Causal Effect of Chondroitin, Glucosamine, Vitamin, and Mineral Intake on Kidney Function: A Mendelian Randomization Study.

The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = -0.113%, standard error (SE) = 0.03%, p-value = 2 × 10-4; glucosamine, eGFR change beta = -0.240%, SE = 0.035%, p-value = 6 × 10-12). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, p-value = 1 × 10-25). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.

Genetically Predicted Body Selenium Concentration and estimated GFR: A Mendelian Randomization Study.

Introduction: Selenium is a trace mineral that is commonly included in micronutrient supplements. The effect of selenium on kidney function remains unclear. A genetically predicted micronutrient and its association with estimated glomerular filtration rate (eGFR) can be used to assess the causal estimates by Mendelian randomization (MR). Methods: In this MR study, we instrumented 11 genetic variants associated with blood or total selenium levels from a previous genome-wide association study (GWAS). The association between genetically predicted selenium concentration and eGFR was first assessed by summary-level MR in the chronic kidney disease(CKDGen) GWAS meta-analysis summary statistics, including 567,460 European samples. Inverse-variance weighted and pleiotropy-robust MR analyses were performed, in addition to multivariable MR adjusted for the effects of type 2 diabetes mellitus. Replication analysis was performed with individual-level UK Biobank data, including 337,318 White individuals of British ancestry. Results: Summary-level MR analysis indicated that a genetically predicted 1 SD increase in selenium concentration was significantly associated with lower eGFR (-1.05 [-1.28, -0.82] %). The results were similarly reproduced by pleiotropy-robust MR analysis, including MR-Egger and weighted-median methods, and consistent even in the multivariable MR adjusted for diabetes. In the UK Biobank data, genetically predicted higher selenium concentration was also significantly associated with lower eGFR (- 0.36 [-0.52, -0.20] %), and the results were similar when body mass index, waist circumference, hypertension, and diabetes mellitus covariates were adjusted (-0.33 [-0.50, -0.17] %). Conclusion: This MR study supports the hypothesis that higher genetically predicted body selenium is causally associated with lower eGFR.