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). A3, severely increased albuminuria; ACEi, angiotensin- converting enzyme inhibitor; AIPRI, Angiotensin-Converting Enzyme Inhibitors and Kidney Protection; CI, con dence interval; CKD, chronic kidney disease; events, number of events; GISEN, Gruppo Italiano di Studi Epidemiologici in Nefologia; M-H, Mantel-Haenszel; REIN, Blood- Pressure Control for Renoprotection in Patients with Non-diabetic Chronic Renal Disease; total, number of participants. chapter 3 www.kidney-international.org Recommendation 3.2.2: We suggest starting RASi (ACEi or ARB) for people with high BP, CKD, and moderately increased albuminuria (G1 G4, A2) without diabetes (2C). This recommendation is weak according to GRADE, based on limited evidence from RCTs of suf cient duration to evaluate kidney protection. However, the Work Group judged that most well-informed patients would value the cardio- and renoprotective bene ts of RASi over potential harms from AKI or hyperkalemia. Key information Balance of bene ts and harms. The HOPE study,163 one of the largest RASi studies, found in a prespeci ed subgroup analysis of those with CKD and normal-to-moderately increased albuminuria (creatinine clearance <65 ml/min, estimated by the Cockcroft Gault formula; n 3394; mean follow-up 4.5 years) that ACEi versus placebo reduced the risk for all-cause mortality It should be noted that approximately one-third of patients in the HOPE study had diabetes, and only half had high BP. In the overall HOPE study, the CV bene ts of ramipril versus placebo were also present in those with moderately increased There were no studies speci cally evaluating the effect of RASi on slowing kidney disease progression in patients with CKD without diabetes and A2; therefore, HOPE provides the best guide for this subpopulation. Cinotti et al. 