Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial)

Abstract Background The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT. Methods FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT. Results FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P <  0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P = 0.002). Conclusion The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation. Trial registration clinicaltrials.gov, NCT02730117. Registered 6 April 2016

Additional file 1: of Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial)

Table S1. Demographic, clinical, and biochemical data between FST-nonresponsive and FST-responsive patients. Table S2. Multivariable logistic regression on parameters to predict RRT. Table S3. Comparison of severity score and plasma biomarkers in the intervention trial. Table S4. Adverse events in the intervention trial. Appendix 1. Inclusion and exclusion criteria for patients in the FST study. Appendix 2. Definitions of safety outcomes related to the administration of RRT or vascular access for RRT. Figure S1. Survival curves of patients in the standard RRT arm who received and did not receive RRT (blue line, no RRT group; red line, RRT group). The figure shows the Kaplan-Meier curve of the probability of survival from randomization to day 28. (DOCX 520 kb