Renin as a Marker of Tissue-Perfusion and Prognosis in Critically Ill Patients*

Objectives: To characterize renin in critically ill patients. Renin is fundamental to circulatory homeostasis and could be a useful marker of tissue-perfusion. However, diurnal variation, continuous renal replacement therapy and drug-interference could confound its use in critical care practice. Design: Prospective observational study. Setting: Single-center, mixed medical-surgical ICU in Europe. Patients: Patients over 18 years old with a baseline estimated glomerular filtration rate greater than 30 mL/min/1.73 m(2) and anticipated ICU stay greater than 24 hours. Informed consent was obtained from the patient or next-of-kin. Interventions: Direct plasma renin was measured in samples drawn 6-hourly from arterial catheters in recumbent patients and from extracorporeal continuous renal replacement therapy circuits. Physiologic variables and use of drugs that act on the renin-angiotensin-aldosterone system were recorded prospectively. Routine lactate measurements were used for comparison. Measurements and Main Results: One-hundred twelve arterial samples (n = 112) were drawn from 20 patients (65% male; mean +/- sd, 60 +/- 14 yr old) with septic shock (30%), hemorrhagic shock (15%), cardiogenic shock (20%), or no circulatory shock (35%). The ICU mortality rate was 30%. Renin correlated significantly with urine output (repeated-measures correlation coefficient = -0.29; p = 0.015) and mean arterial blood pressure (repeated-measures correlation coefficient = -0.35; p < 0.001). There was no diurnal variation of renin or significant interaction of renin-angiotensin-aldosterone system drugs with renin in this population. Continuous renal replacement therapy renin removal was negligible (mass clearance +/- sd 4% +/- 4.3%). There was a significant difference in the rate of change of renin over time between survivors and nonsurvivors (-32 +/- 26 mu U/timepoint vs + 92 +/- 57 mu U/timepoint p = 0.03; mean +/- SEM), but not for lactate (-0.14 +/- 0.04 mM/timepoint vs + 0.15 +/- 0.21 mM/timepoint; p = 0.07). Maximum renin achieved significant prognostic value for ICU mortality (receiver operator curve area under the curve 0.80; p = 0.04), whereas maximum lactate did not (receiver operator curve area under the curve, 0.70; p = 0.17). Conclusions: In an heterogeneous ICU population, renin measurement was not significantly affected by diurnal variation, continuous renal replacement therapy, or drugs. Renin served as a marker of tissue-perfusion and outperformed lactate as a predictor of ICU mortality.