NDT Advance Access published online on November 23, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh562
© 2004 by European Renal Association - European Dialysis and Transplant Association
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Renal Research Group, Institute of Internal Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway
* To whom correspondence should be addressed. Background. The antifibrotic substance pirfenidone and the angiotensin II type I receptor antagonist candesartan cilexetil, given alone and in combination, were tested in rats with chronic anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). Methods. Male Wistar rats with anti-GBM GN were treated for 8 weeks with candesartan (4 mg/kg body weight/day), pirfenidone (500 mg/kg body weight/day) or a combination of both drugs. One GN group received no treatment and untreated non-GN-rats were used as controls. Blood pressure and urinary protein excretion were measured after 3 and 7 weeks. Kidney histology was complemented by ultrastructural investigation and by quantification of collagen I Results. The percentage of glomeruli with adsorption droplets in podocytes correlated well with the amount of proteinuria (r= 0.873, P<0.01) and was significantly lowered in rats treated with candesartan (8.3 vs GN 24.6%), pirfenidone (9.8%) and combined treatment (2.6%, P<0.05 vs candesartan alone). A comparable lowering was seen for segmental sclerosis (GN 11%, candesartan 0.7%, P<0.05 vs GN, pirfenidone 1.8%, P = 0.09 vs GN, candesartan/pirfenidone 0.1%, P>0.5 vs candesartan alone). Cortical collagen I Conclusion. Pirfenidone has a beneficial effect on morphological changes in anti-GBM GN comparable with candesartan although with a trend to slightly better results with candesartan treatment. Moreover, our results suggest an additive effect of combination treatment.
Accepted September 24, 2004
Original Articles
Pirfenidone and candesartan ameliorate morphological damage in mild chronic anti-GBM nephritis in rats
yvind Vaagnes 2,
2 Renal Research Group, Institute of Internal Medicine, University of Bergen, Norway
3 Marnac Inc., Dallas, TX, USA
4 Renal Research Group, Institute of Internal Medicine, University of Bergen, Bergen, Norway
5 Renal Research Group, Institute of Internal Medicine, University of Bergen, Bergen, Norway; Renal Unit, Department of Medicine, Central Finland Health District Hospital of Jyväskylä, Jyväskylä, Finland
Sabine Leh, E-mail: sabine.leh{at}helse-bergen.no
Abstract 
mRNA. mRNA expression was significantly decreased in all treatment groups. Ultrastructural investigation showed an amelioration of basement membrane alterations and podocyte damage in the treatment groups. Candesartan caused significant blood pressure reduction and the effect was significantly enhanced by combination therapy after 3 weeks. Rats treated with pirfenidone showed blood pressure values similar to control rats.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. M. Bivol, R. K. Berge, and B. M. Iversen Tetradecylthioacetic acid prevents the inflammatory response in two-kidney, one-clip hypertension Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R438 - R447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Boor, K. Sebekova, T. Ostendorf, and J. Floege Treatment targets in renal fibrosis Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3391 - 3407. [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Cho, D. C. Smith, M. H. Branton, S. R. Penzak, and J. B. Kopp Pirfenidone Slows Renal Function Decline in Patients with Focal Segmental Glomerulosclerosis Clin. J. Am. Soc. Nephrol., September 1, 2007; 2(5): 906 - 913. [Abstract] [Full Text] [PDF]
|
|