NDT Advance Access originally published online on February 17, 2007
Nephrology Dialysis Transplantation 2007 22(5):1323-1331; doi:10.1093/ndt/gfl691
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
PDGF-D inhibition by CR002 ameliorates tubulointerstitial fibrosis following experimental glomerulonephritis
1Division of Nephrology, RWTH University of Aachen, Germany, 2Department of Clinical and Experimental Pharmacology, Slovak Medical University, Bratislava, Slovakia and 3CuraGen Corporation, Branford, Connecticut, USA
Correspondence and offprint requests to: Peter Boor MD, Division of Nephrology, University Hospital Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany. Email: boor{at}email.cz
 |
Abstract |
|---|
Background. Arresting or regressing kidney scarring is of major clinical relevance. Platelet-derived growth factor D (PDGF-D) is widely expressed in fibrotic kidneys. Administration of the PDGF-D neutralizing fully human monoclonal antibody CR002 in the acute phase of progressive anti-Thy 1.1 glomerulonephritis reduced glomerular and secondary tubulointerstitial damage.
Methods. Using this model, we now assessed the effects of CR002 (n = 15) vs irrelevant control IgG (n = 17) administered on days 17, 28 and 35 after disease induction, i.e. after acute glomerular damage had subsided.
Results. In vitro, CR002 inhibited the PDGF-D- but not the PDGF-B-induced proliferation of rat renal fibroblasts. Following the first CR002 injection on day 17, exposure to therapeutic levels was maintained until day 49. Proteinuria in the CR002-treated group was transiently reduced between days 49 and 77 (–19 to –23% in comparison with the controls; P < 0.05). On day 100, CR002 treatment reduced the number of rats that had doubled their serum creatinine (CR002: 40 vs controls: 71%; P < 0.05). Compared with controls, the CR002 animals, on day 100, significantly lowered glomerular expression of vimentin and collagens as well as tubulointerstitial damage scores, interstitial fibrosis, vimentin and cortical PDGF-D mRNA levels.
Conclusions. PDGF-D antagonism, even after the phase of acute glomerular damage, exerts beneficial effects on the course of tubulointerstitial damage, i.e. the final common pathway of most renal diseases.
Keywords: CR002; fibroblasts; PDGF-D; renal fibrosis
Received for publication: 3. 8.06
Accepted in revised form: 25.10.06
CiteULike 
Connotea 
Del.icio.us What's this?
Related articles in NDT:
- In this issue ...
NDT 2007 22: i.[Extract] [FREE Full Text]
This article has been cited by other articles:
|
|
 |
|
  J. Floege, F. Eitner, and C. E. Alpers A New Look at Platelet-Derived Growth Factor in Renal Disease J. Am. Soc. Nephrol., January 1, 2008; 19(1): 12 - 23. [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]
|
|