Post on 09-Apr-2018
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Clinical Management of
Kidney Transplants
Dr. Michael HadjigavrielDirector Nephrology
Larnaca General Hospital Cyprus - 2009
-Overview--Overview-
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Pre-transplant Management
Donors/Recipients
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Donors/Recipients
ABO compatibility
AA, AAB
BB, BAB
ABABOO, OA, OB, OAB
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)
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Donors/Recipients
Non ABO Compatible Donors To increase graft availability
some centers started to usenon ABO compatible donors
after specific treatment withrituximab(chimericmonoclonal antibody againstthe protein CD20) andplasmapheresis.
Results are comparable andvery promising
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Donors/Recipients
HLA Compatibility
more common HLA antigens
between donor and recipient
> better graft survival.
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HLA Typing
Process of identifyinggenetic markers(antigens) on leucocytes
3 general groups of HLA:A, B, DR
Each group is inherited aspart of a set from eachparent and its known asHaplotype
There are many HLAproteins:
HLA A 325, HLA-B 592,HLA-DR 451
220 genes coding MHC
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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
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Donors/Recipients
Cross match
Positive:presence ofantibodies against
donor antigens. Negative:
No antibodiesagainst donorantigens
In normal practice to proceed to Tx cross match must be
NEGATIVE
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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 centersproceed to transplantation after removal ofcytotoxic antibodies* from recipients withmedications (rituximab, etc) andplasmapheresis (prior and after txaccordingly).
Results are comparable and very promising(*These antibodies usually occur after pregnancy, blood
transfusions or previous transplantations)
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Donors/Recipients
Donors Excluded Age >70 years: Special
criteria applied
Carriers of chronicinfections: HIV, Hep. B,
Hep C, etc.: Specialcriteria applied
Carriers of chronicdiseases: diabetes, cancer,amyloidosis, vascular
patients, autoimmunediseases, renal dysfunction,
etc.: Special criteriaapplied
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Donors/Recipients
Recipients excluded: Age >70: Special
criteria applied
High risk patients for majorsurgery:
severe cardiovascular disease,etc
High risk patients for: cancer,acute or chronic infections, etc
Surgical impediments: calcified
vessels, bladder diseases(neurogenic, BPH) etc.
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Donor / Recipient preparation
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Donor Preparation
General biochemistry
Hematology
Viral studies (HBsAg, HCV, HIV, CMV, EBV, HSV)Abs or DNA accord.
Hormones (PSA, CEA,CA 9-19, CA 125, AFP, etc)
Urine (routine, culture, 24 hour protein, creatinineclearance)
Imaging (US, IVP, MRA, chest x-ray)
Specialized evaluation (ECG, cardiac echo, stresstest, etc)
Any other test or Specialized evaluation if indicated.
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Recipient preparation
General biochemistry
Hematology
Viral studies (HBsAg, HCV, HIV, CMV, EBV, HSV)Abs 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.
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Recipient Preparation
Pre-transplant immunosuppression:Protocol used:
24 hours before Tx:
Steroids (prednisone) 5mg/kg/bw (in divideddoses)
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
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Post-transplant Management
Recipients
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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)
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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
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Recipients
Usually 7-10 days after initial dosing, doses ofimmunosuppressants are adjusted to obtain desiredlevels.
Drug serum levels depend on protocol (combinationof immunosuppressants) used.
Special attention to other drugs influencing serumlevels of immunosuppressants.
Drug monitoring should be scheduled and performedperiodically together with patient follow up.
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Kidney Transplants
Post-transplantcomplications
Surgical Complications
renal artery thrombosis /
stenosis venous thrombosis /
stenosis
urinary leak (from UV
anastomosis, ureter) UV stenosis
lymphoceles
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KidneyTransplants
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.)
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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
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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, infectionand parathyroid function
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Specific and General Information
on Kidney Tx
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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 frequentneed for HD after TX.
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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 complexon the surface of circulating human T cells.
ATGAM: lymphocyte immune globulin, anti-thymocyteglobulin [equine].
Rituximab: Chimeric monoclonal antibody against theprotein CD20.
Plasmapheresis
Irradiation of graft (abandoned method in majority ofcenters)
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Specific Information
CAN( Chronic Allograft Nephropathy)
Etiology: Cold Ischemia time
Renal injury Degree of immunosuppression N of acute rejections Drug toxicity
Etc.
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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).
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Specific Information
CAN (Chronic allograftnephropathy)
Treatment:
Change protocol of
immunosuppression (?) Eliminate worsening cofactors
(nephrotoxic drugs, stabilize
hemodynamics, etc.)
If acute on chronic rejection is
suspected treat accordingly.
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Thanks
Any Questions?