A blood test-derived skeletal muscle index combined with handgrip strength identifies a sarcopenia-related high-risk phenotype in non-dialysis-dependent chronic kidney disease
Shunsuke Yamada, Shigeru Tanaka, Kenji Harada, Hisako Yoshida, Hiromasa Kitamura, Hokuto Arase, Masumi Shojima, Kazuhiko Tsuruya, Toshiaki Nakano, Tetsuro AgoAbstract
Background
Sarcopenia is associated with adverse outcomes in CKD, but direct assessment of skeletal muscle mass is not always available. We examined whether serum creatinine- and cystatin C-derived estimated skeletal muscle index (SMI), combined with handgrip strength, identifies a sarcopenia-related high-risk phenotype in non-dialysis-dependent CKD.
Methods
We derived a new equation for appendicular skeletal muscle mass using bioelectrical impedance analysis as the reference in 100 patients with non-dialysis-dependent CKD. In an independent multicenter cohort of 1,403 patients, SMI was estimated using this equation and a published creatinine-cystatin C-based formula. The sarcopenia-related high-risk phenotype was defined as low handgrip strength plus low estimated SMI using sex-specific cutoffs. Outcomes were all-cause, cardiovascular, and non-cardiovascular mortality.
Results
During 5 years, 173 patients died, including 43 from cardiovascular causes. Low estimated SMI was identified in 218 patients (15.5%) with the published formula and 312 (22.2%) with the new equation; the corresponding phenotype prevalences were 11.9% and 11.7%. The phenotype was independently associated with all-cause mortality using either formula: adjusted hazard ratios were 1.54 (95% confidence interval [CI], 1.07-2.21) for the published formula and 2.14 (95% CI, 1.52-3.00) for the new equation. Four-category and sensitivity analyses yielded consistent findings.
Conclusions
Combining handgrip strength with creatinine- and cystatin C-derived estimated SMI identifies a sarcopenia-related high-risk phenotype and stratifies mortality risk in non-dialysis-dependent CKD. This approach may support screening when direct muscle mass assessment is unavailable but requires further validation before use as a diagnostic substitute.