24th June 2023

Renal transplantation

Pre-transplant factors

Assessment for transplant

Transplant should be considered for all patients with advanced CKD and those on dialysis, as it is recognised to provide a better quality of life and life expectancy. The assessment process in the UK is outlined by NHS Blood and Transplant (NHSBT). It aims to ensure that a patient will be able to tolerate the procedure itself, as well as the immunosuppression thereafter. Assessment includes:

Blood group, HLA typing, antibody screening
Viral screening – cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), hepatitis B and C, human immunodeficiency virus (HIV). Vaccinations against hepatitis B and VZV (if needed) should be offered pre-transplant.
Psychological evaluation – to evaluate the likelihood that a patient will be compliant with their post-transplant medication and follow-up care.
Cardiovascular risk – to identify high-risk surgical patients that may not qualify for listing and patients that may be eligible for an angiographic/surgical coronary intervention and listing thereafter.
Malignancy screen – patients should have been in remission for at least two years before being considered for transplant.
Risk of renal disease recurrence – disease recurrence of some conditions can reduce the chances of graft survival.
Other serious comorbidities

Types of organ donation

Living donation – improved long-term function compared to cadaveric donation:
- Related donor, e.g. sibling, parent, child
- Unrelated donor, e.g. friend, spouse or through a paired exchange scheme
Cadaveric donation:
- DBD – donation after brain death
- DCD – donation after circulatory death

Organ matching

Blood group – organs are generally allocated to a patient of a compatible blood group in a similar manner to blood transfusions. If a patient has antibodies that recognise donor ABO antigens, this can lead to hyperacute rejection. ABO-incompatible transplants are feasible with desensitisation therapy – usually immunosuppression and plasma exchange.
HLA mismatch – coded on chromosome 6, one of each inherited from each parent, the most important antigens in transplant are HLA-A, HLA-B and HLA-DR. Degree of mismatch for each antigen is used – for example, identical twins would have a 0-0-0 mismatch, whereas a donor: recipient pair who shared none would be a 2-2-2 mismatch.
Anti-HLA antibodies – a recipient can develop these following blood transfusion, pregnancy, or previous organ transplant. These can lead to the development of organ rejection post-transplant, especially if they are donor-specific antibodies.

At time of transplantation

Surgical

The donor kidney is transplanted into the iliac fossa of the recipient, vasculature is anastomosed to the external iliac vessels and the ureter is implanted into the bladder (usually with a stent that is removed after 4-6 weeks). The kidney is sited outside of the peritoneum. The native kidneys are usually left in situ.

Medical

Immunosuppression:
- Induction (i.e. at the time of surgery) – practice varies between transplant units, commonly involving an interleukin-2 receptor antagonist, e.g. basiliximab, or T-cell depleting antibodies, e.g. alemtuzumab or ATG (anti-human thymocyte immunoglobulin)
- Maintenance – generally a combination of a calcineurin inhibitor, e.g. tacrolimus, an antiproliferative agent, e.g. mycophenolate mofetil or azathioprine and occasionally steroids.
Prophylaxis:
- PCP (Pneumocystis jirovecii) prophylaxis – e.g. co-trimoxazole
- CMV prophylaxis – e.g. valganciclovir, decisions depend on the donor and recipient’s viral status

Complications of transplantation

Surgical/postoperative complications

Bleeding
Infection
Urinary leak/obstruction
Thrombosis of renal artery or vein
Lymphocele
Renal artery stenosis
Bladder dysfunction (capacity reduces if a patient was anuric)

Issues with graft

Delayed graft function – this is the requirement for dialysis post-transplantation. Risk factors include DCD donors, prolonged cold ischaemic time and donor acute kidney injury.
Acute rejection – commonly T-cell mediated, can be antibody-mediated or a combination of the processes. A transplant biopsy is often performed for confirmation, and findings are classified using the Banff classification. Treatment depends on the findings but often utilises high dose intravenous steroids and optimisation of immunosuppressive drugs.
Chronic graft dysfunction – multiple potential causes (immune and non-immune), including chronic antibody-mediated or T-cell-mediated rejection, calcineurin-inhibitor toxicity, recipient factors such as hypertension and donor factors such as DCD kidney or older age.
Disease recurrence, e.g. focal segmental glomerulosclerosis
Viral infection, e.g. BK nephropathy