The 2 main studies demon- strating kidney bene t from RASi independent of BP control in diabetes were the three-arm IDNT162 and the two-arm www.kidney-international.org chapter 3 studies where ARB was compared with placebo200 or with placebo and with CCB in a double-blinded manner.162 IDNT excluded participants with normal BP; RENAAL included those with and without high BP. Both studies included only participants with severely increased albuminuria. Irbesartan in the IDNT study resulted in a 20% (RR: 0.80; 95% CI: 0.66 0.97) risk reduction in the primary composite endpoint (doubling of serum creatinine, ESKD, death from any cause) versus placebo and a 23% reduction versus amlodipine (RR: 0.77; 95% CI: 0.63 0.93); while losartan in the RENAAL study caused a 16% (RR: 0.84; 95% CI: 0.72 0.98) reduction in the composite outcome of death, dialysis, and doubling of serum creatinine compared to placebo. These studies demonstrated that RASi therapy improved the composite outcome in patients with diabetes, signi cant albuminuria (IDNT: 2.9 g/d proteinuria, baseline serum creatinine of 1.67 mg/dl [148 mmol/l]; RENAAL: albumin creatinine ratio 1237 mg/g [124 mg/mmol], baseline serum creatinine 1.9 g/dl [168 mmol/l]), and G3 G4, A3. Further, the RENAAL study demonstrated that in patients who have already doubled their serum creatinine during the study, remaining on RASi therapy signi cantly delayed the onset of dialysis by a mean of 6 months. In the IDNT study, hyperkalemia necessitating a stop in therapy occurred in only 2% of patients with RASi, versus 0.5% of patients in the other arms. Overall, serious adverse events were actually lower in the RASi group than in the control group. Therefore, in those with diabetes and CKD G3 G4, A3, there is strong evidence supporting the treatment with RASi because of their renoprotective effects. 