Biomarkers in acute kidney injury settings to predict interventions and outcomes: the MARKISIO study

Abstract

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. 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 h after the occurrence of severe AKI when feasible, depending on the availability of trained research staff and appropriate sample storage infrastructure. The primary endpoint was the onset of precise criteria for RRT initiation within 72 h 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). Among the 256 patients, 101 (39%) met at least one criterion for RRT initiation or died within 72 h. No biomarker demonstrated satisfactory predictive performance for the primary endpoint. No novel biomarker was significantly associated with the occurrence of MAKE60. In multivariable analysis, ‘SAPSIII’ and ‘Serum potassium level at D0’ were significantly associated with the occurrence of MAKE60. 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.