Timing of renal replacement therapy initiation for acute kidney injury in critically ill patients: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis

Abstract

Background Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical prognosis. Renal replacement therapy (RRT) has been widely used in critically ill patients with AKI. However, in patients without urgent indications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, the optimal timing of RRT initiation is still under debate. We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of early RRT initiation versus delayed RRT initiation. Methods We searched databases (PubMed, EMBASE and Cochrane Library) from inception through to July 20, 2020, to identify eligible RCTs. The primary outcome was 28-day mortality. Two authors extracted the data independently. When the I2 values < 25%, we used fixed-effect mode. Otherwise, the random effects model was used as appropriate. TSA was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive. Results Eleven studies involving 5086 patients were identified. Two studies included patients with sepsis, one study included patients with shock after cardiac surgery, and eight others included mixed populations. The criteria for the initiation of RRT, the definition of AKI, and RRT modalities existed great variations among the studies. The median time of RRT initiation across studies ranged from 2 to 7.6 h in the early RRT group and 21 to 57 h in the delayed RRT group. The pooled results showed that early initiation of RRT could not decrease 28-day all-cause mortality compared with delayed RRT (RR 1.01; 95% CI 0.94–1.09; P = 0.77; I2 = 0%). TSA result showed that the required information size was 2949. The cumulative Z curve crossed the futility boundary and reached the required information size. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients and was associated with a higher incidence of hypotension (RR 1.42; 95% CI 1.23–1.63; P < 0.00001; I2 = 8%) and RRT-associated infection events (RR 1.34; 95% CI 1.01–1.78; P = 0.04; I2 = 0%). Conclusions This meta-analysis suggested that early initiation of RRT was not associated with survival benefit in critically ill patients with AKI. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients, resulting in a waste of health resources and a higher incidence of RRT-associated adverse events. Maybe, only critically ill patients with a clear and hard indication, such as severe acidosis, pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.

Soluble Urokinase-Type Plasminogen Activator Receptor Levels as a Predictor of Kidney Replacement Therapy in Septic Patients with Acute Kidney Injury: An Observational Study

“…Moreover, an early start of KRT may lead to unnecessary exposure to KRT in some patients, resulting in a higher incidence of KRT-associated adverse events, the increased use of ICU resources, and the correspondingly higher nursing workload. Perhaps only critically ill patients with specific clinical indication, such as severe acidosis, pulmonary edema, and hyperkalemia, may benefit from the early initiation of KRT [ 39 ]. Our study was designed to be observational; KRT in patients with AKI was initiated according to the KDIGO AKI guidelines and the beneficial effects of an early vs. late start of KRT were not compared.…”

Prioritization of ICU beds with renal replacement therapy support by court order and mortality in a Brazilian metropolitan area

“…Although we did not assess the time between RRT indication and initiation, a significant part of the mortality observed in our study may be due to the delayed RRT initiation after its indication, as patients needed to request treatment in court. Though the proper timing for initiating RRT (early or delayed RRT indication) remains controversial and uncertain 24 , 35 , in the presence of severe complications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, RRT should be performed urgently for being the cornerstone of AKI treatment in these patients 35 – 37 . Moreover, the delayed ICU-RRT admission also postponed the therapeutic and monitoring optimization of the contributing factors of AKI, such as sepsis, the most common etiologic factor of AKI 25 , 34 .…”

Post–Liver Transplant Acute Kidney Injury

“…(89) A recent systematic review and meta-analysis by Li et al also demonstrated no survival benefit of early initiation of RRT but more adverse events. (90) In terms of timing of RRT specifically for LT recipients who develop AKI, there is a paucity of data. A study by Ren and colleagues also found that early initiation of continuous RRT (CRRT) as defined by urine output >0.05 mL/kg per hour in the 24 hours before CRRT start compared with late CRRT initiation as defined by urine output <0.05 mL/kg per hour in the 24 hours before CRRT start did not confer a mortality benefit.…”