RENAL TRANSPLANTATION AN OVERVIEW. Patients Selection For Kidney Transplanatation. All patients with ESRD are condidates for KT unless Systemic malignancy. Chronic infection. Severe cardiovascular disease. Neuropsychiatric disorder. Extremes of age (relative).
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All patients with ESRD are condidates for KT unless
Projected years of life for patients 20-39 years old:
Non diabetic 20 31 years
Diabetic 8 25years
An adult donor kidney transplanted to the left iliac fossa of an adult recipient.
Kidney Donor of an adult recipient.
Beating and non-beating heart.
CRITERIA FOR LIVING DONOR SELECTION of an adult recipient.
CRITERIA FOR CADAVER DONOR SELECTION of an adult recipient.
History of stone disease
History of frequent UTI
A- Tissue typing
Determined by 6 antigens located on cell surface encoded for by the HLA gen located on the short arm of chromosom 6.
Class I antigens (HLA-A and HLA-B) are expressed on the surface of most nucleated cells.
Class II antigen (HLA-DR) are expressed on surface of APC and activated lymphocytes.
These 6 antigens are refered to as major transplant antigens.
The match between donor and recepient can range from 0 to six.
B- Cross matching
C- Compatible ABO blood group.
The beneficial effect of HLA B and DR matching in patients with and without the benefit of cyclosporine.
Relative incidence of causes of allograft dysfunction during the year following transplantation.
Death with functioning graft.
What Are The Most Common causes Of Death After Kidney Transplantation?
Immune responses to renal allograft Transplantation?
Contraindications To Renal Transplantation Transplantation?
Renal Allograft Rejection Transplantation?
Is mediated by preformed antibodies that recognize HLA antigens in donor organ.
Usually these are formed as a consequence of blood transfusion, pregnancy, prior organ transplantation, autoimmune diseases.
Fibrinoid necrosis lead to immediate graft loss.
Delayed form may occur several days following transplantation.
Plasmapheresis and pulse steroid may be used.
Hyperacute rejection. Transplantation?
Acute Renal Allograft Rejection Transplantation?
Histology of acute cellular rejection Transplantation?
How Common Is acute Rejection ? Transplantation?
CSA, Aza, Steroid+Simulect is 36%
ST, Rapa+ (MM For FK) + Simulect is~ 18%
Treatment Of Acute Rejection Transplantation?
Chronic rejection with tubulointerstitial lesions. Transplantation?
• Drug toxicity (CsA, FK)
• Ischaemic injury
• Viral infection (CMV)
BANFF GRADE HISTOLOGY I Interstitial edema and tubulitis (i.e., lymphocytic invasion of tubular basement membranes.
II More severe tubulitis with or without mild vasculitis characterized by intimal lymphocytic infiltrates
III Severe vasculitis with fibrinoid necrosis.
1- The benefits of a successful transplant outweight the risks of chronic immunosuppression.
2- Immunosuppressive therapy is required indefinitely.
3- Multidrug regimens are generally employed.
4- Large doses of immunosuppressant drugs are used in the early transplant period.
agents Calcineurin inhibitors
Antimetabolites Purine inhibitors: nonselective
Purine inhibitors:lymphocyte selective
Mycophenolate mofetil (RS-61443)
Poorly understood mechanisms
*Experimental or not yet approved by Food and Drug Administration (FDA).
Sites of action of immunosuppressive drugs. rejection.
Side Effects of Glucocoriticoids rejection.
Side Effects of Immunophiline-binding Agents rejection.
Side Effect Cyclosporine Tacrolimus Sirolimus
Nephrotoxicity ++ ++
Neurotoxicity + ++ -
Hirsutism ++ - -
Gingival hyperplasia + - -
Hypertension ++ +
Hyperlipidemia ++ +/- +++
Glucose intolerance + +++
Bone marrow suppression - - ++
Side Effects of Antimetabolites rejection.
Side effect Azathioprine Mycophenolate
Bone marrow suppression +++ ++
Gastrointestinal + ++
- polyclonal (ATGAM, thymoglobin).
- Monoclonal (Simulect, Zinapax, OKT3).
Side effect OKT3 Polyclonals Anti-CD25
Fever +++ + _
Headache ++ + _
Myalgias ++ + _
Gastrointestinal ++ _ _
Respiratory distress + +/- _
1- Prednisolon + Azathiaprine
2- Prednisolon + cyclosporine (or tacrolimus)
3- Prednisolon + cyclosporine + Azathioprine
4- MMF (cell cept) may replace Azathioprine.
5- Sirolimus (Rapaimmune) may replace Azathioprine or cyclosprine
- Drugs acting on cytochrome P450 affect the metabolism of CsA, tacrolimus, and sirolimus.
1- ↑ Metabolism ↓ level
• Anticonvulsants • Antituberculous
2- ↓ Metabolism ↑ level
• anti-fungus (ketoconazole..)
• erythromycin and clarithromycin
• calcium channel blockers
- Azathioprine and allopurinol.
Sonogram showing a lympgocele adjacent to a kidney. Immunosuppressive drugs
Lodohippurate sodium 1131 renal scan, showing urine extravasation
Sonogram consistent with ureteral obstruction extravasation
Acute pyelonephritis in a renal which ultimately required nephrectomy, secondary to associated obstruction.
Diffuse perihilar inflitrate secondary to cytomegalovirus infection in an 18 year old man with a rapidly deteriorating febrile condition 5 weeks posttransplant, after a course of antilymphocyte globulin (for rejection).
Kaposi’s sarcoma infection in an 18 year old man with a rapidly deteriorating febrile condition 5 weeks posttransplant, after a course of antilymphocyte globulin (for rejection).
Bone scan of the hip in later stage aseptic necrosis, showing increased perfusion of the femoral heads (arrows).
In geneal, renal transplantation should be recommended as the preferred mode of RRT for most patients with ESRD in whome surgery and subsequent I.S. is safe and feasible.
A healthy child born to a female transplant recipient, 3 years after a successful engraftment.