Renal Transplants

Last updated on 17th December 2014 by Chris Isles

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.

What Types of Transplant Are There?

1. Cadaveric transplantation remains most common and still accounts for around two thirds of all transplants
2. Living donor transplantation, both related eg parent to child and unrelated eg husband to wife, is increasing.
3. Simultaneous pancreas-kidney transplants are a treatment option for patients with kidney failure and type 1 (but not type 2) 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. Click links to Transplant Donor Work Up Pathway and Transplant Recipient Work Up Pathway for more detail.

What us Meant by Donation After Brain Death?

1. Donation after brain death is also known as heart beating kidney donation. The typical donor is a patient with a significant brain injury requiring life support by ventilation who has been confirmed as brain stem dead by satisfying the following criteria:
   1. No pupil reflexes.
   2. No corneal reflex.
   3. No nystagmus when ice cold water is run into each ear.
   4. No response to painful stimulus.
   5. No gag reflex.
   6. No attempt to breathe unaided when the ventilator is switched off and the PaCO2 is allowed to rise over 6.5kPa at a time when the patient continues to receive oxygen.

What is Meant by Donation After Cardiac Death?

1. Donation after cardiac death is also known as non heart beating kidney donation.
2. This is a more difficult area. The doctors looking after the patient, who will invariably be in the intensive care unit, need to separate discussion about futility from discussion about organ donation.
3. There is then a two hour window between stopping therapy and death during which retrieval of a viable kidney is possible. Not all patients in whom active treatment is withdrawn will die and not all of those who do die will do so within two hours.

Which Immunosuppressive Drugs Are Used To Prevent Rejection?

1. Nearly all patients will receive initial triple therapy with prednisolone, mycophenolate and tacrolimus.
2. Dose of prednisolone is 20mg od initially reducing in 5mg increments to 5mg at 3 months.
3. Mycophenolate is an anti-proliferative drug. Initial dose is 1000mg bd initially with view to reducing to 500mg bd at 6 months if all going well.
4. Tacrolimus is a calcineurin inhibitor (CNI). Doses are determined by trough levels taken 12-16 hours after previous dose, aiming for trough 5-7ng/ml in forst 6 months
5. Mycophenolate and tacrolimus are more potent, more modern and more expensive than their predecessors azathioprine and ciclosporin respectively.
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).

What Do You Need To Do When You See A Transplant Patient At The Clinic?

Check weight, BP and dip the urine for blood and protein
Review immunosuppressive drug dose and compliance
3. Check bloods including trough tacrolimus or ciclosporin at 12-16 hours after last dose – goes in EDTA tube to biochem.
Review CMV prophylaxis with valganciclovir – usually given for 200 days if donor positive and recipient negative for CMV.
Review Pneumocystis and urinary prophylaxis with cotrimoxazole – usually give for 3 months but may be longer if UTIs troublesome
Determine time interval for next clinic visit eg 2-3 visits/wk in first month then 1-2 visits/wk in second and third month
Click link to Medical Management of Kidney Transplant Recipient for more details

What Are The Causes of Kidney Injury In A Transplant?

1. 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
   2. Ciclosporin or tacrolimus toxicity
   3. Infection
   4. Obstruction
   5. Transplant artery stenosis
   6. Recurrence of the original disease
2. Two types of rejection are recognised: cell mediated and vascular. Vascular rejection is often antibody mediated and usually more aggressive.
3. Focal segmental glomerulosclerosis and IgA nephropathy both have a tendency to recur in a transplant.
4. The approach to such a problem is fairly straightforward. A patient in whom the creatinine has risen more than you would expect should have an urgent repeat U&E followed by transplant ultrasound, urine culture and trough ciclosporin/tacrolimus level if the raised creatinine is confirmed.
5. If these tests do not give the answer then they must be referred for a transplant biopsy.
6. Click link to Evaluation of Acute Transplant Dysfunction for more details

What Other Risks Are There Apart From Graft Failure?

1. 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.
2. The most important opportunistic organisms in a transplant patient are cytomegalovirus (CMV), varicella zoster virus (VZV) and pneumocystis carinii (PCP)
3. 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.

What Should You Do With Immunosuppressive Therapy When A Patient Develops A Severe Infection?

1. It is best to stop the anti-proliferative (azathioprine/mycophenolate), and either continue or stop their CNI (ciclosporin/tacrolimus) depending on severity of infection, while continuing steroids alone as hydrocortisone IV in the acute phase.
2. Patients on long term low-dose steroid should have the dose increased to cover the acute illness and reduced in convalescence.
3. 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.
4. As the patient recovers from their illness, reintroduce immunosuppression at a lower dose eg prednisolone and tacrolimus rather than prednisolone, mycophenolate and tacrolimus.

Links

Transplant Donor Work Up Pathway.
Transplant Recipient Work Up Pathway.
Medical Management of Kidney Transplant Recipient.
Evaluation of Acute Transplant Dysfunction.