# Serum renin levels refine acute kidney injury prediction in critically ill children

## TL;DR

This study shows that measuring serum renin levels can improve the prediction of severe acute kidney injury in critically ill children.

## Contribution

The study demonstrates that serum renin levels refine risk stratification for severe acute kidney injury in pediatric intensive care.

## Key findings

- Serum renin levels increase progressively across severe AKI risk strata in critically ill children.
- Adding renin ≥ 100 pg/mL to existing biomarkers improves the specificity and positive predictive value of severe AKI prediction.
- Higher renin levels are independently associated with increased mortality in critically ill children.

## Abstract

Studies demonstrate that elevated renin is associated with adverse outcomes in critical illness. We aimed to evaluate whether serum renin enhances acute kidney injury (AKI) risk stratification in critically ill children.

A prospective, observational pilot study of PICU patients from the TAKING FOCUS 2 (TF2) study for whom direct renin levels were measured within 48 h of PICU admission. TF2 employed the Renal Angina Index (RAI) (RAI +  ≥ 8) and urine neutrophil gelatinase-associated lipocalin (uNGAL; uNGAL +  ≥ 150 ng/mL) to aid in the risk prediction of severe AKI (sAKI; ≥ KDIGO stage 2) at PICU day 2–4. We examined renin levels across TF2 algorithm branchpoints, assessed the additive predictive performance of renin ≥ 100 pg/mL for sAKI, and assessed associations between elevated renin and outcomes.

Among 107 patients (53% male, median age 8 [2–15] years), 30 (28%) were RAI–, 77 (72%) were RAI+ , and 43 (40%) had sAKI. Median renin concentration was 61.3 [16.5–143.8] pg/mL, increasing progressively across sAKI risk strata: RAI+  > RAI– (70.4 [24.7–182.1] vs. 33.3 [11.2–93.9] pg/mL, p = 0.006) and RAI+ /uNGAL +  > RAI+ /uNGAL– (103.7 [47–507] vs. 42.1 [15.9–125] pg/mL, p = 0.01). Patients with sAKI had higher renin (102 [35.2–374] vs. 41.6 [11.4–111] pg/mL, p = 0.002), including after adjustment for covariates (p = 0.001). Renin ≥ 100 pg/mL was independently associated with mortality (aOR 4.0, 95% CI 1.06–14.9, p = 0.041). Adding renin ≥ 100 pg/mL to RAI+ /uNGAL+ improved specificity (93% from 84%) and PPV (81% from 77%) of day 2–4 sAKI prediction.

Serum renin levels increase progressively across sAKI risk strata and appear to enhance sAKI prediction.

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

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

The online version contains supplementary material available at 10.1007/s00467-025-07061-0.