Angiotensin Receptor Blockers and Type 2 Diabetic Nephropathy
Angiotensin Receptor Blockers and Type 2 Diabetic Nephropathy
European Endocrine Review 2006
Published: October 2008
Published: October 2008
The DETAIL study also demonstrated a much lower incidence of cardiovascular morbidity and mortality than predicted by epidemiological data in patients who were at very high cardiovascular risk; indeed, approximately half of the patients already had evidence of cardiovascular disease at trial entry. These benefits are postulated to be due, at least in part, to blockade of the RAAS by these agents.
In patients with urinary albumin excretion of more than 500mg/day, the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study revealed that losartan, compared with placebo, brought about a 16% reduction in the risk of a doubling of serum creatinine, end-stage renal disease or death.11
Patients in the Irbesartan Diabetic Nephropathy Trial (IDNT) had somewhat higher levels of urinary albumin excretion (>900mg/day).12 Irbesartan reduced the risk of the doubling of serum creatinine, end-stage renal disease or death by 20% compared with placebo, and by 23% compared with the calcium channel blocker amlodipine.
On-going Studies
In the Renin Angiotensin System Study of Diabetic Nephropathy (RASS), the effect of losartan with or without enalapril is being evaluated to determine whether dual blockade of the RAAS using an ARB and an ACE inhibitor confers additional renoprotection.13
The Randomised Olmesartan And Diabetes Microalbuminuria Prevention (ROADMAP) study is assessing the effect of the ARB on onset of microalbuminuria in patients with type 2 diabetes.14
The renoprotective efficacy of telmisartan is being extensively studied within the Programme of Research to show Telmisartan End-organ Protection (PROTECTION).15 One study is comparing the effect of telmisartan with that of the ACE inhibitor ramipril on one of the earliest markers of damage to the renal vasculature – endothelial dysfunction – in patients with type 2 diabetes with normo- or microalbuminuria. Two studies are comparing the renoprotective efficacy of long-acting telmisartan with that of either losartan or valsartan in overt type 2 diabetic nephropathy. A fourth study is assessing the effect of different doses of telmisartan on incipient type 2 diabetic nephropathy.
Existing evidence strongly supports the use of ARBs for the prevention of type 2 diabetic nephropathy progression. There is currently little direct comparison of the efficacy of ARBs with varying pharmacological features in the management of diabetic nephropathy. This is being addressed in ongoing studies.
References:
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- Dworkin L D, Shemin D G, “The role of hypertension in progression of chronic renal disease”, in: Schrier R W (ed),Atlas of Diseases of the Kidney, Blackwell Scientific, Malden (1999): pp. 6.1–6.18.
- Bakris G L, Williams M, Dworkin L D et al., “Preserving renal function in adults with hypertension and diabetes: aconsensus approach”, Am. J. Kidney Dis. (2000);36: pp. 646–661.
- Lazarus J M, Bourgoignie J J, Buckalew V M et al., “Achievement and safety of a low blood pressure goal in chronic renaldisease”, Hypertension (1997);29: pp. 641–650.
- National Kidney Foundation, “K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronickidney disease”, Am. J. Kidney Dis. (2004);43: pp. S1–S290.
- Sica D A, “Combination angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy: its role in clinicalpractice”, J. Clin. Hypertens. (2003);5: pp. 414–420.
- Ruiz-Ortega M, Ruperez M, Esteban V et al., “Molecular mechanisms of angiotensin II-induced vascular injury”, Curr.Hypertens. Rep. (2003);5: pp. 73–79.
- Parving H H, Lehnert H, Brochner-Mortensen J et al., “The effect of irbesartan on the development of diabetic nephropathyin patients with type 2 diabetes”, N. Engl. J. Med. (2001);345: pp. 870–878.
- Viberti G, Wheeldon N M, “Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a bloodpressure-independent effect”, Circulation (2002);106: pp. 672–678.
- Barnett A H, Bain S C, Bouter P et al., “Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2diabetes and nephropathy”, N. Engl. J. Med. (2004);351: pp. 1,952–1,961.
- Brenner B M, Cooper M E, de Zeeuw D et al., “Effects of losartan on renal and cardiovascular outcomes in patients withtype 2 diabetes and nephropathy”, N. Engl. J. Med. (2001);345: pp. 861–869.
- Lewis E J, Hunsicker L G, Clarke W R et al., “Renoprotective effect of the angiotensin-receptor antagonist irbesartan inpatients with nephropathy due to type 2 diabetes”, N. Engl. J. Med. (2001);345: pp. 851–860.
- Mauer M, Zinman B, Gardiner R et al., “ACE-Is and ARBs in early diabetic nephropathy” J. Renin AngiotensinAldosterone Syst. (2002);3: pp. 262–269.
- Halimi S, “Primary cardiorenal prevention in patients with type-2 diabetes. The Roadmap study”, Presse Med.(2005);34: pp. 1,300–1,302.
- Weber M, “The telmisartan Programme of Research tO show Telmisartan End-organ proteCTION (PROTECTION)programme”, J. Hypertens. (2003);21(suppl. 6): pp. S37–S46.
- 11 September 2010
