Biomarkers to predict the need for renal replacement therapy in severe acute kidney injury: an ancillary analysis of a multicenter randomized controlled trial

Abstract Introduction Predicting the need for renal replacement therapy (RRT) in acute kidney injury (AKI) remains challenging. The utility of biomarkers was explored during previous studies which were biased as RRT indications relied on clinician opinion rather than evidence. Those studies preceded trials that clarified RRT initiation criteria. We aimed to assess biomarkers in predicting criteria for RRT initiation in severe AKI patients. Material and methods This is an ancillary study of the AKIKI2 trial. Patients with severe AKI (stage 3) receiving invasive mechanical ventilation and/or vasopressors were included. Blood and urine samples were collected within 12 hours after the occurrence of severe AKI. The primary endpoint was the onset of rigorous criteria for RRT initiation within 72 hours after severe AKI. We analyzed routine serum biomarkers (pH, serum potassium, serum creatinine) and novel urinary and serum biomarkers (CCL14, KIM1, nicotinamide and its metabolites, cDPP3, plasma proenkephalin A 119–159). Results Among the 256 patients, 101 (39%) met at least one criterion for RRT initiation or died within 72 hours. No biomarker demonstrated satisfactory predictive performance for the primary endpoint. Urinary CCL14 showed potential interest in toxic-induced AKI (AUC 0.74 0.57–0.90). No novel biomarker was significantly associated with the occurrence of MAKE60. In multivariate analysis, ‘SAPSIII’ and ‘Serum potassium level at D0’ were significantly associated with the occurrence of MAKE60. Conclusion Neither routine nor novel biomarkers demonstrated conclusive predictive accuracy for the need for RRT in severe AKI patients. Given evidence-based criteria for initiating RRT, the tested biomarkers may not effectively guide RRT initiation.