Endocrine Abstracts

The activity of the renin–angiotensin system (RAAS) is elevated in the circulation and in various tissues and organ tissues. The increased RAAS activity plays an important role in the haemodynamic and non-haemodynamic pathogenetic mechanisms involved in kidney and vascular (CV) disease. Previous studies have demonstrated that albuminuria is not only a marker of glomerular lesions but also a progression promoter and finally a powerful predictor of the long term beneficial effect of blood pressure lowering therapy. Furthermore albuminuria ia a harbinger of CV disease. Randomized blinded studies of patients with diabetic nephropathy have demonstrated:

–Angiotensin II receptor blockers (ARB) can prevent/delay development of microalbuminuria and diabetic nephropathy independently of its beneficial blood lowering effect in hypertensive patients with type 2 diabetes and normoalbuminuria/microalbuminuria (BENEDICT and IRMA 2)

–Early ARB treatment is projected to improve life expentancy and reduce cost in hypertensive patients with type 2 diabetes and microalbuminuria. Later use of ARB in overt nephropathy is also superior to standard care, but ARB should be started earlier and continued long term.

–Two landmark studies (RENAAL and IDNT) lead to the following conclusion: ‘Losartan and Irbesartan conferred significant renal benefit in patients with type 2 diabetes and nephropathy. This protection is independent of the reduction in blood pressure it causes. The ARB is genrally safe and well-tolerated’.

–Albuminuria is an important factor predicting cardiovascular risk in patients with type 2 diabetic nephropathy. Reducing albuminuria with ARB in the first 6 months appears to afford cardiovascular protection in these patients.

–The antiproteinuric effect of ARB explains a large part of the specific renoprotective characteristic. Proteinuria should be considered a risk marker for progressive renal function loss in type 2 diabetes with nephropathy, as well as target for therapy. Lowering of residual proteinuria is a goal for the future.

–Recent studies suggest that remission of nephrotic range albuminuria induced by aggressive antihypertensive treatment is associated with a slower progression in diabetic nephropathy and a substantial improved survival.

–Recent studies have suggested new renoprotective treatment modalities, e.g. ultrahigh dose of RAAS-blockade, combination of ACEI and ARB, aldosterone blockers and direct rennin inhibition.

Intensified multifactorial intervention – with tight glucose regulation and the use of renin–angiotensin system blockers, aspirin, and lipid-lowering agents – has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes melleitus and microalbuminuria. We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes.

In the Steno-2 study we randomly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy; the mean treatment period was 7.8 years. Patients were subsequently followed observationally for a mean of 5.5 years until December 31, 2006. The primary end point at 13.3 years of follow-up was the time of death from any cause.

Twenty-four patients in the intensive-therapy group died, as compared with 40 in the conventional-therapy group (hazard ratio, 0.54; 95% CI 0.32 to 0.89; P=0.02). Intensive therapy was associated with lower risk of death from cardiovascular causes (hazard ratio, 0.43; 95% CI, 0.19 to 0.94; P=0.04) and of cardiovascular events (hazard ratio, 0.41; 95% CI, 0.25 to 0.67; P<0.001). One patient in the intensive-therapy group had progression to end-stage renal disease, as compared with six patients in the conventional-therapy group (P=0.04). Fewer patients in the intensive-therapy group required retinal photocoagulation (relative risk, 0.45; 95% CI, 0.23 to 0.86; P=0.02). Few major side effects were reported.

In at-risk patients with type 2 diabetes, intensive intervention with multiple drug combinations and behaviour modification has sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes.