Received July 7, 2008
Accepted on October 2, 2008

ORIGINAL ARTICLES

Design of Combination Angiotensin Receptor Blocker and Angiotensin-Converting Enzyme Inhibitor for Treatment of Diabetic Nephropathy (VA NEPHRON-D)

Linda F. Fried ^*1, William Duckworth , Jane Hongyuan Zhang , Theresa O'Connor , Mary Brophy , Nicholas Emanuele ^¶, Grant D. Huang ^||, Peter A. McCullough ^**, Paul M. Palevsky ^*, Stephen Seliger , Stuart R. Warren , Peter Peduzzi , and for VA NEPHRON-D Investigators

*Veterans Affairs (VA) Pittsburgh Healthcare System and Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylviania; Carl T. Hayden VA Medical Center, School of Life Sciences, Arizona State University, and Department of Medicine, University of Arizona, Phoenix, Arizona, West Haven VA Cooperative Studies Program Coordinating Center, West Haven, Connecticut; VA Boston Healthcare System and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; ¶Hines VA and Department of Medicine, Loyola University Medical Center, Hines Illinois; ||Cooperative Studies Program Headquarters, VA Office Research and Development, Washington, District of Columbia; **Department of Medicine, William Beaumont Hospital, Royal Oak, Michigan; VA Maryland Medical Center and Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, VA Cooperative Studies Program Research Pharmacy and University of New Mexico College of Pharmacy, Albuquerque, New Mexico

¹ To whom correspondence should be addressed. E-mail: Linda.Fried{at}va.gov.

	Abstract

Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can slow the progression of diabetic nephropathy. Even with ACEI or ARB treatment, the proportion of patients who progress to end-stage renal disease (ESRD) remains high. Interventions that achieve more complete blockade of the renin–angiotensin system, such as combination ACEI and ARB, might be beneficial. This approach may decrease progression of nondiabetic kidney disease. In diabetic nephropathy, combination therapy decreases proteinuria, but its effect in slowing progression is unknown. In addition, the potential for hyperkalemia may limit the utility of combined therapy in this population. VA NEPHRON-D is a randomized, double-blind, multicenter clinical trial to assess the effect of combination losartan and lisinopril, compared with losartan alone, on the progression of kidney disease in 1850 patients with diabetes and overt proteinuria.