Muscle matters: Transforming the care of intensive care unit acquired sarcopenia and myosteatosis

Table 2 Biomarkers for assessing muscle wasting in intensive care unit

Biomarker	What it measures	Advantages	Limitations	Clinical utility
3-MH (urine)	Myofibrillar protein breakdown (release of 3-MH from muscle proteins)	Specific marker of skeletal muscle catabolism and quantifies muscle protein breakdown	Affected by diet and renal function; not routinely available in clinical laboratories	Used in research to quantify muscle breakdown; rarely clinical due to confounders and complexity
Creatinine-based indices (e.g., creatinine height index)	Muscle mass proxy based on creatinine production (muscle-derived creatinine per 24 hours or per body size)	Simple, historically used in nutrition assessment; based on urine or blood creatinine	Assumes stable renal function, confounded by fluid shifts, and insensitive to acute changes	Limited in ICU; low creatinine may indicate low muscle mass but requires caution without renal failure
Muscle enzymes (e.g., CK)	Muscle fiber damage or necrosis (CK leaks into blood with muscle membrane injury)	Widely available; elevated CK indicates acute muscle injury (e.g., rhabdomyolysis)	Not a marker of chronic atrophy; normal CK can mask wasting, while elevations may reflect other injuries	Detects acute muscle injury but not ICU sarcopenia; normal CK with weakness suggests critical illness myopathy over necrosis
Inflammatory markers (CRP, interleukin-6, tumour necrosis factor-α)	Systemic inflammatory response driving catabolic state	Easily measured (e.g., CRP); elevated levels reflect illness severity and catabolic drive	Non-specific; do not assess muscle directly; sustained inflammation promotes muscle breakdown and organ dysfunction	Helps identify patients at risk of muscle loss from catabolic inflammation; highlights need for anti-inflammatory and nutritional strategies, but not a direct muscle metric
Hormonal signals (e.g., IGF-1, cortisol, myostatin)	Anabolic vs catabolic hormonal milieu (IGF-1 promotes muscle synthesis; myostatin inhibits it; cortisol catabolic)	Reflect muscle growth pathway activity; low IGF-1 or high myostatin associate with atrophy in research	Research-only, with specialized assays, complex interactions, and no ICU-specific reference ranges	Studied as therapeutic targets (e.g., myostatin inhibitors, growth hormone axis) in ICU trials; not for routine monitoring

CK: Creatinine kinase; CRP: C-reactive protein; ICU: Intensive care unit; IGF: Insulin-like growth factor; 3-MH: 3-methylhistidine.