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Clinical Management of Kidney Transplants
Dr. Michael HadjigavrielDirector Nephrology
Larnaca General Hospital Cyprus - 2009
-Overview--Overview-
Pre-transplant Management
Donors/Recipients
Donors/Recipients
• ABO compatibilityA»A, A»ABB»B, B»ABAB»AB O»O, O»A, O»B, O»AB
• Rhesus compatibility not necessary
(Blood group antigens that determine blood type are found on all cells while antigens for the rhesus are present only on the red blood cells)
Donors/Recipients
• Non ABO Compatible Donors– To increase graft availability
some centers started to use non ABO compatible donors after specific treatment with rituximab (chimeric monoclonal antibody against the protein CD20) and plasmapheresis.
– Results are comparable and very promising
Donors/Recipients
• HLA Compatibility
more common HLA antigens between donor and
recipient > better graft survival.
HLA Typing
• Process of identifying genetic markers (antigens) on leucocytes
• 3 general groups of HLA: A, B, DR
• Each group is inherited as part of a set from each parent and it’s known as Haplotype
• There are many HLA proteins: HLA –A 325, HLA-B 592, HLA-DR 451
• 220 genes coding MHC
Example
• Patient x has:
-1 to 4 chances to have identical match with his brothers/sisters
(i.e. to share the same 2 haplotypes)
-1 to 2 chances to have partial compatibility with his brothers/sisters
(i.e. to share 1 haplotype)
-1 to 8 chances of compatibility with his cousins
Donors/Recipients
• Cross match– Positive:
presence of antibodies against donor antigens.
– Negative: No antibodies against donor antigens
In normal practice to proceed to Tx cross match must be NEGATIVE
Donors /Recipients
Kidney Transplantation with“Positive x-match” and “Sensitized patients”
To increase number of transplants in positive x-match and/or sensitized patients (until lately non transplantable) some centers proceed to transplantation after removal of cytotoxic antibodies* from recipients with medications (rituximab, etc) and plasmapheresis (prior and after tx accordingly).
• Results are comparable and very promising(*These antibodies usually occur after pregnancy, blood transfusions or previous transplantations)
Donors/Recipients
Donors Excluded • Age >70 years: Special
criteria applied• Carriers of chronic
infections: HIV, Hep. B, Hep C, etc.: Special criteria applied
• Carriers of chronic diseases: diabetes, cancer, amyloidosis, vascular patients, autoimmune diseases, renal dysfunction, etc.: Special criteria applied
Donors/Recipients
Recipients excluded:• Age >70: Special
criteria applied• High risk patients for major
surgery:severe cardiovascular disease, etc
• High risk patients for: cancer, acute or chronic infections, etc
• Surgical impediments: calcified vessels, bladder diseases (neurogenic, BPH) etc.
Donor / Recipient preparation
Donor Preparation
• General biochemistry• Hematology• Viral studies (HBsAg, HCV, HIV, CMV, EBV, HSV)
Ab’s or DNA accord.• Hormones (PSA, CEA,CA 9-19, CA 125, AFP, etc)• Urine (routine, culture, 24 hour protein, creatinine
clearance)• Imaging (US, IVP, MRA, chest x-ray)• Specialized evaluation (ECG, cardiac echo, stress
test, etc)• Any other test or Specialized evaluation if
indicated.
Recipient preparation
• General biochemistry• Hematology• Viral studies (HBsAg, HCV, HIV, CMV, EBV, HSV)
Ab’s or DNA accordingly.• Hormones (PSA, CEA, AFP,CA 9-19, CA 125, etc)• Imaging (US abdomen,Plain Abdomen & pelvis,
Chest x-ray)• Specialized evaluation (ECG, cardiac echo, stress
test, urodynamics, etc)• Any other test or Specialized evaluation if indicated.
Recipient Preparation
• Pre-transplant immunosuppression:Protocol used:24 hours before Tx: – Steroids (prednisone) 5mg/kg/bw
(in divided doses)– MMF 500-1000 mg BD – 1 hour before Tx:
basiliximab (Simulect) 20mg iv (stat) (To be repeated on day 4 after tx).
• All recipients are started on Gancyclovir and Broad Spectrum Antibiotic Prophylaxis before surgery
Post-transplant Management
Recipients
Recipients
Post-transplant immunosuppression:
Different Protocols in use:
• CyA+MMF+Pred• CyA+SIR+Pred• CyA+EVER+Pred• TAC+MMF+Pred• TAC+SIR+Pred• SIR+MMF+Pred
+ Basiliximab or daclizumab : monoclonal antibodies anti inter leukin – 2 receptor antagonist (IL-2R)
Recipients
Right after TX and or within 24 hrs:
- Solumedrol 125-500 mg BD x 3 days and
Accordingly (Initial Dose):- CyA: ~8mg/kg/bw/day in 2 doses - MMF ~1000-2000 mg/day in 2 doses - TAC ~0.1-0.2/kg/bw/day in 2 doses- EVER ~1.5mg/day in 2 doses- SIR ~5mg/day in 2 doses
Recipients
• Usually 7-10 days after initial dosing, doses of immunosuppressants are adjusted to obtain desired levels.
• Drug serum levels depend on protocol (combination of immunosuppressants) used.
• Special attention to other drugs influencing serum levels of immunosuppressants.
• Drug monitoring should be scheduled and performed periodically together with patient follow up.
Kidney Transplants
Post-transplant complications
Surgical Complications• renal artery thrombosis /
stenosis• venous thrombosis /
stenosis• urinary leak (from UV
anastomosis, ureter) • UV stenosis• lymphoceles
Kidney Transplants
Post-transplant complicationsMedical (pathology) immediate or chronic
Complications• Rejection: Hyperacute/acute/chronic (CAN)• Infection: viral/ bacterial/ mycotic/
opportunistic• Cardiovascular: CAD/ CHF/ CVA/ HT• Cancer: skin/ blood/ solid organs• Diabetes / cataract/ hirsutism/ alopecia/
gum hypertrophy/ obesity/ impotence/ etc• Drug toxicity (calcineurin inhibitors, etc.)
Kidney Transplants
Follow up schedule for Tx patients:
1st month: 3 times a week
1-3months: once a week
3-6months: once every 2 weeks
6 months-2 years: once a month
2 years and over: every 2 months
Follow up schedule should include :
• Haematology• General biochemistry• Urine (MSU, 24 hr collection)• Drug level monitoring• Detailed Clinical examination • Diagnostic imaging
(when necessary)• Tx Biopsy (when necessary)• Special attention to:
cardiovascular disease, neoplastic disease, infection and parathyroid function
Specific and General Information
on Kidney Tx
Specific Information
• Kidneys from LRD:
Less cold ischemia time, less ATN, prompt diuresis, usually no need for HD after TX.
• Kidneys from CAD:
longer cold ischemia time, more ATN, delayed diuresis, more frequent need for HD after TX.
Specific Information
Treatment of Acute rejection:• Steroid boluses: Methylprednisolone • ATG: Polyclonal antibody, Rabbit antihuman
activated T-Lymphocyte globulin.• OKT3: murine monoclonal IgG2a antibody that
specifically reacts with the T cell receptor-CD3 complex on the surface of circulating human T cells.
• ATGAM: lymphocyte immune globulin, anti-thymocyte globulin [equine].
• Rituximab: Chimeric monoclonal antibody against the protein CD20.
• Plasmapheresis• Irradiation of graft (abandoned method in majority of
centers)
Specific Information
CAN ( Chronic Allograft Nephropathy)Etiology: • Cold Ischemia time• Renal injury• Degree of immunosuppression• N° of acute rejections• Drug toxicity• Etc.
Specific Information
CAN (Chronic Allograft nephropathy)Clinical signs and symptoms:• Chronic reduction of renal function: rising creatinine,
reduced GFR, etc.• Biopsy: CAN (lymphomonocytic infiltration, sclerosis,
etc)• US: increased ecogenicity of graft• Other signs and symptoms of progressive CRF
(hypertension, proteinuria, etc).
Specific Information
CAN (Chronic allograft nephropathy)
Treatment:• Change protocol of
immunosuppression (?)• Eliminate worsening
cofactors (nephrotoxic drugs, stabilize hemodynamics, etc.)
• If acute on chronic rejection is suspected treat accordingly.
Thanks
Any Questions?