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Kidney Transplantation. Best treatment of chronic renal failure. HEMODIALYSIS. PERITONEAL DIALYSIS. Renal transplantation needs donor kidney. Organ Source. Cadaver Living donor. Yalnız kalp atacak. HLA TYPING. HLA ANTIGENS A B C DR LOCUS
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Organ Source • Cadaver • Living donor
Yalnız kalp atacak
HLA TYPING • HLA ANTIGENS • A • B • C • DR LOCUS HLA A21,A24,B7,B9,DR22
MAJOR HISTOCOMPATABILITY COMPLEX • Class I - present on almost all nucleated cells (interesting exceptions include sperm and the cells of the trophoblast). • Class II- present on Antigen Presenting Cells (macrophages, B cells, and dendritic cells). • Class III- are not surface molecules, but instead are various proteins typically which have some immunological role (C2,C4,Tumor necrosis factor alpha and beta, various HSPs) Human HLA region [Highly Simplified version !] ---DP--DQ--DR------------C4--C2--Bf---------------B--C--A--- Protein Products: DPa and DPb Complement HLA-B (a) DQa and DQb TNF a & b HLA-C (a) DRa and DRb HSP proteins HLA-A (a)
HLA TYPING • A-MATCH…FULL • B-MATCH..ONE ANTIGEN DIFFERENT • C-MATCH..TWO ANTIGENS DIFFERENT • …..SO ON • THE MORE CLOSER TO A-MATCH, THE MORE SUCCESSFULL KIDNEY TRANSPLANTATION
The TcR-CD3 complex on helper (CD4+) or cytotoxic/suppressor (CD8+) T cells
IMMUNOSUPRESSIVE AGENTS • T-CELL BLOCKERS • GLUCOCORTICOIDS • SITOTOXIC AGENTS • MONOCLONAL ANTIBODIES
T-CELL BOCKERS • CYCLOSPORINE-A • TACROLIMUS • SIROLIMUS CYCLOSPORINE AND TACROLIMUS ARE SELECTIVE CALCINEURIN INHIBITORS INHIBITION OF Th INDUCTION WHICH IS ACTIVATED BY IL-2
NFAT :Nuclear factor of activated T-cells FKBP: FK Binding protein
TOXIC EFFECTS OF TACROLIMUS AND CYCLOSPORINE . NEPHROTOXICITY (C>T) . NEUROTOXICITY (T>C) . GASTROINTESTINAL PROBLEMS(T) . HYPERTENSION(C>>T) . HYPERKALEMIA(T) . HPERGLICEMIA AND DIABETES(T>C) . INFECTION AND MALIGN TUMORS(BOTH)
SIROLIMUS(RAPAMYCINE) • Blockage of mTOR kinase • Side Effects: • Hyperlipidemia • Anemia • Leucopenia, trombositopenia • Fever • GI effects, • Hypo and hyperkalemia
IMMUNOSUPRESSIVE EFFECTS OF GLUCOCORTICOIDS -Inhibition of release of cytokines in T-Cells -Inhibition of antibody production in B-Cells -Inhibition of macrophages,monocytes,PMNL’s -Blockage of complement system
SIDE EFFECS OF STEROIDS -Cushing Syndrome -Glucose intolerance -Infections -Osteoporosis -Muscle weakness
Antineoplastic drugs as immunosupressive agents -Mycophenolat Mofetil (Inhibition of IMP dehydrogenase) -Azathioprine (Inhibition of nucleotid synthesis) -Cyclophosphamide (Alkylating agents) -Methotrexate(Inhibitor of dihydrofolate reductase)
BIOLOGIC IMMUNOSUPPRESSION -Antilymphosite globulines(Polyclonal antibodies) (Atgam, timoglobulin) -Anti-CD3 monoclonal antibodies (OKT3, muromonab-CD3) all -mab, -imab and -umab suffixes -Anti-Tac, Anti-CD25 monoclonal antibodies (Basiliximab, daclizumab) Anti-CD25 Monoclonal Antibodies (Basiliximab and Daclizumab) Anti-CD52 Monoclonal Antibody Alemtuzumab (Campath-1h) Anti-CD20 (Rituximab) Monoclonal Antibodies to Adhesion Molecules anti–LFA-1 mAb (efalizumab) anti-CD4 mAb (priliximab)
Meryem (28 years old) Kidney transplantation: 7 June 1997 Marriage : 2001 Baby : 2002