Treatment after Transplants, and Complications of Transplants

PCL 13 - Sisters
Amber Hartley

Treatment after Transplants, and Complications of Transplants

Renal transplant offers great potential for patients in end-stage renal failure.
Advantages include:
 Freedom from dietary and fluid restriction
 Anaemia corrected
 Infertility corrected
 Need for parathyroidectomy is reduced

The kidney to be transplanted may be taken from a cadaveric donor, or from a living relative. If the kidney comes from a living relative, the donor must undergo extensive testing first. These tests include:
 Clinical examination
 Measurement of renal function
 Tests for carriage of hepatitis B, C, HIV, and CMV
 Detailed imaging of renal anatomy

Both the kidney and the associated ureter are taken from the donor, and transplanted into the recipient.




Attempts are made to match recipients and donors as closely as possible for the HLA molecule. HLA-DR antigens have been shown to have the greatest impact on transplant survival. Complete compatibility at A, B and DR points of the HLA molecule give the greatest rates of success, followed by a single HLA mismatch. However, completely mismatched kidneys are often transplanted. In all cases, unless the kidney is taken from an identical twin, immunosuppression is needed following transplantation.

Immunosuppression is lifelong and aimed at preventing the rejection of donor organs. The risk of rejection is highest in the first 3 months following transplantation. In these three months, rejection episodes occur in 30% of cases where a cadaver donor was used.

There are a number of drugs used for immunosuppression, each with different mechanisms of action and side effects.
1. Corticosteroids
o Non-specific anti-inflammatory and immunosuppressive action
o High doses can be used for acute rejection
2. Azathioprine
o Blocks purine synthesis and replication of lymphocytes, hence preventing cell-mediated rejection
o Side effects: suppression of RBC and platelet production, increased incidence of infections, hepatotoxicity.
o Cannot be used with allopurinol
3. Mycophenolate mofetil
o Blocks an enzyme required for purine synthesis, more specific for lymphocytes than for other cells
o More potent than azathioprine
o Side effects: nausea, vomiting, diarrhoea
o Can be used with allopurinol
4. Ciclosporin (CSA)
o Prevents activation of T lymphocytes in response to new antigens
o Highly effective in preventing rejection while leaving the functioning of the rest of the immune system largely intact
o Side effects: nephrotoxicity
o Minor side effects: anorexia, lethargy, hirsutism, tremor, paraesthesia (tingling sensation), gum hypertrophy, gastrointestinal disturbances
o Expensive
o Poorly absorbed by mouth but can be given orally, or intravenously by infusion.
5. Tacrolimus
o Blocks T cell activation (similar to Ciclosporin)
o More potent than CSA, hence used for acute rejection episodes, as well as maintenance of transplant
o Side effects: diabetogenic
6. Sirolimus
o Prevents entry of cell into G1 phase of cell cycle
o Side effects: poor wound healing, delay of the recovery of proximal tubular cell injury sustained during transplantation, thrombocytopenia, hyperlipidemia
7. Antibodies
o Antibodies directed against lymphocyte surface marker proteins, enabling neutralising or killing of lymphocytes
o Mainly used for treating steroid-resistant rejections and for induction therapy for high immunological risk patients.

Complications of Renal Transplants
1. Acute tubular necrosis (ATN)
o Commonest cause of cadaveric transplant dysfunction
o Associated with worse long-term outcome and rejection
2. Technical failures
o Incorrect or incomplete surgical procedure during transplantation, surgical intervention may be required
3. Acute rejection
o Seen in up to 30% of cases
4. Infection
o In the first month after transplantation, infections are those typically seen following any surgery
o CMV is common in weeks or months after transplantation
o Prophylaxis often given against Pneumocystis carinii and oral candidiasis
o Polyomavirus infections are a serious complication for transplant outcome
5. Post-transplantation lymphoproliferative disorders
6. Chronic allograft nephropathy (CAN)
o Most common cause of late graft failure
o Mediated by immunological and non-immunological factors, results in progressive, irreversible decline in transplant function
o No treatment available for this complication
7. Development of Malignancy
o Immunosuppressive drugs increase risk of cancers, including basal and squamous cell carcinoma, renal, cervical and vaginal cancers.
8. Cardiovascular disease
o Due to increased incidence of hypertension, obesity, diabetes and lipid disorders
9. Post-transplant osteoporosis
o Common following treatment with immunosuppressive steroids

Sources:
Kumar and Clark (2005), “Clinical Medicine,” 6th edition. p 678-681
Rang and Dale (2003), “Pharmacology,” 6th edition, p 242-243