TOPLINE:

In a cohort study using UK Biobank participants, the creatinine muscle index (CMI) — a blood biomarker calculated from serum creatinine and cystatin C — demonstrated a moderate-to-good positive correlation with MRI-derived muscle mass. Lower CMI values were significantly associated with increasing baseline frailty and multimorbidity and an increased risk for mortality.

METHODOLOGY:

• Researchers conducted an observational cohort study to compare the CMI with gold standard muscle mass measurements and to assess associations between CMI, frailty, comorbidities, and mortality in UK Biobank participants.
• A total of 450,812 UK Biobank participants (median age, 57 years for women and 58 years for men) with baseline serum creatinine and cystatin C measurements were included; 33,799 participants had MRI-derived muscle mass data, 34,728 had DEXA measurements, and 25,727 had both.
• The CMI estimated body surface area-normalised creatinine filtration, a surrogate of creatinine generation and muscle mass, and was calculated by multiplying the estimated glomerular filtration rate on the basis of cystatin C by serum creatinine and 14.4.
• Participants underwent assessments for sarcopenia, frailty, and comorbidity; area under the receiver operating characteristic curve analysis assessed the ability of the CMI to discriminate low muscle mass.
• The association between the CMI and all-cause mortality was assessed over an 8-year follow-up period.

TAKEAWAY:

• The CMI showed a moderate-to-good positive correlation with MRI-derived total thigh fat-free muscle volume (correlation coefficient [R], 0.68 [95% CI, 0.60-0.76] for men and R, 0.65 [95% CI, 0.56-0.73] for women).
• The CMI was able to discriminate very low muscle mass (≤ 2.5 SD below the mean), with area under the curve values of 0.80 (95% CI, 0.75-0.86) in men and 0.84 (95% CI, 0.78-0.89) in women.
• In the whole cohort, the CMI decreased with increasing age, higher Charlson Comorbidity Index, and increased frailty as measured using the Fried frailty phenotype.
• During follow-up, lower CMI values were associated with a higher risk for mortality in a non-linear manner, with adjusted hazard ratios of 0.61 (95% CI, 0.58-0.66) for men and 0.72 (95% CI, 0.66-0.78) for women, comparing individuals at the 25th vs 75th centile of the CMI.

IN PRACTICE:

"CMI could be an effective, simple and useful biological signature for screening individuals at risk of low muscle mass," the authors wrote.

"CMI may also serve as a surrogate endpoint for early phase interventional studies assessing muscle targeted interventions in chronic disease or after acute illness and as a screening tool for identifying potential muscle loss in the community and after recovery from acute illness," they added.

SOURCE:

This study was led by Giada Azzopardi, The Royal London Hospital, Barts Health NHS Trust, London, England. It was published online on May 09, 2026, in Clinical Kidney Journal.

LIMITATIONS:

The majority of participants had low levels of chronic disease and ill health. Muscle mass and blood biomarker measurements were often not performed simultaneously, with a median interval of 9.1 years, which may have influenced the results. Additionally, only 1.5% of the total cohort had a serum creatinine-based estimated glomerular filtration rate ≤ 60 mL/min/1.73 m², underrepresenting individuals with advanced chronic kidney disease.

DISCLOSURES:

Azzopardi reported receiving funding from the Barts Charity Academic Clinical Fellowship Support Grant. One author reported receiving honoraria for consultancy, educational support, and speaker fees from various pharmaceutical companies. Another author reported serving as the chair of the Acute Kidney Injury Scientific Section for the European Society of Intensive Care Medicine.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.