PERSEVERE Biomarkers Predict Severe Acute Kidney Injury and Renal Recovery in Pediatric Septic Shock

Rationale: Acute kidney injury (AKI), a common complication of sepsis, is associated with substantial morbidity and mortality and lacks definitive disease-modifying therapy. Early, reliable identification of at-risk patients is important for targeted implementation of renal protective measures. The updated Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) is a validated, multibiomarker prognostic enrichment strategy to estimate baseline mortality risk in pediatric septic shock. Objectives: To assess the association between PERSEVERE-II mortality probability and the development of severe, sepsis associated AKI on Day 3 (D3 SA-AKI) in pediatric septic shock. Methods: We performed secondary analysis of a prospective observational study of children with septic shock in whom the PERSEVERE biomarkers were measured to assign a PERSEVERE-II baseline mortality risk. Measurements and Main Results: Among 379 patients, 65 (17%) developed severe D3 SA-AKI. The proportion of patients developing severe D3 SA-AKI increased directly with increasing PERSEVERE-II risk category, and increasing PERSEVERE-II mortality probability was independently associated with increased odds of severe D3 SA-AKI after adjustment for age and illness severity (odds ratio, 1.4; 95% confidence interval, 1.2-1.7; P <0.001). Similar associations were found between increasing PERSEVERE-II mortality probability and the need for renal replacement therapy. Lower PERSEVERE-II mortality probability was independently associated with increased odds of renal recovery among patients with early AKI. A newly derived model incorporating the PERSEVERE biomarkers and Day 1 AKI status predicted severe D3 SAAKI with an area under the received operating characteristic curve of 0.95 (95% confidence interval, 092-0.98). Conclusions: Among children with septic shock, the PERSEVERE biomarkers predict severe D3 SA-AKI and identify patients with early AKI who are likely to recover.