Creatinine muscle index in UK Biobank: comparison with MRI and associations with frailty and mortality.

Abstract

Background: Skeletal muscle wasting due to aging, acute illness, and chronic disease is associated with adverse outcomes including mortality, frailty, and multi-morbidity. We investigated the relationship of creatinine muscle index (CMI), a serum biological signature of muscle mass, in UK Biobank participants with gold standard muscle measurement and adverse outcomes. Method(s): We compared CMI with Magnetic Resonance Imaging (MRI) measured muscle mass in 33 799 participants using linear regression. We then assessed CMI's ability to discriminate low muscle mass (<=2.5 SD below the mean). In the full UK Biobank cohort (n = 450 812), we utilized Cox-proportional hazards models to investigate associations between CMI with mortality, frailty and comorbidity. Result(s): CMI demonstrated moderate to good linear correlation with gold-standard MRI muscle mass measurements [R males: 0.68 (0.60-0.76); females: 0.65 (0.56-0.73)], after accounting for data imbalance. CMI discriminated muscle mass <=2.5 standard deviations from the mean, with an area under the curve of 0.80 (95% CI:0.75-0.86) in males and 0.84 (95% CI:0.78-0.89) in females. CMI consistently decreased with increasing age, frailty and comorbidity. Over an 8-year follow-up, lower CMI was associated with higher morality: adjusted hazard ratio for the 25th vs 75th CMI centiles were 0.61 (95% CI: 0.58-0.66) in males and 0.72 (95% CI: 0.66-0.78) in females. Conclusion(s): In over 450 000 UK Biobank participants, low CMI was significantly associated with baseline comorbidity, frailty and survival on follow-up (independent of age, sex, and comorbidity). This study supports CMI as a potential biological signature for skeletal muscle wasting in clinical and research settings. Copyright © The Author(s) 2026. Published by Oxford University Press on behalf of the ERA. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.