Modifiers of Plasma 25-Hydroxyvitamin D and Chronic Kidney Disease Outcomes in Black Americans: The Jackson Heart Study

Abstract

Background: 25-hydroxyvitamin D [25(OH)D] is lower in black compared with white Americans but is not consistently associated with outcomes in this group, possibly due to genetic and other biological differences. We examined the association of plasma 25(OH)D and renal outcomes in black Americans with a focus on effect modifiers.

Methods: We studied associations between baseline 25(OH)D with (i) annual rate of estimated glomerular filtration rate (eGFR) decline and (ii) incident chronic kidney disease (CKD) in the Jackson Heart Study, a prospective cohort of black Americans. Plasma 25(OH)D levels were corrected for monthly variation in sunlight exposure using the residual method. We used adjusted generalized linear models to evaluate outcomes and assessed potential effect modification by diabetes mellitus, vitamin D binding protein (DBP) genotype, obesity, dietary sodium intake, and use of renin-angiotensin-aldosterone system inhibitors.

Results: Among 5164 participants with 25(OH)D available, plasma 25(OH)D was 14.5 ± 6.5 ng/mL (mean ± SD), and eGFR was 94.1 ± 22.0 mL/min/1.73 m2. Over a median of 8 years, eGFR decline was 1.3 ± 2.0 mL/min/1.73 m2 per year in 3228 participants with complete data, and 220 out of 1803 eligible participants developed incident CKD. Overall, 25(OH)D was not associated with eGFR decline in fully adjusted models. However, higher 25(OH)D was associated with slower eGFR decline among those with diabetes: each 5 ng/mL higher 25(OH)D was associated with a 0.27 mL/min/1.73 m2/y slower eGFR decline (95% CI, 0.13 to 0.41; P < 0.001). Higher 25(OH)D was not associated with incident CKD overall, but it was associated with lower odds of incident CKD among participants with the GG or GT genotype at rs7041 in the gene encoding DBP [OR, 0.69 per 5 ng/mL higher 25(OH)D; 95% CI, 0.51 to 0.93; P-interaction = 0.005]. Other interactions were not significant.

Conclusion: These findings support a potential benefit of higher 25(OH)D for kidney health in black Americans with diabetes or specific variants in DBP.