Timing of kidney replacement therapy initiation for acute kidney injury.

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.

Timing of renal replacement therapy initiation for acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs), and is associated with high death. Renal replacement therapy (RRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate RRT so as to improve clinical outcomes remains uncertain.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 RRT 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 23 August 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also searched LILACS to 11 September 2017. SELECTION CRITERIA: We included all randomised controlled trials (RCTs). We included all patients with AKI in ICU regardless of age, comparing early versus standard RRT 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 differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included five studies enrolling 1084 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to standard treatment, early initiation may reduce the risk of death at day 30, although the 95% CI does not rule out an increased risk (5 studies, 1084 participants: RR 0.83, 95% CI 0.61 to 1.13; I2 = 52%; low certainty evidence); and probably reduces the death after 30 days post randomisation (4 studies, 1056 participants: RR 0.92, 95% CI 0.76 to 1.10; I2= 29%; moderate certainty evidence); however in both results the CIs included a reduction and an increase of death. Earlier start may reduce the risk of death or non-recovery kidney function (5 studies, 1076 participants: RR 0.83, 95% CI 0.66 to 1.05; I2= 54%; low certainty evidence). Early strategy may increase the number of patients who were free of RRT after RRT discontinuation (5 studies, 1084 participants: RR 1.13, 95% CI 0.91 to 1.40; I2= 58%; low certainty evidence) and probably slightly increases the recovery of kidney function among survivors who discontinued RRT after day 30 (5 studies, 572 participants: RR 1.03, 95% CI 1.00 to 1.06; I2= 0%; moderate certainty evidence) compared to standard; however the lower limit of CI includes the null effect. Early RRT initiation increased the number of patients who experienced adverse events (4 studies, 899 participants: RR 1.10, 95% CI 1.03 to 1.16; I2 = 0%; high certainty evidence). Compared to standard, earlier RRT start may reduce the number of days in ICU (4 studies, 1056 participants: MD -1.78 days, 95% CI -3.70 to 0.13; I2 = 90%; low certainty evidence), but the CI included benefit and harm. AUTHORS' CONCLUSIONS: Based mainly on low quality of evidence identified, early RRT may reduce the risk of death and may improve the recovery of kidney function in critically patients with AKI, however the 95% CI indicates that early RRT might worsen these outcomes. There was an increased risk of adverse events with early RRT. Further adequate-powered RCTs using appropriate criteria to define the optimal time of RRT are needed to reduce the imprecision of the results.