Abstract
BACKGROUND: Although sarcopenia is associated with an increased risk of chronic kidney disease (CKD), its potential associations with subsequent comorbidities among patients with CKD remain unknown. METHODS: This prospective study included 19,502 participants with CKD, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2). Sarcopenia is characterized according to muscle strength, muscle mass, and physical performance; low muscle strength, commonly measured using handgrip strength, is considered the most important indicator. The study outcome was post-CKD comorbidity. Multivariable Cox proportional hazards models were used to analyze the effect of sarcopenia on comorbidities. Population attributable fractions (PAFs) and potential impact fractions (PIFs) were used to quantify the population-level burden and potential benefit of improving handgrip strength. RESULTS: During a median follow-up of 10.6 years, 5,374 participants developed one comorbidity, 2,972 developed two comorbidities, and 2,434 developed three or more comorbidities. Sarcopenia was associated with a graded increase in multimorbidity risk (approximately 12, 24, and 33% higher for one, two, and three or more comorbidities, respectively, versus non-sarcopenia). Lower handgrip strength exhibited a clear exposure-response, and the lowest tertiles was associated with the greatest risk across outcomes. Among individual comorbid diseases, the strongest association was observed with osteoporosis. PAFs indicated that 5.21, 13.72, and 23.46% of cases involving one, two, or three or more comorbidities, respectively, were attributable to sarcopenia. Analysis of PIFs indicated that improving handgrip strength throughout the population (i.e., shifting lower to higher tertiles) could reduce the burden of one, two, and three or more comorbidities by approximately 12, 16, and 22%, respectively. CONCLUSION: The results indicate that sarcopenia, especially low handgrip strength, increases the risk of developing comorbidities, particularly osteoporosis, among patients with CKD. Quantification of PAFs and PIFs underscores the clinical and public health potential of muscle strength assessment and strength-preserving interventions to mitigate the CKD-associated comorbidity burden.