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ObjectiveTo evaluate the effects of drug interventions that may modify the progression of chronic kidney disease (CKD) in adults with CKD stages 3 and 4.DesignSystematic review and meta-analysis.MethodsSearching MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, International Clinical Trials Registry Platform, Health Technology Assessment, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index and Clinical Trials Register, from March 1999 to July 2018, we identified randomised controlled trials (RCTs) of drugs for hypertension, lipid modification, glycaemic control and sodium bicarbonate, compared with placebo, no drug or a drug from another class, in ≥40 adults with CKD stages 3 and/or 4, with at least 2 years of follow-up and reporting renal function (primary outcome), proteinuria, adverse events, maintenance dialysis, transplantation, cardiovascular events, cardiovascular mortality or all-cause mortality. Two reviewers independently screened citations and extracted data. For continuous outcomes, we used the ratio of means (ROM) at the end of the trial in random-effects meta-analyses. We assessed methodological quality with the Cochrane Risk of Bias Tool and confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.ResultsWe included 35 RCTs and over 51 000 patients. Data were limited, and heterogeneity varied. Final renal function (estimated glomerular filtration rate) was 6% higher in those taking glycaemic control drugs (ROM 1.06, 95% CI 1.02 to 1.10, I2=0%, low GRADE confidence) and 4% higher in those taking lipid-modifying drugs (ROM 1.04, 95% CI 1.00 to 1.08, I2=88%, very low GRADE confidence). For RCTs of antihypertensive drugs, there were no significant differences in renal function. Treatment with lipid-modifying drugs led to a 36% reduction in cardiovascular disease and 26% reduction in all-cause mortality.ConclusionsGlycaemic control and lipid-modifying drugs may slow the progression of CKD, but we found no pooled evidence of benefit nor harm from antihypertensive drugs. However, given the data limitations, further research is needed to confirm these findings.PROSPERO registration numberCRD42015017501.

ObjectiveTo estimate the proportion of systematic reviews that meet the optimal information size (OIS) and assess the impact heterogeneity and effect size have on the OIS estimate by type of outcome (eg, mortality, semiobjective or subjective).MethodsWe carried out searches of Medline and Cochrane to retrieve meta-analyses published in systematic reviews from 2010 to 2012. We estimated the OIS using Trial Sequential Analysis software (TSA V.0.9) and based on several heterogeneity and effect size scenarios, stratifying by type of outcome (mortality/semiobjective/subjective) and by Cochrane/non-Cochrane reviews.ResultsWe included 137 meta-analyses out of 218 (63%) potential systematic reviews (one meta-analysis from each systematic review). Of these reviews, 83 (61%) were Cochrane and 54 (39%) non-Cochrane. The Cochrane reviews included a mean of 6.5 (SD 6.1) studies and the non-Cochrane included a mean of 13.2 (SD 10.2) studies. The mean number of patients was 2619.1 (SD 6245.8 or median 586.0) for the Cochrane and 19 888.5 (SD 32 925.7 or median 6566.5) patients for the non-Cochrane reviews. The percentage of systematic reviews that achieved the OIS for all-cause mortality outcome were 0% Cochrane and 25% for non-Cochrane reviews; for semiobjective outcome 17% for Cochrane and 46% for non-Cochrane reviews and for subjective outcome 45% for Cochrane and 72% for non-Cochrane reviews.ConclusionsThe number of systematic reviews that meet an optimal information size is low and varies depending on the type of outcome and the type of publication. Less than half of primary outcomes synthesised in systematic reviews achieve the OIS, and therefore the conclusions are subject to substantial uncertainty.