Clinical Management Kidney Transplantation

8/8/2019 Clinical Management Kidney Transplantation

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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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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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CAN( Chronic Allograft Nephropathy)

Etiology: Cold Ischemia time

Renal injury Degree of immunosuppression N of acute rejections Drug toxicity

Etc.


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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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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?

Clinical Management Kidney Transplantation

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