Urea-to-Creatinine Ratio as a Marker of Metabolic Transition in Septic Shock: A Comparison With Indirect Calorimetry

Urea-to-Creatinine Ratio as a Marker of Metabolic Transition in Septic Shock: A Comparison with Indirect Calorimetry

INTRODUCTION: Patients with septic shock develop profound metabolic alterations characterized by hypermetabolism and accelerated protein catabolism, leading to loss of lean body mass and worse clinical outcomes. Indirect calorimetry is the gold standard for assessing energy expenditure and metabolic demand in critically ill patients; however, it is not widely available in ICUs.

The urea-to-creatinine ratio has been proposed as a simple and readily available marker of protein catabolism. Nevertheless, its relationship with measured energy expenditure remains unclear.

HYPOTHESIS: The urea/creatinine ratio may be an efficient catabolism marker to guide nutritional therapy in critically ill patients. Evidence to confirm this hypothesis can be obtained by comparing the urea-to-creatinine ratio with indirect calorimetry, which is the gold standard for evaluating energy expenditure and metabolic demands in these patients.

OBJECTIVES: The primary objective of this study is to evaluate the correlation between the urea-to-creatinine ratio and energy expenditure measured by indirect calorimetry in patients with septic shock, in order to identify the transition from the catabolic to the anabolic phase. This transition is expected to be reflected by a reduction in the urea-to-creatinine ratio accompanied by a decrease in measured energy expenditure.

Secondary objectives include the analysis of inflammatory activity over time, as assessed by C-reactive protein (CRP) levels.

METHODS: This is a prospective observational cohort study including adult patients with septic shock, defined according to Sepsis-3 criteria, admitted to a 53-bed medical-surgical intensive care unit between April 2026 and March 2027. Eligible patients will be required to have undergone invasive mechanical ventilation for at least three consecutive days and to have had energy expenditure measured by indirect calorimetry.

Indirect calorimetry assessments will be performed on days 1, 4, 7, 11, 14, 17, and 20 after ICU admission. Patients will be excluded if they had a serum creatinine level greater than 4.0 mg/dL at hospital admission, chronic kidney disease requiring dialysis, initiation of renal replacement therapy during ICU stay, or if they require an inspired oxygen fraction (FiO₂) greater than 70% on the fourth day of mechanical ventilation.

Energy expenditure measurements will be obtained using the E-COVX module integrated into the Carescape B650 monitor (GE Healthcare, Helsinki, Finland). Urea and creatinine levels will be collected daily, and the urea-to-creatinine rati calculated accordingly. CRP levels will also be measured as an indicator of systemic inflammation.

For analysis, energy expenditure, urea-to-creatinine ratio, and CRP values will be grouped into three time periods based on days since initiation of mechanical ventilation: days 1-4, days 7-11, and days 14-20.

Demographic and clinical data to be collected include age, sex, Simplified Acute Physiology Score III (SAPS III), Sequential Organ Failure Assessment (SOFA) score at admission, admission category (medical or surgical), the sepsis focus and relevant comorbidities. Data will be collected prospectively using standardized case report forms.

Written informed consent will be obtained from patients or their legal representatives. The study protocol will be submitted for approval to the Research Ethics Committee of Hospital São Domingos