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

Abstract

BackgroundThe 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.MethodsFST 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.ResultsFST 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).ConclusionThe 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 registrationclinicaltrials.gov, NCT02730117. Registered 6 April 2016.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2021-1) contains supplementary material, which is available to authorized users.

Comparison between watchful waiting strategy and early initiation of renal replacement therapy in the critically ill acute kidney injury population: an updated systematic review and meta-analysis

“…We analyzed subgroups on the basis of the patient population (medical, surgical, or mixed), the use of high plasma NGAL as an enrollment criterion (yes or no), and study design (excluding or including patients with emergent need for RRT before randomization) in all nine enrolled RCTs with available outcomes. No significant modification effects were observed for three subgroup variables: mortality (included in all nine RCTs), ICU LOS (included in six RCTs: [28,48,[55][56][57][58]), and MV days (included in six RCTs: [28,[55][56][57][58]) (Tables 1 and 2). However, all subgroup variables exerted significant modification effects on RRT days (included in six RCTs: [54][55][56][57][58][59]).…”

“…No significant modification effects were observed for three subgroup variables: mortality (included in all nine RCTs), ICU LOS (included in six RCTs: [28,48,[55][56][57][58]), and MV days (included in six RCTs: [28,[55][56][57][58]) (Tables 1 and 2). However, all subgroup variables exerted significant modification effects on RRT days (included in six RCTs: [54][55][56][57][58][59]). The results demonstrated that RCTs that enrolled a surgical population (P for interaction = .001), enrolled a population with high plasma NGAL (P for interaction = .031 [result was nonsignificant after alpha error correction]), and did not exclude patients with the emergent need for RRT (P for interaction < .001) had favorable outcomes in the early RRT initiation group compared with the late RRT initiation group (Table 2).…”

“…Only six [48,[54][55][56][57][58] of the nine RCTs fulfilled our predefined criteria for examining the safety of the watchful waiting strategy ( Table 3). The pooled data of these six studies revealed no significant intergroup differences in primary and secondary outcomes (Additional file 1: Table S8A, B).…”

“…We attempted to supplement previous findings by including three recent RCTs (EARLY-RRT, 2018 [59]; FST trial, 2018 [58]; and IDEAL-ICU, 2018 [57]) in this meta-analysis to examine the effect of early RRT initiation in the AKI population with high plasma NGAL, and we assessed the safety of the watchful waiting strategy in this population.…”

Timing of initiation of renal replacement therapy in acute kidney injury: an updated meta-analysis of randomized controlled trials

“…Among them, 9 studies were from Asia, 8 were from Europe, and 1 was from North America. A variety of outcomes were recorded in these studies, including mortality (n ¼ 18; 100%) [3,[7][8][9][11][12][13][18][19][20][21][22][24][25][26][27]29,30], incidence of dialysis independence (n ¼ 9; 50%) [7-9,11-13,20,30], incidence of the need for RRT Table 2.…”