Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy

• Published in: The New England journal of medicine Vol. 369; no. 20; pp. 1892 - 1903
• Main Authors: Fried, Linda F, Emanuele, Nicholas, Zhang, Jane H, Brophy, Mary, Conner, Todd A, Duckworth, William, Leehey, David J, McCullough, Peter A, O'Connor, Theresa, Palevsky, Paul M, Reilly, Robert F, Seliger, Stephen L, Warren, Stuart R, Watnick, Suzanne, Peduzzi, Peter, Guarino, Peter
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 14.11.2013
• Subjects: Adult; Albumin; Angiotensin II Type 1 Receptor Blockers - adverse effects; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Angiotensin-converting enzyme inhibitors; Angiotensin-Converting Enzyme Inhibitors - adverse effects; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Associated diseases and complications; Biological and medical sciences; Creatinine; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - complications; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - mortality; Diabetic nephropathy; Double-Blind Method; Drug therapy; Drug Therapy, Combination; End-stage renal disease; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; General aspects; Glomerular Filtration Rate; Humans; Hyperkalemia; Kaplan-Meier Estimate; Kidney diseases; Kidney Failure, Chronic - etiology; Kidneys; Lisinopril - adverse effects; Lisinopril - therapeutic use; Losartan - adverse effects; Losartan - therapeutic use; Male; Medical sciences; Middle Aged; Mortality; Nephrology. Urinary tract diseases; Nephropathy; Patients; Proteinuria; Safety; Urinary system involvement in other diseases. Miscellaneous; Veterans; United States > US; Pittsburgh Pennsylvania; Endocrinopathy; Kidney disease; Medicine; Concomitant disease; Urinary system disease; Treatment; Diabetes mellitus; Angiotensin; Diabetic nephropathy
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1303154

In this study, patients with type 2 diabetes, albuminuria, and mild-to-moderate renal dysfunction received losartan followed by lisinopril or placebo. The study was stopped early because of increased risks of hyperkalemia and acute kidney injury with combination therapy. Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in the United States. 1 Persons with diabetes and proteinuria are at high risk for progression to ESRD. 2 Blockade of the renin–angiotensin system decreases the progression of proteinuric kidney disease, 3 – 5 and the degree of reduction in proteinuria correlates with the extent to which the decrease in the glomerular filtration rate (GFR) is slowed. 2 , 6 Given these observations, it has been hypothesized that interventions that further lower proteinuria will further reduce the risk of progression. 6 Combination therapy with an angiotensin-converting–enzyme (ACE) inhibitor and an angiotensin II–receptor blocker (ARB) results in . . .