-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

• 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 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 :

• 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?