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Observational Study
. 2023 Sep;38(9):3099-3108.
doi: 10.1007/s00467-023-05930-0. Epub 2023 Mar 20.

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

Natalja L Stanski  1   2 , Naomi Pode Shakked  3   4 , Bin Zhang  5 , Natalie Z Cvijanovich  6 , Julie C Fitzgerald  7 , Parag N Jain  8 , Adam J Schwarz  9 , Jeffrey Nowak  10 , Scott L Weiss  7 , Geoffrey L Allen  11 , Neal J Thomas  12 , Bereketeab Haileselassie  13 , Stuart L Goldstein  3   14
Affiliations
Observational Study

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

Natalja L Stanski et al. Pediatr Nephrol. 2023 Sep.

Abstract

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. A higher resolution version of the Graphical abstract is available as Supplementary information.

Keywords: Acute kidney injury; Mortality; Pediatrics; Renin; Sepsis.

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Figures

Figure 1:
Figure 1:. Proposed Mechanism of Renin-Angiotensin-Aldosterone System Derangement in the Setting of Septic Shock.
Under normal circumstances, inactive prorenin undergoes proteolytic activation to renin in the kidney, where active renin is stored and released immediately upon stimulation of the juxtaglomerular apparatus. In the setting of septic shock and associated endothelial dysfunction and/or damage, angiotensin-converting enzyme (ACE) function is proposed to be impaired, resulting in acutely decreased production of angiotensin II, decreased production of aldosterone, and resultant increase in serum renin concentrations secondary to release of active enzyme. While proteolytic activation of prorenin to renin is also ongoing, this process is influenced more by chronic stimuli as opposed to acute stimuli.
See this image and copyright information in PMC

Comment in

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