Mechanisms and management of acute renal allograft rejection.
We used RT-PCR for the molecular characterization of human renal graft rejection. The studies showed that intragraft display of mRNA encoding cytotoxic attack molecule granzyme B, and immunoregulatory cytokines IL-10 or IL-2 are correlates of acute rejection, and intrarenal expression of TGF-1 mRNA, of chronic rejection. The current immunosuppressive protocol involves the use of multiple drugs, each directed at a discrete site in the T-cell activation cascade and each with distinct side effects. The immunosuppressants can be classified as inhibitors of: transcription (CsA, tacrolimus); nucleotide synthesis (azathioprine, mycophenolate mofetil, and mizoribine); growth factor signal transduction (sirolimus); and differentiation (DSG). Polyclonal antibodies and monoclonal antibodies directed at cell surface proteins are quite effective as induction therapy or anti-rejection drugs.
Suthanthiran
M
M
Division of Nephrology, New York Hospital-Cornell Medical Center, New York, USA.
Strom
T B
TB
D000208:Acute Disease; D000906:Antibodies / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D053804:Granzymes; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D009711:Nucleotides / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D014184:Transplantation, Homologous
D000906:Antibodies; D000911:Antibodies, Monoclonal; D006133:Growth Substances; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D009711:Nucleotides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases