Reduced urinary levels of angiotensin-converting enzyme 2 activity predict acute kidney injury in critically ill patients

Abstract

Objective: Angiotensin-converting enzyme 2 activity reflects non-classical renin-angiotensin system upregulation. We assessed the association of urinary angiotensin-converting enzyme 2 (uACE2) activity with acute kidney injury (AKI). Design, setting and participants: A prospective observational study in which we measured uACE2 activity in 105 critically ill patients at risk of AKI. We report AKI stage 2 or 3 at 12 hours of urine collection (AKI12h) and AKI stage 2 or 3 at any time during intensive care unit stay in patients free from any stage of AKI at inclusion (AKIICU). AKI prediction was assessed using area under the receiver-operating characteristics curve (AUROC) and net reclassification indices (NRIs). Main outcome measure: AKI stage 2 or 3 at 12 hours of urine collection. Results: Within 12 hours of inclusion, 32 of 105 patients (30%) had developed AKI12h. Corrected uACE2 activity was significantly higher in patients without AKI12h compared with those with AKI12h (median [interquartile range], 13 [6-24] v 7 [4-10] pmol/min/mL per mmol/L of urine creatinine; P < 0.01). A 10-unit increase in uACE2 was associated with a 28% decrease in AKI12h risk (odds ratio [95% CI], 0.72 [0.46-0.97]). During intensive care unit admission, 39 of 76 patients (51%) developed AKIICU. uACE2 had an AUROC for the prediction of AKI12h of 0.68 (95% CI, 0.57-0.79), and correctly reclassified 28% of patients (positive NRI) to AKI12h. Patients with uACE2 > 8.7 pmol/min/mL per mmol/L of urine creatinine had a significantly lower risk of AKIICU on log-rank analysis (52% v 84%; P < 0.01). Conclusions: Higher uACE2 activity was associated with a decreased risk of AKI stage 2 or 3. Our findings support future evaluations of the role of the non-classical renin-angiotensin system during AKI.