In patients with CKD with and without diabetes, a large network meta-analysis compared dual blockade to monotherapy and included 17,750 participants. Two of these studies excluded participants with There was no signi cant difference in all-cause mortality from dual blockade versus monotherapy in 7 studies of 16,862 patients with a mean follow-up of 3.4 years. There was also no difference in progression to ESKD and no improvement of CV events based on 7 studies of 16,507 patients with a mean follow-up of 40 months. On the other hand, a traditional pair-wise meta-analysis performed by the ERT demonstrated harm for dual blockade compared to monotherapy. In studies of patients with CKD with and without diabetes, dual blockade compared to mon- otherapy caused a slightly higher risk of all-cause mortality of borderline signi cance (HR: 1.09; 95% CI: 1.00 1.20) based on data from 10,615 patients in 4 studies with a mean follow-up of and (Supplementary Table S31). Importantly, in studies of patients with CKD with or without diabetes, there was evidence that dual therapy increased the incidence of AKI by 40% (RR: 1.60; 95% CI: 1.26 2.04), compared to monotherapy, based on data from 6139 patients in with a mean follow-up of 39 months (Supplementary Table S31). 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 ). 