Transcript ABO compatibility A

-Overview-
Clinical Management of
Kidney Transplants
Dr. Michael Hadjigavriel
Director Nephrology
Larnaca General Hospital Cyprus - 2009
Pre-transplant Management
Donors/Recipients
Donors/Recipients
• ABO compatibility
A»A, A»AB
B»B, B»AB
AB»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
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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:
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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 complications
Medical (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 :
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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, antithymocyte 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?