Adverse muscle composition is an independent and strong predictor of all-cause mortality in CKD, with affected individuals facing a hazard ratio of 4.21 after full adjustment for demographic, lifestyle, and clinical factors.
Key Findings
Results
Adverse muscle composition (AMC) was highly prevalent in the CKD population studied, affecting nearly one-third of participants.
Prevalence of AMC was 32.3% among 894 participants with CKD
AMC was defined as the coexistence of low muscle volume (z-score <25th percentile, <-0.68 SD) and high muscle fat infiltration (MFI >75th percentile; >7.69% in men and >8.82% in women)
Thresholds were based on published UK Biobank imaging reference values
The cohort had a mean age of 72.2±5.8 years, BMI of 29±5.3 kg/m², and mean eGFR of 53.5±6.4 ml/min per 1.73 m²
Results
AMC was significantly associated with higher all-cause mortality in unadjusted analyses.
Unadjusted hazard ratio for all-cause mortality with AMC vs. normal muscle composition was 6.17 (95% CI, 2.36 to 16.15; P < 0.001)
50 participants died during a mean follow-up of 3.6 years
Mortality differences were visualized using Kaplan-Meier curves
Total cohort included 894 participants with CKD (eGFR CystatinC <60 ml/min per 1.73 m²) and available mortality data
Results
The association between AMC and all-cause mortality remained significant after full adjustment for multiple confounders.
Adjusted hazard ratio was 4.21 (95% CI, 1.49 to 11.84; P = 0.007)
Covariates adjusted for included sex, age, BMI, proteinuria, low hand grip strength, physical activity, smoking, alcohol, previous diagnosis of cancer, prevalent cardiovascular heart diseases, and type 2 diabetes
The adjusted model attenuated but preserved the strong association seen in unadjusted analyses (HR reduced from 6.17 to 4.21)
Cox regression was used for both unadjusted and adjusted analyses
Methods
Muscle composition was quantified non-invasively using MRI-based methods, including both muscle volume and muscle fat infiltration.
Thigh fat-free muscle volume and MFI were quantified using magnetic resonance imaging and AMRA Researcher software
Muscle volume was expressed as a sex-invariant and BMI-invariant z-score to allow standardized comparisons
Participants were identified from the UK Biobank imaging study cohort with eGFR CystatinC <60 ml/min per 1.73 m²
Mortality data were obtained through the UK Biobank's linkage to national death registries
Results
The study cohort was predominantly older, overweight, and slightly more male than female.
52.5% of participants were male
Mean age was 72.2±5.8 years
Mean BMI was 29±5.3 kg/m², indicating an overweight population on average
Mean eGFR was 53.5±6.4 ml/min per 1.73 m², consistent with CKD stages G3a-G3b
Conclusions
The authors concluded that preservation of muscle composition may represent an important therapeutic target in CKD management.
AMC was described as identifying 'a high-risk population' within CKD
The authors stated that 'preservation of muscle composition may represent an important therapeutic consideration and potential target for future interventions in CKD management'
Muscle health evaluation was proposed to 'identify patients at high risk and support targeted prevention strategies'
Prior literature linked AMC to comorbidity, poor function in CKD, and increased mortality in metabolic disorders and the general population
What This Means
This research suggests that people with chronic kidney disease (CKD) who have poor muscle health — specifically, low muscle volume combined with excess fat within their muscles — face a dramatically higher risk of dying prematurely. Using MRI scans from nearly 900 UK Biobank participants with CKD, the researchers found that about one in three had this 'adverse muscle composition,' and those individuals were more than four times as likely to die during the roughly 3.6-year follow-up period, even after accounting for age, sex, obesity, lifestyle factors, and other medical conditions like heart disease and diabetes.
The study used advanced MRI analysis to measure both the amount of muscle in participants' thighs and how much fat had infiltrated that muscle tissue. This dual measure — capturing both muscle quantity and quality — proved to be a powerful predictor of survival, stronger than many traditional risk factors used in kidney disease management. The finding held up even after statistically controlling for factors like hand grip strength, physical activity, smoking, and the presence of cancer or cardiovascular disease.
This research suggests that routinely assessing muscle health in CKD patients could help clinicians identify those at the highest risk of premature death, potentially opening the door to targeted interventions aimed at preserving or improving muscle composition. While the study does not specify which interventions would be most effective, it highlights muscle health as a potentially important and underappreciated consideration in the care of people with kidney disease.
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A. Indurain, Markus Karlsson, Anders Fernström, Fredrik Uhlin, Ma˚rten Segelmark, O. Dahlqvist Leinhard. (2026). Adverse Muscle Composition Is Associated with All-Cause Mortality in CKD: A UK Biobank Imaging Study.. American Society of Nephrology. Clinical Journal. https://doi.org/10.2215/cjn.0000001049