Association between chronic kidney disease and sarcopenia: a national cohort study and two-step Mendelian randomization analysis.

OBJECTIVE

To investigate the causal relationships between chronic kidney disease (CKD) and sarcopenia using cohort data and Mendelian randomization (MR), and to further assess the mediating roles of physical activity and sedentary behavior using two-step MR.

METHODS

Data from 5648 participants in the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. A linear mixed-effects model was used to evaluate the relationship between CKD and sarcopenia. Two-sample MR was then utilized to assess the causality of the observed association. Additionally, we applied a two-step MR to evaluate the mediating role of physical activities in the pathway from CKD to sarcopenia.

RESULTS

Chronic kidney disease demonstrated a persistent and statistically significant association with elevated sarcopenia risk throughout the entire study period (P < 0.01). Similarly, lower estimated glomerular filtration rate (eGFR) showed a significant positive association with increased sarcopenia risk (P = 0.017). MR analysis further indicates a causal relationship between CKD and sarcopenia (Low hand grip strength: OR[95 %CI] = 0.920[0.874 to 0.969], P < 0.01) (Appendicular lean mass: β[95 %CI] = -0.028[-0.053 to -0.004], P = 0.024). Mediation analysis showed that sedentary behavior (mediation proportion = 3.050 %) and physical activity (mediation proportion = 2.869 %) had mediating effects.

CONCLUSIONS

CKD is an independent risk factor for sarcopenia, with a clear temporal association. Mendelian randomization studies confirm this link and identify sedentary behavior and physical activity as mediators. These results underscore the need for early screening and individualized intervention strategies in CKD patients to prevent sarcopenia.