Timing of kidney replacement therapy initiation for acute kidney injury

Abstract

Background: Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs) and is associated with high numbers of deaths. Kidney replacement therapy (KRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate KRT so as to improve clinical outcomes remains uncertain. This is an update of a review first published in 2018. This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury.

Objectives: To assess the effects of different timing (early and standard) of KRT initiation on death and recovery of kidney function in critically ill patients with AKI.

Search methods: We searched the Cochrane Kidney and Transplant's Specialised Register to 4 August 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register, ClinicalTrials and LILACS to 1 August 2022.

Selection criteria: We included all randomised controlled trials (RCTs). We included all patients with AKI in the ICU regardless of age, comparing early versus standard KRT initiation. For safety and cost outcomes, we planned to include cohort studies and non-RCTs.

Data collection and analysis: Data were extracted independently by two authors. The random-effects model was used, and results were reported as risk ratios(RR) for dichotomous outcomes and mean difference(MD) for continuous outcomes, with 95% confidence intervals (CI).

Main results: We included 12 studies enrolling 4880 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to standard treatment, early KRT initiation may have little to no difference on the risk of death at day 30 (12 studies, 4826 participants: RR 0.97,95% CI 0.87 to 1.09; I²= 29%; low certainty evidence), and death after 30 days (7 studies, 4534 participants: RR 0.99, 95% CI 0.92 to 1.07; I² = 6%; moderate certainty evidence). Early KRT initiation may make little or no difference to the risk of death or non-recovery of kidney function at 90 days (6 studies, 4011 participants: RR 0.91, 95% CI 0.74 to 1.11; I² = 66%; low certainty evidence); CIs included both benefits and harms. Low certainty evidence showed early KRT initiation may make little or no difference to the number of patients who were free from KRT (10 studies, 4717 participants: RR 1.07, 95% CI 0.94 to1.22; I² = 55%) and recovery of kidney function among survivors who were free from KRT after day 30 (10 studies, 2510 participants: RR 1.02, 95% CI 0.97 to 1.07; I² = 69%) compared to standard treatment. High certainty evidence showed early KRT initiation increased the risk of hypophosphataemia (1 study, 2927 participants: RR 1.80, 95% CI 1.33 to 2.44), hypotension (5 studies, 3864 participants: RR 1.54, 95% CI 1.29 to 1.85; I² = 0%), cardiac-rhythm disorder (6 studies, 4483 participants: RR 1.35, 95% CI 1.04 to 1.75; I² = 16%), and infection (5 studies, 4252 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%); however, it is uncertain whether early KRT initiation increases or reduces the number of patients who experienced any adverse events (5 studies, 3983 participants: RR 1.23, 95% CI 0.90 to 1.68; I² = 91%; very low certainty evidence). Moderate certainty evidence showed early KRT initiation probably reduces the number of days in hospital (7 studies, 4589 participants: MD-2.45 days, 95% CI -4.75 to -0.14; I² = 10%) and length of stay in ICU (5 studies, 4240 participants: MD -1.01 days, 95% CI -1.60 to -0.42; I² = 0%).

Authors' conclusions: Based on mainly low to moderate certainty of the evidence, early KRT has no beneficial effect on death and may increase the recovery of kidney function. Earlier KRT probably reduces the length of ICU and hospital stay but increases the risk of adverse events. Further adequate-powered RCTs using robust and validated tools that complement clinical judgement are needed to define the optimal time of KRT in critical patients with AKI in order to improve their outcomes. The surgical AKI population should be considered in future research.

Trial registration: ClinicalTrials.gov NCT01932190 NCT01819038 NCT02730117 NCT01682590 NCT02568722 NCT01557361 NCT03396757 NCT00076219 NCT01560650 NCT00529139 NCT01077349 NCT00675818 NCT00965328 NCT01191905 NCT00221013 NCT00322530 NCT00322933 NCT00561431 NCT03175328 NCT02937961 NCT00837057 NCT02937935 NCT03343340.