Plasma Renin as a Predictor of AKI, Mortality, and Severity of Illness in Pediatric Extracorporeal Membrane Oxygenation

Background: Extracorporeal membrane oxygenation (ECMO) is used in children with cardiorespiratory failure. Acute kidney injury (AKI) is associated with mortality in children requiring ECMO. Renin has been investigated in adults as a biomarker for AKI and mortality. Renin has not been evaluated as a prognostic biomarker in children requiring ECMO. We hypothesized that elevated plasma renin following initiation of ECMO would predict AKI, mortality, and severity of illness. Methods: Single center study of pediatric ICU patients requiring ECMO between 2015 and 2024. Patients with CKD or renal replacement therapy (RRT) prior to ECMO were excluded. Plasma renin levels were serially measured with ELISA before, after, and during the first 8 days of ECMO. Diagnosis of AKI was based on KDIGO serum creatinine criteria. Pediatric Sepsis-related Organ Failure Assessment (pSOFA) was used to assess severity of illness. Results: Cohort included 27 patients between 1 month and 17 years of age. Common ECMO indications were sepsis (67%, n = 18) and cardiac failure (26%, n = 7). Venovenous (VV) ECMO was the most common modality (67%, n = 18) with an average duration of 191 hours. Mortality was 26% (n = 7). 70% of patients required RRT (n = 19) with an average duration of 10 days. Higher plasma renin level at hours 6 (p = 0.013) and 24 (p = 0.027) of ECMO were associated with AKI. Pre-ECMO levels were associated with mortality (p = 0.003). Levels following completion of ECMO were associated with mortality (p = 0.026) and RRT duration (p = 0.007, r2 0.573). Levels at 4 hours were associated with 24h pSOFA (p = 0.047, r2 0.175). Levels at 24 hours were associated with length of stay (LOS) (p = 0.03, r2 0.238). Levels in venoarterial (VA) ECMO were higher than VV during the first 48 hours with significant elevations at hours 2, 4, and 6 (p = 0.02, 0.042, and 0.023, respectively). Conclusion: Renin increases with ECMO and higher levels within the first 24 hours predict AKI, mortality, and LOS. Most notably, pre-ECMO levels predict mortality, further underlying its role as an early, prognostic biomarker in critically-ill children. Further study with intervention-based studies is needed as the renin-angiotensin-aldosterone system is a modifiable target.