Kidney Transplantation

Who Gets One?

1. Renal transplants have been shown to improve survival and quality of life in patients who are under 75 years of age. This is not to say that patients over 75 will not benefit simply that no evidence exists of a survival advantage.
2. Older patients are certainly at more risk of having a heart attack or stroke at the time of their surgery or shortly afterwards. Risks and benefits should be considered carefully in all age groups.

Types of Transplant

1. Cadaveric transplantation remains most common and still accounts for around two thirds of all transplants. There are two types: donation after brain death (DBD) and donation after cardiac death (DCD). DBD typically occurs in a patient with significant brain injury requiring life support by ventilation who has been confirmed as brain stem dead by satisfying specific criteria.
2. Living donor transplantation, both related e.g. parent to child and unrelated e.g. husband to wife, is increasing. These transplants are associated with better patient and graft outcomes
3. Simultaneous pancreas-kidney (SPK) or simultaneous islet & kidney or pancreas/Islet transplant after kidney transplant are the treatment options for patients with end stage kidney disease and type 1 (but not type 2) diabetes. If the pancreas transplant is successful, this will hopefully cure them of their type 1 diabetes.
4. Pre-emptive transplantation means receiving a kidney before starting dialysis.
5. Altruistic donation is the giving of a kidney from a living person to a friend or to a stranger.
6. Some patients have transplants via the National Kidney Sharing Scheme (NKSS) which pairs people with appropriate donors when their own potential donors are not a match

Immunosuppression Regimes in Kidney Transplant

1. Nearly all patients will receive initial triple therapy with steroids, calcineurin inhibitor (CNI), and an anti-proliferative drug. The vast majority of patients are on prednisolone, tacrolimus and mycophenolate mofetil (MMF).
2. Dose of prednisolone is 20mg od initially reducing in 5mg increments to 5mg maintenance at 3 months.
3. Tacrolimus is a calcineurin inhibitor (CNI). Doses are determined by trough levels taken 12-14 hours after previous dose, usually aiming for trough 5-8ng/ml in first 6 months. However, patients will often have individualized targets based on their risk of rejection, complications or side effects. Please do not adjust a patient’s tacrolimus dose without liaising with the on-call renal team (32177 during working hours and oncall consultant via switchboard our-of-hours).
4. Mycophenolate is an anti-proliferative drug. Initial dose is 1000mg bd with a view to reducing to 500mg bd at 6 months if all going well. Patients may be on lower doses if they have had recurrent infections, leucopaenia or had diarrhoea (a very common side effect of MMF).  
5. Some patients with old transplants, or have had complications with the standard immunosuppression regime, may be on ciclosporin (as CNI) or azathioprine (as anti-proliferative).
6. Dose reduction or drug switch to one of the less common immunosuppressant drugs may be necessary if a patient develops an unacceptable drug side effect (e.g. switch to sirolimus in a patient with recurrent skin malignancy).
7. Patients are also prescribed:
   • Nystatin for 1 month to prevent candidiasis/candidaemia.
   • Co-trimoxazole 480mg once daily for 6 months as Pneumocystits pneumonia(PCP) prophylaxis.
   • Omeprazole 20mg OD as gastric protection while on steroids.
   • Valganciclovir for 6 months as CMV prophylaxis if CMV mismatch (D+, R-), dose adjusted as per transplant CrCl.

Reviewing a Kidney Transplant Patient in Hospital

1. Patients with a kidney transplant are likely to be admitted to hospital with AKI, infection or complications of vascular disease (particularly cardiac).

Acute Transplant Dysfunction

Patients with a transplant can experience all the usual causes of AKI (see elsewhere) but are more likely to have a cause that is directly related to their transplant:

1. Rejection. Two types of rejection are recognised: cell mediated and vascular. Vascular rejection is often antibody mediated and usually more aggressive.
2. Tacrolimus or ciclosporin toxicity. Tacrolimus toxicity often presents with neurological symptoms (e.g. tremors, headaches, confusion, seizures). Diarrhoea and Covid-19 infection can dramatically elevate tacrolimus levels. Management is mostly supportive.
3. Infection. The patients are immunosuppressed and are at high risk of atypical presentations or infections (CMV, EBV, BKV to name few). However, urinary tract infection remains the most common, even without classic features of dysuria or frequency.
4. Obstruction. This commonly occurs at the point of the anastomosis of the transplant ureter to the bladder. Patients often have a ureteric stent in for the first 6-8 weeks post-surgery, and it is important to establish whether this is still in situ.
5. Transplant artery stenosis. This typically presents with hypertension and AKI, ± flash pulmonary oedema.
6. Recurrence of the original disease. The likelihood of this will depend on the underlying primary renal diagnosis. Focal segmental glomerulosclerosis (FSGS) and IgA nephropathy are particularly common to recur.  Updating relevant immunology (ANCA in vasculitis, ANA in lupus nephritis) may be beneficial.

Initial Approach to Transplant AKI

The initial approach to transplant AKI is fairly straightforward. Patients should have:

1. Urine culture, and blood cultures if febrile or systemically unwell
2. Trough tacrolimus/ciclosporin level
3. IV fluid replacement if felt to be volume deplete/clinically dehydrated as per the usual guidelines
4. 4Renal transplant Doppler USS
5. Consider CMV/EBV/BK PCR blood testing
6. Early involvement with the renal on-call team
7. If these tests do not give the answer then they must be discussed with the transplant team in Glasgow and a transplant biopsy (done at QEUH, Glasgow) considered.

Please liaise with the on-call renal team at point of discharge so we can arrange appropriate follow up, and make plans for their immunosuppression.

Other Acute Medical Issues

The three big risks are opportunistic infections, vascular disease and cancer. All three are related at least in part to the use of immunosuppressive drugs.

1. Infection. As discussed above, transplant patients are at high risk of infection, including atypical infections. CMV and PCP are important to consider. CMV may present with diarrhoea, deranged LFTs or abnormal neurology. PCP may present with high oxygen requirements or bilateral pulmonary infiltrates. However, these are less likely if the patient has been taking prophylaxis as detailed above. Ensure cultures of blood and urine are sent (ideally prior to antibiotics), and consider viral swabs (Covid/Flu/RSV etc) and CMV/EBV/BK PCR blood testing.
2. Cancers are also more common in transplant patients as a result of immunosuppression. Most cancers are only slightly commoner than in the generally population, though skin cancers, lymphomas and cervical cancers pose special risks. Patients should get annual skin surveillance from the dermatology team. Any persistent fevers, night sweats, new lumps or bumps, or unintentional weight loss should be paid careful consideration to and may require further investigation. Post-transplant lymphoproliferative disorder (PTLD) is a B cell disorder associated with EBV that can progress to/present as lymphoma.
3. Post-transplant hyperglycaemia is common, due to high dose steroids, CNIs and improved insulin excretion by the functioning transplant. This can worsen pre-existing diabetic control, or represent a new diagnosis of diabetes post transplantation. Patients should have diabetes team input for education, blood glucose monitoring training, and advice on medical therapy.
4. Vascular disease. The majority of kidney transplant patients have hypertension, diabetes or cardiovascular disease, and therefore acute vascular events are very common in this population.

Adjusting Immunosuppression in Infection

1. Double up the steroid dose. If there is any concern regarding patients ability to take medications (low GCS, swallowing difficulties) or absorption (vomiting or diarrhoea), the steroids should be given as IV hydrocortisone. Prednisolone 10mg equates to 50mg Hydrocortisone IV TDS. If patients are hypotensive, consider giving a stat dose of steroid.
2. Suspend the anti-proliferative (azathioprine/mycophenolate). This can usually restarted once the course of antibiotics is complete.
3. Continue the CNI (tacrolimus/ciclosporin) unless under the specific advice of the renal team. This is usually only suspended in life threatening sepsis. Ensure that a trough level is checked.
4. There is a theoretical risk the kidney might reject but in practice this hardly ever happens and anyway it would be better to have a live patient on dialysis than a dead one as a result of pneumonia…

Content by Robert Ker & Thalakunte Muniraju