Quick link - The sick transplant patient
Dialysis merely improves the symptoms of chronic renal failure; renal transplantation can cure them. Successful transplantation also extends the life expectancy of patients with end stage renal failure.
Improvements in immunosuppression and technique have improved graft survival to >85% at 1 year, and the ‘half-life’ of successful grafts to over 10 years, with longer survival expected for well-matched or live donor grafts. In all countries shortage of donors is a problem. Cadaver organ transplantation is usually restricted to relatively low risk patients. Live donor transplantation is associated with excellent results and low risk to (health-screened) donors and is increasingly relied on in many nations.
The allograft may be kept on ice for 24 hours or longer, but extended ‘cold ischaemia’ time is associated with poorer outcomes. The donor renal vessels are most commonly anastomosed to recipient iliac vessels and the donor ureter tunneled into the bladder. The kidney lies in the iliac fossa; native kidneys are untouched.
Blood group: Donor must usually be ABO compatible (Rhesus type not important). For cadaver organ transplantation a ‘same blood group’ rule is usually maintained, to prevent disadvantaging group O recipients.
Tissue type: Matching for HLA types HLA-DR, HLA-A and HLA-B have been shown to affect graft survival. HLA-DR has the strongest effect, but ‘6-antigen matches’, i.e. with no mismatching for HLA-DR, A or B, have much improved survival. National organ sharing protocols aim to achieve this as often as possible.
Age, size, quality: These and other non-immune factors also have powerful effects on graft survival, so that for live donor transplantation, HLA match is not so important.
A widely used triple therapy comprises
- tacrolimus or cyclosporine (ciclosporin)
- azathioprine or mycophenolate mofetil
- relatively low-dose prednisolone.
Some centres also use anti-lymphocyte antibodies (e.g. anti-IL2 receptor, or anti-CD52, or anti-T cell) or newer agents in attempt to reduce the rate of acute rejection still further.
Rejection is most likely to occur in the first few weeks after transplantation, but can occur after months or years, for example if immunosuppression is interrupted. Early rejection can usually be reversed by high-dose steroids or by anti-lymphocyte antibodies, but may leave the graft damaged. With modern immunosuppression, signs of rejection may be minimal and suspicion may only be aroused by changes in renal function.
As the risk of acute rejection falls, levels of immunosuppression are reduced.
Alternative regimens with lower or no use of calcineurin inhibitors (tacrolimus, ciclosporin) are under investigation.
Delayed graft function is common after cadaveric ('deceased donor' is now the favoured term) organ transplantation and dialysis may need to continue for days to weeks. This makes it difficult to assess rejection and protocol biopsies may be undertaken. Tacrolimus and cyclosporine are nephrotoxic and this complicates assessment of renal function; in the long term, they may cause renal failure. Short term (and dose-related) toxicity is mostly reversible.
Technical problems usually become apparent within days, though delayed obstruction or vascular occlusion are sometimes a problem. A ureteric stent is commonly left in situ for several weeks to reduce early urine leaks.
Acute rejection is usually signalled by a rise in serum creatinine. Doppler ultrasound is a useful investigation to exclude major vascular mishap or ureteric obstruction. Biopsy confirms the diagnosis, there are still no reliable non-invasive tests. Risk is highest in the first weeks and months but can occur at any time if immunosuppression is interrupted.
Infections Immunosuppression is at its most intense in the first few weeks, which is therefore the period of greatest risk of serious viral or other opportunistic infection. Those given additional treatment for acute rejection are at greatest risk. CMV is a particular problem; prophylactic ganciclovir or other therapies are commonly used for CMV seronegative patients exposed to a CMV positive graft. Primary EBV infection may cause the pre-malignant condition post-transplant lymphoproliferative disorder (PTLD), and sometimes overt lymphomas. Serious renal infections with polyoma virus may occur after about 3 months and closely resemble rejection, but their management is the opposite.
Long term risks In the long term there is a substantially increased risk of skin tumours and patients should avoid exposure to much direct sunlight. Lymphomas and some other cancers (especially virally mediated) are increased.
Patients are immunosuppressed and need to continue immunosuppression for ever. They are therefore at risk of opportunistic infections. Immunosuppression (especially corticosteroids) may mask the development of acute infections, including graft pyelonephritis, and other pathology. Acute rejection or technical problems (notably obstruction) associated with the allograft are always a possible explanation for illness; serum creatinine is a useful guide.
Malignancies, particularly those thought to have a viral etiology (lymphoma, carcinoma of the cervix), are increased from the early post-transplant period. Women should have regular cervical cytology.
Most patients are hypertensive. Many have some degree of continuing renal impairment, and therefore are at risk of all the problems associated with renal failure. At least in part because of their history, transplant patients continue to have a high incidence of cardiovascular and other vascular disease.
If a transplant patient is admitted to hospital for any reason, their transplant team should be notified and advice sought if necessary.