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

Area of Science:

• Nephrology
• Endocrinology
• Genetics

Background:

• The kidney is crucial for vitamin D metabolism.
• The impact of vitamin D on kidney function remains unclear due to conflicting studies.
• Previous research may be affected by reverse causation and confounding.

Purpose of the Study:

• To investigate the causal relationship between vitamin D metabolites and kidney function.
• To obtain unconfounded estimates of vitamin D's effect on eGFR and UACR.
• To utilize Mendelian randomization for robust causal inference.

Main Methods:

• Two-sample Mendelian randomization (MR) using genetic variants for 25(OH)D.
• One-sample MR analysis with individual-level data for 25(OH)D and 1,25(OH)2D.
• Analysis of summary statistics from genome-wide association meta-analyses and cohort data.

Main Results:

• A negative causal effect of 25(OH)D on eGFR was observed (β = -0.013, P = 0.003).
• Individual-level data confirmed this association and showed a significant effect of 1,25(OH)2D on eGFR (β = -0.094, P = 0.008).
• A 10% increase in 25(OH)D corresponds to a 0.3% decrease in eGFR; no effect on UACR was found.

Conclusions:

• Circulating vitamin D metabolite levels are negatively associated with eGFR.
• The findings suggest a causal link between vitamin D and kidney function.
• Further research is required to understand the underlying biological mechanisms.