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?