The association of serum magnesium and chronic kidney disease: a two-sample mendelian randomization study of European descent

Abstract

Background: Previous observational studies focused on the association of serum magnesium (SMg) and chronic kidney disease (CKD), but the conclusion was inconsistent. To investigate the causal relationship of SMg and CKD, we performed a two-sample mendelian randomization (TSMR) analysis using publicly datasets.

Method: In mendelian randomization (MR) analysis, we used single nucleotide polymorphisms (SNPs) which had genetic statistical significance with SMg but not associated with kidney function and confounding factors as instrumental variable (IV). To select SNPs, we used publicly database of Genome Wide Association Study (GWAS) and Chronic Kidney Disease Genetics (CKDGen) Confirms. We used inverse-variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode approaches in TSMR analysis.

Results: We selected 4 SNPs (rs4072037, rs7965584, rs11144134 and rs448378) as IV. In IVW approach, the result of MR analysis for CKD was OR = 0.55, 95% CI: 0.06, 4.75, P = 0.58; for estimated glomerular filtration rate from creatinine (eGFR)crea was β = -0.06, 95% CI: -1.08, 0.07, P = 0.39; for estimated glomerular filtration rate from cystatin C (eGFR)cys was β = -0.03, 95% CI: -0.43, 0.36, P = 0.86, respectively per SD increase in SMg. When subgroup by diabetes mellitus (DM), the results for DM-eGFRcrea was β = -0.33, 95% CI: -0.85, 0.19, P = 0.21; and for non-DM-eGFRcrea was β = -0.03, 95% CI: -0.16, 0.11, P = 0.71. The results of other four MR approaches were consistent with IVW approach (all P > 0.05).

Conclusion: Our TSMR analysis showed that SMg had no causal effect on kidney function and progress CKD in European descent. As for the results about overall population, the verified study is needed in future study.