Types of studies

We will include all RCTs investigating diuretics as a prevention and treatment modality, including those with cross‐over designs, provided the data before cross‐over is available (to avoid a carry‐over phenomenon). We will also include cluster RCTs.

Types of participants

Types of interventions

We will consider all types of diuretics administered (see Types of interventions), including those with hydration, even if the amount of hydration is different among the groups. Although dopamine may increase salt and water excretion, it has many other effects and for the purposes of this review, we will not regard it as a diuretic. We will include other types of concurrent medication, provided they are used equally in both groups.

We will also include all types of comparisons such as placebo, no treatment, and standard care.

Types of outcome measures

The outcomes selected include the relevant SONG core outcome sets as specified by the Standardised Outcomes in Nephrology initiative (SONG 2017).

Electronic searches

We will search the Cochrane Kidney and Transplant Register of Studies through contact with the Information Specialist using search terms relevant to this review. The Register contains studies identified from the following sources.

1. Monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL)

2. Weekly searches of MEDLINE OVID SP

3. Searches of kidney and transplant journals, and the proceedings and abstracts from major kidney and transplant conferences

4. Searching the current year of EMBASE OVID SP

5. Weekly current awareness alerts for selected kidney and transplant journals

6. Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Studies contained in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane Kidney and Transplant. Details of search strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available on the Cochrane Kidney and Transplant website under CKT Register of Studies.

See Appendix 1 for search terms used in strategies for this review.

Searching other resources

1. Reference lists of review articles, relevant studies and clinical practice guidelines.

2. Contacting relevant individuals/organisations seeking information about unpublished or incomplete studies.

3. Grey literature sources (e.g. abstracts, dissertations and theses), in addition to those already included in the Cochrane Kidney and Transplant Register of Studies, will be searched.

Selection of studies

The search strategy described will be used to obtain titles and abstracts of studies that may be relevant to the review. The titles and abstracts will be screened independently by two authors, who will discard studies that are not applicable, however, studies and reviews that might include relevant data or information on trials will be retained initially. Two authors will independently assess retrieved abstracts and, if necessary the full text, of these studies to determine which studies satisfy the inclusion criteria. Disagreements will be resolved in consultation with a third author.

Data extraction and management

Data extraction will be carried out independently by two authors using standard data extraction forms. Disagreements will be resolved in consultation with a third author. Studies reported in non‐English language journals will be translated before assessment. Where more than one publication of one study exists, reports will be grouped together and the publication with the most complete data will be used in the analyses. Where relevant outcomes are only published in earlier versions these data will be used. Any discrepancy between published versions will be highlighted.

Assessment of risk of bias in included studies

The following items will be independently assessed by two authors using the risk of bias assessment tool (Higgins 2022) (see Appendix 2).

• Was there adequate sequence generation (selection bias)?

• Was allocation adequately concealed (selection bias)?

• Was knowledge of the allocated interventions adequately prevented during the study?

  • Participants and personnel (performance bias)

  • Outcome assessors (detection bias)

• Were incomplete outcome data adequately addressed (attrition bias)?

• Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?

• Was the study apparently free of other problems that could put it at risk of bias?

Measures of treatment effect

For dichotomous outcomes (e.g. death, need for KRT, incidence of adverse effects)  will be expressed as risk ratio (RR) with 95% confidence intervals (CI). Where continuous scales of measurement are used to assess the effects of treatment (e.g. SCr), the mean difference (MD) will be used, or the standardised mean difference (SMD) if different scales have been used. Change score will be used where needed (e.g. changes in SCr, changes in estimated glomerular filtration rate (eGFR)). If the studies included in our review include a mixture of final value scores and change‐from‐baseline, we calculate the change scores by subtracting the baseline value from the final value (Higgins 2022).

Unit of analysis issues

We will consider studies with cluster or cross‐over designs, and multiple arms, as specified in the Cochrane Handbook for Systematic Reviews of Interventions (Elbourne 2002; Higgins 2022). For multiple arms studies, we will include each buffered pair‐wise comparison separately and divide the sample size of the diuretics group among the comparisons.

Dealing with missing data

Any further information required from the original author will be requested by written correspondence (e.g. emailing corresponding author/s) and any relevant information obtained in this manner will be included in the review. Evaluation of important numerical data such as screened, randomised patients, as well as intention‐to‐treat, as‐treated, and per‐protocol population, will be carefully performed. Attrition rates, for example, drop‐outs, losses to follow‐up and withdrawals will be investigated. Issues of missing data and imputation methods (e.g. last‐observation‐carried‐forward) will be critically appraised (Higgins 2022).

Assessment of heterogeneity

We will assess the heterogeneity by visual inspection of the forest plot and quantify statistical heterogeneity using the I² statistic, which describes the percentage of total variation across studies attributable to heterogeneity rather, than sampling error (Higgins 2022). Guidance for interpreting I² values is as follows:

• 0% to 40%: might not be important

• 30% to 60%: may represent moderate heterogeneity

• 50% to 90%: may represent substantial heterogeneity

• 75% to 100%: considerable heterogeneity.

The importance of the observed value of I² depends on the magnitude and direction of treatment effects and the strength of evidence for heterogeneity (e.g. P value from the Chi² test, or a confidence interval for I²) (Higgins 2022).

Assessment of reporting biases

If possible, funnel plots will be used to assess for the potential existence of small study bias (Higgins 2022).

Data synthesis

We will perform quantitative analyses using RevMan. Considering heterogeneous designs and participants, we will use random‐effects models for all analyses, regardless of the statistical amount of heterogeneity. We will tabulate and evaluate the adverse effects using descriptive techniques because they tend to vary for different treatments. We will also estimate the risk difference (RD) with 95% CI for each adverse effect, where applicable, compared to placebo or other treatments.

Subgroup analysis and investigation of heterogeneity

We will perform subgroup analysis to evaluate heterogeneity due to age (≥ 16 years or < 16 years), types of patients at risk for AKI situation (patients undergoing all types of surgeries at risk for AKI, patients undergoing procedures associated with AKI, including the use of radiocontrast media, patients with heart failure, patients with CKD, patients requiring critical care), the definition of AKI (KDIGO, AKIN, or RIFLE), and types of diuretics.

Sensitivity analysis

Review authors will perform sensitivity analyses to explore the influence of several factors on effect size. The analyses included are as follows:

• Repeating the analysis including only placebo‐controlled trials (studies investigating diuretics with hydration as the intervention will be excluded because the amount of hydration would differ among the groups)

• Repeating the analysis including only studies with a low overall risk of bias

Summary of findings and assessment of the certainty of the evidence

We will present the main results of the review in 'Summary of findings' tables. These tables present key information concerning the certainty of the evidence, the magnitude of the effects of the interventions examined, and the sum of the available data for the main outcomes (Schunemann 2022a). The 'Summary of findings' tables also include an overall grading of the evidence related to each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach (GRADE 2008; GRADE 2011). The GRADE approach defines the certainty of a body of evidence as to the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. This will be assessed by two authors. The certainty of a body of evidence involves consideration of within‐trial risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias (Schunemann 2022b). We plan to present the following outcomes in the 'Summary of findings' tables.