Genetic African Ancestry and Markers of Mineral Metabolism in CKD

Abstract

Background and objectives: Disorders 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, & measurements: In 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).

Results: Compared 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).

Conclusions: A 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.

Keywords: African Americans; Cohort Studies; Fibroblast Growth Factors; Humans; Phosphorus; Renal Insufficiency, Chronic; chronic kidney disease; mineral metabolism; parathyroid hormone.

Copyright © 2016 by the American Society of Nephrology.

Figures

Figure 1.

Flow diagram indicating derivation of final analyzed study sample.

Figure 2.

Differences in markers of phosphorus metabolism by self-reported race and across quartiles of African ancestry among African Americans. Mean (SD) values of (A) serum phosphorus (mg/dL), (B) 24-hour urinary phosphorus (mg/day), and (C) fractional excretion of phosphorus (%) in European Americans (EA) compared with African Americans (AA), and across quartiles of percentage genetic African ancestry among African Americans (Q1–Q4). The range of percentage African ancestry in each quartile is as follows: Q1 <73.6%; Q2 73.6%–79.6%; Q3 79.7%–83.8%; Q4: >83.8%. *P<0.05 comparing European Americans to African Americans; †Ptrend <0.05 across Q1–Q4 African Americans.