Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Teumer, 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, PM.
Negative effect of vitamin D on kidney function: a Mendelian randomization study.
Nephrol Dial Transplant. 2018; 33(12): 2139-2145.
Doi: 10.1093/ndt/gfy074
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- Co-Autor*innen der Med Uni Graz
- März Winfried
- Pilz Stefan
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- Abstract:
- 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). 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. 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). Our study suggests that circulating vitamin D metabolite levels are negatively associated with eGFR. Further studies are needed to elucidate the underlying mechanisms.
- Find related publications in this database (Keywords)
- albuminuria
- causality
- glomerular filtration rate
- Mendelian randomization
- vitamin D