Elevated Renin Is Associated With Poor Outcomes in Children With Sepsis and Acute Kidney Injury

Tuesday, March 24, 2026

8:55 AM - 9:55 AM Central Time

Location: Connections Central Theater 1

Imogen Clover-Brown, MD (she/her/hers)

Cincinnati Children's Hospital Medical Center

Disclosure(s): No relevant financial relationship(s) to disclose.
GC

Giovanni Ceschia, MD

Pediatric Nephrologist
University Hospital of Padova, Padua, Italy

Disclosure information not submitted.
SS

Stephen Standage, MD

Assistant Professor
Cincinnati Childrens Hospital Medical Center

Disclosure information not submitted.
SG

Stuart Goldstein, MD

Professor
Cincinnati Children's Hospital Medical Center

Disclosure information not submitted.
Natalja L. Stanski, MD (she/her/hers)

Cincinnati Children's Hospital Medical Center, Ohio

Disclosure information not submitted.

Introduction: Sepsis-associated acute kidney injury (SA-AKI) is a heterogeneous syndrome associated with high morbidity and mortality in PICU patients. Prognostic enrichment tools may facilitate targeted kidney protection. Renin-angiotensin system derangement, evidenced by elevated renin levels, is associated with poor outcomes in critically ill adults and children, but this association has not been assessed in pediatric SA-AKI. We hypothesized higher serum renin levels would be associated with poor outcomes in this population.

Methods: Secondary analysis of a multicenter, prospective, observational cohort study of children (1 week - 18 yrs) with septic shock and early SA-AKI (≥KDIGO Stage 1 on Day 1-2) admitted to 10 US PICUs from January 2002 - February 2025. Direct renin levels (pg/ml) were measured from residual serum on Day 1. Patients were divided into 3 renin tertiles (T1, T2, T3) for comparison. Multivariable regression (MVR) was used to assess for associations between the highest tertile (T3) and outcomes, after adjustment for age, illness severity, vasoactive inotropic score (VIS), and AKI severity.

Results: Among 708 patients, 302 (43%) were female, median age was 5.4 [IQR 1.4-12.8] yrs, and median Day 1 renin level was 97.8 [26.7-405] pg/ml. 235 patients were assigned to T1 ( < 46 pg/ml), 239 to T2 (46-247 pg/ml), and 234 to T3 (>247 pg/ml). T3 patients had higher PRISM III scores (14 [10-21] vs. 8 [13-19] T2 vs. 7 [7-17] T1, p< 0.001) and were more often mechanically ventilated on Day 1-2 (78% vs. 71% T2 vs. 62% T1, p< 0.001), but did not differ by Day 1-2 peak VIS. T3 patients had more Day 7 severe AKI (≥KDIGO Stage 2) (47% vs. 32% T2 vs. 27% T1, p< 0.001), fewer PICU free days (14 [0-22] vs. 19 [7-24] T2 vs. 22 [12-25] T1, p< 0.001) and higher mortality rates (21% vs. 10% T2 vs. 11% T1, p< 0.001). There was no difference in Day 1-7 CRRT receipt (p=0.29). On MVR, T3 was associated with higher odds of Day 7 severe AKI (aOR 1.8, 95%CI 1.3-2.7, p=0.002), mortality (aOR 1.9, 95%CI 1.2-3.1, p=0.008), and 3.5 fewer PICU free days (SE 0.75, p< 0.001).

Conclusions: Children with early SA-AKI and elevated renin concentrations (T3) have worse outcomes. Renin levels may serve as a prognostic biomarker in this population, though larger studies are needed.