odds ratio (AOR) (95% CI):3.5 (1.61-7.8)); who discussed transplantation with spouses (AOR(95% CI):5.25 (2.22-12.41)); whose spouses agreed that they discussed transplantation with patients (AOR (95%CI):5.20 (1.76-15.37)) and whose children discussed transplantation with patients' physicians (AOR (95%CI):7.4 (1.3-40.0)). Universal patient-physician discussion of LT does not occur despite patient preferences. Rates of family-physician discussions are low, and rates of family discussions vary. Early family-physician discussion of LT, use of allied health professionals to promote family discussion of LT and the institution of culturally appropriate programs to enhance discussion of LT in AA families could improve rates of discussion and enhance patients' access to LT.

White individuals who are on dialysis experience much higher overall and cardiovascular mortality rates than black individuals despite a more favorable risk factor profile, but the incidence of nonfatal cardiovascular disease (CVD) to this racial disparity has not been well studied. A longitudinal study of 16,103 people who had ESRD and were enrolled in the United Renal Data System from 1993 to 1996 was conducted. The incidence of new and recurrent atherosclerotic CVD (ASCVD) events was determined using Medicare claims for hospitalizations and mortality among blacks and whites, stratified by ASCVD at baseline. ASCVD was defined as coronary heart disease, peripheral vascular disease, and cerebrovascular disease. Incidence of new ASCVD in people without ASCVD at baseline was 146.9 per 1000 person-years in whites and 118.7 per 1000 person-years in blacks. Incidence of recurrent ASCVD was 404.1 per 1000 person-years in whites and 317.5 per 1000 person-years in blacks. Whites were 1.35 (95% confidence interval, 1.18 to 1.55) times more likely to develop incident ASCVD compared with blacks and 1.25 (95% confidence interval, 1.14 to 1.36) times more likely to develop recurrent disease after adjusting for traditional CVD and dialysis-related risk factors. Excess risk for recurrent ASCVD in whites compared with blacks was consistently present no matter the duration of dialysis: Hazard ratio 1.42 for 0 to 6 mo and 1.40 for 6 to 12 mo. Whites who are treated with dialysis have a higher incidence of ASCVD than blacks who are on dialysis, both new and recurrent. Although differences in survival before the initiation of dialysis may contribute to the observed difference in ASCVD risk, it is not explained by baseline traditional and dialysis-related ASCVD risk factors.

Mortality from end-stage renal disease (ESRD) is often due to cardiac causes. Although cardiovascular complications of ESRD have long been recognized, only recently has the presence of traditional cardiovascular risk factors been associated with late cardiovascular complications. This review presents a history of cardiac involvement in ESRD, the pathophysiology of accelerated atherosclerosis and left ventricular hypertrophy, and a summary of the literature on cardiovascular risk assessment in children. Techniques for non-invasive assessment of cardiac end-organ injury are also discussed. Recommendations for monitoring of risk factors and treatment in the pediatric ESRD population are presented.

Chronic renal failure is, fortunately, an unusual occurrence in children; however, many children with various underlying illnesses develop acute renal failure, and transiently require renal replacement therapy - peritoneal dialysis, intermittent hemodialysis (IHD), or continuous renal replacement therapy (CRRT). As children with acute and chronic renal failure often have multiple comorbid conditions requiring drug therapy, generalists, intensivists, nephrologists, and pharmacists need to be aware of the issues surrounding the management of drug therapy in pediatric patients undergoing renal replacement therapy. This article summarizes the pharmacokinetics and dosing of many drugs commonly prescribed for pediatric patients, and focuses on the management of drug therapy in pediatric patients undergoing IHD and CRRT in the intensive care unit setting. Peritoneal dialysis is not considered in this review. Finally, a summary table with recommended initial dosages for drugs commonly encountered in pediatric patients requiring IHD or CRRT is presented.

Growth in children with chronic renal failure caused by polyuric, salt-wasting diseases may be hampered if ongoing sodium and water losses are not corrected. Twenty-four children were treated with polyuric chronic renal insufficiency (CRI; creatinine clearance <65 ml/min per 1.73 m(2)) with low-caloric-density, high-volume, sodium-supplemented feedings. Subsequent growth was compared with that of children in two control groups: a national historic population control from the US Renal Data System database (n = 42), and a literature control (n = 12). Members of the three groups were 81 to 96% white, and 58 to 70% were boys. Obstructive uropathy and dysplasia were the cause of CRI in 92% of the treatment group, 75% of the literature control group, and 30% of the population control group. Treatment effect was assessed in a multivariate, retrospective analysis of the height standard deviation score (SDS), simultaneously controlling for the severity of disease by renal replacement therapy, primary cause of CRI, and initial height SDS. The change in SDS (Delta SDS) for height by regression analysis at 1 yr was significantly greater by +1.37 in the treatment group versus the population control (P = 0.017). The 2-yr height Delta SDS by regression analysis adjusted for creatinine clearance was significantly greater by +1.83 in the treatment group versus the literature control (P = 0.003). Nutritional support with sodium and water supplementation can maintain or improve the growth of children with polyuric, salt-wasting CRI. This inexpensive intervention may delay the need for renal replacement therapy, growth hormone treatment, or both in many of these children and may be used in any clinical setting.