The role of angiotensin II antagonism in type 2 diabetes mellitus: a review of renoprotection studies.
BACKGROUND
Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in Western and Asian countries. Effective antihypertensive therapy reduces the rate of decline in renal function and postpones ESRD in patients with diabetic nephropathy.


OBJECTIVE
This review presents evidence from studies on how blood pressure control, plasma glucose control, and the presence of proteinuria determine outcomes in diabetic patients. The role of angiotensin II (All) in the development of diabetic nephropathy and the reno- and cardiobeneficial effects of AII antagonism in patients with type 2 diabetes mellitus (DM-2) and diabetic nephropathy also are addressed.


METHODS
Articles included in this review were found using a MEDLINE search for studies published from 1991 to 2001 and including the search terms diabetic nephropathy, type 2 diabetes mellitus, microalbuminuria, proteinuria, angiotensin receptor blockade, angiotensin-converting enzyme inhibition, and cardiovascular disease. Articles reporting new data, new mechanisms, major clinical trials, and our own data were included.


RESULTS
Recently, the Reduction of Endpoints in NIDDM (non-insulin-dependent diabetes mellitus) with the Angiotensin II Antagonist Losartan (RENAAL) trial provided sufficient data to conclude that the blockade of the All AT1 receptor with losartan confers renoprotection in patients with DM-2 and nephropathy. Similar results were obtained with irbesartan in the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria study (IRMA 2). The results of RENAAL indicate that the renoprotective effects of losartan were attributable to effects beyond blood pressure control. In addition to the favorable impact of the All blockade on blood pressure and renal hemodynamics, the blockade of the growth-promoting, profibrotic, nonhemodynamic actions of AII also may be important for renoprotection. Intensive blood pressure control also confers cardiovascular protection in pa- tients with DM-2. Some studies suggest that the blockade of the renin-angiotensin system confers superior cardioprotective effects in patients with DM-2. The RENAAL study also showed cardioprotection with losartan, with an important reduction in the risk for first hospitalization for heart failure.


CONCLUSIONS
Evidence supports the importance of an effective blockade of AII action for both reno- and cardioprotection in patients with DM-2.
Zanella
Maria-Teresa
MT
Division of Nephrology, Hospital do Rim e Hipertensão, Federal University of São Paulo, São Paulo, Brazil. tereza.zanella@hrim.com.br
Ribeiro
Artur B
AB
D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D000077405:Irbesartan; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000517:prevention & control; D019808:Losartan / Q000627:therapeutic use; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan; D019808:Losartan