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

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.

[1]  Leszek Czupryniak,et al.  Nowy rok, stare problemy, ale i nowe możliwości , 2014 .

[2]  R. Bilous,et al.  KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. , 2012, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[3]  R. Nelson,et al.  Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy , 2012, Kidney international.

[4]  W. Knowler,et al.  Early renal function decline in type 2 diabetes. , 2012, Clinical journal of the American Society of Nephrology : CJASN.

[5]  B. Kasiske,et al.  Proteinuria as a surrogate outcome in CKD: report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[6]  H. Parving,et al.  Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. , 2009, Annals of internal medicine.

[7]  Samy Suissa,et al.  Renal and retinal effects of enalapril and losartan in type 1 diabetes. , 2009, The New England journal of medicine.

[8]  P. Bennett,et al.  Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians. , 2006, JAMA.

[9]  S. Wild,et al.  Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. , 2004, Diabetes care.

[10]  P. Savage,et al.  Sustained reduction of proteinuria in Type 2 (non-insulin-dependent) diabetes following diet-induced reduction of hyperglycaemia , 1984, Diabetologia.

[11]  J. Ahmad,et al.  Effect of 5-year enalapril therapy on progression of microalbuminuria and glomerular structural changes in type 1 diabetic subjects. , 2003, Diabetes research and clinical practice.

[12]  Oluf Pedersen,et al.  Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. , 2003, The New England journal of medicine.

[13]  R. Bilous,et al.  Does ACE inhibition slow progression of glomerulopathy in patients with Type 2 diabetes mellitus? , 2001, Diabetic medicine : a journal of the British Diabetic Association.

[14]  B. Brenner,et al.  Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. , 2001, The New England journal of medicine.

[15]  H. Parving,et al.  The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. , 2001, The New England journal of medicine.

[16]  E. Lewis,et al.  Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. , 2001, The New England journal of medicine.

[17]  Kukin Ml The Heart Outcomes Prevention Evaluation Study. , 2001, Current cardiology reports.

[18]  T. Meyer,et al.  Evolution of incipient nephropathy in type 2 diabetes mellitus. , 2000, Kidney international.

[19]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[20]  G. Dahlquist,et al.  Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus , 1999, Diabetologia.

[21]  Standards of Medical Care for Patients With Diabetes Mellitus , 1998, Diabetes Care.

[22]  N. Chaturvedi Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria , 1997, The Lancet.

[23]  T. Meyer,et al.  Podocyte loss and progressive glomerular injury in type II diabetes. , 1997, The Journal of clinical investigation.

[24]  G. Beck,et al.  Progression of overt nephropathy in non-insulin-dependent diabetes. , 1995, Kidney international.

[25]  M. Steffes,et al.  Glomerular Structure in Nonproteinuric IDDM Patients With Various Levels of Albuminuria , 1994, Diabetes.

[26]  M. Steffes,et al.  Structural-functional relationships in diabetic nephropathy. , 1984, The Journal of clinical investigation.

[27]  E. Weibel Practical methods for biological morphometry , 1979 .

[28]  H. Grady,et al.  Determination of creatinine by means of automatic chemical analysis. , 1960, Technical bulletin of the Registry of Medical Technologists. American Society of Clinical Pathologists. Registry of Medical Technologists.