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

Background: 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. Methods: 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. Results: 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. Conclusions: Serum renin levels increase progressively across sAKI risk strata and appear to enhance sAKI prediction.