NN&I - June 2010

Clinical 22 Nephrology News & Issues June 2010Subscribe to our free eNewsletter at www.nephronline.com Takeda submits new drug application for hypertension treatment azilsartan medoxomilProtein loss in the urine harmful for people with high blood pressure Takeda Pharmaceutical Company Limited announced that it submitted a New Drug Application to the U.S. Food and Drug Administration for azilsartan medox -omil, an angiotensin II receptor blocker under investigation to treat hypertension. Azilsartan medoxomil is designed to lower blood pressure by blocking the action of a vasopressor hormone, angiotensin II. The NDA submission was supported by seven Phase 3 clinical trials involving more than 5,900 patients.Healthy people with high blood pressure and who excrete a slight excess of protein in the urine raise their risk of developing kidney and heart complications, accord-ing to a study appearing in the April 29 online issue of the Clinical Journal of the American Society of Nephrology. Research shows that diabetic patients with hypertension who excrete slightly increased amounts of protein in the urinea condition known as microalbuminuriahave an elevated risk of developing heart and kidney problems. Investigators have wondered whether microal- buminuria (occurring in 10% to 30% of individuals, depending on age and clinical conditions) may have similar effects in non-diabetic patients with hypertension. For nearly 12 years, Roberto Pontremoli, MD, PhD (University of Genoa, Italy) and his colleagues fol-lowed the health of 917 hyperten-sive, non-diabetic patients enrolled in the MAGIC (Microalbuminuria: A Genoa Investigation on Com-plications) study between 1993 and 1997. The investigators found that patients with microalbuminuria at the start of the study were 7.6 times as likely to develop chronic kidney disease and 2.1 times as likely to develop cardiovascular complica-tions, such as heart disease or stroke, compared with individuals without microalbuminuria. Study participants with microalbuminuria also had a 3.2-fold increased risk of developing both kidney and cardio-vascular conditions. High vitamin B doses may accelerate kidney damagePatients with diabetic nephropathy who received high dose B-vitamin ther -apy experienced a more rapid decline in kidney function and had a higher rate of heart attack and stroke than patients who received placebo, acc-ording to a study in the April 28 issue of the Journal of the American Medi- cal Association . Andrew A. House, MD, of the University of Western Ontario, and J. David Spence, MD, of the Robarts Research Institute, London, Ontario, and colleagues conducted a study to examine whether B-vitamin therapy would slow the progression of diabet -ic nephropathy and prevent vascular events in 238 patients with type 1 or type 2 diabetes. The randomized, pla-cebo-controlled trial was conducted at five university medical centers in Canada between May 2001 and July 2007. Patients received a single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B6 (25 mg/d), and vita-min B12 (1 mg/d), or matching place-bo. The primary outcome was change in radionuclide glomerular filtration rate between baseline and 36 months. Other outcomes included dialysis and a composite of heart attack, stroke, revascularization, and all-cause death. Plasma total homocysteine was mea-sured. Participants were followed-up for an average of 31.9 months. Among the results, the researchers found that participants assigned to the B-vitamin group had a greater decrease in radionuclide GFR (and subsequently poorer kidney function) compared with the placebo group. Also, participants randomized to receive B vitamins had a significantly greater number of cardio -vascular and cerebrovascular events, with the 36-month risk of a composite outcome, including heart attack, stroke, revascularization, and all-cause mor -tality that was double in the B-vitamin group, compared to the placebo group. There was no difference in requirement of dialysis. Regarding plasma total homo -cysteine levels, at 36 months, partici- pants in the B-vitamin group had an average decrease while participants in the placebo group had an aver- age increase."Given the recent large-scale clin-ical trials showing no treatment benefit, and our trial demonstrating harm, it would be prudent to discour -age the use of high-dose B vitamins as a homocysteine-lowering strate -gy outside the framework of prop- erly conducted clinical research," the authors concluded. Clinical_NNI0610_5.indd 22 5/14/10 2:53:36 PM