Search

Context: A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease., Objective: To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease., Design, Setting, and Participants: A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008., Main Outcome Measures: All-cause mortality and end-stage renal disease., Results: At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of end-stage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m(2)., Conclusion: Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.

Extended-release dipyridamole plus low-dose aspirin (ERDP/ASA) prolongs primary unassisted graft patency of newly created hemodialysis arteriovenous grafts, but the individual contributions of each component are unknown. Here, we analyzed whether use of aspirin at baseline associated with primary unassisted graft patency among participants in a randomized trial that compared ERDP/ASA and placebo in newly created grafts. We used Cox proportional hazards regression, adjusting for prespecified baseline comorbidities and covariates. Of all participants, 43% reported use of aspirin at baseline; of these, 82% remained on nonstudy aspirin (i.e., excluding ERDP/ASA) at 1 year. After 1 year of follow-up, the incidence of primary unassisted patency among participants using aspirin at baseline was 30% (95% CI: 24 to 35%) and among those not using aspirin was 23% (95% CI: 18 to 27%). Use of aspirin at baseline associated with a dose-dependent prolongation of primary unassisted graft patency that approached statistical significance (adjusted HR, 0.83; 95% CI: 0.68 to 1.01; P=0.06). Use of aspirin at baseline did not associate with prolongation of cumulative graft patency or participant survival. In conclusion, use of aspirin associates with a trend toward longer primary unassisted patency of newly placed hemodialysis grafts similar to that observed for ERDP/ASA., (Copyright © 2011 by the American Society of Nephrology)

Background and Objectives: Dyslipidemia confers a paradoxical survival advantage in patients with kidney failure. Data are limited in the earlier stages of chronic kidney disease (CKD)., Design, Setting, Participants, and Measurements: This was a cohort study in 840 subjects with stage 3 to 4 CKD enrolled in the Modification of Diet in Renal Disease study. Cox models were used to examine the relationship of total cholesterol (TC), non-HDL-cholesterol (NHDL-C), triglycerides (TG), and HDL-cholesterol (HDL-C) with all-cause and cardiovascular disease (CVD) mortality and progression to kidney failure., Results: During a mean follow-up of 10 years, there were 208 deaths, 128 deaths from CVD, and 554 subjects reached kidney failure. There was no association between tertiles of any of the lipid variables and mortality; the lowest HDL-C tertile (1.44, 1.18 to 1.78) had increased risk of kidney failure but covariate adjustment abolished this association. In analyses with lipids as continuous variables, there was a significant association with all-cause mortality for TC (hazard ratio [HR] per 10-mg/dl increase, 95% confidence intervals [CI] = 1.03, 1.0 to 1.06) that disappeared with covariate adjustment; there was no association of TG, HDL-C, and NHDL-C as continuous variables with all-cause or CVD mortality. There was a significant inverse association between HDL-C and kidney failure (HR = 0.93, CI = 0.87 to 0.99) in an unadjusted Cox model that was attenuated after adjustment for covariates (HR = 0.98 CI = 0.91 to 1.06)., Conclusions: In this cohort, with predominantly nondiabetic CKD patients, hyperlipidemia is not an independent predictor of long-term outcomes.

Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50-60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups.

Hispanics are the fastest growing minority group in the United States. The incidence of end-stage renal disease (ESRD) in Hispanics is higher than non-Hispanic Whites and Hispanics with chronic kidney disease (CKD) are at increased risk for kidney failure. Likely contributing factors to this burden of disease include diabetes and metabolic syndrome, both are common among Hispanics. Access to health care, quality of care, and barriers due to language, health literacy and acculturation may also play a role. Despite the importance of this public health problem, only limited data exist about Hispanics with CKD. We review the epidemiology of CKD in US Hispanics, identify the factors that may be responsible for this growing health problem, and suggest gaps in our understanding which are suitable for future investigation.

Background: Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values., Objective: To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation., Design: Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates., Setting: Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006., Participants: 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES., Measurements: GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age., Results: In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%)., Limitation: The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR., Conclusion: The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use., Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.

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.

Recruitment of diverse populations into clinical trials remains challenging but is needed to fully understand disease processes and benefit the general public. Greater knowledge of key factors among ethnic and racial minority populations associated with the decision to participate in clinical research studies may facilitate recruitment and enhance the generalizibility of study results. Therefore, during the recruitment phase of the African American Study of Kidney Disease and Hypertension (AASK) trial, we conducted a telephone survey, using validated questions, to explore potential facilitators and barriers of research participation among eligible candidates residing in seven U.S. locations. Survey responses included a range of characteristics and perceptions among participants and non-participants and were compared using bivariate and step-wise logistic regression analyses. One-hundred forty-one respondents in the one-hundred forty (70 trial participants and 71 non-participants) completed the survey. Trial participants and non-participants were similar in multiple demographic characteristics and shared similar views on discrimination, physician mistrust, and research integrity. Key group differences were related to their perceptions of the impact of their research participation. Participants associated enrollment with personal and societal health benefits, while non-participants were influenced by the health risks. In a step-wise linear regression analysis, the most powerful significant positive predictors of participation were acknowledgement of health status as important in the enrollment decision (OR=4.54, p=0.006), employment (OR=3.12, p = 0.05) and healthcare satisfaction (OR=2.12, p<0.01). Racially-based mistrust did not emerge as a negative predictor and subjects' decisions were not influenced by the race of the research staff. In conclusion, these results suggest that health-related factors, and not psychosocial perceptions, have predominant influence on research participation among African Americans.

Background and Objectives: All glomerular filtration rate (GFR) estimating equations have been developed from cross-sectional data. The aims of this study were to examine the concordance between use of measured GFR (mGFR) and estimated GFR (eGFR) in tracking changes in kidney function over time among patients with moderately severe chronic kidney disease., Design, Setting, Participants, & Measurements: A retrospective cohort study of subjects who had been enrolled in the MDRD Study A and who had two or more contemporaneous assessments of mGFR and eGFR (n = 542; mGFR range, 25 to 55 ml/min per 1.73 m(2)) during the chronic phase (month 4 and afterwards). mGFR was based on urinary iothalamate clearance; eGFR was based on the 4-variable MDRD Study equation. Temporal changes in GFR were assessed by within-subject linear regression of time on GFR., Results: Median follow-up time for all subjects was 2.6 yr; median number of GFR measurements was six. The eGFR slope tended to underestimate measured decrements in GFR. The absolute value of the difference in mGFR and eGFR slopes was

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: No study has compared cystatin C level, serum creatinine concentration, and estimated glomerular filtration rate (GFR) as risk factors for outcomes in chronic kidney disease (CKD), and none has compared measured GFR with CKD in any population., Objective: To compare cystatin C level with serum creatinine concentration and iothalamate GFR as risk factors for death and kidney failure., Design: Observational study using serum cystatin C assayed from baseline samples of the Modification of Diet in Renal Disease Study (1989-1993)., Setting: 15 clinical centers in the United States that participated in the Modification of Diet in Renal Disease Study., Participants: 825 trial participants with stage 3 or 4 nondiabetic CKD who had measurements of serum cystatin C., Measurements: All-cause mortality, cardiovascular (CVD) mortality, and kidney failure until December 2000., Results: Mean cystatin C level, creatinine concentration, and GFR were 2.2 mg/L (SD, 0.7), 212.16 micromol/L (SD, 88.4) (2.4 mg/dL [SD, 1.0]), and 33 mL/min per 1.73 m2 (SD, 12), respectively. Median follow-up was 10 years. Twenty-five percent of patients (n = 203) died of any cause, 15% (n = 123) died of CVD, and 66% (n = 548) reached kidney failure. In multivariate-adjusted models, 1-SD decreases in 1/creatinine, GFR, and 1/cystatin C were associated with increased risks for all-cause mortality of 1.27 (95% CI, 1.06 to 1.49), 1.27 (CI, 1.08 to 1.49), and 1.41 (CI, 1.18 to 1.67), respectively. For CVD mortality, the increased risks were 1.32 (CI, 1.05 to 1.64), 1.28 (CI, 1.04 to 1.59), and 1.64 (CI, 1.28 to 2.08), respectively. For kidney failure, the increased risks were 2.81 (CI, 2.48 to 3.18), 2.41 (CI, 2.15 to 2.70), and 2.36 (CI, 2.10 to 2.66), respectively., Limitation: The Modification of Diet in Renal Disease Study cohort may not be representative of all patients with nondiabetic CKD because participants were more likely to reach kidney failure than death in follow-up., Conclusion: The association of cystatin C level with all-cause and CVD mortality was as strong as or perhaps stronger than that of iothalamate GFR with these outcomes in stage 3 or 4 CKD.

Purpose: We sought to reexpress the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation for estimation of glomerular filtration rate (GFR) using serum creatinine (S(cr)) standardized to reference methods., Methods: Serum specimens included creatinine reference materials prepared by the College of American Pathologists (CAP), traceable to primary reference material at the NIST, with assigned values traceable to isotope dilution mass spectrometry (IDMS), a calibration panel prepared by the Cleveland Clinic Research Laboratory (CCRL), and frozen samples from the MDRD Study. Split specimens were measured at the CCRL using the Roche enzymatic and Beckman CX3 kinetic alkaline picrate assays., Results: Roche enzymatic assay results on CAP samples were comparable to IDMS-assigned values. Beckman CX3 assay results in 2004-2005 were significantly higher than but highly correlated with simultaneous Roche enzymatic assay results (r(2) = 0.9994 on 40 CCRL samples) and showed minimal but significant upward drift from Beckman CX3 assay results during the MDRD Study in 1989-1991 (r(2) = 0.9987 in 253 samples). Combining these factors, standardized S(cr) = 0.95 x original MDRD Study S(cr). The reexpressed 4-variable MDRD Study equation for S(cr) (mg/dL) is GFR = 175 x standardized S(cr)(-1.154) x age(-0.203) x 1.212 (if black) x 0.742 (if female), and for S(cr) (micromol/L) is GFR = 30849 x standardized S(cr)(-1.154) x age(-0.203) x 1.212 (if black) x 0.742 (if female) [GFR in mL x min(-1) x (1.73 m(2))(-1)]., Conclusion: When the calibration of S(cr) methods is traceable to the S(cr) reference system, GFR should be estimated using the MDRD Study equation that has been reexpressed for standardized S(cr).

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 relationship between total homocysteine (tHcy) and outcomes has not been investigated in patients with chronic kidney disease stages 3 to 4., Methods and Results: The Modification of Diet in Renal Disease Study was a randomized, controlled trial of 840 patients. Serum tHcy was measured in frozen samples collected at baseline (n=804). Survival status and cause of death were obtained from the National Death Index. To evaluate its association with all-cause and cardiovascular disease (CVD) mortality, tHcy was evaluated both as tertiles (<14.7, 14.7 to 19.5, > or =19.6 micromol/L) and as a continuous variable (per 10/micromol/L). Participants had a mean age of 52+/-12 years and glomerular filtration rate (GFR) of 33+/-12 mL/min per 1.73 m2; 60% were male, and 85% were white. During a median follow-up of 10 years, 195 (24%) died from any cause, and 118 (15%) from CVD. The level of GFR was lower and proteinuria higher in the highest tHcy tertile. There was no association between the highest tertile of tHcy and all-cause (hazard ratio [HR]; 95% confidence interval [CI[, 1.32, 0.94 to 1.85) or CVD (HR; 95% CI, 1.50, 0.96 to 2.34) mortality in univariate analyses; this association was further attenuated by adjustment for GFR (HR; 95% CI all-cause, 1.04, 0.72 to 1.51; CVD, 1.20, 0.73 to 1.95). There was no association between tHcy as a continuous variable and all-cause (0.98, 0.83 to 1.16) or CVD (1.04, 0.85 to 1.27) mortality., Conclusions: Hyperhomocystinemia does not appear to be a risk factor for all-cause or CVD mortality in the Modification of Diet in Renal Disease Study. Prior studies demonstrating an association between tHcy and CVD risk may have inadequately adjusted for the confounding effects of kidney function.

In the general population, hyperglycemia in the absence of diabetes may be associated with increased risk for mortality. Hyperglycemia is prevalent in chronic kidney disease; however, the relationship between glycosylated hemoglobin (HbA(1c)) as a marker of chronic hyperglycemia and outcomes has not been studied in nondiabetic chronic kidney disease. HbA(1c) was measured at baseline in the randomized cohort of the Modification of Diet in Renal Disease Study (n = 840). Participants with diabetes (n = 43), fasting glucose levels >126 mg/dl (n = 20), or missing HbA(1c) levels (n = 9) were excluded. Survival status until December 2000 was obtained from the National Death Index. Death was classified as cardiovascular (CVD) when the primary cause was International Classification of Disease, Ninth Revision codes 390 to 459. Cox models were performed to assess the relationship of HbA(1c) with all-cause and CVD mortality. Mean (SD) age was 52 (12) years, and mean (SD) GFR was 32 (12) ml/min per 1.73 m(2). Eighty-six percent of participants were white, and 61% were male. Mean (SD) HbA(1c) was 5.6% (0.5). A total of 169 (22%) patients died, 96 (13%) from CVD. After adjustment for randomization assignments and demographic, CVD, and kidney disease factors, HbA(1c) was a predictor of all-cause mortality (hazard ratio per 1% increase 1.73; 95% confidence interval 1.24 to 2.41; P = 0.001). There was a trend toward statistical significance in the relationship between HbA(1c) and CVD mortality (hazard ratio per 1% increase 1.53; 95% confidence interval 0.96 to 2.43; P = 0.07). HbA(1c) is associated with increased mortality in nondiabetic kidney disease. Hyperglycemia may be a potential therapeutic target and HbA(1c) may be important as a risk stratification tool in this high-risk population.

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: Hypertension is a risk factor for progression of chronic kidney disease. The optimal blood pressure to slow progression is unknown., Objective: To evaluate the effects of a low target blood pressure on kidney failure and all-cause mortality., Design: Long-term follow-up of the Modification of Diet in Renal Disease Study, a randomized, controlled trial conducted from 1989 to 1993., Setting: 15 outpatient nephrology practices., Participants: 840 persons with predominantly nondiabetic kidney disease and a glomerular filtration rate of 13 to 55 mL/min per 1.73 m2., Intervention: A low target blood pressure (mean arterial pressure < 92 mm Hg) or a usual target blood pressure (mean arterial pressure < 107 mm Hg)., Measurements: After the randomized trial was completed, kidney failure (defined as initiation of dialysis or kidney transplantation) and a composite outcome of kidney failure or all-cause mortality were ascertained through 31 December 2000., Results: Kidney failure occurred in 554 participants (66%), and the composite outcome occurred in 624 participants (74%). After Cox proportional hazards modeling and intention-to-treat analysis, the adjusted hazard ratios were 0.68 (95% CI, 0.57 to 0.82; P < 0.001) for kidney failure and 0.77 (CI, 0.65 to 0.91; P = 0.0024) for the composite outcome in the low target blood pressure group compared with the usual target blood pressure group. Evidence was insufficient to conclude that the benefit of a low target blood pressure differed according to the cause of kidney disease, baseline glomerular filtration rate, or degree of proteinuria., Limitations: The exact mechanism underlying the benefit of a low target blood pressure is unknown., Conclusions: Assignment to a low target blood pressure slowed the progression of nondiabetic kidney disease in patients with a moderately to severely decreased glomerular filtration rate.

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: Risk for coronary heart disease is high among patients with chronic kidney disease., Objective: To compare the prevalence of low apolipoprotein A1 levels and elevated apolipoprotein B, plasma fibrinogen, lipoprotein(a), homocysteine, and C-reactive protein levels by estimated glomerular filtration rate (GFR)., Design: Cross-sectional study., Setting: Third National Health and Nutrition Examination survey., Participants: 12 547, 3180, and 744 persons with estimated GFRs of at least 90, 60 to 89, or less than 60 mL/min per 1.73 m2, respectively, who were at least 18 years of age., Measurements: Chronic kidney disease was defined as an estimated GFR of less than 60 mL/min per 1.73 m2 based on the abbreviated Modification of Diet in Renal Disease formula., Results: After standardization for age, race or ethnicity, and sex, lower estimated GFR (> or =90, 60 to 89, or <60 mL/min per 1.73 m2) was associated with lower average levels of apolipoprotein A1 (1.44, 1.43, and 1.35 g/L) and higher levels of apolipoprotein B (1.03, 1.06, and 1.08 g/L), plasma fibrinogen (8.43, 8.44, and 9.53 micromol/L), homocysteine (8.5, 10.0, and 13.2 micromol/L), and C-reactive protein (3.0, 2.9, and 3.9 mg/L) (P < 0.05 for all values). The multivariate-adjusted odds ratios of an apolipoprotein A1 level of less than 1.2 g/L, a serum lipoprotein(a) level of at least 1.61 micromol/L (> or =45.3 mg/dL), a plasma fibrinogen level of at least 10.35 micromol/L, a serum homocysteine level of at least 15 micromol/L, and a C-reactive protein level of at least 10.0 mg/L for participants with chronic kidney disease compared with those with a GFR of at least 90 mL/min per 1.73 m2 or greater were 1.92 (95% CI, 1.02 to 3.63), 1.82 (CI, 1.06 to 3.13), 1.74 (CI, 1.35 to 2.24), 8.23 (CI, 5.00 to 13.6), and 1.93 (CI, 1.33 to 2.81), respectively., Conclusions: Levels of apolipoprotein A1 are decreased and levels of homocysteine, lipoprotein(a), fibrinogen, and C-reactive protein are increased among patients with chronic kidney disease.

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.)

Background: The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. However, approximately half of AVFs fail to mature. The use of angiotensin converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) exerts favorable endothelial effects and may promote AVF maturation. We tested associations of ACE-I and ARBs, CCBs, beta-blockers, and diuretics with the maturation of newly created AVFs.Methods: We evaluated 602 participants from the Hemodialysis Fistula Maturation Study, a multi-center, prospective cohort study of AVF maturation. We ascertained the use of each medication class within 45 days of AVF creation surgery. We defined maturation outcomes by clinical use within 9 months of surgery or 4 weeks of initiating hemodialysis.Results: Unassisted AVF maturation failure without intervention occurred in 54.0% of participants, and overall AVF maturation failure (with or without intervention) occurred in 30.1%. After covariate adjustment, CCB use was associated with a 25% lower risk of overall AVF maturation failure (95% CI 3%-41% lower) but a non-significant 10% lower risk of unassisted maturation failure (95% CI 23% lower to 5% higher). ACE-I/ARB, beta-blocker, and diuretic use was not significantly associated with AVF maturation outcomes. None of the antihypertensive medication classes were associated with changes in AVF diameter or blood flow over 6 weeks following surgery.Conclusions: CCB use may be associated with a lower risk of overall AVF maturation failure. Further studies are needed to determine whether CCBs might play a causal role in improving AVF maturation outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) and it is especially common among Blacks. Left ventricular hypertrophy (LVH) is an important subclinical marker of CVD, but there are limited data on racial variation in left ventricular structure and function among persons with CKD. METHODS In a cross-sectional analysis of the Chronic Renal Insufficiency Cohort Study, we compared the prevalence of different types of left ventricular remodeling (concentric hypertrophy, eccentric hypertrophy, and concentric remodeling) by race/ethnicity. We used multinomial logistic regression to test whether race/ethnicity associated with different types of left ventricular remodeling independently of potential confounding factors. RESULTS We identified 1,164 non-Hispanic Black and 1,155 non-Hispanic White participants who completed Year 1 visits with echocardiograms that had sufficient data to categorize left ventricular geometry type. Compared to non-Hispanic Whites, non-Hispanic Blacks had higher mean left ventricular mass index (54.7 ± 14.6 vs. 47.4 ± 12.2 g/m2.7; P < 0.0001) and prevalence of concentric LVH (45.8% vs. 24.9%). In addition to higher systolic blood pressure and treatment with >3 antihypertensive medications, Black race/ethnicity was independently associated with higher odds of concentric LVH compared to White race/ethnicity (odds ratio: 2.73; 95% confidence interval: 2.02, 3.69). CONCLUSION In a large, diverse cohort with CKD, we found significant differences in left ventricular mass and hypertrophic morphology between non- Hispanic Blacks and Whites. Future studies will evaluate whether higher prevalence of LVH contribute to racial/ethnic disparities in cardiovascular outcomes among CKD patients. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic kidney disease (CKD). In this study, we examined the association between inflammation and AF in 3,762 adults with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. AF was determined at baseline by self-report and electrocardiogram (ECG). Plasma concentrations of interleukin(IL)-1, IL-1 Receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, transforming growth factor-β, high sensitivity C-Reactive protein, and fibrinogen, measured at baseline. At baseline, 642 subjects had history of AF, but only 44 had AF in ECG recording. During a mean follow-up of 3.7 years, 108 subjects developed new-onset AF. There was no significant association between inflammatory biomarkers and past history of AF. After adjustment for demographic characteristics, comorbid conditions, laboratory values, echocardiographic variables, and medication use, plasma IL-6 level was significantly associated with presence of AF at baseline (Odds ratio [OR], 1.61; 95% confidence interval [CI], 1.21 to 2.14; P = 0.001) and new-onset AF (OR, 1.25; 95% CI, 1.02 to 1.53; P = 0.03). To summarize, plasma IL-6 level is an independent and consistent predictor of AF in patients with CKD. [ABSTRACT FROM AUTHOR]

Background: Anemia is common among patients with chronic kidney disease (CKD) but its health consequences are poorly defined. The aim of this study was to determine the relationship between anemia and cognitive decline in older adults with CKD.Methods: We studied a subgroup of 762 adults age ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) study. Anemia was defined according to the World Health Organization criteria (hemoglobin <13 g/dL for men and <12 g/dL for women). Cognitive function was assessed annually with a battery of six tests. We used logistic regression to determine the association between anemia and baseline cognitive impairment on each test, defined as a cognitive score more than one standard deviation from the mean, and mixed effects models to determine the relation between anemia and change in cognitive function during follow-up after adjustment for demographic and clinical characteristics.Results: Of 762 participants with mean estimated glomerular filtration rate of 42.7 ± 16.4 ml/min/1.73 m(2), 349 (46 %) had anemia. Anemia was not independently associated with baseline cognitive impairment on any test after adjustment for demographic and clinical characteristics. Over a median 2.9 (IQR 2.6-3.0) years of follow-up, there was no independent association between anemia and change in cognitive function on any of the six cognitive tests.Conclusions: Among older adults with CKD, anemia was not independently associated with baseline cognitive function or decline. [ABSTRACT FROM AUTHOR]

Background: Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function. Methods: Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory. Results: LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001), IL-1RA (1.23 [1.13, 1.34], p<0.0001), IL-6 (1.25 [1.14, 1.36], p<0.001) and TNF-α (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001) and IL-6 (1.34 [1.21, 1.49], p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005). Conclusion: In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction. [ABSTRACT FROM AUTHOR]

Background: Previous reports of the longitudinal association between achieved blood pressure (BP) and end-stage renal disease (ESRD) among patients with chronic kidney disease (CKD) have not incorporated time-updated BP with appropriate covariate adjustment. Objective: To assess the association between baseline and time-updated systolic blood pressure (SBP) with CKD progression. Design: Observational, prospective cohort study. (ClinicalTrials .gov: NCT00304148) Setting: 7 U.S. clinical centers. Patients: Patients in the Chronic Renal Insufficiency Cohort Study (n = 3708) followed for a median of 5.7 years (25th to 75th percentile, 4.6 to 6.7 years). Measurements: The mean of 3 seated SBP measurements made up the visit-specific SBP. Time-updated SBP was the mean of that and all previous visits. Outcomes were ESRD and the composite end point of ESRD or halving of the estimated glomerular filtration rate. Analyses investigating baseline and time-updated SBP used Cox proportional hazards models and marginal structural models, respectively. Results: Systolic blood pressure was 130 mm Hg or greater at all visits in 19.2% of patients. The hazard ratio for ESRD among patients with SBP of 130 to 139 mm Hg, compared with SBP less than 120 mm Hg, was 1.46 (95% CI, 1.13 to 1.88) using only baseline data and 2.37 (CI, 1.48 to 3.80) using time-updated data. Among patients with SBP of 140 mm Hg or greater, corresponding hazard ratios were 1.46 (CI, 1.18 to 1.88) and 3.37 (CI, 2.26 to 5.03) for models using only baseline data and those using time-updated data, respectively. Limitation: Blood pressure was measured once annually, and the cohort was not a random sample. Conclusion: Time-updated SBP greater than 130 mm Hg was more strongly associated with CKD progression than analyses based on baseline SBP. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the reliability and validity of the Kidney Disease Quality of Life Short Form 36 (KDQOL-36™) in Hispanics with mild-to-moderate chronic kidney disease (CKD). Design: Cross-sectional Setting: Chronic Renal Insufficiency Cohort Study Participants: 420 Hispanic (150 English- and 270 Spanish-speakers), and 409 non-Hispanic White individuals, matched by age (mean 57 years), sex (60% male), kidney function (mean estimated glomerular filtration rate 36m1/min/1 .73m²), and diabetes (70%). Methods: To measure construct validity, we selected instruments, comorbidities, and laboratory tests related to at least one KDQOL-36™ subscale. Reliability was determined by calculating Cronbach's alpha. Results: Reliability of each KDQOL-36TM subscale [SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS), Symptoms/Problems, Burden of Kidney Disease and Effects of Kidney Diseasel was very good (Cronbach's alpha >0.8). Construct validity was supported by expected negative correlation between MCS scores and the Beck Depression Inventory in all three subgroups (r= -0.56 to -0.61, P<.0001). There was inverse correlation between the Symptoms/ Problems subscale and the Patient Symptom Form (r= -0.70 to -0.77, P<.0001). We also found significant, positive correlation between the PCS score and a physical activity survey (r= +0.29 to +0.38, P<.003); and between the PCS and MCS scores and the Kansas City Questionnaire (r= +0.31 to +0.64, P<.0001). Reliability and validity were similar across all racial/ethnic groups analyzed separately. Conclusion: Our findings support the use of the KDQOL-36™ as a measure of HRQOL in this cohort of US Hispanics with CKD. [ABSTRACT FROM AUTHOR]

The article presents a study seeking to determine whether the drug clopidogrel reduces early failure of hemodialysis fistulas among patients treated with hemodialysis. The design, setting, and participants of the double-blind, placebo controlled trial involving 877 patients with end-stage renal disease or advanced chronic kidney disease are detailed. The main outcomes measured were fistula thrombosis and failure of the fistula to become suitable for dialysis. Researchers conclude that clopidogrel was capable of reducing the frequency of early thrombosis of arteriovenous fistulas, but it failed to increase the proportion of fistulas that became suitable for dialysis.

The article discusses the effects of Renin-Angiotensin system-blocking therapy for the hypertensive chronic kidney disease (CKD) of African Americans in the U.S. According to the authors, CKD is a major public health problem in the country, especially among the black subjects. They said that 4.5 million Americans have hypertensive CKD, and another 110,000 persons have end-stage renal diseases (ESRD) due to hypertension. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and a low blood pressure goal stabilize the glomerular filtration rate and prevent ESRD during 4.5 years.

In patients with hypertensive nephrosclerosis, the African American Study of Kidney Disease and Hypertension (AASK) demonstrated the superiority of angiotensin-converting enzyme inhibitor therapy in blunting progression of renal disease compared with a β blocker and a dihydropyridine calcium channel blocker. In addition, the study found that a blood pressure treatment strategy that resulted in an achieved blood pressure of 128/78 mm Hg (low blood pressure goal)was no more effective in slowing the progression of renal disease than a strategy that resulted in a blood pressure of 141/85 mm Hg (usual blood pressure goal). AASK, which enrolled only African Americans with mild to moderate chronic renal insufficiency, also provided an opportunity to evaluate recruitment methods in minority populations. Eighty-three percent of patients were recruited through screening in clinical practice. To randomize 635 patients, 558, 295 charts were reviewed (approximately 879 charts per randomized patient). More than half of the randomized patients (n=635 or 58%) were found by chart review. Sixty percent of women with creatinine levels considered within the normal range had at least mild chronic renal insufficiency. Screening in clinical practice was the most effective strategy to recruit participants with mild to moderate chronic renal insufficiency and hypertension into the clinical trial. This technique may also be an effective approach in trials of other essentially asymptomatic conditions. [ABSTRACT FROM AUTHOR]

Background: Risk for coronary heart disease is high among patients with chronic kidney disease. Objective: To compare the prevalence of low apolipoprotein A1 levels and elevated apolipoprotein B, plasma fibrinogen, lipoprotein(a), homocysteine, and C-reactive protein levels by estimated glomerular filtration rate (GFR). Design: Cross-sectional study.Setting: Third National Health and Nutrition Examination survey. Participants: 12 547, 3180, and 744 persons with estimated GFRs of at least 90, 60 to 89, or less than 60 mL/min per 1.73 m², respectively, who were at least 18 years of age.Measurements: Chronic kidney disease was defined as an estimated GFR of less than 60 mL/min per 1.73 m² based on the abbreviated Modification of Diet in Renal Disease formula. Results: After standardization for age, race or ethnicity, and sex, lower estimated GFR (≥ 90, 60 to 89, or <60 mL/min per 1.73 m² ) was associated with lower average levels of apolipoprotein A1 (1.44, 1.43, and 1.35 g/L) and higher levels of apolipoprotein B (1.03, 1.06, and 1.08 g/L), plasma fibrinogen (8.43, 8.44, and 9.53 μmol/L), homocysteine (8.5, 10.0, and 13.2 μmol/L), and C-reactive protein (3.0, 2.9, and 3.9 mg/L) ( P < 0.05 for all values). The multivariate-adjusted odds ratios of an apolipoproteinA1 level of less than 1.2 g/L, a serum lipoprotein(a) level of at least 1.61 μmol/L (≥ 45.3 mg/dL), a plasma fibrinogen level of at least 10.35 μmol/L, a serum homocysteine level of at least 15 μmol/L, and a C-reactive protein level of at least 10.0 mg/L forparticipants with chronic kidney disease compared with those with a GFR of at least 90 mL/min per 1.73 m² or greater were 1.92 (95% CI, 1.02 to 3.63), 1.82 (CI, 1.06 to 3.13), 1.74 (CI, 1.35 to 2.24), 8.23 (CI, 5.00 to 13.6), and 1.93 (CI, 1.33 to 2.81), respectively. Conclusions: Levels of apolipoprotein A1 are decreased and levels of homocysteine, lipoprotein(a), fibrinogen, and C-reactiveprotein are incre... [ABSTRACT FROM AUTHOR]

Background: Hematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study.Methods: Participants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD. Presence of hematuria (positive dipstick) from a single urine sample was the primary predictor. Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and death, over a median follow-up of 7.3 years, analyzed using Cox Proportional Hazards models. Net reclassification indices (NRI) and C statistics were calculated to evaluate their predictive performance.Results: Hematuria was observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and higher levels of urinary albumin > 1.0 g/day (36% vs. 10%). In multivariable-adjusted analysis, individuals with hematuria had a greater risk for all outcomes during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68, Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2: 1.77), and these associations were attenuated, thereafter. Based on NRIs and C-statistics, no clear improvement in the ability to improve prediction of study outcomes was observed when hematuria was included in multivariable models.Conclusion: In a large adult cohort with CKD, hematuria was associated with a significantly higher risk of CKD progression and death in the first 2 years of follow-up but did not improve risk prediction. [ABSTRACT FROM AUTHOR]

Although iron is commonly used to correct iron deficiency anemia (IDA) in chronic kidney disease (CKD), its effect on kidney function is unclear. To assess this, we randomly assigned patients with stage 3 and 4 CKD and IDA to either open-label oral ferrous sulfate (69 patients to 325 mg three times daily for 8 weeks) or intravenous iron sucrose (67 patients to 200 mg every 2 weeks, total 1 g). The primary outcome was the between-group difference in slope of measured glomerular filtration rate (mGFR) change over two years. The trial was terminated early on the recommendation of an independent data and safety monitoring board based on little chance of finding differences in mGFR slopes, but a higher risk of serious adverse events in the intravenous iron treatment group. mGFR declined similarly over two years in both treatment groups (oral -3.6 ml/min per 1.73 m(2), intravenous -4.0 ml/min per 1.73 m(2), between-group difference -0.35 ml/min per 1.73 m(2); 95% confidence interval -2.9 to 2.3). There were 36 serious cardiovascular events among 19 participants assigned to the oral iron treatment group and 55 events among 17 participants of the intravenous iron group (adjusted incidence rate ratio 2.51 (1.56-4.04)). Infections resulting in hospitalizations had a significant adjusted incidence rate ratio of 2.12 (1.24-3.64). Thus, among non-dialyzed patients with CKD and IDA, intravenous iron therapy is associated with an increased risk of serious adverse events, including those from cardiovascular causes and infectious diseases. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated impact of the gene encoding apolipoprotein L1 (APOL1) variants on chronic kidney disease progression. It describes design, oversight and procedures of the African American Study of Kidney Disease and Hypertension (AASK) and the Chronic Renal Insufficiency Cohort (CRIC) study. It also explores end-stage renal disease risk for African American patients, APOL1 risk based on proteinuria status and APOL1 risk based on randomized blood pressure.

Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this, we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331-420 days) of baseline. Baseline plasma FGF23 was not associated with the prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its coreceptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: Despite the large burden of chronic kidney disease (CKD) in Hispanics, this population has been underrepresented in research studies. We describe the recruitment strategies employed by the Hispanic Chronic Renal Insufficiency Cohort Study, which led to the successful enrollment of a large population of Hispanic adults with CKD into a prospective observational cohort study. Recruitment efforts by bilingual staff focused on community clinics with Hispanic providers in high-density Hispanic neighborhoods in Chicago, academic medical centers, and private nephrology practices. Methods of publicizing the study included church meetings, local Hispanic print media, Spanish television and radio stations, and local health fairs. From October 2005 to July 2008, we recruited 327 Hispanics aged 21–74years with mild-to-moderate CKD as determined by age-specific estimated glomerular filtration rate (eGFR). Of 716 individuals completing a screening visit, 49% did not meet eGFR inclusion criteria and 46% completed a baseline visit. The mean age at enrollment was 57.1 and 67.1% of participants were male. Approximately 75% of enrolled individuals were Mexican American, 15% Puerto Rican, and 10% had other Latin American ancestry. Eighty two percent of participants were Spanish-speakers. Community-based and academic primary care clinics yielded the highest percentage of participants screened (45.9% and 22.4%) and enrolled (38.2% and 24.5%). However, academic and community-based specialty clinics achieved the highest enrollment yield from individuals screened (61.9% to 71.4%). A strategy focused on primary care and nephrology clinics and the use of bilingual recruiters allowed us to overcome barriers to the recruitment of Hispanics with CKD. [Copyright &y& Elsevier]

Background: Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR. Methods: Using cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials. Results: Mean measured GFRs were 68 and 70 ml per minute per 1.73 m2 of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine–cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m2 with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m2 with the creatinine equation and the cystatin C equation (P=0.07 and P=0.05), respectively. Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m2, respectively [P=0.001 and P<0.001]), and the results were more accurate (percentage of estimates that were >30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P<0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m2, the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m2 or greater than or equal to 60 ml per minute per 1.73 m2 (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 as having a GFR of 60 ml or higher per minute per 1.73 m2. Conclusions: The combined creatinine–cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.) [ABSTRACT FROM PUBLISHER]

This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. [ABSTRACT FROM AUTHOR]

Background. Chronic kidney disease (CKD) is a major public health burden in Western countries but little is known about its impact in developing countries. We estimated the prevalence and absolute burden of CKD in the general adult population in China. Methods. A cross-sectional survey was conducted in a nationally representative sample of 15,540 Chinese adults aged 35 to 74 years in 2000 and 2001. Serum creatinine was measured using the modified kinetic Jaffe reaction method at a central laboratory calibrated to the Cleveland Clinic Foundation laboratory. Glomerular filtration rate (GFR) was estimated using the simplified equation developed by the Modification of Diet in Renal Disease study. CKD was defined as an estimated GFR <60 mL/min/1.73m2. Results. Overall, the age-standardized prevalences of GFR 60 to 89, 30 to 59, and <30 mL/min/1.73m2 were 39.4%, 2.4%, and 0.14%, respectively, in Chinese adults aged 35 to 74 years. The overall prevalence of CKD (GFR <60 mL/min/1.73m2) was 2.53%, representing 11,966,653 persons (1.31% or 3,185,330 men and 3.82% or 8,781,323 women). The age-specific prevalence of CKD was 0.71%, 1.69%, 3.91%, and 8.14% among persons 35 to 44, 45 to 54, 55 to 64, and 65 to 74 years old, respectively. The age-standardized prevalence of CKD was similar in urban (2.60%) and rural (2.52%) residents but was higher in south China (3.05%) than in north China (1.78%) residents. Conclusion. Although the prevalence of CKD in China was relatively low, the population absolute burden is substantial. These data warrant a national program aimed at detection, prevention, and treatment of CKD in China. [ABSTRACT FROM AUTHOR]

Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins.Background.Data are limited on the determinants of homocysteine (tHcy) and its relationship with nutritional indices, and dietary protein intake, in the earlier stages of chronic kidney disease (CKD).Methods.Levels of tHcy were assayed at baseline (N= 804) and 1 year postrandomization (N= 678) in the Modification of Diet in Renal Disease (MDRD) Study[study A, glomerular filtration rate (GFR) 25 to 55 mL/min/1.73 m2 and study B GFR 13 to 24 mL/min/1.73 m2]. Participants were randomly assigned to different blood pressure targets and protein diets and all subjects received a multivitamin supplement containing 1 mg of folic acid, 10 mg pyridoxal 5′-phosphate (PLP) and 6μg of vitamin B12. Multivariable analyses were used to evaluate determinants of tHcy at baseline and 1 year.Results.The prevalence of hyperhomocysteinemia (tHcy>15μmol/L) at baseline was 56% in study A and 85% in study B. Baseline tHcy was negatively correlated with measures of body fat and dietary protein intake. Folate, vitamin B12, and GFR were the major determinants of tHcy levels. Of the patients with hyperhomocysteinemia at baseline, 49% and 24% reduced their tHcy levels at 1 year to≤15μmol/L in study A and study B, respectively. There was no association between dietary protein intake and odds of developing hyperhomocysteinemia at 1 year in study A (P= 0.94) or study B (P= 0.10).Conclusion.Hyperhomocysteinemia is partly amenable to correction by vitamin supplementation in CKD stages 3 and 4. There is insufficient evidence to suggest that low tHcy is associated with poor nutritional status in the MDRD Study cohort. B vitamins and GFR, but not dietary protein, are the major determinants of tHcy in this patient population. [ABSTRACT FROM AUTHOR]

Racial differences in health-related quality of life among hemodialysis patients. Background. Despite technical progress in therapy, hemodialysis patients continue to report health-related quality of life (HRQOL) substantially lower than that of the general population. While African Americans with end-stage renal disease (ESRD) survive longer than members of other races, few studies have compared the HRQOL of African Americans with that of non-African Americans. Methods. We examined differences in sociodemographic, clinical, and HRQOL variables by race. A multiple regression model assessed the extent to which race was associated with differences in HRQOL scores after adjustment for sociodemographic and clinical variables. Racial differences in the relationship between comorbid disease severity and HRQOL were explored. Results. In adjusted models, African Americans had higher scores in the Index of Well-Being and burden of kidney disease, but lower scores in cognitive function (all P < 0.05). For scales reflecting symptoms and effects of kidney disease, sleep quality, and the Physical Component Summary, the fall in HRQOL with increasing comorbidity was significantly greater in non-African Americans (all P < 0.05). After adjustment, there were no racial differences in scores on the Mental Component Summary, social support, dialysis staff encouragement, or patient satisfaction. Conclusion. To our knowledge, ESRD is the only chronic illness for which African Americans report significantly better psychologic well being and a lower burden of disease than non-African Americans. Further research is needed to understand whether these experiences affect health care utilization, medical decision making, and patient survival. Clarification of the reasons for race differences may suggest measures to improve HRQOL for all patients with ESRD. [ABSTRACT FROM AUTHOR]

Background: Restricting protein intake and controlling hypertension delay the progression of renal disease in animals. We tested these interventions in 840 patients with various chronic renal diseases. Methods: In study 1, 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were randomly assigned to a usual-protein diet or a low-protein diet (1.3 or 0.58 g of protein per kilogram of body weight per day) and to a usual- or a low-blood-pressure group (mean arterial pressure, 107 or 92 mm Hg). In study 2, 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were randomly assigned to the low-protein diet (0.58 g per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement, and a usual- or a low-blood-pressure group (same values as those in study 1). An 18-to-45-month follow-up was planned, with monthly evaluations of the patients. Results: The mean follow-up was 2.2 years. In study 1, the projected mean decline in the glomerular filtration rate at three years did not differ significantly between the diet groups or between the blood-pressure groups. As compared with the usual-protein group and the usual-blood-pressure group, the low-protein group and the low-blood-pressure group had a more rapid decline in the glomerular filtration rate during the first four months after randomization and a slower decline thereafter. In study 2, the very-low-protein group had a marginally slower decline in the glomerular filtration rate than did the low-protein group (P = 0.07). There was no delay in the time to the occurrence of end-stage renal disease or death. In both studies, patients in the low-blood-pressure group who had more pronounced proteinuria at base line had a significantly slower rate of decline in the glomerular filtration rate. Conclusions: Among patients with moderate renal insufficiency, the slower decline in renal function that started four months after the introduction of a low-protein diet suggests a small benefit of this dietary intervention. Among patients with more severe renal insufficiency, a very-low-protein diet, as compared with a low-protein diet, did not significantly slow the progression of renal disease. (N Engl J Med 1994;330:877-84.) [ABSTRACT FROM AUTHOR]