Document Detail

SDZ-RAD prevents manifestation of chronic rejection in rat renal allografts.
MedLine Citation:
PMID:  10708101     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Chronic rejection remains the most frequent cause of renal graft loss over the long term. However, effective treatment of this process is not yet available. SDZ-RAD (40-O-[2-hydroxyethyl]-rapamycin) is a new, orally active rapamycin derivative with potent immunosuppressive activity. We have examined the effects of SDZ-RAD in a well-established model of chronic renal allograft rejection in rats. METHODS: Kidneys of Fisher (F334) rats were orthotopically transplanted into bilaterally nephrectomized Lewis recipients. To suppress an initial episode of acute rejection, rats were briefly treated with low doses of cyclosporine for the first 10 days. Thereafter they received either SDZ-RAD (0.5 mg/kg(day) or vehicle. At 24 weeks, functional evaluations were performed, kidneys were harvested, and histological, immunohistological, and reverse transcription-polymerase chain reaction evaluations were performed. RESULTS: Animals treated with SDZ-RAD developed lower proteinuria and less glomerulosclerosis as compared with controls. Additionally SDZ-RAD reduced the infiltration of macrophages and lymphocytes and the expression of intercellular adhesion molecule-1, laminin, and fibronectin. Furthermore, we observed a reduced expression of growth factor mRNA (transforming growth factor-beta and platelet-derived growth factor-AA) in these animals. CONCLUSION: Our results demonstrated that SDZ-RAD effectively ameliorates chronic renal allograft rejection in rats, probably mediated by suppression of growth factors.
O Viklický; H Zou; V Müller; J Lacha; A Szabó; U Heemann
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  69     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-23     Completed Date:  2000-03-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  497-502     Citation Subset:  IM    
Department of Nephrology, University Hospital, Essen, Germany.
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MeSH Terms
Cyclosporine / therapeutic use
Glomerulosclerosis, Focal Segmental / pathology
Graft Rejection / prevention & control
Growth Substances / genetics
Immunosuppressive Agents / therapeutic use*
Intercellular Adhesion Molecule-1 / analysis
Kidney / chemistry
Kidney Transplantation / immunology*
Polymerase Chain Reaction
RNA, Messenger / drug effects,  metabolism
Rats, Inbred F344
Rats, Inbred Lew
Sirolimus / analogs & derivatives*,  therapeutic use
Transplantation, Homologous / immunology
Reg. No./Substance:
0/Growth Substances; 0/Immunosuppressive Agents; 0/RNA, Messenger; 126547-89-5/Intercellular Adhesion Molecule-1; 159351-69-6/everolimus; 53123-88-9/Sirolimus; 59865-13-3/Cyclosporine

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