PDGF-D inhibition by CR002 ameliorates tubulointerstitial fibrosis following experimental glomerulonephritis.

@article{citeulike:1457689, 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.}, address = {Division of Nephrology, University Hospital Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany. boor@email.cz}, author = {Boor, P. and Konieczny, A. and Villa, L. and Kunter, U. and van Roeyen, C. R. and LaRochelle, W. J. and Smithson, G. and Arrol, S. and Ostendorf, T. and Floege, J. }, citeulike-article-id = {1457689}, issn = {0931-0509}, journal = {Nephrol Dial Transplant}, month = {May}, number = {5}, pages = {1323--1331}, posted-at = {2007-07-15 15:52:00}, priority = {2}, title = {PDGF-D inhibition by CR002 ameliorates tubulointerstitial fibrosis following experimental glomerulonephritis.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/17308324}, volume = {22}, year = {2007} }

TY - JOUR ID - citeulike:1457689 L3 - citeulike-article-id:1457689 TI - PDGF-D inhibition by CR002 ameliorates tubulointerstitial fibrosis following experimental glomerulonephritis. JF - Nephrol Dial Transplant VL - 22 IS - 5 SP - 1323 EP - 1331 AD - Division of Nephrology, University Hospital Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany. boor@email.cz SN - 0931-0509 N2 - 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. AU - Boor, P AU - Konieczny, A AU - Villa, L AU - Kunter, U AU - van Roeyen, CR AU - LaRochelle, WJ AU - Smithson, G AU - Arrol, S AU - Ostendorf, T AU - Floege, J PY - 2007/05// UR - http://view.ncbi.nlm.nih.gov/pubmed/17308324 ER -