Serum renin and prorenin concentrations predict severe persistent acute kidney injury and mortality in pediatric septic shock

Natalja L. Stanski, Naomi Pode Shakked, Bin Zhang, Natalie Z. Cvijanovich, Julie C. Fitzgerald, Parag N. Jain, Adam J. Schwarz, Jeffrey Nowak, Scott L. Weiss, Geoffrey L. Allen, Neal J. Thomas, Bereketeab Haileselassie, Stuart L. Goldstein

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6 Scopus citations


Background: Studies in critically ill adults demonstrate associations between serum renin concentrations (a proposed surrogate for renin–angiotensin–aldosterone system dysregulation) and poor outcomes, but data in critically ill children are lacking. We assessed serum renin + prorenin concentrations in children with septic shock to determine their predictive ability for acute kidney injury (AKI) and mortality. Methods: We conducted a secondary analysis of a multicenter observational study of children aged 1 week to 18 years admitted to 14 pediatric intensive care units (PICUs) with septic shock and residual serum available for renin + prorenin measurement. Primary outcomes were development of severe persistent AKI (≥ KDIGO stage 2 for ≥ 48 h) in the first week and 28-day mortality. Results: Among 233 patients, day 1 median renin + prorenin concentration was 3436 pg/ml (IQR 1452–6567). Forty-two (18%) developed severe persistent AKI and 32 (14%) died. Day 1 serum renin + prorenin predicted severe persistent AKI with an AUROC of 0.75 (95% CI 0.66–0.84, p < 0.0001; optimal cutoff 6769 pg/ml) and mortality with an AUROC of 0.79 (95% CI 0.69–0.89, p < 0.0001; optimal cutoff 6521 pg/ml). Day 3/day 1 (D3:D1) renin + prorenin ratio had an AUROC of 0.73 (95% CI 0.63–0.84, p < 0.001) for mortality. On multivariable regression, day 1 renin + prorenin > optimal cutoff retained associations with severe persistent AKI (aOR 6.8, 95% CI 3.0–15.8, p < 0.001) and mortality (aOR 6.9, 95% CI 2.2–20.9, p < 0.001). Similarly, D3:D1 renin + prorenin > optimal cutoff was associated with mortality (aOR 7.6, 95% CI 2.5–23.4, p < 0.001). Conclusions: Children with septic shock have very elevated serum renin + prorenin concentrations on PICU admission, and these concentrations, as well as their trend over the first 72 h, predict severe persistent AKI and mortality. Graphical abstract: [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)3099-3108
Number of pages10
JournalPediatric Nephrology
Issue number9
StatePublished - Sep 2023

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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