Despite their renal benefit to reduce DKD progression observed from large kidney outcome trials, Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [125] and the Irbesartan Diabetic Nephropathy Trial [136], ACE inhibitors and ARBs have demonstrated no evidence to reduce the composite of cardiovascular endpoints (cardiovascular death, myocardial infarction, hospitalization for heart failure, hospitalization for angina or lower limb amputation above the ankle). This evidence concerns the gene ACE and diabetic kidney disease.