A Research Study to Evaluate the Renal (Kidney) Protective Effects of Losartan in Patients With Non-insulin Dependent Diabetes (0954-147)(COMPLETED)

Summary

Evaluate the effect of Losartan in reducing kidney disease in patients with Non-insulin Dependent Diabetes and Nephropathy (kidney damage that usually accompanies late stage Diabetes Mellitus).

Timeline

Start

1996-05

Primary completion

2001-02

Completion

2001-04

Publications

• Background Arredondo A, Burke TA, Carides GW, Lemus E, Querol J. The impact of losartan on the lifetime incidence of ESRD and costs in Mexico. Rev Invest Clin. 2005 May-Jun;57(3):399-405.
• Background Carides GW, Shahinfar S, Dasbach EJ, Keane WF, Gerth WC, Alexander CM, Herman WH, Brenner BM; RENAAL Investigators. The impact of losartan on the lifetime incidence of end-stage renal disease and costs in patients with type 2 diabetes and nephropathy. Pharmacoeconomics. 2006;24(6):549-58. doi: 10.2165/00019053-200624060-00003.
• Background Appel GB, Radhakrishnan J, Avram MM, DeFronzo RA, Escobar-Jimenez F, Campos MM, Burgess E, Hille DA, Dickson TZ, Shahinfar S, Brenner BM; RENAAL Study. Analysis of metabolic parameters as predictors of risk in the RENAAL study. Diabetes Care. 2003 May;26(5):1402-7. doi: 10.2337/diacare.26.5.1402.
• Background Bakris GL, Weir MR, Shanifar S, Zhang Z, Douglas J, van Dijk DJ, Brenner BM; RENAAL Study Group. Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study. Arch Intern Med. 2003 Jul 14;163(13):1555-65. doi: 10.1001/archinte.163.13.1555.
• Background Remuzzi G, Ruggenenti P, Perna A, Dimitrov BD, de Zeeuw D, Hille DA, Shahinfar S, Carides GW, Brenner BM; RENAAL Study Group. Continuum of renoprotection with losartan at all stages of type 2 diabetic nephropathy: a post hoc analysis of the RENAAL trial results. J Am Soc Nephrol. 2004 Dec;15(12):3117-25. doi: 10.1097/01.ASN.0000146423.71226.0C.
• Background de Zeeuw D, Ramjit D, Zhang Z, Ribeiro AB, Kurokawa K, Lash JP, Chan J, Remuzzi G, Brenner BM, Shahinfar S. Renal risk and renoprotection among ethnic groups with type 2 diabetic nephropathy: a post hoc analysis of RENAAL. Kidney Int. 2006 May;69(9):1675-82. doi: 10.1038/sj.ki.5000326.
• Background Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345(12):861-9. doi: 10.1056/NEJMoa011161.
• Background de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004 Jun;65(6):2309-20. doi: 10.1111/j.1523-1755.2004.00653.x.
• Background Mohanram A, Zhang Z, Shahinfar S, Keane WF, Brenner BM, Toto RD. Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy. Kidney Int. 2004 Sep;66(3):1131-8. doi: 10.1111/j.1523-1755.2004.00863.x.
• Background de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation. 2004 Aug 24;110(8):921-7. doi: 10.1161/01.CIR.0000139860.33974.28. Epub 2004 Aug 9.
• Background Keane WF, Brenner BM, de Zeeuw D, Grunfeld JP, McGill J, Mitch WE, Ribeiro AB, Shahinfar S, Simpson RL, Snapinn SM, Toto R; RENAAL Study Investigators. The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int. 2003 Apr;63(4):1499-507. doi: 10.1046/j.1523-1755.2003.00885.x.
• Background Jafar TH, Schmid CH, Stark PC, Toto R, Remuzzi G, Ruggenenti P, Marcantoni C, Becker G, Shahinfar S, De Jong PE, De Zeeuw D, Kamper AL, Strangaard S, Levey AS. The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis. Nephrol Dial Transplant. 2003 Oct;18(10):2047-53. doi: 10.1093/ndt/gfg317.
• Background Herman WH, Shahinfar S, Carides GW, Dasbach EJ, Gerth WC, Alexander CM, Cook JR, Keane WF, Brenner BM. Losartan reduces the costs associated with diabetic end-stage renal disease: the RENAAL study economic evaluation. Diabetes Care. 2003 Mar;26(3):683-7. doi: 10.2337/diacare.26.3.683.
• Background Eijkelkamp WB, Zhang Z, Remuzzi G, Parving HH, Cooper ME, Keane WF, Shahinfar S, Gleim GW, Weir MR, Brenner BM, de Zeeuw D. Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial. J Am Soc Nephrol. 2007 May;18(5):1540-6. doi: 10.1681/ASN.2006050445. Epub 2007 Apr 4.
• Background Eijkelkamp WB, Zhang Z, Brenner BM, Cooper ME, Devereux RB, Dahlof B, Ibsen H, Keane WF, Lindholm LH, Olsen MH, Parving HH, Remuzzi G, Shahinfar S, Snapinn SM, Wachtell K, de Zeeuw D. Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies. J Hypertens. 2007 Apr;25(4):871-6. doi: 10.1097/HJH.0b013e328014953c.
• Background Keane WF, Zhang Z, Lyle PA, Cooper ME, de Zeeuw D, Grunfeld JP, Lash JP, McGill JB, Mitch WE, Remuzzi G, Shahinfar S, Snapinn SM, Toto R, Brenner BM; RENAAL Study Investigators. Risk scores for predicting outcomes in patients with type 2 diabetes and nephropathy: the RENAAL study. Clin J Am Soc Nephrol. 2006 Jul;1(4):761-7. doi: 10.2215/CJN.01381005. Epub 2006 May 17.
• Background Mohanram A, Zhang Z, Shahinfar S, Lyle PA, Toto RD. The effect of losartan on hemoglobin concentration and renal outcome in diabetic nephropathy of type 2 diabetes. Kidney Int. 2008 Mar;73(5):630-6. doi: 10.1038/sj.ki.5002746. Epub 2007 Dec 19.
• Background Parving HH, de Zeeuw D, Cooper ME, Remuzzi G, Liu N, Lunceford J, Shahinfar S, Wong PH, Lyle PA, Rossing P, Brenner BM. ACE gene polymorphism and losartan treatment in type 2 diabetic patients with nephropathy. J Am Soc Nephrol. 2008 Apr;19(4):771-9. doi: 10.1681/ASN.2007050582. Epub 2008 Jan 16.
• Background Tershakovec AM, Keane WF, Zhang Z, Lyle PA, Appel GB, McGill JB, Parving HH, Cooper ME, Shahinfar S, Brenner BM. Effect of LDL cholesterol and treatment with losartan on end-stage renal disease in the RENAAL study. Diabetes Care. 2008 Mar;31(3):445-7. doi: 10.2337/dc07-0196. Epub 2007 Dec 10.
• Jongs N, Gasparyan SB, Frison L, Schloemer P, Brinker M, Little DJ, Heerspink HJL. Use of eGFR Slope Thresholds as End Point Components in a Kidney Disease Progression Hierarchical Composite End Point. J Am Soc Nephrol. 2025 Dec 1;36(12):2421-2430. doi: 10.1681/ASN.0000000766. Epub 2025 Jun 17.
• de Vries ST, Pena MJ, Tye SC, Peters SAE, van Raalte DH, Arnott C, Voors AA, Mol PGM, Denig P, Heerspink HJL. Sex differences in the efficacy of angiotensin receptor blockers on kidney and cardiovascular outcomes among individuals with type 2 diabetes and diabetic kidney disease: post hoc analyses of the RENAAL and IDNT trials. Diabetologia. 2025 Mar;68(3):507-515. doi: 10.1007/s00125-024-06325-y. Epub 2024 Dec 10.
• Natale P, Palmer SC, Navaneethan SD, Craig JC, Strippoli GF. Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD006257. doi: 10.1002/14651858.CD006257.pub2.
• Heerspink HJL, Jongs N, Schloemer P, Little DJ, Brinker M, Tasto C, Karpefors M, Wheeler DC, Bakris G, Perkovic V, Nkulikiyinka R, Rossert J, Gasparyan SB. Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression. J Am Soc Nephrol. 2023 Dec 1;34(12):2025-2038. doi: 10.1681/ASN.0000000000000243. Epub 2023 Oct 24.
• Miao Y, Ottenbros SA, Laverman GD, Brenner BM, Cooper ME, Parving HH, Grobbee DE, Shahinfar S, de Zeeuw D, Lambers Heerspink HJ. Effect of a reduction in uric acid on renal outcomes during losartan treatment: a post hoc analysis of the reduction of endpoints in non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan Trial. Hypertension. 2011 Jul;58(1):2-7. doi: 10.1161/HYPERTENSIONAHA.111.171488. Epub 2011 May 31.

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