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Rationale & Objective: Plasma kidney injury molecule 1 (KIM-1) is a sensitive marker of proximal tubule injury, but its association with risks of adverse clinical outcomes across a spectrum of kidney diseases is unknown., Study Design: Prospective, observational cohort study., Setting & Participants: 524 individuals enrolled into the Boston Kidney Biopsy Cohort (BKBC) Study undergoing clinically indicated native kidney biopsy with biopsy specimens adjudicated for semiquantitative scores of histopathology by 2 kidney pathologists and 3,800 individuals with common forms of chronic kidney disease (CKD) enrolled into the Chronic Renal Insufficiency Cohort (CRIC) Study., Exposure: Histopathologic lesions and clinicopathologic diagnosis in cross-sectional analyses, baseline plasma KIM-1 levels in prospective analyses., Outcomes: Baseline plasma KIM-1 levels in cross-sectional analyses, kidney failure (defined as initiation of kidney replacement therapy) and death in prospective analyses., Analytical Approach: Multivariable-adjusted linear regression models tested associations of plasma KIM-1 levels with histopathologic lesions and clinicopathologic diagnoses. Cox proportional hazards models tested associations of plasma KIM-1 levels with future kidney failure and death., Results: In the BKBC Study, higher plasma KIM-1 levels were associated with more severe acute tubular injury, tubulointerstitial inflammation, and more severe mesangial expansion after multivariable adjustment. Participants with diabetic nephropathy, glomerulopathies, and tubulointerstitial disease had significantly higher plasma KIM-1 levels after multivariable adjustment. In the BKBC Study, CKD in 124 participants progressed to kidney failure and 85 participants died during a median follow-up time of 5 years. In the CRIC Study, CKD in 1,153 participants progressed to kidney failure and 1,356 participants died during a median follow-up time of 11.5 years. In both cohorts, each doubling of plasma KIM-1 level was associated with an increased risk of kidney failure after multivariable adjustment (hazard ratios of 1.19 [95% CI, 1.03-1.38] and 1.10 [95% CI, 1.06-1.15] for BKBC and CRIC, respectively). There was no statistically significant association of plasma KIM-1 levels with death in either cohort., Limitations: Generalizability and unmeasured confounding., Conclusions: Plasma KIM-1 is associated with underlying tubulointerstitial and mesangial lesions and progression to kidney failure in 2 cohort studies of individuals with kidney diseases., (Copyright © 2021. Published by Elsevier Inc.)

Rationale & Objective: Adults with chronic kidney disease (CKD) may be at increased risk of adverse effects from use of potentially inappropriate medications (PIMs). Our objective was to assess whether PIM exposure has an independent association with CKD progression, hospitalizations, mortality, or falls., Study Design: Retrospective observational study., Setting & Participants: Chronic Renal Insufficiency Cohort (CRIC) study; 3,929 adults with CKD enrolled 2003-2008 and followed prospectively until December 2011., Exposure: PIM exposure was defined as prescriptions for any medications to be avoided in older adults as defined by the 2015 American Geriatrics Society Beers Criteria., Outcome: Hospitalization count, death, a composite kidney disease end point of CKD progression or initiation of kidney replacement therapy (KRT), KRT, and fall events assessed 1 year after PIM exposure., Analytical Approach: Logistic regression and Poisson regression to estimate the associations of PIM exposure with each outcome., Results: The most commonly prescribed PIMs were proton pump inhibitors and α-blockers. In unadjusted models, any PIM exposure (compared to none) was associated with hospitalizations, death, and fall events. After adjustment, exposure to 1, 2, or≥3 PIMs had a graded association with a higher hospitalization rate (rate ratios of 1.09 [95% CI, 1.01-1.17], 1.18 [95% CI, 1.07-1.30], and 1.35 [95% CI, 1.19-1.53], respectively) and higher odds of mortality (odds ratios of 1.19 [95% CI, 0.91-1.54], 1.62 [95% CI, 1.21-2.17], and 1.65 [95% CI, 1.14-2.41], respectively). In a cohort subset reporting falls (n=1,109), prescriptions for≥3 PIMs were associated with an increased risk of falls (adjusted OR, 2.85 [95% CI, 1.54-5.26]). PIMs were not associated with CKD progression or KRT. Age did not modify the association between PIM count and outcomes., Limitations: Measurement bias; confounding by indication., Conclusions: Adults of any age with CKD who are prescribed PIMs have an increased risk of hospitalization, mortality, and falls with the greatest risk occurring after more than 1 PIM prescription., (Published by Elsevier Inc.)

Rationale & Objective: Identification of novel risk factors for chronic kidney disease (CKD) progression may inform mechanistic investigations and improve identification of high-risk subgroups. The current study aimed to characterize CKD progression across levels of numerous risk factors and identify independent risk factors for CKD progression among those with and without diabetes., Study Design: The Chronic Renal Insufficiency Cohort (CRIC) Study is a prospective cohort study of adults with CKD conducted at 7 US clinical centers., Setting & Participants: Participants (N=3,379) had up to 12.3 years of follow-up; 47% had diabetes., Predictors: 30 risk factors for CKD progression across sociodemographic, behavioral, clinical, and biochemical domains at baseline., Outcomes: Study outcomes were estimated glomerular filtration rate (eGFR) slope and the composite of halving of eGFR or initiation of kidney replacement therapy., Analytical Approach: Stepwise selection of independent risk factors was performed stratified by diabetes status using linear mixed-effects and Cox proportional hazards models., Results: Among those without and with diabetes, respectively, mean eGFR slope was-1.4±3.3 and-2.7±4.7mL/min/1.73m 2 per year. Among participants with diabetes, multivariable-adjusted hazard of the composite outcome was approximately 2-fold or greater with higher levels of the inflammatory chemokine CXCL12, the cardiac marker N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the kidney injury marker urinary neutrophil gelatinase-associated lipocalin (NGAL). Among those without diabetes, low serum bicarbonate and higher high-sensitivity troponin T, NT-proBNP, and urinary NGAL levels were all significantly associated with a 1.5-fold or greater rate of the composite outcome., Limitations: The observational study design precludes causal inference., Conclusions: Strong associations for cardiac markers, plasma CXCL12, and urinary NGAL are comparable to that of systolic blood pressure≥140mm Hg, a well-established risk factor for CKD progression. This warrants further investigation into the potential mechanisms that these markers indicate and opportunities to use them to improve risk stratification., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Traditional risk estimates for atherosclerotic vascular disease (ASVD) and death may not perform optimally in the setting of chronic kidney disease (CKD). We sought to determine whether the addition of measures of inflammation and kidney function to traditional estimation tools improves prediction of these events in a diverse cohort of patients with CKD., Study Design: Observational cohort study., Setting & Participants: 2,399 Chronic Renal Insufficiency Cohort (CRIC) Study participants without a history of cardiovascular disease at study entry., Predictors: Baseline plasma levels of biomarkers of inflammation (interleukin 1β [IL-1β], IL-1 receptor antagonist, IL-6, tumor necrosis factor α [TNF-α], transforming growth factor β, high-sensitivity C-reactive protein, fibrinogen, and serum albumin), measures of kidney function (estimated glomerular filtration rate [eGFR] and albuminuria), and the Pooled Cohort Equation probability (PCEP) estimate., Outcomes: Composite of ASVD events (incident myocardial infarction, peripheral arterial disease, and stroke) and death., Analytical Approach: Cox proportional hazard models adjusted for PCEP estimates, albuminuria, and eGFR., Results: During a median follow-up of 7.3 years, 86, 61, 48, and 323 participants experienced myocardial infarction, peripheral arterial disease, stroke, or death, respectively. The 1-decile greater levels of IL-6 (adjusted HR [aHR], 1.12; 95% CI, 1.08-1.16; P<0.001), TNF-α (aHR, 1.09; 95% CI, 1.05-1.13; P<0.001), fibrinogen (aHR, 1.07; 95% CI, 1.03-1.11; P<0.001), and serum albumin (aHR, 0.96; 95% CI, 0.93-0.99; P<0.002) were independently associated with the composite ASVD-death outcome. A composite inflammation score (CIS) incorporating these 4 biomarkers was associated with a graded increase in risk for the composite outcome. The incidence of ASVD-death increased across the quintiles of risk derived from PCEP, kidney function, and CIS. The addition of eGFR, albuminuria, and CIS to PCEP improved (P=0.003) the area under the receiver operating characteristic curve for the composite outcome from 0.68 (95% CI, 0.66-0.71) to 0.73 (95% CI, 0.71-0.76)., Limitations: Data for cardiovascular death were not available., Conclusions: Biomarkers of inflammation and measures of kidney function are independently associated with incident ASVD events and death in patients with CKD. Traditional cardiovascular risk estimates could be improved by adding markers of inflammation and measures of kidney function., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Cardiovascular disease (CVD) is common and overall graft survival is suboptimal among kidney transplant recipients. Although albuminuria is a known risk factor for adverse outcomes among persons with native chronic kidney disease, the relationship of albuminuria with cardiovascular and kidney outcomes in transplant recipients is uncertain., Study Design: Post hoc longitudinal cohort analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial., Setting & Participants: Stable kidney transplant recipients with elevated homocysteine levels from 30 sites in the United States, Canada, and Brazil., Predictor: Urine albumin-creatinine ratio (ACR) at randomization., Outcomes: Allograft failure, CVD, and all-cause death., Analytical Approach: Multivariable Cox models adjusted for age; sex; race; randomized treatment allocation; country; systolic and diastolic blood pressure; history of CVD, diabetes, and hypertension; smoking; cholesterol; body mass index; estimated glomerular filtration rate (eGFR); donor type; transplant vintage; medications; and immunosuppression., Results: Among 3,511 participants with complete data, median ACR was 24 (Q1-Q3, 9-98) mg/g, mean eGFR was 49±18 (standard deviation) mL/min/1.73m 2 , mean age was 52±9 years, and median graft vintage was 4.1 (Q1-Q3, 1.7-7.4) years. There were 1,017 (29%) with ACR < 10mg/g, 912 (26%) with ACR of 10 to 29mg/g, 1,134 (32%) with ACR of 30 to 299mg/g, and 448 (13%) with ACR ≥ 300mg/g. During approximately 4 years, 282 allograft failure events, 497 CVD events, and 407 deaths occurred. Event rates were higher at both lower eGFRs and higher ACR. ACR of 30 to 299 and ≥300mg/g relative to ACR < 10mg/g were independently associated with graft failure (HRs of 3.40 [95% CI, 2.19-5.30] and 9.96 [95% CI, 6.35-15.62], respectively), CVD events (HRs of 1.25 [95% CI, 0.96-1.61] and 1.55 [95% CI, 1.13-2.11], respectively), and all-cause death (HRs of 1.65 [95% CI, 1.23-2.21] and 2.07 [95% CI, 1.46-2.94], respectively)., Limitations: No data for rejection; single ACR assessment., Conclusions: In a large population of stable kidney transplant recipients, elevated baseline ACR is independently associated with allograft failure, CVD, and death. Future studies are needed to evaluate whether reducing albuminuria improves these outcomes., (Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.)

Rationale & Objective: Few studies have examined incident type 2 diabetes mellitus (T2DM) in chronic kidney disease (CKD). Our objective was to examine rates of and risk factors for T2DM in CKD, using several alternative measures of glycemic control., Study Design: Prospective cohort study., Setting & Participants: 1,713 participants with reduced glomerular filtration rates and without diabetes at baseline, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study., Predictors: Measures of kidney function and damage, fasting blood glucose, hemoglobin A 1c (HbA 1c ), HOMA-IR (homeostatic model assessment of insulin resistance), demographics, family history of diabetes mellitus (DM), smoking status, medication use, systolic blood pressure, triglyceride level, high-density lipoprotein cholesterol level, body mass index, and physical activity., Outcome: Incident T2DM (defined as fasting blood glucose ≥ 126mg/dL or prescription of insulin or oral hypoglycemic agents)., Analytical Approach: Concordance between fasting blood glucose and HbA 1c levels was assessed using κ. Cause-specific hazards modeling, treating death and end-stage kidney disease as competing events, was used to predict incident T2DM., Results: Overall T2DM incidence rate was 17.81 cases/1,000 person-years. Concordance between fasting blood glucose and HbA 1c levels was low (κ for categorical versions of fasting blood glucose and HbA 1c  = 13%). Unadjusted associations of measures of kidney function and damage with incident T2DM were nonsignificant (P ≥ 0.4). In multivariable models, T2DM was significantly associated with fasting blood glucose level (P = 0.002) and family history of DM (P = 0.03). The adjusted association of HOMA-IR with T2DM was comparable to that of fasting blood glucose level; the association of HbA 1c level was nonsignificant (P ≥ 0.1). Harrell's C for the models ranged from 0.62 to 0.68., Limitations: Limited number of outcome events; predictors limited to measures taken at baseline., Conclusions: The T2DM incidence rate among individuals with CKD is markedly higher than in the general population, supporting the need for greater vigilance in this population. Measures of glycemic control and family history of DM were independently associated with incident T2DM., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Abnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality., Study Design: Prospective study., Setting & Participants: We studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD., Predictor: We measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD., Outcomes: All-cause mortality after dialysis therapy initiation., Analytical Approach: Cox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality., Results: Over a mean of 2.9 years between pre- and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P<0.001) and LVESV (18.6 to 20.2mL/m 2.7 ; P<0.001). During this time, there was improvement in left ventricular mass index (60.4 to 58.4g/m 2.7 ; P=0.005) and diastolic relaxation (11.11% to 4.94% with moderately/severely abnormal; P=0.02). Changes in left atrial volume (4.09 to 4.15mL/m 2 ; P=0.08) or LVEDV (38.6 to 38.4mL/m 2.7 ; P=0.8) were not significant. Worsening from CKD to ESRD of LVEF (adjusted HR for every 1% decline in LVEF, 1.03; 95% CI, 1.00-1.06) and LVESV (adjusted HR for every 1mL/m 2.7 increase, 1.04; 95% CI, 1.02-1.07) were independently associated with greater risk for postdialysis mortality., Limitations: Some missing or technically inadequate echocardiograms., Conclusions: In a longitudinal study of patients with CKD who subsequently initiated dialysis therapy, LVEF and LVESV worsened and were significantly associated with greater risk for postdialysis mortality. There may be opportunities for intervention during this transition period to improve outcomes., (Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.)

Background: Few studies have investigated the changes in weight that may occur over time among adults with the progression of chronic kidney disease (CKD). Whether such weight changes are independently associated with death after the onset of end-stage renal disease has also not been rigorously examined., Study Design: Prospective cohort study., Setting & Participants: We studied 3,933 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a longitudinal cohort of patients with CKD. We also performed similar analyses among 1,067 participants of the African American Study of Kidney Disease and Hypertension (AASK)., Predictors: Estimated glomerular filtration rate (eGFR) and weight change during CKD., Outcome: Weight and all-cause mortality after dialysis therapy initiation., Results: During a median follow-up of 5.7 years in CRIC, weight change was not linear. Weight was stable until cystatin C-based eGFR (eGFR cys ) decreased to <35mL/min/1.73m 2 ; thereafter, weight declined at a mean rate of 1.45 kg (95% CI, 1.19-1.70) for every 10 mL/min/1.73m 2 decline in eGFR cys . Among the 770 CRIC participants who began hemodialysis or peritoneal dialysis therapy during follow-up, a >5% annualized weight loss after eGFR decreased to <35mL/min/1.73m 2 was associated with a 54% higher risk for death after dialysis therapy initiation (95% CI, 1.17-2.03) compared with those with more stable weight (annualized weight changes within 5% of baseline) in adjusted analysis. Similar findings were observed in the AASK., Limitations: Inclusion of research participants only; inability to distinguish intentional versus unintentional weight loss., Conclusions: Significant weight loss began relatively early during the course of CKD and was associated with a substantially higher risk for death after dialysis therapy initiation. Further studies are needed to determine whether interventions to optimize weight and nutritional status before the initiation of dialysis therapy will improve outcomes after end-stage renal disease., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Half of surgically created arteriovenous fistulas (AVFs) require additional intervention to effectively support hemodialysis. Postoperative care and complications may affect clinical maturation., Study Design: Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study., Setting & Participants: 491 patients with single-stage AVFs who had neither thrombosis nor AVF intervention before a 6-week postoperative ultrasonographic examination and who required maintenance hemodialysis., Predictors: Postoperative care processes and complications., Outcomes: Attempted cannulation, successful cannulation, and unassisted and overall clinical maturation as defined by the HFM Study criteria., Results: AVF cannulation was attempted in 443 of 491 (90.2%) participants and was eventually successful in 430 of these 443 (97.1%) participants. 263 of these 430 (61.2%) reached unassisted and 118 (27.4%) reached assisted AVF maturation (overall maturation, 381/430 [88.6%]). Attempted cannulation was less likely in patients of surgeons with policies for routine 2-week versus later-than-2-week first postoperative visits (OR, 0.21; 95% CI, 0.06-0.70), routine second postoperative follow-up visits (OR, 0.39; 95% CI, 0.15-0.97), and a routine clinical postoperative ultrasound (OR, 0.28; 95% CI, 0.14-0.55). Attempted cannulation was also less likely among patients undergoing procedures to assist maturation (OR, 0.51; 95% CI, 0.27-0.98). Unassisted maturation was more likely for patients treated in facilities with access coordinators (OR, 1.91; 95% CI, 1.17-3.12), but less likely after precannulation nonstudy ultrasounds (OR per ultrasound, 0.42 [95% CI, 0.26-0.68]) and initial unsuccessful cannulation attempts (OR per each additional attempt, 0.90 [95% CI, 0.83-0.98]). Overall maturation was less likely with infiltration before successful cannulation (OR, 0.44; 95% CI, 0.22-0.89). Among participants receiving maintenance hemodialysis before AVF surgery, unassisted and overall maturation were less likely with longer intervals from surgery to initial cannulation (ORs for each additional month of 0.81 [95% CI, 0.76-0.88] and 0.93 [95% CI, 0.89-0.98], respectively) and from initial to successful cannulation (ORs for each additional week of 0.87 [95% CI, 0.81-0.94] and 0.88 [95% CI, 0.83-0.94], respectively)., Limitations: Surgeons' management policies were assessed only by questionnaire at study onset. Most participants received upper-arm AVFs, planned 2-stage AVFs were excluded, and maturation time windows were imposed. Some care processes may have been missed and the observational design limits causal attribution., Conclusions: Multiple processes of care and complications are associated with AVF maturation outcomes., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality., Study Design: Cohort study., Setting & Participants: The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B-based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs., Predictor: Serum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization., Results: During a median follow-up of 4.0 years, the cohort had 436 CVD events, 238 transplant failures, and 348 deaths. Proportional hazards modeling revealed that each 1-mg/dL higher serum phosphorus level was not associated with a significant increase in CVD risk (HR, 1.06; 95% CI, 0.92-1.22), but increased transplant failure (HR, 1.36; 95% CI, 1.15-1.62) and total mortality risk associations (HR, 1.21; 95% CI, 1.04-1.40) when adjusted for treatment allocation, traditional CVD risk factors, kidney measures, type of kidney transplant, transplant vintage, and use of calcineurin inhibitors, steroids, or lipid-lowering drugs. These associations were strengthened in models without kidney measures: CVD (HR, 1.14; 95% CI, 1.00-1.31), transplant failure (HR, 1.72; 95% CI, 1.46-2.01), and mortality (HR, 1.34; 95% CI, 1.15-1.54)., Limitations: We lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites., Conclusions: Serum phosphorus level is marginally associated with CVD and more strongly associated with transplant failure and total mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of phosphorus-lowering therapy on these hard outcomes may be warranted., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

Background: Disturbances in vitamin D metabolism are common in patients with end-stage renal disease and may contribute to vascular dysfunction., Study Design: Cross-sectional., Setting & Participants: We evaluated 558 of 602 participants at baseline of the Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study of a cohort of patients with chronic kidney disease awaiting arteriovenous fistula (AVF) creation surgery., Factor: 4 vitamin D metabolites measured with liquid chromatography-tandem mass spectroscopy from samples obtained within 4 weeks prior to AVF surgery., Outcomes: Vasodilator functions and measurements of arterial stiffness., Measurements: Trained HFM Study personnel measured brachial artery flow-mediated dilation, nitroglycerin-mediated dilation, and carotid-femoral and carotid-radial pulse wave velocities (PWVs) prior to AVF creation. We evaluated associations after basic adjustment for sex, age, and clinical site and more fully adjusted additionally for baseline education, smoking, body mass index, diabetes, dialysis status, and medication use., Results: Mean participant age was 55±13 (SD) years and 65% were receiving maintenance dialysis. None of the vitamin D metabolites were significantly associated with flow-mediated dilation, carotid-femoral PWV, or carotid-radial PWV in basic or fully adjusted analyses. Higher serum concentrations of bioavailable vitamin D and 1,25-dihydroxyvitamin D were associated with 0.62% and 0.58% greater nitroglycerin-mediated dilation values, respectively, in basic models; however, these associations were no longer statistically significant with full adjustment. There were no significant associations of vitamin D metabolites with carotid-femoral or carotid-radial PWV in fully adjusted analyses., Limitations: Cross-sectional ascertainment of vitamin D metabolites and vascular functions late during the course of kidney disease., Conclusions: Serum concentrations of vitamin D metabolites are not associated with vasodilator functions or vascular stiffness at baseline in a cohort study of patients with chronic kidney disease awaiting AVF creation surgery. Laboratory measurements of vitamin D metabolites are unlikely to provide useful information regarding vascular functions in this setting., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

Background: Cardiovascular disease (CVD) is the leading cause of death in kidney transplant recipients. Whether aspirin may reduce the risk for CVD, death, and kidney failure outcomes is uncertain., Study Design: Post hoc cohort analysis of FAVORIT, a randomized trial examining the effect of homocysteine-lowering vitamins on CVD in kidney transplant recipients., Setting & Participants: Prevalent adult kidney transplant recipients with hyperhomocysteinemia and stable kidney function from the United States, Canada, and Brazil participating in FAVORIT, with no known history of CVD., Predictor: Aspirin use, with aspirin users matched to nonusers using a propensity score., Outcomes: Incident CVD events, kidney failure, all-cause mortality, a composite of CVD events or mortality, and a composite of kidney failure or mortality. Cox proportional hazards models with a robust variance to account for the correlation in outcomes within matched pairs were sequentially adjusted for demographic, clinical, and laboratory characteristics to assess the association between aspirin use and events., Results: 981 aspirin users were matched to 981 nonusers. During a 4-year mean follow up, there were 225 CVD events, 200 deaths, 126 kidney failure events, 301 composite kidney failure or mortality events, and 324 composite CVD or mortality events. Adjusted models showed no significant difference associated with aspirin use in risk for CVD events, all-cause mortality, kidney failure, composite of kidney failure or mortality, or composite of primary CVD events or mortality (HRs of 1.20 [95% CI, 0.92-1.58], 0.92 [95% CI, 0.69-1.23], 1.19 [95% CI, 0.81-1.74], 1.03 [0.82-1.31], and 1.11 [95% CI, 0.88-1.38], respectively)., Limitations: We did not examine dose or continued use of aspirin after randomization. CVD history is dependent on participant report at baseline. Aspirin use was non-randomly assigned., Conclusions: Aspirin use is not associated with reduced risk for incident CVD, all-cause mortality, or kidney failure in stable kidney transplant recipients with no history of CVD., (Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.)

Background: It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy., Study Design: Prospective cohort study., Setting & Participants: The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation., Predictors: The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point., Outcomes: All-cause mortality within 1 year after initiating hemodialysis therapy., Measurements: Multivariable Cox proportional hazards., Results: Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76)., Limitations: Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data., Conclusions: Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD., (Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.)

Background: Serum β-trace protein (BTP) and β2-microglobulin (B2M) are independently associated with end-stage renal disease (ESRD) and mortality in the general population and high-risk groups with diabetes or advanced chronic kidney disease (CKD). Less is known about their associations with outcomes and predictive ability in adults with moderate CKD., Study Design: Prospective cohort study., Setting & Participants: 3,613 adults from the CRIC (Chronic Renal Insufficiency Cohort) Study (45% women; mean age, 57.9 years; 41.0% non-Hispanic black; 51.9% with diabetes)., Predictors: BTP and B2M levels with a reciprocal transformation to reflect their associations with filtration, creatinine-based estimated glomerular filtration rate (eGFRcr), measured GFR, and a 4-marker composite score combining BTP, B2M, creatinine, and cystatin C levels. Predictors were standardized as z scores for comparisons across filtration markers., Outcomes: ESRD, all-cause mortality, and new-onset cardiovascular disease., Results: During a 6-year median follow-up, 755 (21%) participants developed ESRD, 653 died, and 292 developed new-onset cardiovascular disease. BTP, B2M, and the 4-marker composite score were independent predictors of ESRD and all-cause mortality, and B2M and the 4-marker composite score of cardiovascular events, after multivariable adjustment. These associations were stronger than those observed for eGFRcr (P vs eGFRcr≤0.02). The 4-marker composite score led to improvements in C statistic and 2.5-year risk reclassification beyond eGFRcr for all outcomes., Limitations: Filtration markers measured at one time point; measured GFR available in subset of cohort., Conclusions: BTP and B2M levels may contribute additional risk information beyond eGFRcr, and the use of multiple markers may improve risk prediction beyond this well-established marker of kidney function among persons with moderate CKD., (Copyright © 2016 National Kidney Foundation Inc. All rights reserved.)

Background: β-Trace protein (BTP) and β2-microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers., Study Design: Study of diagnostic test accuracy., Setting & Participants: Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m2 (N=3,551; MDRD [Modification of Diet in Renal Disease] Study, AASK [African American Study of Kidney Disease and Hypertension], and CRIC [Chronic Renal Insufficiency Cohort] Study)., Index Tests: GFR estimated using creatinine, cystatin C, BTP, or B2M level., Reference Test: GFR measured as the urinary clearance of iothalamate., Results: For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine-cystatin C equation was not more accurate than the CKD-EPI creatinine-cystatin C equation., Limitations: No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race., Conclusions: BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use., (Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.)

Background: Cardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD., Study Design: Cross-sectional and longitudinal observational analysis., Setting & Participants: Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study., Predictor: Quartiles of plasma CX3CL1 levels at baseline., Outcomes: Baseline estimated glomerular filtration rate from a creatinine and cystatin C-based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1c level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality., Results: Among 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, and higher levels of inflammatory cytokines, as well as prevalent CVD (OR, 1.09; 95% CI, 1.01-1.19; P=0.03). Higher CX3CL1 level also was associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16-1.38; P<0.001) in adjusted models. During a mean follow-up of 6 years, there were 352 deaths, 176 myocardial infarctions, and 484 composite outcomes. In fully adjusted models, 1-SD higher CX3CL1 level increased the hazard for all-cause mortality (1.11; 95% CI, 1.00-1.22; P=0.02) and the composite outcome (1.09; 95% CI, 1.00-1.19; P=0.04)., Limitations: Study design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect., Conclusions: Circulating CX3CL1 level may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects the pathogenesis of atherosclerosis and diabetes., (Copyright © 2015 National Kidney Foundation, Inc. All rights reserved.)

Background: Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria)., Study Design: Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study., Setting & Participants: 3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008., Predictor: Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration., Outcomes: Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011., Measurements: Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories)., Results: There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths., Limitations: Urine NGAL was measured only once., Conclusions: Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths., (Copyright © 2015 National Kidney Foundation, Inc. All rights reserved.)

Background: Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized., Study Design: Prospective cohort study., Setting & Participants: The Chronic Renal Insufficiency Cohort (CRIC) Study (N=3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race., Predictors: Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors., Outcomes: Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR<15mL/min/1.73m(2), (3) eGFR halving and <15mL/min/1.73m(2), (4) eGFR decrease of 20mL/min/1.73m(2), (5) eGFR halving or decrease of 20mL/min/1.73m(2), and (6) eGFR decrease of 25% and change in CKD stage., Results: Mean entry eGFR was 44.9mL/min/1.73m(2). Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively., Limitations: Participants may not be representative of the entire CKD population., Conclusions: Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression., (Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.)

Background: A large proportion of newly created arteriovenous fistulas cannot be used for dialysis because they fail to mature adequately to support the hemodialysis blood circuit. The Hemodialysis Fistula Maturation (HFM) Study was designed to elucidate clinical and biological factors associated with fistula maturation outcomes., Study Design: Multicenter prospective cohort study., Setting & Participants: Approximately 600 patients undergoing creation of a new hemodialysis fistula will be enrolled at 7 centers in the United States and followed up for as long as 4 years., Predictors: Clinical, anatomical, biological, and process-of-care attributes identified pre-, intra-, or postoperatively., Outcomes: The primary outcome is unassisted clinical maturation, defined as successful use of the fistula for dialysis for 4 weeks without maturation-enhancing procedures. Secondary outcomes include assisted clinical maturation, ultrasound-based anatomical maturation, fistula procedures, fistula abandonment, and central venous catheter use., Measurements: Preoperative ultrasound arterial and venous mapping, flow-mediated and nitroglycerin-mediated brachial artery dilation, arterial pulse wave velocity, and venous distensibility; intraoperative vein tissue collection for histopathologic and molecular analyses; postoperative ultrasounds at 1 day, 2 weeks, 6 weeks, and prior to fistula intervention and initial cannulation., Results: Assuming complete data, no covariate adjustment, and unassisted clinical maturation of 50%, there will be 80% power to detect ORs of 1.83 and 1.61 for dichotomous predictor variables with exposure prevalences of 20% and 50%, respectively., Limitations: Exclusion of 2-stage transposition fistulas limits generalizability. The requirement for study visits may result in a cohort that is healthier than the overall population of patients undergoing fistula creation., Conclusions: The HFM Study will be of sufficient size and scope to: (1) evaluate a broad range of mechanistic hypotheses, (2) identify clinical practices associated with maturation outcomes, (3) assess the predictive utility of early indicators of fistula outcome, and (4) establish targets for novel therapeutic interventions to improve fistula maturation., (Copyright © 2013 National Kidney Foundation, Inc. All rights reserved.)

Background: Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment., Study Design: Cross-sectional study., Setting & Participants: 588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study., Predictor: Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels., Outcomes: Neuropsychological battery of 6 cognitive tests., Measurements: Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions., Results: The mean age of the cohort was 65.3±5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment., Limitations: Unknown temporal relationship between retinopathy and impairment., Conclusions: In adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment., (Published by Elsevier Inc.)

Background: Glomerular filtration rate (GFR) is considered the best measure of kidney function, but repeated assessment is not feasible in most research studies., Study Design: Cross-sectional study of 1,433 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study (ie, the GFR subcohort) to derive an internal GFR estimating equation using a split-sample approach., Setting & Participants: Adults from 7 US metropolitan areas with mild to moderate chronic kidney disease; 48% had diabetes and 37% were black., Index Test: CRIC GFR estimating equation., Reference Test or Outcome: Urinary (125)I-iothalamate clearance testing (measured GFR [mGFR])., Other Measurements: Laboratory measures, including serum creatinine and cystatin C, and anthropometrics., Results: In the validation data set, the model that included serum creatinine level, serum cystatin C level, age, sex, and race was the most parsimonious and similarly predictive of mGFR compared with a model additionally including bioelectrical impedance analysis phase angle, CRIC clinical center, and 24-hour urinary creatinine excretion. Specifically, root mean square errors for the separate models were 0.207 versus 0.202, respectively. Performance of the CRIC GFR estimating equation was most accurate for the subgroups of younger participants, men, nonblacks, non-Hispanics, those without diabetes, those with body mass index <30 kg/m(2), those with higher 24-hour urine creatinine excretion, those with lower high-sensitivity C-reactive protein levels, and those with higher mGFRs., Limitations: Urinary clearance of (125)I-iothalamate is an imperfect measure of true GFR; cystatin C level is not standardized to certified reference material; lack of external validation; small sample sizes limit analyses of subgroup-specific predictors., Conclusions: The CRIC GFR estimating equation predicts mGFR accurately in the CRIC cohort using serum creatinine and cystatin C levels, age, sex, and race. Its performance was best in younger and healthier participants., (Copyright © 2012 National Kidney Foundation, Inc. All rights reserved.)

Background: Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied., Study Design: Cross-sectional analysis., Settings & Participants: Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008., Measurement: Depressive symptoms measured by Beck Depression Inventory (BDI)., Predictors: Demographic and clinical factors., Outcomes: Elevated depressive symptoms (BDI score ≥11) and antidepressant medication use., Results: Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each)., Limitations: Absence of clinical diagnosis of depression and use of nonpharmacologic treatments., Conclusions: Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications., (Published by Elsevier Inc.)

Background: Identification of persons with chronic kidney disease (CKD) who are at highest risk to progress to end-stage renal disease (ESRD) is necessary to reduce the burden of kidney failure. The relative utility of traditional markers of kidney function, including estimated glomerular filtration rate (eGFR) and serum creatinine level, and emerging markers of kidney function, including cystatin C and beta-trace protein (BTP) levels, to predict ESRD and mortality has yet to be established., Study Design: Randomized clinical trial followed by an observational cohort study., Setting & Participants: 865 African American individuals with hypertensive CKD enrolled in a clinical trial of 2 levels of blood pressure control and 3 different antihypertensive drugs as initial therapy and subsequently followed by an observational cohort study., Predictors: Quintile of measured GFR (mGFR) by iothalamate clearance, serum creatinine, serum creatinine-based eGFR, cystatin C, and BTP values., Outcomes & Measurements: Incidence of ESRD and mortality., Results: 246 participants reached ESRD during a median follow-up of 102 months. The incidence rate of ESRD was higher with higher quintiles of each marker. The association between higher BTP level and ESRD was stronger than those for the other markers, including mGFR. All markers remained significantly associated with ESRD after adjustment for mGFR and relevant covariates (all P < 0.05), with BTP level retaining the strongest association (HR for highest vs lowest quintile, 5.7; 95% CI, 2.2-14.9). Associations with the combined end point of ESRD or mortality (n = 390) were weaker, but remained significant for cystatin C (P = 0.05) and BTP levels (P = 0.004)., Limitations: The ability of these markers to predict ESRD and mortality in other racial and ethnic groups and in individuals with CKD due to other causes is unknown., Conclusions: Plasma BTP and cystatin C levels may be useful adjuncts to serum creatinine level and mGFR in evaluating risk of progression of kidney disease., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Little is known regarding chronic kidney disease (CKD) in Hispanics. We compared baseline characteristics of Hispanic participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies with non-Hispanic CRIC participants., Study Design: Cross-sectional analysis., Setting & Participants: Participants were aged 21-74 years with CKD using age-based estimated glomerular filtration rate (eGFR) at enrollment into the CRIC/H-CRIC Studies. H-CRIC included Hispanics recruited at the University of Illinois in 2005-2008, whereas CRIC included Hispanics and non-Hispanics recruited at 7 clinical centers in 2003-2007., Factor: Race/ethnicity., Outcomes: Blood pressure, angiotensin-converting enzyme (ACE)-inhibitor/angiotensin receptor blocker (ARB) use, and CKD-associated complications., Measurements: Demographic characteristics, laboratory data, blood pressure, and medications were assessed using standard techniques and protocols., Results: Of H-CRIC/CRIC participants, 497 were Hispanic, 1,650 were non-Hispanic black, and 1,638 were non-Hispanic white. Low income and educational attainment were nearly twice as prevalent in Hispanics compared with non-Hispanics (P < 0.01). Hispanics had self-reported diabetes (67%) more frequently than non-Hispanic blacks (51%) and whites (40%; P < 0.01). Blood pressure >130/80 mm Hg was more common in Hispanics (62%) than blacks (57%) and whites (35%; P < 0.05), and abnormalities in hematologic, metabolic, and bone metabolism parameters were more prevalent in Hispanics (P < 0.05), even after stratifying by entry eGFR. Hispanics had the lowest use of ACE inhibitors/ARBs among the high-risk subgroups, including participants with diabetes, proteinuria, and blood pressure >130/80 mm Hg. Mean eGFR was lower in Hispanics (39.6 mL/min/1.73 m(2)) than in blacks (43.7 mL/min/1.73 m(2)) and whites (46.2 mL/min/1.73 m(2)), whereas median proteinuria was higher in Hispanics (protein excretion, 0.72 g/d) than in blacks (0.24 g/d) and whites (0.12 g/d; P < 0.01)., Limitations: Generalizability; observed associations limited by residual bias and confounding., Conclusions: Hispanics with CKD in the CRIC/H-CRIC Studies are disproportionately burdened with lower socioeconomic status, more frequent diabetes mellitus, less ACE-inhibitor/ARB use, worse blood pressure control, and more severe CKD and associated complications than their non-Hispanic counterparts., (Published by Elsevier Inc.)

Background: A low serum bicarbonate level is prevalent in chronic kidney disease (CKD); however, its relationship to long-term outcomes is unclear., Study Design: Cohort study., Setting & Participants: The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 942 screened but non-randomized individuals and 839 randomized participants with baseline serum bicarbonate measurements with stage 2-4 CKD., Factor: Serum bicarbonate level categorized into quartiles., Outcomes: Kidney failure, all-cause mortality, and a composite outcome of mortality and kidney failure., Measurements: Local laboratories at each participating site measured bicarbonate in fasting serum samples. Kidney failure outcomes were obtained from the US Renal Data System, and mortality data, from the National Death Index., Results: Mean glomerular filtration rate (GFR) was 39 ± 21 (SD) mL/min/1.73 m(2) and serum bicarbonate level was 23.3 ± 3.8 mEq/L. Kidney failure rates were 72%, 64%, 50%, and 41%; mortality rates were 31%, 25%, 21%, and 25%, and rates of the composite outcome were 78%, 71%, 58%, and 54% in bicarbonate quartiles 1, 2, 3, and 4, respectively. In analyses adjusted for demographic and cardiovascular disease factors, serum albumin level, proteinuria, and cause of kidney disease, compared with quartile 4, quartile 1 was associated with a 2.22 HR (95% CI, 1.83-2.68) of kidney failure; 1.39 HR (95% CI, 1.07-1.18) of all-cause mortality; and 1.36 HR (95% CI, 1.15-1.62) of the composite outcome. These associations were rendered nonsignificant with adjustment for GFR (kidney failure HR, 1.05 [95% CI, 0.87-1.28]; all-cause mortality HR, 0.99 [95% CI, 0.75-1.13]; composite HR, 1.04 [95% CI, 0.87-1.24])., Limitations: Single baseline measurement of serum bicarbonate., Conclusions: Low serum bicarbonate level was associated with increased risk of long-term outcomes in nondiabetic patients with CKD. However, this risk is not independent of baseline GFR. Clinical trials are necessary to evaluate whether bicarbonate supplementation slows the progression of CKD., (Copyright © 2010 National Kidney Foundation, Inc. All rights reserved.)

Background: Hyperuricemia is prevalent in patients with chronic kidney disease (CKD); however, data are limited about the relationship of uric acid levels with long-term outcomes in this patient population., Study Design: Cohort study., Setting & Participants: The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial (N = 840) conducted from 1989 to 1993 to examine the effects of strict blood pressure control and dietary protein restriction on progression of stages 3 to 4 CKD. This analysis included 838 patients., Predictor: Uric acid level., Outcomes & Measurements: The study evaluated the association of baseline uric acid levels with all-cause mortality, cardiovascular disease (CVD) mortality, and kidney failure., Results: Mean age was 52 +/- 12 (SD) years, glomerular filtration rate was 33 +/- 12 mL/min/1.73 m(2), and uric acid level was 7.63 +/- 1.66 mg/dL. During a median follow-up of 10 years, 208 (25%) participants died of any cause, 127 (15%) died of CVD, and 553 (66%) reached kidney failure. In multivariate models, the highest tertile of uric acid was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.07 to 2.32), a trend toward CVD mortality (HR, 1.47; 95% CI, 0.90 to 2.39), and no association with kidney failure (HR, 1.20; 95% CI, 0.95 to 1.51) compared with the lowest tertile. In continuous analyses, a 1-mg/dL greater uric acid level was associated with 17% increased risk of all-cause mortality (HR, 1.17; 95% CI, 1.05 to 1.30) and 16% increased risk of CVD mortality (HR, 1.16; 95% CI, 1.01 to 1.33), but was not associated with kidney failure (HR, 1.02; 95% CI, 0.97 to 1.07)., Limitations: Primary analyses were based on a single measurement of uric acid. Results are generalizable primarily to relatively young white patients with predominantly nondiabetic CKD., Conclusions: In patients with stages 3 to 4 CKD, hyperuricemia appears to be an independent risk factor for all-cause and CVD mortality, but not kidney failure.

Background: The long-term effect of a very low-protein diet on the progression of kidney disease is unknown. We examined the effect of a very low-protein diet on the development of kidney failure and death during long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study., Study Design: Long-term follow-up of study B of the MDRD Study (1989-1993)., Setting & Participants: The MDRD Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 255 trial participants with predominantly stage 4 nondiabetic chronic kidney disease., Intervention: A low-protein diet (0.58 g/kg/d) versus a very low-protein diet (0.28 g/kg/d) supplemented with a mixture of essential keto acids and amino acids (0.28 g/kg/d)., Outcomes: Kidney failure (initiation of dialysis therapy or transplantation) and all-cause mortality until December 31, 2000., Results: Kidney failure developed in 227 (89%) participants, 79 (30.9%) died, and 244 (95.7%) reached the composite outcome of either kidney failure or death. Median duration of follow-up until kidney failure, death, or administrative censoring was 3.2 years, and median time to death was 10.6 years. In the low-protein group, 117 (90.7%) participants developed kidney failure, 30 (23.3%) died, and 124 (96.1%) reached the composite outcome. In the very low-protein group, 110 (87.3%) participants developed kidney failure, 49 (38.9%) died, and 120 (95.2%) reached the composite outcome. After adjustment for a priori-specified covariates, hazard ratios were 0.83 (95% confidence interval, 0.62 to 1.12) for kidney failure, 1.92 (95% confidence interval, 1.15 to 3.20) for death, and 0.89 (95% confidence interval, 0.67 to 1.18) for the composite outcome in the very low-protein diet group compared with the low-protein diet group., Limitations: Lack of dietary protein measurements during follow-up., Conclusion: In long-term follow-up of the MDRD Study, assignment to a very low-protein diet did not delay progression to kidney failure, but appeared to increase the risk of death.

Background: Hyperhomocysteinemia may be a modifiable risk factor for the prevention of arteriosclerotic outcomes in patients with chronic kidney disease (CKD). Few clinical trials of homocysteine lowering have been conducted in persons with CKD before reaching end-stage renal disease. Kidney transplant recipients are considered individuals with CKD., Objectives: To describe the baseline characteristics of renal transplant recipients enrolled in a clinical trial of homocysteine lowering with a standard multivitamin containing high doses of folic acid and vitamins B(6) and B(12) aimed at reducing arteriosclerotic outcomes. Factors considered were level of kidney function, total homocysteine concentration, and prevalence of diabetes and previous cardiovascular disease (CVD)., Study Design: Cross-sectional survey within a randomized controlled trial cohort., Setting & Participants: Participants were recruited from kidney transplant clinics in the United States, Canada, and Brazil. Eligible participants had increased levels of homocysteine (> or =12.0 micromol/L in men and > or =11.0 micromol/L in women) and kidney function measured by means of Cockroft-Gault estimated creatinine clearance of 30 mL/min or greater., Results: Of 4,110 randomly assigned participants, 38.9% had diabetes and 19.5% had previous CVD. Mean total homocysteine concentration was 17.1 +/- 6.3 (SD) micromol/L, whereas mean creatinine clearance was 66.4 +/- 23.2 mL/min. Approximately 90% of the trial cohort had an estimated glomerular filtration rate consistent with stages 2 to 3 CKD (i.e., 30 to 89 mL/min)., Limitations: Analysis is based on cross-sectional data from a randomized controlled trial, self-report of comorbid illnesses, and level of kidney function was estimated., Conclusions: A large population of stable renal transplant recipients who are at high risk of the development of CVD (both de novo and recurrent) has been recruited into the Folic Acid for Vascular Outcome Reduction in Transplantation Trial and are likely to experience a sufficient number of events to address the primary hypothesis of the trial.

Background: Greater body mass index (BMI) is associated with worse survival in the general population, but appears to confer a survival advantage in patients with kidney failure treated by hemodialysis. Data are limited on the relationship of BMI with mortality in patients in the earlier stages of chronic kidney disease (CKD)., Study Design: Cohort study., Setting & Participants: The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 1,759 subjects., Predictor: BMI., Outcomes & Measurements: Cox models were used to evaluate the relationship of quartiles of BMI with all-cause and cardiovascular disease (CVD) mortality., Results: Mean GFR and BMI were 39 +/- 21 (SD) mL/min/1.73 m(2) and 27.1 +/- 4.7 kg/m(2), respectively. During a mean follow-up of 10 years, there were 453 deaths (26%), including 272 deaths (16%) from CVD. In unadjusted Cox models, quartiles 3 (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.11 to 1.90) and 4 (HR, 1.58; 95% CI, 1.21 to 2.06) were associated with increased risk of all-cause mortality compared with quartile 1. Adjustment for demographic, CVD, and kidney disease risk factors and randomization status attenuated this relationship for quartiles 3 (HR, 0.81; 95% CI, 0.60 to 1.09) and 4 (HR, 0.83; 95% CI, 0.61 to 1.20). In unadjusted Cox models, quartiles 3 (HR, 1.66; 95% CI, 1.17 to 2.36) and 4 (HR, 1.63; 95% CI, 1.15 to 2.33) were associated with increased risk of CVD mortality. Multivariable adjustment attenuated this relationship for quartiles 3 (HR, 0.92; 95% CI, 0.63 to 1.36) and 4 (HR, 0.85; 95% CI, 0.57 to 1.27)., Limitations: Primary analyses were based on single measurement of BMI. Because the MDRD Study cohort included relatively young white subjects with predominantly nondiabetic CKD, results may not be generalizable to all patients with CKD., Conclusions: In this cohort of subjects with predominantly nondiabetic CKD, BMI does not appear to be an independent predictor of all-cause or CVD mortality.

Background: The long-term effect of a low-protein diet on the progression of chronic kidney disease is unknown. We evaluated effects of protein restriction on kidney failure and all-cause mortality during extended follow-up of the Modification of Diet in Renal Disease Study., Methods: Study A was a randomized controlled trial from 1989 to 1993 of 585 patients with predominantly nondiabetic kidney disease and a moderate decrease in glomerular filtration rate (25 to 55 mL/min/1.73 m(2) [0.42 to 0.92 mL/s/1.73 m(2)]) assigned to a low- versus usual-protein diet (0.58 versus 1.3 g/kg/d). We used registries to ascertain the development of kidney failure (initiation of dialysis therapy or transplantation) or a composite of kidney failure and all-cause mortality through December 31, 2000. We used Cox regression models and intention-to-treat principles to compute hazard ratios for the low- versus usual-protein diet, adjusted for baseline glomerular filtration rate and other factors previously associated with the rate of decrease in glomerular filtration rate. We estimated hazard ratios for the entire follow-up period and then, in time-dependent analyses, separately for 2 consecutive 6-year periods of follow-up., Results: Kidney failure and the composite outcome occurred in 327 (56%) and 380 patients (65%), respectively. After adjustment for baseline factors, hazard ratios were 0.89 (95% confidence interval [CI], 0.71 to 1.12) and 0.88 (95% CI, 0.71 to 1.08), respectively. Adjusted hazard ratios for both outcomes were lower during the first 6 years (0.68; 95% CI, 0.51 to 0.93 and 0.66; 95% CI, 0.50 to 0.87, respectively) than afterward (1.27; 95% CI, 0.90 to 1.80 and 1.29; 95% CI, 0.94 to 1.78; interaction P = 0.008 and 0.002, respectively). Limitations include lack of data for dietary intake and clinical conditions after conclusion of the trial., Conclusion: The efficacy of a 2- to 3-year intervention of dietary protein restriction on progression of nondiabetic kidney disease remains inconclusive. Future studies should include a longer duration of intervention and follow-up.

Background: The African American Study of Kidney Disease and Hypertension was a multicenter trial comparing the effects of 2 levels of blood pressure control (usual or low goal) and initial therapy with metoprolol, ramipril, or amlodipine. We examined effects of treatment-group assignment on health-related quality of life (HRQOL) measures and reported symptoms during 4 years of follow-up., Methods: HRQOL was assessed at baseline and annually by using the Medical Outcomes Study 36-Item Short Form (SF-36) and a symptom checklist. Using a 2-slope model, treatment effects were evaluated for change from baseline to year 1 and for average change during the first 4 years of follow-up., Results: A total of 1,094 participants were randomly assigned. Average age was 55 years, 61% were men, and the mean of the first glomerular filtration rate in the study was 46 mL/min/1.73 m2 (0.76 mL/s). No significant differences in HRQOL were seen between the low- and usual-blood-pressure groups. Reported side effects also were similar between blood-pressure groups. Mean Physical Health Component (PHC) and Mental Health Component (MHC) scores had a significantly smaller decrease in the ramipril than metoprolol group in both the initial period from baseline to year 1 (PHC, 2.08 +/- 0.56; MHC, 1.89 +/- 0.62) and during the first 4 years of follow-up (PHC, 1.60 +/- 0.44; MHC, 1.48 +/- 0.48). The MHC also had a slightly smaller decrease during the first 4 years in the ramipril group than amlodipine group (1.20 +/- 0.61)., Conclusion: Aggressive blood pressure control is well tolerated in African Americans with hypertensive kidney disease, measured by using the SF-36 and reported symptoms. The clinical significance of smaller decreases in PHC and MHC scores in the ramipril compared with metoprolol group is not clear.

Background: The timing of medical therapies has been shown to influence the outcomes and side effects of treatments for disease. This report examines the extent to which hemodialysis treatment time of day was associated with cardiovascular mortality and morbidity and all-cause mortality in a secondary analysis of the Hemodialysis Study., Methods: Dialysis start time defined dialysis shift: morning beginning between 0400 and 0930 hours (n = 822); midday, between 0930 and 1530 hours (n = 851); and evening, between 1530 and 2200 hours (n = 172). Outcome measures included all-cause mortality, cardiac death, composite end point of all-cause mortality or first cardiac hospitalization, and composite end point of first cardiac hospitalization or cardiac death., Results: Morning hemodialysis was associated with a lower likelihood of cardiovascular events compared with the evening shift in all-cause mortality or first cardiac hospitalization (evening versus morning, relative risk [RR], 1.29; 95% confidence interval [CI], 1.01 to 1.65; P = 0.043), as well as first cardiac hospitalization or cardiac death (evening versus morning, RR, 1.44; 95% CI, 1.11 to 1.89; P = 0.007). No differences were noted in the other 2 outcomes, and there was no statistically significant difference between the morning and midday shifts. Although crude mortality rates were greater in the midday compared with morning (RR, 1.21; 95% CI, 1.05 to 1.39; P = 0.008), this association was attenuated after adjustment (RR, 1.04; 95% CI, 0.89 to 1.22; P = 0.64)., Conclusion: Making extensive adjustment for patient characteristics, this report does not support the association of lower all-cause mortality with morning hemodialysis or a particular benefit for older patients.

Background: Abnormalities of mineral metabolism are prevalent in patients with kidney failure and are associated with increased risk for cardiovascular events. There are limited data investigating relationships of phosphorus and calcium-phosphorus product with outcomes in patients with chronic kidney disease (CKD) stages 3 to 4., Methods: Serum phosphorus and calcium were measured at baseline in 840 participants from the randomized cohort of the Modification of Diet in Renal Disease Study. Survival status until December 31, 2000, was obtained from the National Death Index. Cox models were performed to assess the relationship of serum phosphorus level and calcium-phosphorus product with all-cause and cardiovascular disease (CVD) mortality., Results: Mean serum phosphorus level was 3.8 +/- 0.7 mg/dL (1.23 +/- 0.23 mmol/L), calcium-phosphorus product was 34.7 +/- 6.3 mg2/dL2, and glomerular filtration rate (GFR) was 33 +/- 12 mL/min/1.73 m2 (0.55 +/- 0.20 mL/s/1.73 m2). All-cause and CVD mortality rates were 25% and 15%. Serum phosphorus level was not related to all-cause mortality in multivariable models (P = 0.46). In unadjusted analysis, serum phosphorus level was associated with (hazard ratio [HR] per 1 mg/dL increase, 1.34; 95% confidence interval [CI], 1.05 to 1.71; P = 0.02) increased risk for CVD mortality, but this association was partly attenuated and not statistically significant after adjustment for GFR and other confounders (HR, 1.27; 95% CI, 0.94 to 1.73; P = 0.12). Calcium-phosphorus product was not associated with all-cause mortality in unadjusted (P = 0.23) or multivariate analysis (P = 0.35). Calcium-phosphorus product was related to CVD mortality in unadjusted (HR per 10 mg2/dL2 increase, 1.30; 95% CI, 1.01 to 1.69; P = 0.04) analysis, but this association was not statistically significant after adjustment for GFR and other confounders (HR, 1.22; 95% CI, 0.89 to 1.66; P = 0.23)., Conclusion: In the Modification of Diet in Renal Disease Study cohort, serum phosphorus level and calcium-phosphorus product were not statistically associated with all-cause or CVD mortality after adjustment for GFR; however larger studies with additional statistical power are needed to evaluate these relationships, especially in the context of current practice patterns in patients with CKD.

Background: It is unclear whether lipoprotein(a) (Lp[a]) levels in patients with chronic kidney disease (CKD) are elevated as a result of reduced glomerular filtration rate (GFR) or other factors associated with CKD. The goal of this study is to describe the association of Lp(a) level with GFR in the context of apoprotein(a) (apo[a]) isoform size, race, and other kidney disease-related factors, such as proteinuria, serum albumin level, C-reactive protein (CRP) level, and serum lipid levels., Methods: Lp(a) and apo(a) isoforms were measured in serum samples obtained at baseline from 804 participants in the Modification of Diet in Renal Disease study (GFR range, 13 to 55 mL/min/1.73 m2). The cross-sectional association between Lp(a) level and GFR, apo(a) isoform size, race, and other variables was analyzed in univariate and multivariate linear regression., Results: Median Lp(a) level was greater in blacks than whites (97.5 versus 28.1 nmol/L; P < 0.001). Those with a low-molecular-weight apo(a) isoform size had greater Lp(a) levels than those with a high-molecular-weight apo(a) isoform size (57.5 versus 21.3 nmol/L; P < 0.001). Lp(a) level was not associated with GFR. Low-molecular-weight apo(a), black race, and greater levels of proteinuria, CRP, and triglycerides were independently associated with greater Lp(a) levels., Conclusion: In this population with CKD stages 3 to 4, GFR was not associated with Lp(a) level, whereas other factors related to CKD, such as proteinuria, CRP level, and triglyceride level, as well as genetic factors such as apo(a) isoform size and race, were associated with Lp(a) level.

Background: C-Reactive protein (CRP) level is elevated in kidney failure and may be related to malnutrition and cardiovascular disease (CVD). Data are limited regarding relationships between CRP levels and glomerular filtration rate (GFR), nutritional indices, and CVD in patients with earlier stages of kidney disease., Methods: CRP was assayed from samples from the Modification of Diet in Renal Disease (MDRD) Study (n = 801). CRP distributions were compared between the MDRD Study and National Health and Nutrition Examination Survey (NHANES; 1999 to 2000). Associations between CRP level and GFR, nutritional indices, serum albumin levels, and CVD risk factors were examined in the MDRD Study., Results: Geometric means of CRP, adjusted for age and sex, were similar in NHANES (0.23 mg/dL) and the MDRD Study (0.22 mg/dL). In the MDRD Study, CRP level was related directly to measures of body fat and CVD risk factors, inversely with serum albumin level and energy intake, and unrelated to GFR. In multivariable analysis adjusting for other determinants of serum albumin level, high CRP level (>0.6 mg/dL) was associated with a 0.07-g/dL (0.7-g/L; 95% confidence interval [CI], 0.03 to 0.12) lower mean serum albumin level. After adjusting for traditional CVD risk factors, the odds of CVD were 1.73 (95% CI, 1.07 to 2.78) times greater in subjects with a high CRP level., Conclusion: GFR level does not appear to influence CRP level in the earlier stages of chronic kidney disease. CRP levels are independently associated with serum albumin level and CVD prevalence. Inflammation may be involved in the pathophysiological state of malnutrition and CVD in the earlier stages of predominantly nondiabetic kidney disease.

Background: Pathological similarities between atherosclerosis and glomerulosclerosis suggest that risk factors for the two processes may be similar. Elevated total homocysteine (tHcy) levels and low B vitamin levels are risk factors for atherosclerosis, but have not been evaluated sufficiently as risk factors for the progression of kidney disease., Methods: Frozen samples from the Modification of Diet in Renal Disease Study were assayed for serum tHcy, cysteine, pyridoxal 5-phosphate (PLP), folate, and vitamin B12 levels in 804 participants. These factors were evaluated in both continuous and categorical analyses as risk factors for glomerular filtration rate (GFR) decline by using univariate and multivariable analyses., Results: At baseline, mean tHcy levels in study A (GFR, 25 to 55 mL/min/1.73 m2) and study B (GFR, 13 to 24 mL/min/1.73 m2) were 16.9 micromol/L (median, 15.6 micromol/L) and 23.0 micromol/L (median, 20.5 micromol/L), respectively. Mean follow-up was 2.2 years. Mean GFR declines were -4.35 and -3.65 mL/min/y in studies A and B, respectively. There was no significant association between change in GFR with baseline level of tHcy in univariate (-0.26 mL/min/y per 1-SD unit increase in tHcy level; 95% confidence interval [CI], -0.67 to 0.15) or multivariable (-0.18 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.53 to 0.17) analysis in study A or univariate (0.07 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.36 to 0.51) or multivariable (0.24 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.16 to 0.64) analysis in study B. Similarly, higher cysteine levels and lower B vitamin levels were not associated with faster rates of GFR decline in multivariable analysis in either study., Conclusion: Higher tHcy or cysteine levels and lower folate, PLP, and vitamin B12 levels are not independent risk factors for progression of nondiabetic kidney disease., (Copyright 2002 by the National Kidney Foundation, Inc.)

Microalbuminuria (MA) is associated with adverse health outcomes in diabetic and hypertensive adults. The prevalence and clinical significance of MA in nondiabetic populations is less clear. The purpose of this study was to generate national estimates of the prevalence of MA in the US population. Untimed urinary albumin concentrations (UACs) and creatinine concentrations were evaluated in a nationally representative sample of 22,244 participants aged 6 years and older. Persons with hematuria and menstruating or pregnant women were excluded from analysis. The percent prevalence of clinical proteinuria (UAC > or = 300 mg/L) was similar for males and females. However, the prevalence of MA (urinary albumin-creatinine ratio [ACR], 30 to 299 mg/g) was significantly lower in males (6.1%) compared with females (9.7%). MA prevalence was greater in children than young adults and increased continuously starting at 40 years of age. MA prevalence was greater in non-Hispanic blacks and Mexican Americans aged 40 to 79 years compared with similar-aged non-Hispanic whites. MA prevalence was 28.8% in persons with previously diagnosed diabetes, 16.0% in those with hypertension, and 5.1% in those without diabetes, hypertension, cardiovascular disease, or elevated serum creatinine levels. In adults aged 40+ years, after excluding persons with clinical proteinuria, albuminuria (defined as ACR > or = 30 mg/g) was independently associated with older age, non-Hispanic black and Mexican American ethnicity, diabetes, hypertension, and elevated serum creatinine concentration. MA is common, even among persons without diabetes or hypertension. Age, sex, race/ethnicity, and concomitant disease contribute to the variability of MA prevalence estimates., (Copyright 2002 by the National Kidney Foundation, Inc.)

We measured health-related quality of life (HRQL) by using the Medical Outcomes Study 36-Item Short-Form (SF-36) in a cross-sectional study of 1,094 African American men and women with mild to moderate chronic renal insufficiency (mean glomerular filtration rate, 45.7 mL/min/1.73 m2) caused by hypertension before randomization onto the African American Study of Kidney Disease and Hypertension (AASK) Trial. Scales contributing to physical health and a summary measure, the Physical Component Summary (PCS) score (mean, 43.4 +/- 10.9 [SD]), were significantly lower than scales relating to mental health and the Mental Component Summary (MCS) score (51.3 +/- 10.3). All scales (except Role-Physical) and the PCS and MCS were significantly higher in men (44.3 +/- 10.9 and 51.8 +/- 10.0, respectively) than women (41.9 +/- 10.8 and 50.5 +/- 10.6, respectively). In multivariate analysis, employment status, education level, household income, body mass index, comorbid medical conditions, years of hypertension, number of antihypertensive drugs prescribed, exercise status, and male sex were significant independent predictors of PCS. Fewer factors predicted MCS and included employment status, marital status, current smoking, age, comorbid medical conditions, and male sex. In the entire AASK cohort, mean scores for individual scales, except Mental Health, and the PCS were lower, but the mean MCS score was slightly higher than values for the US general population. Values for individual scales of the SF-36 and the PCS were substantially higher among AASK participants compared with African-American hemodialysis patients. Six of the eight scales were lower in the AASK cohort compared with groups of racially mixed and exclusively African-American hypertensive subjects. We conclude that physical aspects of quality of life are substantially reduced compared with mental components among AASK participants, and a number of demographic and clinical characteristics significantly impact on HRQL., (Copyright 2002 by the National Kidney Foundation, Inc.)

The nutritional status of the first 1,000 patients randomized into the Hemodialysis (HEMO) Study was analyzed at baseline when they received their typical dialysis dose (equilibrated Kt/V = 1.30 +/- 0.22) and dialysis membrane. This is the largest study to date of the nutritional status of chronic hemodialysis patients. The mean (+/- SD) values for these parameters included a serum albumin level of 3.65 +/- 0.38 g/dL, a dietary energy intake of 22.9 +/- 8.4 kcal/kg/day, a dietary protein intake of 0.93 +/- 0.36 g/kg/day, and a double pool normalized protein catabolic rate (enPCR) of 1.00 +/- 0.25 g/kg/day. The percentage of patients below HEMO Study nutritional standards of care included 29% of patients with a serum albumin level less than 3.5 g/dL, 76% of patients with a dietary energy intake less than 28 kcal/kg/day, 61% of patients with a dietary protein intake less than 1.0 g/kg/day, and 52% of patients with an enPCR of less than 1.0 g/kg/day. There was a strong correlation between dietary protein intake and dietary energy intake (r = 0.74, P < 0.0001). Significant correlations were also evident between serum albumin and double pool PCR and between dietary protein intake and double-pool PCR. Kt/V and membrane flux were not predictive of baseline dietary protein intake, dietary energy intake, or serum albumin level. Thus, a majority of patients in the HEMO Study had protein and energy intake levels and enPCR levels that were below National Kidney Foundation Kidney Dialysis Outcome Quality Improvement (NKF-K/DOQI) guidelines., (Copyright 2002 by the National Kidney Foundation, Inc.)