Creatinine production rate is an integrative indicator to monitor muscle status in critically ill patients

Background Both quantitative and qualitative aspects of muscle status significantly impact clinical outcomes in critically ill patients. Comprehensive monitoring of baseline muscle status and its changes is crucial for risk stratification and management optimization. However, repeatable and accessible indicators are lacking. We hypothesized that creatinine production rate (CPR) could serve as an integrative indicator of skeletal muscle status. Methods We conducted a series of animal and clinical studies. First, animal experiments were performed to determine whether CPR reflects not only muscle volume, but also qualitative muscle properties. We also evaluated the effects of acute systemic inflammation, a common feature of critical illness, on CPR, as well as its impact on muscle volume and metabolism. In clinical studies, we analyzed CPR, calculated based on urinary creatinine excretion and changes in serum creatinine, of critically ill patients. We assessed the factors affecting CPR on ICU admission and its temporal changes. Finally, we evaluated the clinical utility of CPR by examining the associations of the CPR index (CPR divided by height squared) on ICU admission and its changes with one-year survival. Results Animal studies revealed that CPR is determined by muscle volume, creatine content, and metabolic status. Systemic inflammation accompanied by muscle loss led to reduced CPR. Moreover, even without muscle loss, systemic inflammation decreased CPR, likely due to metabolic derangements. In ICU patients, CPR on admission strongly correlated with muscle cross-sectional area (CSA), with age and sex as additional significant factors. In contrast, the percent change in CPR showed a weak correlation with muscle CSA changes. Additionally, the acute-phase CPR trajectories did not show a consistent decline, suggesting multifactorial influences. In a cohort of 629 ICU patients, lower baseline CPR index (hazard ratio [HR] 1.125 per 0.1 g/day/m(2) less, P < .001) and a decrease in CPR over the first three days (HR 1.028 per 5%, P = 0.032) were independently associated with higher one-year mortality. Conclusions CPR represents an integrative indicator of skeletal muscle status in critically ill patients, reflecting both quantitative and qualitative aspects. Monitoring CPR in the ICU may facilitate risk stratification and optimization of patient care.