Organ and tissue transplantation

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CHAPTER 21 Organ and tissue transplantation

Classification 466
Organ and tissue donors 466
Organ preservation 472
Siting of the transplant 472
Rejection 473
Immunosuppression 473
Specific organs 476
General complications 480

Transplantation has developed from an experimental procedure over 50 years ago, to an established therapeutic option for most types of end-stage organ failure. For kidney, heart and liver transplantation, a 1-year graft survival in excess of 85% can be expected.

Classification

This depends on the relationship between donor and recipient.

Autograft

Tissue is transferred from one area of the body to another in the same individual, e.g. skin grafts.

Isografts

Tissue is transferred between genetically identical individuals (e.g. monozygotic twins).

Allografts

Tissue is transferred between genetically dissimilar individuals of the same species (e.g. deceased donor renal transplants).

Xenografts

Tissue is transferred between species. The only clinically applicable xenografts at the present time are temporary porcine skin grafts in human burns victims.

Organ and tissue donors

Organs and tissues may be obtained from:

• deceased donors – donation after brain death (DBD; heart beating donors) or donation after cardiac death (DCD; non-heart beating donors)
• living donors.

Deceased donors

Donation after brain death (DBD)

General criteria

(→ Table 21.1)

TABLE 21.1 General criteria for deceased donors

Brainstem dead with intact circulation
Cause of death:

• cerebral trauma
• cerebral haemorrhage
• suicide
• primary cerebral tumour (histologically proven)
• cardiac arrest with brain death

Exclusions: Absolute

• HIV infection
• Creutzfeldt–Jakob disease (CJD) – plus any patient who has received a dura mater graft or human pituitary growth hormone

Relative

• chronic renal disease
• metastasizing malignancy
• severe hypertension
• Hepatitis B and C infection (can be considered in recipients who are HBV- or HCV-positive)
• i.v. drug abuse
• age >75 years
• prolonged renal warm ischaemia
• oliguric renal failure
• death from sepsis or viral infection

As the organ shortage became more severe, it was realized that ideal requirements for selection of organ donors were not feasible. Selection criteria for solid organ donors have therefore recently been relaxed. Organs that long ago would not have been considered for transplantation, are currently being used, bringing in a new class of organ donor termed the ‘expanded criteria donor; ECD’ formerly known as ‘marginal’ donor. ECD is any brain-dead donor aged >60 years or a donor aged >50 with two of the following conditions: a history of hypertension; a terminal serum creatinine level >150 μmol/L, or death resulting from a cerebrovascular accident. Selection of liver and heart and heart/lung donors depends on size match with the recipient. Also, no attempt is made to match other than on blood group compatibility with these organs. HLA typing and cross-matching are not currently undertaken.

Obtaining permission for deceased organ donation

1. A potential donor should be identified by the consultant in charge of the patient.
2. Contact may be made with a transplant team prior to establishment of brainstem death to assess if the donor is suitable for organ donation.
3. The first set of brainstem death criteria are carried out. If they are satisfied, the question of organ donation may be raised with the relatives. Consent should not be obtained until two sets of brainstem death criteria have been obtained.
4. If the relatives wish to know more about what is involved in transplantation, the Transplant Coordinators will speak to them and explain the details.
5. Blood is taken for tissue typing, blood group, HIV and hepatitis B and C screening.
6. Confidentiality must always be maintained.
7. Bereavement counselling and follow-up support should be arranged for the family; the Transplant Coordinators can also help with this.

Donation after cardiac death (DCD)

This type of organ donation applies to renal transplantation and liver transplantation only but tissues such as heart valves, corneas, bone, etc. can also be removed from this type of donor. The distinction between a DBD and DCD donor lies in the mode of death. DBD donors usually die from an intracranial catastrophe (→ Table 21.1), the mode of death being classified as ‘brainstem death’. In DCD donors, the patient dies from a cardiorespiratory arrest, their death being classified as a ‘cardiac death’. After death, kidneys are viable for around 30 min (maximum of 45 min in young donors).

There are four types of DCD donors (Maastricht criteria). They may be classified as controlled (cardiac arrest is anticipated and gives time for organization of necessary resources; category III) or uncontrolled (donor dies without warning, thus the ischaemic time is longer as resources are not readily available; categories I, II and IV). The groups of DCD donors are classified as follows:

I. Dead on arrival at hospital
II. Unsuccessful resuscitation
III. Awaiting cardiac arrest
IV. Cardiac arrest in brainstem dead patient.

Brainstem death

This is covered in Chapter 18, as this is the province of doctors independent of the transplant team.

Living donors

This type of organ donation relates chiefly to renal transplantation, although it is now possible to transplant segments of pancreas, segments of liver and lobes of lung from living donors. At the present time, more than 30% of transplants in the UK are carried out from living donors owing to the shortage of deceased donors. Living donation, like deceased donation, is regulated by the Human Tissue Authority under the Human Tissue Act 2004.

Organ donation and transplantation is governed by the Human Tissue Act 2004, which supercedes the Human Organ Transplant Act 1989. The Human Tissue Authority (HTA) was established in 2005 to implement the provisions of the Act, which came into force in 2006.

Categories of living donation established under the Act are:

1. Directed (i.e. the organ is directed to a known recipient)

— genetically related (formerly living related)
— emotionally related (living unrelated)
— paired.

2. Non-directed (i.e. the organ is for a recipient whose identity is unknown as with deceased donation)

— domino
— altruistic.

Directed

Genetically and emotionally related

This is donation to a known person, i.e. brother to sister, parent to child, husband to wife or between friends. Under the Human Tissue Act, the approval process is the same for directed genetically and directed emotionally related organ donation. Both will be dealt with by a local independent assessor who is trained and accredited by the HTA and who will assess all donor/recipient pairs, and where the requirements have been met, will give approval for the transplant to proceed.

Paired donation

This relates to circumstances where a close relation, friend or partner is fit and able to donate but is not well-matched to the potential recipient. That couple can be matched to another couple in a similar situation so that both people in need of a transplant receive a well-matched organ, i.e. Mrs A wants to give Mr A a kidney. Mrs B wants to give Mr B a kidney. Mrs A does not match Mr A. Mrs B does not match Mr B but Mrs B matches Mr A and Mrs A matches Mr B. In these circumstances, Mrs B gives a kidney to Mr A, while Mrs A gives a kidney to Mr B. Hopefully, everyone lives happily ever after!

Non-directed

Domino

This is when a normal organ is removed as part of a patient’s treatment. It may then be suitable for transplantation into another person. For a patient requiring a lung transplant, e.g. a cystic fibrosis sufferer, it is technically easier to transplant the heart and lungs as a unit, removing the recipient’s normal heart. This can then be offered for a recipient in heart failure in the same way as a heart from a deceased donor.

Altruistic

This is when a person offers to donate an organ to anyone who might benefit, i.e. a complete stranger. Before such organ transplants are undertaken, it is essential that all medical, surgical and psychiatric assessments necessary to ensure fitness to donate have been completed. The independent assessor must be satisfied that all procedures have been fully complied with before any application for a non-directed altruistic donation is sent to the HTA panel for approval.

Independent assessors

Independent assessors are trained persons, i.e. medical consultants or someone of equivalent registered professional status, independent of the transplant team. They are trained to approve all living organ donations, both directed and non-directed. The role of the independent assessor is to act on behalf of the HTA in an altruistic capacity and in order to satisfy the requirements of the Human Tissue Act. The independent assessor must be satisfied that:

• A registered medical practitioner has given the donor an explanation of the nature of the medical procedure and risks involved
• The donor understands the nature of the medical procedure and the risks and consents to removal of the organ in question
• The donor’s consent to the removal of the organ in question was not obtained by coercion or the offer of an inappropriate inducement
• The donor understands that he or she is entitled to withdraw consent at any time and understands the consequences of withdrawal for the recipient
• The donor–recipient relationship is as stated
• There were no difficulties in communicating with the donor and/or recipient and if so how these were overcome
• Any interpreter used should have no personal involvement with either party to the transplant.

Work-up for a living donor

For a genetically related donor, there are three potential histocompatibility matches:

• ‘Perfect match’ (2 haplotype match): all antigens match. There is a 25% chance of this occurring
• ‘Half match’ (1 haplotype mismatch): half the antigens match. There is a 50% chance of this occurring
• ‘No match’: no antigens match. There is a 25% chance of this occurring. In the past it was rare to use such a donor but it is now clear that the results from a ‘no-matched’ live related donor are almost as good as those from a well-matched deceased donor.

The following sequence is undertaken:

• Identify a potential donor
• Take blood for blood group, tissue typing and cross match to identify compatibility
• Give full explanation of procedure and risks
• Urinalysis: exclude proteinuria, haematuria, infection
• FBC, ESR, U&Es, creatinine, LFTs, glucose
• Infection screen: HBV, HCV, HIV, HTLV (counselling required prior to HIV testing)
• Creatinine clearance, GFR via 51Cr-EDTA
• CXR
• ECG.

If all of the above are satisfactory, the patient undergoes an angiography (usually CT angiography and urography) to assess the renal vasculature and to check for any abnormality in the excretory system. It is ideal that at least one kidney should have a single artery to anastomose to the recipient’s artery (either end-to-end) to the recipient’s internal iliac artery (or end-to-side) to the recipient’s external iliac artery. Although kidneys with multiple arteries can be used in deceased donor transplantation as they can be removed with a Carrel patch of aorta, clearly this is not the case with a living donor. However, with living donors it is possible to use kidneys with multiple arteries, e.g. two equal sized arteries may be anastomosed in a double-barrelled fashion before being anastomosed to the recipient’s arteries; or a small polar artery may be anastomosed to the side of the main renal artery.

If angiography and urography are normal, the donor recipient pair will be referred to the independent assessor who will send a report to the clinician responsible for the donor and a copy to the HTA indicating that the transplant may go ahead.

Living donor nephrectomy

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