Combining data for patients who have both CKD and diabetes (and excluding those without diabetes) from 3 large RCTs, there was no bene t in all-cause mortality; there were www.kidney-international.org chapter 3 9% fewer deaths with monotherapy RASi compared to dual RASi therapy (RR: 0.92; 95% CI: 0.84 1.01) based on data from 10,486 patients with a mean follow-up of 52 months ). There was a marginal reduction of 20% (RR: 0.80; 95% CI: 0.65 1.00) in doubling of serum creatinine by dual therapy, compared to monotherapy, during the study of 10,486 pa- tients from 3 studies with a mean follow-up of 37 months and ONTARGET ). However, the lower con dence interval reaches the null, indicating high uncertainty. The data analysis of the meta-analysis cited above is echoed by the individual large RCTs, including ONTARGET, VA-NEPHRON D, ALTITUDE, and ORIENT. Although dual therapy with ACEi and ARB (or DRI in ALTITUDE) moderately reduces albuminuria and BP compared to monotherapy with either drug, dual therapy does not confer important clinical kidney or CV bene ts, and it causes more hyperkalemia and AKI. Quality of evidence. The overall quality of the evidence for harm was moderate. The network meta-analysis that compared dual RASi with mono RASi exhibited moderate quality of the evidence because of concerns regarding inconsistency for all- cause mortality and CV events and serious imprecision for ESKD due to wide CIs that indicated appreciable bene ts and harms (Supplementary Table S32).169 The ERT review (including Cochrane reviews that were updated259,281 ) rated the quality of evidence to be moderate for studies that compared dual with mono RASi because of study limitations, with unclear reporting for Cochrane risk of bias282 domains, random sequence generation, and allocation concealment (Supplementary Table S31234,277 279,283,284 ). 