(1B) *Approximate equivalents for albumin excretion rate per 24 hours expressed as protein excretion rate per 24 hours, albumin/creatinine ratio, protein/creatinine ratio, and protein reagent strip results are given in Table 1, Chapter 1. RATIONALE K Patients with diabetes and high levels of urine albumin are at a particularly high risk of adverse cardiovascular and kidney outcomes. K There is strong evidence from RCTs conducted in patients with diabetes and CKD demonstrating that ACE-Is and ARBs protect against kidney failure and increases in albumin levels. Individuals with elevated levels of urinary albumin or protein and diabetes have some of the highest rates of cardiovascular events and kidney failure of any group with CKD. For example, in IDNT and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial, the annual risk of the kidney and cardio- vascular end points all approached 10%.182,184,259 261 RCTs. Several RCTs have provided high-quality evidence, both in type 1 diabetes269 that ARBs and ACE-Is reduce the risk of kidney outcomes270 as compared to placebo or a dihydropyridine calcium-channel although no clear effect on cardiovascular out- comes has been established (possibly due to inadequate power) (see Supplementary Tables 37 42 online). How- ever, applicability of study findings to the entire CKD and diabetes population is somewhat limited, because major studies have excluded patients with clinically significant CVD. There is high-quality evidence from trials of high-risk individuals from the general population showing that ARBs and ACE-Is improve cardiovascular outcomes,185,271 276 including in patients with diabetes.277,278 But these studies did not focus on patients with clinically significant albuminuria. In contrast, there was no benefit of ACE-Is as compared to diuretic therapy in the CKD and diabetic subgroups in ALLHAT,279 although, again, few of the study patients were likely to have had frank albuminuria. 