Timing of renal-replacement therapy in intensive care unit-related acute kidney injury

Abstract

Purpose of reviewThe optimal timing of renal-replacement therapy (RRT) initiation for the management of acute kidney injury (AKI) in the intensive care unit (ICU) is frequently controversial. An earlier-strategy has biological rationale, even in the absence of urgent indications; however, a delayed-strategy may prevent selected patients from receiving RRT and avoid complications related to RRT. Recent findingsPrevious studies assessing the optimal timing of RRT initiation found conflicting results, contributing to variation in clinical practice. The recent multinational trial, standard vs. accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI) found no survival benefit and a higher risk of RRT dependence with an accelerated compared to a standard RRT initiation strategy in critically ill patients with severe AKI. Nearly 40% of patients allocated to the standard-strategy group did not receive RRT. The Artificial Kidney Initiation in Kidney Injury-2 (AKIKI-2) trial further assessed delayed compared to moredelayed strategies for RRT initiation. The more-delayed strategy did not confer an increase in RRT-free days and was associated with a higher risk of death. SummaryEarly preemptive initiation of RRT in critically ill patients with AKI does not confer clear clinical benefits. However, protracted delays in RRT initiation may be harmful.

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

“…We report the following metrics for the intervention (accelerated strategy) on the primary endpoint: (1) median of the posterior distribution; (2) posterior distribution 95% highest density interval (HDI); (3) probability of direction (PD; the probability that the effect size is on the side of the point estimate); (4) probability of "significance" based on a region of practical equivalence defined using traditional criteria; and (5) probability that the effect size is at least equal to or greater than what was considered as a minimal clinically important difference (MCID) in favor of the intervention, as defined by a survey of the STARRT-AKI international steering committee members (see Additional file 1); (6) probability that the effect size is at least 1.5 times higher than the one defined as MCID (which we considered as a "large" effect). The thresholds beyond which the effect was considered as "significant" were based on a difference in log(OR) that is equivalent of a standardized mean difference of 0.1 in Cohen's d scale [equivalent to a log(OR) difference of 0.18; to convert from Cohen's d to standardized log(OR) difference in Cohen's d scale, multiply the log(OR) by π/ √ 3 ], which would translate to an odds ratio between 0.83 and 1.19 [16,17].…”

“…Timing of kidney replacement therapy (KRT) initiation in critically ill patients with severe acute kidney injury (AKI) is controversial and has been the focus of several recent randomized trials [1][2][3][4]. These trials have been driven by the premise that earlier KRT can facilitate more rapid correction of metabolic, acid-base, and fluid balance derangements, prevent AKI-related complications, and improve clinical outcomes [5][6][7]. At the same time, KRT is also recognized as an invasive and resource-intensive intervention associated with risks, such as placement of a large central venous catheter, exposure to an extracorporeal circulation, and therapy-related complications, in particular episodes of hemodynamic instability, which may modify the probability of kidney recovery and independence from KRT [2,3,8].…”

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults

“…Indeed, the arbitrary nature of when to use CRRT extends to adults, as was highlighted by a recent review. 26 The detrimental effects of an early initiation of CRRT in adults are not insignificant (increased risk for adverse events, longer term dialysis dependence, and greater health care utilization costs). 26 Thus, any trial or prospective study evaluating CRRT timing in children will need to utilize sequential risk stratification and balance the potential for negative effects.…”

“… 23 Multiple randomized trials in adults evaluating the effect of timing of initiation on CRRT outcomes have yielded conflicting results. 14 , 15 , 24 , 25 , 26 , 27 , 28 , 29 In children, there are no randomized trials evaluating the timing of CRRT initiation and outcomes, and most studies are small, single center in design with varied timing definitions. 11 , 12 , 30 , 31 , 32 , 33 Therefore, a similar controversy as to the optimal timing of CRRT initiation in children exists.…”

Editorial: Introduction to Renal Section, Current Opinion in Critical Care, 2021

“…Jeong et al . [4] discuss the controversial issue of when to initiate renal replacement therapy (RRT) in the ICU patient with moderate–severe AKI. Debate on this topic has raged for many years, and these authors responded to that debate by designing, conducting and reporting the STARRT AKI trial [5] addressing the clinical question and conclude that there is no clinical advantage to early initiation of RRT; rather a watch-and-wait strategy is better.…”