title: Long- and short-term treatment with imatinib attenuates the development of chronic kidney disease in experimental anti-glomerular basement membrane nephritis.
abstract: BACKGROUND
  Imatinib is a selective tyrosine kinase inhibitor that can block platelet-derived growth factor (PDGF) receptor activity. Imatinib is also known as an anti-inflammatory agent. We examined the therapeutic effects of long- or short-term imatinib treatment in Wistar-Kyoto (WKY) rats with established anti-glomerular basement membrane (GBM) nephritis.
  
  
  METHODS
  Nephrotoxic serum (NTS) nephritis was induced in WKY rats on day 0. Groups of animals were given either imatinib or vehicle daily by intraperitoneal injection, from day 7 to day 49 in the long-term treatment study, and from day 7 to 13 in the short-term treatment study; all rats were sacrificed at day 50.
  
  
  RESULTS
  In long-term treatment, imatinib showed marked renoprotective effects; imatinib suppressed proteinuria, improved renal function, attenuated the development of glomerulosclerosis and tubulointerstitial injury and reduced the expression levels of collagen type I and transforming growth factor-beta (TGF-β) in renal cortex. The key finding of the present study was that short-term treatment with imatinib also significantly attenuated the development of renal injury until day 50, although the degree of renoprotection was slightly inferior to that of long-term treatment.
  
  
  CONCLUSIONS
  These results suggest that administration of imatinib is a promising strategy for limiting the progression of glomerulonephritis (GN) to end-stage renal failure. In particular, a short period of treatment at an early stage of GN is more beneficial in terms of cost-effectiveness and reduction of adverse effects in comparison to a continuous and long period of treatment.
authors.affiliation: Department of Medicine, Showa UniversitySchool of Medicine, Tokyo, Japan. iyoda@med.showa-u.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iyoda
authors.forename: Takanori
authors.initials: T
authors.lastname: Shibata
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kuno
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shindo-Hirai
authors.forename: Kei
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000150:complications* / Q000473:pathology; D001549:Benzamides / Q000627:therapeutic use*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011507:Proteinuria; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011921:Rats, Inbred WKY; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D001549:Benzamides; D024042:Collagen Type I; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000068877:Imatinib Mesylate; D003404:Creatinine