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Reduced urinary levels of angiotensin-converting enzyme 2 activity predict acute kidney injury in critically ill patients
Laurent Bitker, Sheila K Patel, Intissar Bittar, Glenn M Eastwood, Rinaldo Bellomo, Louise M Burrell
Crit Care Resusc 2020; 22 (4): 344-354
- Laurent Bitker 1, 2
- Sheila K Patel 3
- Intissar Bittar 4
- Glenn M Eastwood 1
- Rinaldo Bellomo 1, 5
- Louise M Burrell 3
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 (AKI
12h) and AKI stage 2 or 3 at any time during intensive care unit stay in patients free from any stage of AKI at inclusion (AKI ICU). 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 AKI
12h. Corrected uACE2 activity was significantly higher in patients without AKI 12hcompared with those with AKI 12h(median [interquartile range], 13 [6– 24] ν 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 AKI 12hrisk (odds ratio [95% CI], 0.72 [0.46–0.97]). During intensive care unit admission, 39 of 76 patients (51%) developed AKI ICU. uACE2 had an AUROC for the prediction of AKI 12hof 0.68 (95% CI, 0.57–0.79), and correctly reclassified 28% of patients (positive NRI) to AKI 12h. Patients with uACE2 > 8.7 pmol/min/mL per mmol/L of urine creatinine had a significantly lower risk of AKI ICUon log-rank analysis (52% ν 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.
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