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 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