Causal effects of chronic kidney diseases, renal function, and dialysis on sarcopenia: Insights from a Mendelian randomization study.

Objective: Sarcopenia is prevalent among patients with chronic kidney diseases (CKD) with or without dialysis. This research aims to explore the causal effects of CKD, renal function, and dialysis on sarcopenia.

Methods: Instrumental variables including CKD, estimated creatinine-based glomerular filtration rate (eGFRcrea), estimated cystatin C-based GFR (eGFRcys), and dialysis were identified from a comprehensive genome-wide association study (GWAS). Sarcopenia-related traits, including appendicular lean mass (ALM), hand grip strength (HGS; left/right), low HGS (age 60 and above), and usual walking pace (UWP), were obtained from a meta-analysis of GWAS. Analysis was conducted using the two-sample Mendelian randomization (MR) method.

Results: MR analysis demonstrated that eGFRcrea was significantly associated with a risk of low HGS (OR = 3.33; 95% CI: 1.93 - 5.74; p < 0.001), ALM (OR = 0.32; 95% CI: 0.21 - 0.48; p < 0.001), HGS (left) (OR = 0.64; 95% CI: 0.55 - 0.74; p < 0.001), and HGS (right) (OR = 0.61; 95% CI: 0.52 - 0.71; p < 0.001). The Inverse-Variance-Weighting (IVW) analysis also revealed that dialysis was significantly associated with low HGS (OR = 1.07; 95% CI: 1.02 - 1.11; p = 0.0018). Sensitivity analysis indicated that the MR analysis was reliable. However, IVW analysis revealed that eGFRcys and CKD were not significantly associated with sarcopenia.

Conclusions: Our study suggests a causal effect of decline eGFRcrea and dialysis on sarcopenia.