The RIE is one of two kidney transplants in Scotland and covers the East of Scotland including the Borders, Dundee, Aberdeen and parts of the Highlands. The unit performs approximately 100 transplants a year including deceased and living donors.

The RIE is also the only unit that offers pancreatic and islet transplants in Scotland and performs approximately 20 to 30 simultaneous pancreas and kidney transplants a year.

The edren website is an excellent resource managed by the Edinburgh renal unit. There are local protocols and information about how to manage common post operative complications.

Kidney transplant

Kidney transplantation is the gold standard treatment for patients with end-stage renal failure as it offers improved life expectancy and QoL when compared to dialysis. Patients are eligible for transplant when their eGFR <20mls/min and are either on RRT or within 6 months or starting RRT. Absolute contra-indications to transplant include a life expectancy of less than 2 years, any active/uncontrolled malignancy or infection. Relative contra-indications are a life expectancy of 5 years or less; predicted graft survival of less than 50% at 1 year; inability or unwillingness to adhere to lifelong immunosuppression; life-threatening complications secondary to immunosuppression.

Patients can receive kidneys from living or deceased donors. Living donation is superior interns of graft survival with 95-97% graft survival at 1 year whereas the average for deceased donors is 85%.

Potential recipients have a comprehensive immunological profile in order to match to a potential donor. This includes blood group, human leucocyte antigen (HLA) profile and presence of donor specific antibodies (DSA) in the serum.

• Blood group: preferable to match blood group however ABO incompatible transplants can proceed with pre-transplant plasma exchange and induction with additional immunosuppression.

• HLA: antigens are present on the cell surface and are recognised as 'self'. There are 6 main HLA regions within chromosome 6 that make up the major histocompatibility complex (MHC classes I and II) and include HLA-A, -B and -C for class I and HLA-DP, -DQ and -DR for class II (for further information about MHC classes see https://www.msdmanuals.com/en-gb/professional/immu...). Individuals inherit one allele from each parent which are co-expressed. In order to match kidneys BOTH alleles that make up the HLA-A, -B and -DR genes are compared to potential donors and this comparison is termed the 'mismatch'. A complete match is termed a 000 mismatch whereas a single mismatch in all HLA regions would be 111 mismatch and complete mismatch would be 222. The maximum mismatch is 6 (three genes x two alleles). Immunologically HLA-DR is most important to match and the greater the mismatch, the poorer the long term graft survival. Although a 222 mismatch is not desirable it is not a contraindication to transplantation.

• DSA: presence of DSA against HLA antigens (i.e. anti-HLA antibodies) are most commonly due to sensitising events such as blood transfusion, pregnancy and previous transplantation. DSA are detected by a crossmatch where donor and recipient T and B cells are tested for reactivity. A positive crossmatch where there is reactivity between donor and recipient serum is an absolute contraindication for transplantation and would result in hyper-acute rejection due to complement activation at the time of reperfusion. Formation of DSA against the donor graft after transplantation is a risk factor for anti-body mediated rejection which is diagnosed by presence of C4d deposits on biopsy.

Pancreas transplant

Diabetic patients can be considered for simultaneous kidney and pancreas (SPK) transplant or simultaneous islet and kidney transplant (SIK). SPK offers survival benefit compared to kidney transplant alone in diabetic patients.

Criteria for listing a patient for SPK are broadly similar to that of kidney transplant patients (i.e. on HD or eGFR<20mls/mins) with the addition of insulin treated diabetes. Most patients will have type 1 diabetes but selected type 2 diabetics on insulin could be considered.

Absolute contra-indications include excessive cardiovascular risk (MI within 6 months, severe and uncorrectable CAD), active infection, non-curable malignancy, peptic ulceration, non-adherence to treatment or complications for immunosuppression (usually defined as life-threatening). Relative contra-indications include insulin requirement of >100units/day, severe PVD/aorto-iliac disease, EF<50%, BMI>30 for type 2 diabetics, previous disabling stroke and active hep B or C.

The immunological workup and post-operative immunosuppression is the same as that for kidney transplantation.

Islet transplant

Criteria for islet transplantation are as follows

• In combination with kidney transplantation (SIK) in those not fit for SPK

• In diabetic patients with normal or near normal renal function but with severe hypoglycaemia unawareness (documented evidence of two severe episodes in two years).

Patients in the latter group must have demonstrated that they have hypoglycaemic episodes despite maximal medical treatment led by a specialist diabetic team and an undetectable C-peptide in the presence of a glucose >10mmol/l. Patients should have blood group, HLA typing and DSA performed. Contra-indications are the same as pancreas transplant with the addition of active retinopathy or heavy proteinuria (relative contraindications).

Prepared islets are injected into the portal vein and require life-long immunosuppression. Patients often reduce their insulin requirements and a small group with be insulin free. The majority of patients will have improved awareness of hypoglycaemia.

Immunosuppression

Standard immunosuppression is as follows:

Steroids: prednisolone given from induction and continued for at least a year at low dose and reviewed

Basiliximab: IL-2 receptor antagonist (IL2 required for T cell activation). Given at induction and day 4

Tacrolimus: calcineurin inhibitor (tacrolimus also known as FK506) which inhibits IL-2 synthesis. Given daily for the life of the graft. SE include tremor, skin sensitivity, itch and diabetes

Mycophenolate myfetil (MMF): prodrug of mycophenolic acid, it inhibits ionising-5'-monophosphate dehydrogenase which inhibits T and B cell proliferation. Given daily for the life of the graft. Common SE include diarrhoea, nausea, vomiting and skin sensitivity.

Organ donation

Organ donation in Wales and Scotland (as of 26 March 2021) are opt-out systems. Wales was the first nation to employ this strategy and it has shown an increase in the pool of donors since it was introduced in 2015. England is likely to follow within the next 1 to 2 years.

Organ donation is a very controlled process and patients are identified and referred from ITU. Specialist nurses in organ donation (SNODs) lead the donation process, gain consent/authorisation and co-ordinate required tests; organs are offered through a central hub managed by NHS Blood and Transplant.

Eligible donors fall into one of two categories

• Donation after brainstem death (DBD) where patients meet brainstem death criteria listed below

• Donation after cardiac death (DCD, controlled Maastricht III and IV only)

Diagnosing death

There are comprehensive guidelines on diagnosing death on the ODT website which includes step by step instructions and videos demonstrating the process involved. In order to diagnose brain-stem death patients must fulfil the following criteria:

• Irreversible brain injury with known aetiology

• No evidence of potentially reversible metabolic, circulatory or endocrine causes

• No depressant drugs

• No evidence of hypothermia (temperature <34 degrees)

• Apnoeic coma requiring ventilation

• Absence of brain stem reflexes including

  • corneal reflex

  • gag/cough reflex

  • fixed pupils that do not respond to light

  • oculo-vestibular reflex in response to 50mls cold water into the ear canal (caloric test)

  • no response to supraorbital pressure

  • no ventilatory response to hypercapnia. Starting PaCO2 of 6.0 and rise in PaCO2 of at least 0.5kPa after 5 minutes with no respiratory effort

Tests are undertaken by two qualified doctors who have full registration for at least 5 years (one must be a consultant). These are performed twice and the time of death is the time of the first set of tests.

For DCD donors, there must be a statement about futility of treatment by the ITU team. Only Maastricht III/IV donors (controlled) are considered in the UK. After death, there is a 5 minute stand off time and then death is confirmed. Patients are then rapidly transferred to the operating theatre for organ retrieval.

Multi-organ retrieval

The national organ retrieval service (NORS) is responsible for all organ retrievals in the UK. Edinburgh provides the primary abdominal service for Scotland and Northern Ireland but can be called to other units in the UK depending on a activity. There are 7 abdominal teams on at any one time made up from 9 centres. There are 6 cardiothoracics teams and 3 teams are on-call at any one time. In total Edinburgh are called out approximately 150 times a year. The team consists of two surgeons, a scrub nurse and a perfusionist.

There are two categories of deceased donors; DBD (donation after brainstem death) and DCD (donation after circulatory death). Edinburgh routinely uses normothermic machine perfusion (NRP) in DCDs to reduce the impact of warm ischaemia and improve the quality of organs. There is a great deal of research looking into novel technologies, particularly in ex-vivo normothermic and hypothermic machine perfusion in liver and kidney retrieval.

For more information about the organ retrieval service and NORS policies please visit the ODT website