In AASK, a study of patients with a PCR o220 mg/g (o22 mg/mmol), the ACE-I ramipril decreased the urine protein level. It remains to be determined whether this translates into a clinically important benefit.177 In post hoc analyses of the Heart Outcomes Prevention Evaluation (HOPE), which was an RCT involving patients with diabetes or vascular disease and at least one other CVD risk factor, ramipril prevented progression of proteinuria or develop- ment of new-onset microalbuminuria, independent of In a post hoc analysis of Candesartan Antihypertensive Survival Evaluation in Japan (CASE J), which was an RCT comparing the ARB candesartan with the calcium-channel blocker amlodipine,178 candesartan reduced progression of CKD 4 (see Supplementary Table 5 online). In subgroup analyses of the Telmisartan Randomized Assess- ment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND), an RCT that included patients with vascular disease or diabetes, in patients with microalbumi- nuria (defined as an ACR 43.4 mg/mol [434 mg/g]), the ARB telmisartan decreased the risk of the composite kidney outcome (doubling of SCr level, dialysis, or death) in comparison with placebo.179 There was an interaction whereby telmisartan benefited patients with microalbumi- nuria but was associated with harm in those without microalbuminuria (P 0.006 for interaction). Finally, in patients with diabetes, ACE-Is and ARBs have been shown to prevent the development of macroalbuminuria in subjects and we have not found evidence of substantive differences between diabetics and non-diabetics with respect to either BP target or agent. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a large RCT examining the effects of the ACE-I lisinopril, the thiazide chlorthalidone, and the dihydropyridine calcium-channel blocker amlodipine in individuals 455 years of age with hypertension and at least one other CVD risk factor. 