Plasma Renin as a Biomarker for AKI and Mortality in Neonates Undergoing Mechanical Circulatory Support

Background: Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for neonates with severe cardiorespiratory failure. Acute kidney injury (AKI) is associated with mortality in children receiving ECMO. Renin is essential for homeostasis and has been studied as a novel biomarker for predicting AKI and mortality in critically ill adults. Its role as biomarker for AKI and mortality in neonates requiring ECMO support is unknown. We hypothesized that neonates who develop AKI have higher plasma renin levels following ECMO initiation. Methods: Single center study evaluating term neonates admitted to the ICU at Nationwide Children’s Hospital requiring ECMO support between 3/2015 and 12/2018. Baseline renal function was normal in all neonates prior to initiating ECMO. Plasma renin levels were collected daily beginning 2 hours through day 8 after cannulation and analyzed using ELISA. Diagnosis of AKI was based on KDIGO. Results: Cohort included 12 term neonates with 13 ECMO initiations. The most common comorbidities were congenital diaphragmatic hernia (58%, N = 7) and congenital heart disease (42%, N = 5). Most patients were initially placed on venous-arterial (VA) ECMO (85%, N = 11). Mortality rate was 67% (N = 8). Plasma renin levels were highest on days 2 and 8 post-cannulation, regardless of circuit type. On average, day 2 levels were 7-fold higher and day 8 levels were 6-fold higher than day 1 levels. There was no significant difference between peak plasma renin levels on days 2 and 8 (p = 0.38). Higher levels of plasma renin 2 hours and 8 days after cannulation were associated with development of AKI (p = 0.015) and mortality (p = 0.036), respectively. Conclusion: Elevated plasma renin 2 hours after cannulation and day 8 post-cannulation was associated with AKI and mortality, respectively suggesting that plasma renin can be used as a prognostic biomarker in neonates receiving ECMO. Further studies should evaluate the renin-angiotensin-aldosterone system as a potentially modifiable target in preventing AKI and mortality in patients receiving ECMO.