Body Composition and Kidney Outcomes: A Cohort Study of Rapid Kidney Function Decline and a Mendelian Randomization Analysis of CKD Incidence

Abstract

Rationale & Objective

Chronic kidney disease (CKD) is a global health issue, potentially arising from rapid kidney function decline (RKFD). Although body composition influences various metabolic disorders, its relationship with kidney outcomes remains unclear. This study aimed to investigate the impact of body composition on RKFD and CKD risk.

Study Design

A cohort study assessed the relationship between body composition and RKFD. A 2-sample Mendelian randomization approach investigated genetic evidence linking body composition to CKD risk.

Setting & Participants

In total, 229 adults aged 50-70 years with normal kidney function were recruited from Huadong Hospital in Shanghai, China.

Predictors

Body composition indicators include fat mass, lean mass, appendicular lean mass index, fat mass index, total and regional body fat percentages, and sarcopenic obesity, defined by high body fat percentages (>27% in men, >38% in women) and low lean mass (appendicular lean mass index <7.26 kg/m² in men, <5.45 kg/m² in women).

Outcomes

The primary outcome was RKFD. The second was genetically predicted CKD risk.

Analytical Approach

Cox regression and subgroup analyses assessed observational associations. The Mendelian randomization study used two-sample Mendelian randomization, multivariable, and bidirectional Mendelian randomization.

Results

RKFD occurred in 9.9% of participants. Lower appendicular lean mass index and the presence of sarcopenic obesity were associated with higher RKFD risk. In overweight participants and those with baseline estimated glomerular filtration rate >90 mL/min/1.73 m², the negative association between appendicular lean mass index and RKFD remained significant. Mendelian randomization analysis revealed that genetically predicted legs and whole-body fat percentages increased CKD risk, whereas appendicular muscle mass was negatively associated with CKD.

Limitations

Differences between the outcomes require further validation. Some sample overlap in the Mendelian randomization analysis may introduce bias.

Conclusions

Lower appendicular lean mass index and sarcopenic obesity were associated with RKFD. Higher leg and whole-body fat percentages and lower appendicular muscle mass significantly contribute to CKD risk, highlighting the importance of body composition in kidney health.

Plain Language Summary

Body composition, such as fat and muscle mass and percentage, may play a role in kidney outcomes. In this study, we followed a group of middle-aged to old adults with normal kidney function to see how body composition affects how quickly kidney function declines over time. We further explore whether genetically predicted fat percentages and lean mass in certain body parts can increase the risk of developing chronic kidney disease. We found that people with less muscle and with higher body fat percentage were more likely to experience rapid kidney function decline or develop kidney disease, suggesting body composition management may prevent kidney problems.