In the ADVANCE study of patients with CKD G1 G3, A2, the quality of evidence is low according to GRADE.260 The quality of the evidence was downgraded due to serious risk of bias, with unclear allocation concealment, and imprecision, as the bene cial results of diuretics were seen only in the CKD subgroups, when the results were negative in the entire cohort (Supplementary Table S27). The best evidence for renoprotective effects of RASi therapy independent of BP control in patients with diabetes, CKD G3 G4, and severely increased albuminuria comes from the with its active comparator arm, and from the trial. For CV outcomes, the Micro-HOPE study provides the best evidence for patients with moderately There are no RCTs in those with moderately increased albuminuria (A2) powered for hard kid- ney outcomes. Published meta-analyses for patients with dia- betes, hypertension, and CKD provided mixed results. One found a reduction of all-cause mortality, CV mortality, and major CV events in 32,827 people with diabetes treated with ACEi, but this was not found in 23,867 patients treated with A meta-analysis comparing RASi to other antihyper- tensive medications, excluding placebo-controlled trials, in people with diabetes, did not nd CVoutcome improvement.262 There was also no improvement in kidney failure, but the vast majority of included studies enrolled people with normal urine albumin or did not measure albumin at all. These meta-analyses included patients with diabetes and CKD G1 and G2, A1 A3, and G3 and G4, A1 A3, respectively. It is likely that including the low-risk and high-risk groups together led to the lack of statis- tical signi cance for CV outcomes. 