BACKGROUND: Acute kidney injury (AKI) is a well-known complication of critical illnesses, significantly affecting morbidity and the risk of death. Diuretics are widely used to ameliorate excess fluid accumulation and oliguria associated with AKI. Their popularity stems from their ability to reduce the energy demands of renal tubular cells by inhibiting transporters and flushing out intratubular casts. Numerous studies have assessed the effects of diuretics in the context of AKI prevention and treatment. However, a comprehensive systematic review addressing this topic has yet to be conducted. OBJECTIVES: This review aimed to explore the benefits and harms of diuretics for both the prevention and treatment of AKI. SEARCH METHODS: The Cochrane Kidney and Transplant Register of Studies was searched up to May 2024 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 Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) and quasi-RCTs in which diuretics were used to prevent or treat AKI. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data using standardised data extraction forms. Dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment, the standardised mean difference (SMD) was used. The primary review outcomes for AKI prevention studies were the incidence of AKI and any use of kidney replacement therapy (KRT). For treatment studies, the primary outcome was any use of KRT. The certainty of evidence was assessed per outcome using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 64 studies (83 reports, 9871 participants): 53 prevention studies (8078 participants) and 11 treatment studies (1793 participants). Studies were conducted in the following World Health Organization regions: the Americas (15), Eastern Mediterranean (9), Europe (25), South-East Asia (2), and the Western Pacific (13). Thirty-six studies were single-centre studies, 19 were multicentre, and the setting was unclear in nine studies. Diuretics were compared to placebo, no treatment or conventional therapy, saline solutions (isotonic or hypotonic), 5% dextrose, 5% glucose, Hartmann's solution, and Ringer's acetate. Overall, the risk of bias was low in one study, high in 19 studies, and of some concern in 41 studies. Three studies could not be assessed because they did not report any outcomes of interest. For AKI prevention, compared to control, diuretics may reduce the risk of AKI (38 studies, 5540 participants: RR 0.75, 95%, CI 0.61 to 0.92
I AUTHORS' CONCLUSIONS: When used for the prevention of AKI, diuretics may reduce the risk of AKI. However, our confidence in the effect estimate is limited. Diuretics probably reduce the incidence of KRT use, and we are moderately confident in the effect estimate. When used for the treatment of AKI, diuretics may make little or no difference to any use of KRT, and our confidence in the effect estimate is limited. More RCTs are needed to explore the role of diuretics for treating established AKI.