NEJM Publication Shows Potential For Rasilez(R) (aliskiren) To Protect Against Kidney Damage

Main Category: Diabetes
Article Date: 11 Jun 2008 - 5:00 PST

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Data published in this week's New England Journal of Medicine (NEJM) demonstrate that the first-in-class direct renin inhibitor Rasilez® (aliskiren) shows potential kidney-protective benefit independent of its blood pressure lowering effects1.

In the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) study, aliskiren reduced albuminuria by an additional 20% versus placebo in type 2 diabetic patients with kidney disease who also had a diagnosis of hypertension. These patients were already taking the maximum dose of the angiotensin-receptor blocker (ARB) losartan1, which has been shown to slow the progression of diabetic kidney disease1,4. Up to 40% of diabetics in the UK eventually develop kidney complications, known as diabetic nephropathy5. Damage to the kidneys caused by diabetes remains the leading cause of end stage renal disease in the developed world1.

In patients with diabetes, the first sign of kidney disease is the presence of albumin in the urine, a condition called albuminuria2. Albuminuria is a key indicator of kidney disease and cardiovascular disease2. Reducing albuminuria is associated with a reduction of cardiovascular events6 and is also associated with slowing the progression of kidney disease, which can reduce the risk of chronic kidney failure in type 2 diabetic patients with kidney disease and high blood pressure7,8.

"We have already seen that aliskiren, the first direct renin inhibitor is an effective antihypertensive both as monotherapy and in combination, and now aliskiren shows considerable potential to protect against diabetic nephropathy in type 2 diabetic patients at risk of kidney failure and cardiovascular diseases," said Professor Kennedy Cruickshank of Manchester University and Royal Infirmary. "This data is promising news and a positive step forward in identifying the right combination of treatments to manage this rapidly increasing patient population."

In the 24-week AVOID study involving nearly 600 patients, aliskiren was added to the treatment regimen of type 2 diabetic patients diagnosed with hypertension who were already receiving losartan and had albuminuria levels greater than 200 mg/g1. The study showed that overall aliskiren (150 mg increasing to 300 mg daily) reduced albuminuria by an additional 20% when added to the maximum dose of losartan (100 mg)1. Furthermore, a quarter of patients taking aliskiren added to losartan experienced albuminuria reductions greater than 50% compared to those patients taking losartan alone1.

Data from AVOID further showed that aliskiren added to the maximum dose of losartan had similar rates of adverse events as the placebo plus losartan group1. Hyperkalemia (elevated potassium levels) was reported as an adverse event in 5.0% of patients taking aliskiren in addition to losartan, compared to 5.7% of those taking placebo plus losartan1.

The AVOID study is one in a series of trials for aliskiren in the ASPIRE HIGHER clinical trial program which is studying the effect of direct renin inhibition in a variety of conditions, including diabetic kidney disease and heart failure1,9.

Aliskiren, a direct renin inhibitor, is the first of a new drug class to treat high blood pressure to be made available to UK patients in over a decade. Aliskiren acts by directly inhibiting renin3, an enzyme that triggers a process leading to high blood pressure and organ damage. Aliskiren is marketed in the UK under the brand name of Rasilez, and was approved in the European Union in August 2007.

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References

1. Parving H-H et al. Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy. New England Journal of Medicine.

2. National Institute of Diabetes and Digestive and Kidney Diseases. National Kidney and Urologic Diseases Information Clearing House; NIH Publication No. 06-4732. September 2006; http://www.kidney.niddk.nih.gov

3. Rasilez Summary of Product Characteristics. Available at: http://www.medicines.org.uk

4. Brenner B, Cooper M, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 245:861-869.

5. Kidney Research UK - Diabetes http://www.kidneyresearchuk.org/content/view/335/409 (accessed 02 June 2008)

6. de Zeeuw D, Remuzzi G, Parving H-H,et al. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation. 2004;110:921-927.

7. de Zeeuw D, Remuzzi G, Parving H-H, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: Lessons from RENAAL. Kidney International 2004; 65:2309-2320.

8. Ibsen H, Olsen MH, Wachtell K, et al. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study. Hypertension 2005;45:198-202.

9. McMurray JJV et al. Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients with Symptomatic Heart Failure. Circ Heart Fail 2008;1:17-24

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