Kidney Transplantation

Best treatment of chronic renal failure

HEMODIALYSIS

PERITONEAL DIALYSIS

Renal transplantation needs donor kidney

Organ Source Cadaver Living donor

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HLA TYPING HLA ANTIGENS A B C DR LOCUS HLA A21,A24,B7,B9,DR22

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) MAJOR HISTOCOMPATABILITY COMPLEX

Human MHC genes are highly polymorphic

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

RECIPIENT SHOULD NOT HAVE ANY INFECTION

IMMUNUSUPRESSION

The TcR-CD3 complex on helper (CD4+) or cytotoxic/suppressor (CD8+) T cells

IMMUNOSUPRESSIVE AGENTS 1. T-CELL BLOCKERS 2. GLUCOCORTICOIDS 3. SITOTOXIC AGENTS 4.MONOCLONAL ANTIBODIES

T-CELL BOCKERS 1. CYCLOSPORINE-A 2. TACROLIMUS 3. SIROLIMUS CYCLOSPORINE AND TACROLIMUS ARE SELECTIVE CALCINEURIN INHIBITORS INHIBITION OF Th INDUCTION WHICH IS ACTIVATED BY IL-2

TOXIC EFFECTS OF TACROLIMUS AND CYCLOSPORINE. NEPHROTOXICITY (S>T). NEUROTPXICITY (T>S). GASTROINTESTINAL PROBLEMS(T). HYPERTENSION(S>>T). HYPERKALEMIA(T). HPERGLICEMIA AND DIABETES(T>S). INFECTION AND MALIGN TUMORS(BOTH)

SIROLIMUS(RAPAMYCINE) -Blockage of mTOR kinase -Side Effects: -Hyperlipidemia -Anemia -Leucopenia, trombositopenia -Fever -GI effects, -Hypo and hyperkalemia

NFAT :Nuclear factor of activated T-cells FKBP: FK Binding protein

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

- Mycophenolat Mofetil (Inhibition of IMP dehydrogenase) -Azathioprine (Inhibition of nucleotid synthesis) -Cyclophosphamide (Alkylating agents ) -Methotrexate (Inhibitor of dihydrofolate reductase) Antineoplastic drugs as immunosupressive agents

-Antilymphosite globulines (Atgam, timoglobulin) -Anti-CD3 monoklonal antibodies (OKT3, muromonab-CD3) -Anti-Tac, Anti-CD25 monoklonal antibodies (Basiliximab, daclizumab) ANTITHYMOCYTE ANTIBODIES

PROF. DR. MEHMET A. HABERAL

16 DECEMBER 2006

Meryem (28 years old) Kidney transplantation: 7 June 1997 Marriage : 2001 Baby : 2002

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