What are the benefits and risks of diuretics for preventing and treating acute kidney injury?

Key messages

• For prevention of acute kidney injury (AKI; a condition where the kidneys suddenly lose their ability to filter waste from the blood), compared to control, diuretics probably reduce the need for any dialysis and may reduce the risk of developing AKI and death. Diuretics may result in little or no difference in the need for permanent dialysis, hypotension (low blood pressure), low blood potassium, or serum creatinine (a measure of kidney function). The effect of diuretics on irregular heartbeat and urinary output was unclear.

• For AKI treatment, diuretics may make little or no difference to the need for any dialysis, death or low blood potassium. Diuretics may increase hypotension and probably increase irregular heartbeat. It was uncertain whether diuretics increased urinary output.

What is acute kidney injury?

Acute kidney injury (AKI) is a condition where the kidneys suddenly lose their ability to filter waste from the blood, and it develops within hours or days. It is most common in people who are undergoing surgery and in people who need intensive care. This loss of filtering results in a build-up of fluid and waste products in the body. AKI ranges from mild to severe and, if left untreated, can be fatal. However, AKI can be reversed, and people with prior good health usually recover completely.

How do you prevent or treat acute kidney injury?

For people undergoing planned surgical or heart procedures, preventing AKI is an important consideration. Diuretics are a type of medication that stimulates the kidneys to produce more urine, thus getting rid of excess fluids and waste products. During these procedures, diuretics may be given to maintain urine output.

For people with AKI, diuretics may be the first option used to stimulate the kidneys to produce more urine before AKI progresses to a stage where dialysis (a procedure where a machine is used to remove waste products and excess salts and fluid from the blood) is required.

What did we want to find out?

We wanted to find out if diuretics prevent AKI and if they help treat people who have AKI. We also wanted to find out if diuretics were associated with any unwanted effects.

What did we do?

We searched for studies that examined the use of diuretics in people who are at risk of developing AKI or treating those who already have AKI. Diuretics were compared to placebo (dummy medicine) or various solutions aimed at replacing fluids and electrolytes (minerals needed to maintain normal body function). We compared and summarised the results of the studies, and we rated our confidence in the evidence, based on factors such as the methods and size of the study.

What did we find?

We included 64 studies (9871 participants): 53 studies looked at preventing AKI (8078 participants), and 11 studies looked at treating AKI (1793 participants). Studies were conducted in the Americas (15), the 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.

For AKI prevention, compared to control, diuretics probably reduce the need for any dialysis and may reduce the risk of developing AKI and death. Diuretics may result in little or no difference in the need for permanent dialysis, hypotension (low blood pressure), low blood potassium, or serum creatinine (a measure of kidney function). The effect of diuretics on irregular heartbeat and urinary output was unclear.

For AKI treatment, diuretics may make little or no difference to the need for any dialysis, death or low blood potassium. Diuretics may increase hypotension and probably increase irregular heartbeat. It was uncertain whether diuretics increased urinary output. The need for permanent dialysis and changes in serum creatinine were not reported.

What are the limitations of the evidence?

For the prevention of AKI, we are moderately confident that diuretics reduce the need for any dialysis because the majority of studies reported this outcome. We are less confident in the evidence for reducing the risk of AKI because the studies were done in different types of people or used different types of drugs. Not all of the studies provided data about all relevant outcomes.

For the treatment of AKI, we are moderately confident diuretics increase irregular heartbeat; however, we are less confident in the evidence on the incidence of AKI because the studies were done in different types of people or used different types of drugs. Not all of the studies provided data about all relevant outcomes.

How up to date is this evidence?

The evidence is current to May 2024.

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.

Read the full abstract...
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 strategy: 

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; I2 = 77%; low-certainty evidence) and probably reduce any use of KRT (32 studies, 4658 participants: RR 0.63, 95% CI 0.43 to 0.91; I2 = 0%, moderate-certainty evidence) and death (33 studies, 6447 participants: RR 0.73, 95% CI 0.59 to 0.92; I2 = 0%; moderate-certainty evidence). The use of diuretics may result in little or no difference in the need for permanent dialysis (2 studies, 956 participants: RR 0.52, 95% CI 0.08 to 3.47; I2 = 21%; low-certainty evidence), hypotension (7 studies, 775 participants: RR 1.27, 95% CI 0.87 to 1.86; I2 = 0%; low-certainty evidence) and hypokalaemia (6 studies, 1383 participants: RR 1.20, 95% CI 0.88 to 1.73; I2 = 43%; low-certainty evidence), and had uncertain effects on arrhythmias (13 studies, 3375 participants: RR 0.77, 95% CI 0.57 to 1.04; I2 = 53%; very-low certainty evidence). Diuretics may make little or no difference to changes in SCr within 30 days (8 studies, 646 participants: SMD 0.41, 95% CI -0.01, to 0.83; I2 = 82%; low-certainty evidence) but it was uncertain whether diuretics increased urinary output (8 studies, 1155 participants: SMD 1.87, 95% CI -0.20 to 3.95; I2 = 99%; very low-certainty evidence).

For AKI treatment, diuretics may make little or no difference to any use of KRT (8 studies, 1275 participants: RR 0.93, 95% CI 0.83 to 1.04; I2 = 2%; low-certainty evidence) or death (14 studies, 2052 participants: RR 1.08, 95% CI 0.96 to 1.22; I2 = 0%; low-certainty evidence). Diuretics may increase hypotension (2 studies, 720 participants: RR 1.99, 95% CI 1.16 to 3.41; I2 = 90%; low-certainty evidence) and probably increase arrhythmias (6 studies, 1011 participants: RR 1.62, 95% CI 1.12 to 2.33; I2 = 0%; moderate-certainty evidence). Diuretics may result in little or no difference in hypokalaemia (3 studies, 478 participants: RR 1.52, 95% CI 0.70 to 3.31; I2 = 0%; low-certainty evidence). It was uncertain whether diuretics increased urinary output (3 studies, 329 participants: SMD 4.40, 95% CI -0.94 to 9.74; I2 = 99%; very low-certainty evidence). The need for permanent dialysis and changes in serum creatinine were not reported.