Effect of Losartan on Prevention and Progression of Early Diabetic Nephropathy in American Indians With Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 9; pp. 3224 - 3231
• Main Authors: Weil, E. Jennifer, Fufaa, Gudeta, Jones, Lois I., Lovato, Tracy, Lemley, Kevin V., Hanson, Robert L., Knowler, William C., Bennett, Peter H., Yee, Berne, Myers, Bryan D., Nelson, Robert G.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.09.2013
• Subjects: Adult; Aged; Associated diseases and complications; Biological and medical sciences; Clinical trials; Complications and side effects; Development and progression; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Diabetic nephropathies; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - prevention & control; Dosage and administration; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Indians, North American; Kidney diseases; Kidneys; Losartan; Losartan - therapeutic use; Male; Medical sciences; Middle Aged; Native North Americans; Nephrology. Urinary tract diseases; Original Research; Prevention; Risk factors; Side effects; Type 2 diabetes; Urinary system involvement in other diseases. Miscellaneous; Young Adult; United States; Endocrinopathy; Kidney disease; Type 2 diabetes; Imidazole derivatives; Tetrazole derivatives; Urinary system disease; Peptide hormone; Non peptide compound; Metabolic diseases; Prevention; Concomitant disease; Octapeptide; Renin angiotensin system; Biphenyl derivatives; Losartan; Indian; Diabetic nephropathy; Sartan derivatives; Angiotensin antagonist; Angiotensin II
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db12-1512

Angiotensin receptor blockers are renoprotective in hypertensive azotemic patients with type 2 diabetes, but their efficacy in early diabetic kidney disease is uncertain. We performed a 6-year randomized clinical trial in 169 American Indians with type 2 diabetes and normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g; n = 91) or microalbuminuria (ACR 30–299 mg/g; n = 78) at baseline. The primary outcome was decline in glomerular filtration rate (GFR) to ≤60 mL/min or to half the baseline value in subjects who entered with GFR <120 mL/min. Another outcome was differences in glomerular structure at end of treatment. Subjects received 100 mg losartan or placebo daily. GFR was measured annually; 111 subjects underwent kidney biopsies. Only nine subjects reached the GFR outcome, and the unadjusted hazard ratio (losartan vs. placebo) was 0.50 (95% CI, 0.12–1.99). Differences in mesangial fractional volume were not estimated in the combined albuminuria groups because of an interaction with treatment assignment. In separate analyses, mesangial fractional volume was lower in subjects treated with losartan in the microalbuminuria group (18.8 vs. 25.6%; P = 0.02), but not in the normoalbuminuria group (19.6 vs. 17.8%; P = 0.86). Treatment with losartan may preserve some features of kidney structure in American Indians with type 2 diabetes and microalbuminuria.