User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

Reduction of albuminuria by angiotensin receptor blocker beyond blood pressure lowering: Evaluation in megsin/receptor for advanced glycation end products/inducible nitric oxide synthase triple transgenic diabetic nephropathy mouse model

Primary tabs

Ohtomo, Shuichi Ito, Masaki Izuhara, Yuko Van Ypersele de Strihou, Charles [UCL] Miyata, Toshio

Aim: Antihypertensive agents inhibiting the renin-angiotensin system (RAS), such as angiotensin II type 1 receptor blockers (ARB), are now part of the standard treatment of patients with diabetic nephropathy, regardless of the presence of systemic hypertension. Whether ARB achieve better renoprotection than other RAS-independent antihypertensive drugs has been an issue of controversy. Several lines of large clinical studies provided better renoprotection of ARB. However, a recent meta-analysis argued against additional benefits of ARB beyond blood pressure. We generated a novel mouse model of diabetic nephropathy; that is, megsin/receptor for advanced glycation end products/inducible nitric oxide synthase triple transgenic mice. This model is normotensive but progressively develops severe diabetic nephropathy that resembles those observed in humans. Methods: In the present study, we tested whether olmesartan (ARB) achieves better renoprotection than amlodipine (calcium channel blocker). Drug treatment was initiated at the age of 6 weeks and lasted for 12 weeks. Results: This model develops significant glomerular lesions and albuminuria even at the age of 5 weeks. Despite equal blood pressure lowering, only olmesartan suppressed the progression of albuminuria. Neither olmesartan nor amlodipine modified histological lesions. Conclusion: Proteinuria and its reduction are known to predict the progression of diabetic nephropathy. Our results support the additional benefit of ARB beyond blood pressure lowering.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2008
Language Anglais
Journal information "Nephrology" - Vol. 13, no. 6, p. 517-521 (2008)
Peer reviewed yes
Publisher Wiley-Blackwell Publishing Asia (Richmond)
issn 1320-5358
e-issn 1440-1797
Publication status Publié
Affiliations UCL - (SLuc) Service de néphrologie
UCL - MD/MINT - Département de médecine interne
Keywords Albuminuria ; Angiotensin receptor blocker ; Animal model ; Calcium channel blocker ; Diabetic nephropathy
Links
  1. 1.  Mogensen CE . Diabetes and hypertension. Lancet 1979; 1: 388-9.
  2. 2.  Parving HH , Andersen AR , Smidt UM , Svendsen PA . Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1983; 1: 1175-9.
  3. 3.  Jafar TH , Schmid CH , Landa M et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann. Intern. Med. 2001; 135: 73-87.
  4. 4.  Maschio G , Alberti D , Janin G et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N. Engl. J. Med. 1996; 334: 939-45.
  5. 5.  Parving HH , Lehnert H , Brochner-Mortensen J et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N. Engl. J. Med. 2001; 345: 870-8.
  6. 6.  Viberti G , Wheeldon NM . Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus. A blood pressure-independent effect. Circulation 2002; 106: 672-8.
  7. 7.  Remuzzi G , Bertani T . Pathophysiology of progressive nephropathies. N. Engl. J. Med. 1998; 339: 1448-56.
  8. 8.  Keane WF , Lyle PA . Recent advances in management of type 2 diabetes and nephropathy: Lessons from the RENAAL study. Am. J. Kidney Dis. 2003; 41: S22-5.
  9. 9.  Hunsicker LG , Atkins RC , Lewis JB et al. Impact of irbesartan, blood pressure control, and proteinuria on renal outcomes in the Irbesartan Diabetic Nephropathy Trial. Kidney Int. Suppl. 2004; 92: S99-101.
  10. de Zeeuw, Circulation, 110, 921 (2004)
  11. Lewis, N. Engl. J. Med., 345, 851 (2001)
  12. Brenner, N. Engl. J. Med., 345, 861 (2001)
  13. Casas, Lancet, 366, 2026 (2005)
  14. Mann, Nephrol. Dial. Transplant., 21, 2348 (2006)
  15. Rossing, Nephrol. Dial. Transplant., 21, 2354 (2006)
  16. LeLorier, N. Engl. J. Med., 337, 536 (1997)
  17. Breyer, J. Am. Soc. Nephrol., 16, 27 (2005)
  18. Inagi, Diabetes, 55, 356 (2006)
  19. Yamamoto Yasuhiko, Kato Ichiro, Doi Toshio, Yonekura Hideto, Ohashi Seiji, Takeuchi Masayoshi, Watanabe Takuo, Yamagishi Sho-ichi, Sakurai Shigeru, Takasawa Shin, Okamoto Hiroshi, Yamamoto Hiroshi, Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice, 10.1172/jci11771
  20. Miyata, J. Clin. Invest., 102, 828 (1998)
  21. Miyata Toshio, Inagi Reiko, Nangaku Masaomi, Imasawa Toshiyuki, Sato Masahiro, Izuhara Yuko, Suzuki Daisuke, Yoshino Atsusi, Onogi Hiroshi, Kimura Minoru, Sugiyama Satoshi, Kurokawa Kiyoshi, Overexpression of the serpin megsin induces progressive mesangial cell proliferation and expansion, 10.1172/jci0214336
  22. Izuhara, J. Am. Soc. Nephrol., 16, 3631 (2005)
  23. Nangaku, J. Am. Soc. Nephrol., 14, 1212 (2003)
Bibliographic reference Ohtomo, Shuichi ; Ito, Masaki ; Izuhara, Yuko ; Van Ypersele de Strihou, Charles ; Miyata, Toshio. Reduction of albuminuria by angiotensin receptor blocker beyond blood pressure lowering: Evaluation in megsin/receptor for advanced glycation end products/inducible nitric oxide synthase triple transgenic diabetic nephropathy mouse model. In: Nephrology, Vol. 13, no. 6, p. 517-521 (2008)
Permanent URL http://hdl.handle.net/2078.1/36300