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

Nephrol Dial Transplant. 2018 Dec 1;33(12):2139-2145. doi: 10.1093/ndt/gfy074.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cholestanetriol 26-Monooxygenase / genetics
  • Cytochrome P450 Family 2 / genetics
  • Genome-Wide Association Study
  • Glomerular Filtration Rate*
  • Humans
  • Kidney / physiopathology*
  • Mendelian Randomization Analysis*
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Polymorphism, Single Nucleotide*
  • Vitamin D / blood*
  • Vitamins / blood

Substances

  • Vitamins
  • Vitamin D
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • Oxidoreductases Acting on CH-CH Group Donors
  • 7-dehydrocholesterol reductase