# Associations of Creatinine Muscle Index with markers of sarcopenia and mortality in chronic kidney disease: A prospective cohort study

## TL;DR

The study shows that a new muscle index called CMI is linked to better muscle function and lower death risk in people with chronic kidney disease.

## Contribution

The study demonstrates that CMI is a better predictor of sarcopenia and mortality than existing creatinine-cystatin C indices in CKD patients.

## Key findings

- Lower CMI is associated with weaker grip strength and slower walking speed in CKD patients.
- Higher CMI is linked to a 15% lower death risk in men and 23% in women with CKD.
- CMI outperforms other kidney function indices in predicting sarcopenia and mortality in CKD.

## Abstract

Sarcopenia is common in chronic kidney disease (CKD) and linked to higher mortality, but identifying those at risk remains challenging. Indices combining serum creatinine and cystatin C (eGFRratio and eGFRdifference) have been studied, but have tended to perform worse in those with CKD. This study aimed to examine the relationship of Creatinine Muscle Index (CMI), an estimate of glomerular filtration of creatinine, with sarcopenia and mortality in a non-dialysis CKD population.

NURTuRE-CKD is a prospective, multicentre cohort study of people with non-dialysis CKD in the UK. Two thousand nine hundred ninety-six individuals were enrolled between July 2017 and September 2019. Cystatin C measurements were available in 2,930 adults. CMI (mg/day) was calculated as eGFR cystatin C × serum creatinine concentration. The relationships between CMI and: (1) probable sarcopenia (defined as the best hand grip strength of <27 kg for males and <16 kg for females); (2) individual muscle function measures including hand grip strength (kg) and timed get-up-and-go (TUG) (seconds); (3) all-cause mortality were assessed using Spearman’s correlation, logistic regression, and Cox proportional hazards models, stratified by sex and adjusted for age, ethnicity, body mass index, smoking status, Charlson Comorbidity Index, urine albumin-to-creatinine ratio, and C-reactive protein. TUG test is the time taken to stand from a chair, walk 3 m, turn, return, and sit down. Among 1,723 males and 1,207 females, the median (IQR) age was 66 (53–74) years, and the median eGFRcreatinine was 34 (24–47) ml/min/1.73m2. A total of 806 participants (27.5%) had probable sarcopenia, and over a median follow-up period of 50 (41 to 56) months, 527 (18%) died. The adjusted OR for probable sarcopenia per 100 mg/day increase in CMI was OR 0.72 (95% CI 0.67, 0.78 p value <0.001) in males and OR 0.81 (95% CI 0.73, 0.89 p value < 0.001) in females. CMI correlated positively with grip strength (ρ = 0.47 [0.43, 0.50] and 0.45 [0.40, 0.49]) and negatively with TUG (ρ = –0.37 [−0.41, −0.32] and −0.44 [−0.49, −0.40]) in males and females, respectively. In adjusted models, the HR for mortality per 100 mg/day increase in CMI was HR 0.85 (95% CI 0.78, 0.90 p value < 0.001) in males and HR 0.77 (95% CI 0.67, 0.87 p value < 0.001) in females. In males and females, respectively, the C-index of CMI for probable sarcopenia (0.73 and 0.71) and mortality (0.70 and 0.76) was higher than that of the eGFR ratio (probable sarcopenia: 0.64 and 0.61; mortality: 0.60 and 0.65; all p < 0.001) and the eGFR difference (probable sarcopenia: 0.59 and 0.57; mortality: 0.56 and 0.59; all p < 0.001) Limitations include the observational design, the assessment of muscle function without direct measurement of muscle mass, and limited generalisability to CKD populations not followed in secondary care.

In persons with CKD, CMI—a biomarker reflecting creatinine generation—was independently associated with muscle function and mortality, supporting its utility in populations with reduced kidney function.

Loss of muscle mass and strength (sarcopenia) is common in people with chronic kidney disease (CKD) and is linked to a higher risk of death and poorer quality of life.

Creatinine is a marker of kidney function, but is metabolised in muscle. Cystatin C is a measure of kidney function that is independent of muscle mass. Blood tests comparing cystatin C and creatinine have been used to estimate muscle mass, but they have been understudied and less accurate in people with CKD.

The Creatinine Muscle Index (CMI) is a newer measure that better reflects muscle-related creatinine production. Its usefulness in people with CKD had not been adequately tested.

The study included 2,930 adults with non-dialysis CKD from 16 kidney centres across the United Kingdom. Participants had their CMI and muscle function (grip strength and walking speed) measured and were followed for a median of 50 months.

In both men and women, lower CMI (indicating lower muscle mass) was linked to weaker hand grip strength, slower walking speed, and a higher risk of sarcopenia.

Higher CMI was also linked to a lower risk of death. For every 100 mg/day per 1.73 m2 increase in CMI, the risk of death fell by 15% in men and 23% in women. CMI outperformed other cystatin C-creatinine-based measures in predicting mortality and sarcopenia.

Because kidney disease affects how creatinine is processed, it was uncertain whether CMI would work well in people with CKD. This study shows that CMI remains independently associated with both muscle function and survival in this population.

Given the high rates of sarcopenia in CKD, CMI may be a useful tool to help identify people at higher risk of muscle loss and its related complications, supporting better monitoring and potential early interventions.

The main limitations are that this was an observational study and muscle strength was measured, but muscle mass itself was not directly assessed

Thomas McDonnell and colleagues examine the relationship of creatinine muscle index (CMI), an estimate of glomerular filtration of creatinine, with sarcopenia and mortality in a non-dialysis chronic kidney disease population.