The importance of diuretic therapy for lowering BP is suggested by the ADVANCE study comparing treatment with a combination of an ACEi plus diuretic (perindopril plus inda- pamide) to usual care without a thiazide-type diuretic in 11,140 people aged $55 years with diabetes, CV risk, or increased albuminuria (A2 or A3) over a mean of 4.3 years.257 The main outcomes were death from CV disease, non-fatal stroke or non-fatal MI, and new or worsening kidney or dia- betic eye disease. The relative risk of a major macrovascular or chapter 3 www.kidney-international.org microvascular event was reduced by 9% (HR: 0.91; 95% CI: 0.83 1.00); the relative risk of death from CV disease was reduced by 18% (HR: 0.82; 95% CI: 0.68 0.98); and death from any cause was reduced by 14% (HR: 0.86; 95% CI: 0.75 0.98). These improvements in clinical outcomes were associ- ated with a fall in BP of SBP 5.3/DBP 2.1 mm Hg in patients with CKD G1 or G2, and SBP 4.5/DBP 1.8 mm Hg in patients with CKD G3 G5. There was no effect modi cation by the presence of baseline albuminuria. It should be noted that in the ADVANCE study, 49% of the placebo group were already treated with RASi at baseline, which further increased to 73% by the end of the study, while 25% were on diuretics at baseline, which decreased to 21% in the placebo group at the nal visit. This nding suggests that the bene ts seen in ADVANCE might have been due to the addition of the diuretic and/or greater BP lowering in the active treatment group. There is emerging evidence that MRA have bene cial effects on clinical kidney outcomes. 