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Mineral metabolites and CKD progression in African Americans.

ABSTRACT: CKD progresses more rapidly to ESRD among African Americans compared with Caucasians. Disordered mineral metabolism is more severe among African Americans with CKD, which might partially explain the accelerated progression of their kidney disease. Here, using data from the African American Study of Kidney Disease and Hypertension, we evaluated longitudinal changes in serum levels of fibroblast growth factor-23 (FGF23), parathyroid hormone (PTH), phosphate, and 25-hydroxyvitamin D in a subset of 420 participants followed for a median of 4 years. We also examined the association of baseline levels of mineral metabolites with risk for ESRD or death in 809 participants. FGF23, PTH, and phosphate levels rose over time; participants with faster rates of decline in measured GFR had the greatest increases in these parameters (P<0.01 for each). Higher baseline levels of FGF23, PTH, and phosphate each associated with increased risk for ESRD or death independent of GFR. FGF23 exhibited a dose-response relationship with outcomes (HR=1.30 per doubling, 95% CI=1.15-1.47; HR=2.24 for highest compared with lowest quartile, 95% CI=1.39-3.60), whereas PTH and phosphate showed nonlinear relationships. Vitamin D insufficiency (<30 ng/ml) was present in 95% of participants, but lower levels did not independently associate with outcomes. Using death-censored ESRD as the outcome produced qualitatively similar results. In conclusion, abnormalities of mineral metabolism worsen with progressive CKD and associate with higher risk for ESRD among African Americans with hypertensive nephrosclerosis.

SUBMITTER: Scialla JJ

PROVIDER: S-EPMC3537219 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Mineral metabolites and CKD progression in African Americans.

Scialla Julia J JJ Astor Brad C BC Isakova Tamara T Xie Huiliang H Appel Lawrence J LJ Wolf Myles M

Journal of the American Society of Nephrology : JASN 20121214 1

CKD progresses more rapidly to ESRD among African Americans compared with Caucasians. Disordered mineral metabolism is more severe among African Americans with CKD, which might partially explain the accelerated progression of their kidney disease. Here, using data from the African American Study of Kidney Disease and Hypertension, we evaluated longitudinal changes in serum levels of fibroblast growth factor-23 (FGF23), parathyroid hormone (PTH), phosphate, and 25-hydroxyvitamin D in a subset of ...[more]

PMID: 23243213

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Project description:Novel biomarkers that more accurately reflect kidney function and predict future CKD are needed. The human metabolome is the product of multiple physiologic or pathophysiologic processes and may provide novel insight into disease etiology and progression. This study investigated whether estimated kidney function would be associated with multiple metabolites and whether selected metabolomic factors would be independent risk factors for incident CKD.In total, 1921 African Americans free of CKD with a median of 19.6 years follow-up among the Atherosclerosis Risk in Communities Study were included. A total of 204 serum metabolites quantified by untargeted gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry was analyzed by both linear regression for the cross-sectional associations with eGFR (specified by the Chronic Kidney Disease Epidemiology Collaboration equation) and Cox proportional hazards model for the longitudinal associations with incident CKD.Forty named and 34 unnamed metabolites were found to be associated with eGFR specified by the Chronic Kidney Disease Epidemiology Collaboration equation with creatine and 3-indoxyl sulfate showing the strongest positive (2.8 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, 2.1 to 3.5) and negative association (-14.2 ml/min per 1.73 m(2) per +1 SD; 95% confidence interval, -17.0 to -11.3), respectively. Two hundred four incident CKD events with a median follow-up time of 19.6 years were included in the survival analyses. Higher levels of 5-oxoproline (hazard ratio, 0.70; 95% confidence interval, 0.60 to 0.82) and 1,5-anhydroglucitol (hazard ratio, 0.68; 95% confidence interval, 0.58 to 0.80) were significantly related to lower risk of incident CKD, and the associations did not appreciably change when mutually adjusted.These data identify a large number of metabolites associated with kidney function as well as two metabolites that are candidate risk factors for CKD and may provide new insights into CKD biomarker identification.

Project description:Background and objectivesDisorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors.Design, setting, participants, & measurementsIn a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490).ResultsCompared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (P<0.001 for all). Among African Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (Ptrend<0.01) in unadjusted analyses. In linear regression models adjusted for socio-demographic characteristics, kidney function, serum phosphorus, and dietary phosphorus intake, higher percentage of African ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, P<0.001) and fractional excretion of phosphorus (each 10% higher African ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01).ConclusionsA higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional excretion of phosphorus among African Americans with CKD. These findings suggest that genetic variability might contribute to racial differences in urinary phosphorus excretion in CKD.

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Dataset Information

Mineral metabolites and CKD progression in African Americans.

Publications

Mineral metabolites and CKD progression in African Americans.

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