Blood pressure reduction and angiotensin-converting enzyme (ACE) inhibitors slow but do not stop progressive decline of renal function in established diabetic nephropathy (DN), but predictors of this decline in patients undergoing these interventions are unknown. Over a 24-week period, we studied male Sprague-Dawley diabetic and control rats and Sprague-Dawley diabetic rats treated with the ACE inhibitor ramipril, the angiotensin II-AT1 receptor antagonist valsartan, the bradykinin-B2 receptor antagonist HOE 140 (icatibant), and a combination of ramipril and icatibant. Based on their superior renoprotective performance in recent landmark studies, currently ACE inhibitors are the drugs of choice in diabetic patients with microalbuminuria or overt proteinuria. Streptozotocin-induced diabetic rats at 2 weeks were treated with dipyridamole, quinapril or both. It is known that the renin-angiotensin-system is stimulated in diabetic patients with nephropathy and that angiotensin II influences the synthesis of glomerular and mesangial proteins as well as the function of mesangial cells. Eighty patients were enrolled. By means of videocapillaroscopy and laser doppler imaging also distinct changes in microcirculation can be detected.
In this review, we summarize the role of intrarenal RAS activation in the pathogenesis and progression of DKD and the rationale for RAS inhibition in this population. UKMi has published a medicines question and answers resource on the use of a combination of ACE inhibitors with ARBs in patients with heart failure.