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
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 BLOCKERS2. GLUCOCORTICOIDS3. SITOTOXIC AGENTS4.MONOCLONAL ANTIBODIES
T-CELL BOCKERS
1. CYCLOSPORINE-A2. TACROLIMUS3. SIROLIMUS
CYCLOSPORINE AND TACROLIMUS ARE SELECTIVE CALCINEURIN INHIBITORSINHIBITION 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
-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(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 Moleculesanti–LFA-1 mAb (efalizumab)anti-CD4 mAb (priliximab)
BIOLOGIC IMMUNOSUPPRESSION
PROF. DR. MEHMET A. HABERAL
16 DECEMBER 2006
Meryem(28 years old)
Kidney transplantation:7 June 1997
Marriage :2001
Baby : 2002
THE END