Introduction

Many patients face death because a single organ system such as kidney, liver, lungs or heart is failing, but could return to health if organ function could be restored. It is not surprising that physicians have tried over the years to achieve this by transplanting a healthy organ from an animal or another human.

The scene for clinical organ transplantation was set early in the 20th century by Alexis Carrel. He was awarded the Nobel Prize for Physiology and Medicine in 1912 for his pioneering work in vascular surgery and transplantation with Charles Guthrie. Carrel, working with laboratory animals, found that autografts (organs removed and reimplanted into the same animal) could be expected to function indefinitely, whereas allografts (organs transplanted between animals of the same species) rarely functioned for more than a few days. Early attempts at transplantation in man used xenografts (transplantation between different species) to transfer renal tissue from pigs, goats, rabbits and apes; these were uniformly unsuccessful.

The key to organ transplantation lay in the developing field of immunology, first with detection of the mechanisms involved in graft rejection and then the elaboration and application of techniques to minimise or prevent it. The first clinically useful transplant for humans involved pig heart valves. These consisted of simple avascular tissue, treated to render it non-immunogenic to avoid rejection. Porcine cardiac valve transplants have been used regularly since the mid 1970s and have advantages over artificial valves in younger people and where anticoagulation must be avoided.

Chemical immunosuppression designed to attenuate graft rejection has continued to advance, leading to improving success rates with transplantation of an expanding range of organs and tissues (see Table 14.1). Human cornea, kidney, liver, pancreas, heart, heart and lung, single or double lung and bone marrow transplantation are all now standard, although not free of rejection or other complications (see: http://www.ctstransplant.org/). Even face transplants are now achieving success.

Promising results are latterly being achieved with small bowel transplantation, in isolation or together with other intra-abdominal organs such as stomach, duodenum, pancreas and liver in multivisceral transplants. The ultimate goal of transplant surgeons and immunologists is to generate a state of tolerance between graft and the recipient of a transplanted organ.

Organ transplantation already offers improved quality of life to renal transplant recipients and endows life itself to recipients of heart, lung or liver grafts. This surgery is impossible without the generosity of donors and bereaved families in making organs available for transplantation. However, the UK donation rate of 13 donors per million population per year still lags behind the rate of 25–35 per million achieved in comparable European countries such as Belgium, Spain and France. This suggests that many more patients could benefit if the acceptability to the UK community of these innovative procedures could be enhanced. To achieve this, the results of surgery and the ethical basis under which it is conducted need to be promoted more widely.

Tissue typing and transplant sharing schemes

Methods for determining donor and recipient HLA haplotypes (‘HLA typing’) are either based on detecting genetic variation in the expressed HLA molecules using antisera (serological typing), or now almost universally, at DNA sequence level (DNA typing). In kidney transplantation, close HLA matching gives significantly better graft survival, i.e. when donor and recipient are identical at all six loci or differ by only one A or B antigen. HLA typing of individuals is therefore used to match the donor and recipient as closely as possible in kidney (and pancreas) transplantation. HLA matching is not currently regularly performed for other organs such as heart or liver transplants, as the number of available organs is too small to allow optimal matching. However, even a fully HLA matched transplant evokes a profound immunological response from the recipient because of differences in other major (non-A, non-B and non-DR) and minor histocompatibility antigens.

Most developed countries have a national transplant sharing mechanism so that donors and recipients can be matched as closely and fairly as possible. Systems are designed to achieve an optimal balance between utility (the optimum use of an organ in terms of graft survival) and equity of access (the chance that an individual patient will receive a graft within a reasonable period). This typically combines the important matter of tissue matching with other factors such as age and time spent on the waiting list.

ABO blood group compatibility is an obvious prerequisite for organ transplantation which must not be overlooked in the search for ever closer HLA matching.