, when to pause RASi), repeat lab testing, vigilance to prevent hyperkalemia and AKI due to volume depletion and other events, as well as repeat visits to restart RASi if it has been stopped during a hospitalization. On the other hand, there is moderate evidence for RASi treatment with the goal of preventing progressive loss of kidney function, which likely justi es the additional costs and visits required for monitoring. Considerations for implementation. There is insuf cient in- formation to differentiate between men and women for this recommendation, and insuf cient evidence that there are different outcomes by race. Rationale We make this recommendation for RASi because the bene ts of kidney and CV protection outweigh the potential adverse risks; therefore, most well-informed patients with CKD not on dialysis with severely increased albuminuria but without diabetes will opt for treatment with RASi. We feel that pa- tients put a large value on the cardio- and renoprotective bene ts of RASi and are willing to tolerate its potential harms, including hyperkalemia and AKI. These side effects, however, may lead to higher healthcare costs from additional visits and laboratory testing. Favors ACEi Favors placebo Study or subgroup Albuminuria/proteinuria Events Total Events Total Weight M H, random, 95% CI ACEi Placebo/ no treatment Risk ratio M H, random, 95% CI Risk ratio Subtotal (95% CI) Total events Test for overall effect: Z = 2.26 (P = 0.02) Figure 6 | Cardiovascular events in patients with CKD G3 G4, A3 without diabetes. Meta-analysis was conducted by the Cochrane Kidney and Transplant Evidence Review Team as part of the guideline evidence review. GISEN reported data from the REIN Stratum-2 group (baseline proteinuria $3 g/24 h), in contrast to REIN Stratum-1 (baseline proteinuria 1-3 g/24 h). 