Aliskiren (Tekturna | Novartis) may provide additional renoprotection in hypertensive diabetics with nephropathy on routine renoprotective regimen, according to a study by Parving HH, et al., published in the June 2008 issue of New England Journal of Medicine.
Aliskiren is a novel drug, one of its kind, approved by the FDA in 2007 for the treatment of hypertension. Its uniqueness lies in the fact that it blocks the rate-limiting step in the generation of angiotensin II from renin. Production of both angiotensin I and II is interrupted; therefore, it offers distinct advantages over angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). For instance, kinin metabolism is not affected; therefore, dry cough and angioedema, common adverse effects of ACEIs, are rarely seen with aliskiren. ARBs raise the level of angiotensin II, a potent vasoconstrictor, but this effect is not seen with aliskiren. The researchers sought to investigate if this innovative antihypertensive offered any additional renoprotection in diabetics with nephropathy.
In the study, 599 subjects were initially administered losartan for 3 months, following which they were randomized to either receive aliskiren or placebo for 6 months along with the ARB. The dose of aliskiren was 150 mg for the first 3 months, and was doubled during the subsequent 3 months. The early morning urine sample was evaluated for albumin- creatinine ratio. It was observed that the mean albumin-creatinine ratio reduced by 20% in subjects on aliskiren as compared to placebo. Also, a 50% reduction in the ratio was noted in almost one out of four patients on aliskiren. The drug reduced BP by an additional 2 mm Hg systolic and 1 mm Hg diastolic, compared to the placebo group.
Diabetics are susceptible to the development of hypertension and persistent urinary loss of proteins. This is referred to as diabetic nephropathy (DN). It is diagnosed by the presence of more than 30 mg/day albuminuria (termed microalbuminuria) over a period of 3-6 months. Albuminuria is also an indicator of increased cardiovascular risk in diabetics. Over time, DN gradually causes a progressive decline in renal function and may culminate in end stage renal disease (ESRD). Tight blood pressure and blood glucose control is vital in the management of these patients. In addition, prescription of renoprotective agents, such as ACEIs or ARBs has been shown to interrupt or decelerate DN.
Approximately 20-30% of diabetics develop DN, and diabetes is the single most common cause of ESRD today in the US. With the increasing prevalence and lifespan of diabetics, the numbers are expected to rise further in the coming years. Optimal management of diabetes and associated co-morbidities should be stressed in all patients not only to prevent renal complications, but also to delay other end organ damage.
About Novartis: Headquartered in Basel, Switzerland, Novartis is a leading pharmaceutical company, with one of the highest investments in research touching US $6.4 billion in 2007. The company was formed by a merger between Ciba-Geigy and Sandoz in 1996. They employ more than 100,000 people and have received 17 drug approvals in the past 8 years, the highest by any pharma company. Diovan HCT (valsartan and hydrochlorothiazide), Gleevec/Glivec (imatinib mesylate/imatinib), and lamisil (terbinafine) are some of their most popular products.
Reference
1. Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK; AVOID Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008 Jun 5;358(23):2433-2446.
2. Barnett AH. Preventing renal complications in diabetic patients: the Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) study. Acta Diabetol. 2005 Apr;42 Suppl 1:S42-49.
3. Molitch ME, DeFronzo RA, Franz MJ, Keane WF, Mogensen CE, Parving HH, et al. Diabetic nephropathy. Diabetes Care. 2003 Jan;26(Suppl 1):S94-98.
4. Thorp ML. Diabetic nephropathy: common questions. Am Fam Physician. 2005 Jul 1;72(1):96-99.
