Adverse Muscle Composition Is Associated with All-Cause Mortality in CKD: A UK Biobank Imaging Study

Adverse muscle composition is common in CKD; affected individuals face a higher risk of premature death. Adverse muscle composition is an independent and strong predictor of all-cause mortality in CKD. Muscle health evaluation can identify patients at high risk and support targeted prevention strategies.

Adverse muscle composition (AMC), defined by low muscle volume and increased muscle fat infiltration (MFI), has been associated with comorbidity and poor function in CKD, and increased mortality in metabolic disorders and the general population. We investigated whether magnetic resonance imaging-derived muscle composition is associated with all-cause mortality in a UK Biobank (UKB) imaging study among participants with CKD.

UKB participants with CKD (eGFR CystatinC <60 ml/min per 1.73 m 2 ) were identified. Thigh fat-free muscle volume and MFI were quantified using magnetic resonance imaging and AMRA Researcher. Muscle volume was expressed as a sex-invariant and BMI (body mass index)-invariant z -score. AMC was defined as the coexistence of low muscle volume (z-score <25th percentile, <-0.68 SD) and high MFI (>75th percentile; >7.69% in men and >8.82% in women), on the basis of published UKB imaging thresholds. The mortality data were obtained through the UKB's linkage to national death registries. All-cause mortality was investigated using Kaplan-Meier curves and Cox regression. Models were adjusted for sex, age, BMI, proteinuria, low hand grip strength, physical activity, smoking, alcohol, previous diagnosis of cancer, prevalent cardiovascular heart diseases, and type 2 diabetes.

A total of 894 participants with CKD and available mortality data were included (52.5% male, mean±SD age 72.2±5.8 years, BMI 29±5.3 kg/m 2 , eGFR 53.5±6.4 ml/min per 1.73 m 2 ). Prevalence of AMC was 32.3%. During a mean follow-up of 3.6 years, 50 participants died. AMC was significantly associated with higher all-cause mortality compared with normal muscle composition in unadjusted analyses (hazard ratio, 6.17; 95% confidence interval, 2.36 to 16.15, P < 0.001) and remained significant after adjustment for demographic, lifestyle factors, proteinuria, and clinical factors (hazard ratio, 4.21; 95% confidence interval, 1.49 to 11.84; P = 0.007).

AMC is associated with greater risk of all-cause mortality in participants with CKD, identifying a high-risk population. Preservation of muscle composition may represent an important therapeutic consideration and potential target for future interventions in CKD management.