AMSTAR 2 was used to critically appraise systematic re- For systematic reviews of diagnostic test accuracy studies, the QUADAS-2 tool was used to assess study limitations.386 All critical appraisal was conducted independently by 2 ERT members, with disagreements regarding the risk of bias adjudications resolved by consultation with a third review author. Evidence synthesis and meta-analysis. Measures of treatment effect. Dichotomous outcomes (all-cause mortality, CV mortality, kidney failure, CV events [MI, stroke, HF], dementia or cognitive impairment, doubling serum creatinine, AKI, falls, fatigue, body weight, and BP) results were expressed as RR with 95% CI. When continuous scales of measurement were used to assess the effects of treatment, such as body weight, the mean difference (MD) with 95% CI was used. Data synthesis. Data were pooled using the Mantel-Haenszel random-effects model for dichotomous outcomes, and the inverse variance random-effects model for continuous outcomes. The random-effects model was chosen because it provides a conservative estimate of effect in the presence of known and Assessment of heterogeneity. Heterogeneity was assessed by visual inspection of forest plots of standardized mean effect sizes and of risk ratios, and c2 tests. A P value of <0.05 was used to denote statistical heterogeneity, and an I2 was calculated to measure the proportion of total variation in the estimates of treatment effect that was due to heterogeneity beyond chance.384 We used conventions of interpre- tation as de ned by Higgins et al. (2003).387 Assessment of publication bias. We made every attempt to minimize publication bias by including unpublished studies (for example, by searching online trial registries). To assess publication bias, we used funnel plots of the log odds ratio (effect vs. standard error of the effect size) when a suf cient number of studies were Other reasons for the asymmetry of funnel plots were considered. 