Negative effect of vitamin D on kidney function: a Mendelian randomization study.

TitleNegative effect of vitamin D on kidney function: a Mendelian randomization study.
Publication TypeJournal Article
Year of Publication2018
AuthorsTeumer, A, Gambaro, G, Corre, T, Bochud, M, Vollenweider, P, Guessous, I, Kleber, ME, Delgado, GE, Pilz, S, März, W, Barnes, CLK, Joshi, PK, Wilson, JF, de Borst, MH, Navis, G, van der Harst, P, Heerspink, HJL, Homuth, G, Endlich, K, Nauck, M, Köttgen, A, Pattaro, C, Ferraro, PManuel
Corporate AuthorsCKDGen Consortium
JournalNephrology, dialysis, transplantation
Date Published12/2018

Background: The kidney plays a central role in the regulation of vitamin D metabolism. It is not clear, however, whether vitamin D influences kidney function. Previous studies have reported conflicting results, which may have been influenced by reverse causation and residual confounding. We conducted a Mendelian randomization (MR) study to obtain unconfounded estimates of the association between genetically instrumented vitamin D metabolites and estimated glomerular filtration rate (eGFR) as well as the urinary albumin:creatinine ratio (UACR).

Methods: We performed a two-sample MR study based on three single nucleotide variants associated with 25(OH)D levels: rs2282679, rs10741657 and rs12785878, related to the genes GC, CYP2R1 and DHCR7, respectively. Estimates of the allele-dependent effects on serum 25(OH)D and eGFR/UACR were obtained from summary statistics of published genome-wide association meta-analyses. Additionally, we performed a one-sample MR analysis for both 25(OH)D and 1,25(OH)2 D using individual-level data from six cohorts.

Results: The combined MR estimate supported a negative causal effect of log transformed 25(OH)D on log transformed eGFR (β = -0.013, P = 0.003). The analysis of individual-level data confirmed the main findings and also revealed a significant association of 1,25(OH)2 D on eGFR (β = -0.094, P = 0.008). These results show that a 10% increase in serum 25(OH)D levels causes a 0.3% decrease in eGFR. There was no effect of 25(OH)D on UACR (β = 0.032, P = 0.265).

Conclusion: Our study suggests that circulating vitamin D metabolite levels are negatively associated with eGFR. Further studies are needed to elucidate the underlying mechanisms.

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First publication date (online)




Alternate JournalNephrol. Dial. Transplant.
Citation Key / SERVAL ID8864
Peer reviewRefereed
PubMed ID29718335


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