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With the exception of transplant donor-recipient pairs who were monozygotic twins, kidney transplantation had remained for most of the 1960s a high-risk treatment with poor outcomes.
Only in the late 1960s with the introduction of azathioprine did it begin to take its place as a viable long-term treatment for irreversible kidney failure and became an option for many younger and fitter people established on regular dialysis.
From the 1970s onwards there was steady incremental progress towards modern kidney transplantation as now practiced in the 21st century. This included improvements in the organisation and delivery of transplant services, progress in therapeutics, changes in the approach to the use of living donors, and also the use of combined pancreas and kidney transplants for suitable individuals with type 1 diabetes and kidney failure.
Who were the transplant surgeons?
Some early transplant surgeons had been trained in urology, others in vascular surgery. Some of these surgeons with a background in vascular surgery embraced the challenge of providing a vascular access service for the partner renal unit. Only from the 1990s was there a recognised training programme for transplant surgery.
In the early years kidney transplantation, like maintenance dialysis, was developed by enthusiasts without any coordinated regional or national planning. Both nephrology and transplantation started in academic centres, sometimes in a coordinated fashion with a teaching hospital, but in some cases driven separately by highly motivated nephrologists and transplant surgeons who could be slow to integrate their respective services.
Some nephrologists in the 1960s had been quick to appreciate that a developing dialysis service would be overwhelmed by patient numbers unless transplantation was also available for as many suitable patients as possible. All well and good, but even when azathioprine arrived and enabled a 1 year graft survival of some 60%, the proportion of those with uncontrollable acute rejection remained high, many received multiple transplants, and ended up on dialysis virtually untransplantable because they were highly sensitised (i.e. had high titres of multiple anti-HLA antibodies).
Sooner or later a transplant service grew alongside most of the first wave of dialysis centres. As the number of transplant units grew, there was concern among some in the transplant community that smaller units doing fewer transplants might have inferior outcomes, a factor which would be a driver for amalgamating into a smaller number of larger transplant units. A ‘centre effect’ with marked variations between centres in transplant outcomes had been noted and was investigated by the British Transplantation Society (Renal Transplantation in the United Kingdom & Ireland. The Centre Effect. A BTS Report, 1983). Their report did not establish a simple relationship between unit size and clinical outcomes, but nevertheless some consolidation of transplant services gradually followed.
Staffing was one important driver for this consolidation, particularly the number of trained transplant surgeons in the country. Long gone were the early years of the 1960s when a small number of solo transplant surgeons worked heroic hours to transplant across a wide geographical area. A minimum of four transplant surgeons in each rota came to be regarded as a norm compatible with acceptable rotas and hours of work.
A unique problem required consideration in London, which in the 1990s still hosted no fewer than twelve medical schools, of which ten offered kidney transplantation. A London Implementation Group made a wide-ranging review of specialist services across London as result of which only five transplant units continued. A small unit in Stoke also stopped transplanting, the work being subsumed by a West Midlands transplant service based in Birmingham.
However, the number of renal units offering dialysis continued to grow. In 2025 there are 80 renal units in the UK, and 23 transplant centres. Some patients therefore had to travel considerably to access transplantation, and there gradually developed a model of care in which stable transplanted patients would return to their referring renal unit for long term care from 1- 6 months after transplantation.
Access to a Histocompatibility & Immunogenetics laboratory with sufficient resources and expertise also became a mandatory feature of a transplant service. In 2025, there are now 24 such labs in the UK. By the turn of the century these labs were providing HLA typing and anti-HLA antibody screening, as well as acute and virtual cross matching. Data on HLA typing and anti-HLA antibodies provide the basis for UK Kidney Allocation schemes at present administered by NHS Blood & Transplant.
The growth in parallel with kidney transplants of other solid organ transplants (heart, ling, liver) is beyond the scope of this website.
But pancreas transplant emerged from the 1980s as an approach to treat a minority of people with diabetes and renal failure, in whom the progression of other microvascular and macrovascular complications would still be responsive to the restoration of normal glycaemic control. The pancreas transplants were synchronous with a kidney transplant or sequential.
In the 1990s UK centres (Leicester and Oxford were the first) began to explore the alternative approach of intrahepatic infusion of isolated human donor islets. Insulin independence was sometimes achieved but did not prove sustainable. Islet transplant is now reserved for those with severe and resistant hypoglycaemia, independent of their need for a kidney transplant.
By 2025 these procedures were only being performed in the UK nationally designated centres: eight for pancreas transplantation, five for islet transplants.
In 1970, azathioprine with corticosteroids had become the standard maintenance immunosuppression. In retrospect it is now clear that in an important minority of patients this regimen could achieve very long-term graft survival; there are some in the UK with excellent transplant function after more than 50 years on azathioprine.
Nevertheless, using the steroid/azathioprine regimen early episodes of acute cellular rejection still occurred in approximately 50% of cases. High dose oral or intravenous corticosteroid was usually the first line treatment for acute rejection, and recurrence was most often treated with an antilymphocyte globulin (ALG). A horse ALG developed in Edinburgh was commonly used. Other centres favoured ATG or OKT3. Still others preferred Campath-1H, a Cambridge developed anti-CD52.
From the 1990s, additional immunosuppression began to be used at the time of transplant (induction therapy). for selected patients at higher risk of acute rejection, for example second and subsequent transplants. ATG, alemtuzumab, Campath-1 were all used as induction agents.
In retrospect it is notable that corticosteroid dosing especially in the immediate period after transplantation remained high, perhaps reflecting familiarity with the regimens that had been necessary before azathioprine was available. The penalty was being paid for that in continuing adverse effects of corticosteroids both in the short and long term. Mollie McGeown and colleagues in Belfast were the first in the UK to show in retrospective data that an initial dose as low as prednisolone 20mg daily did not worsen graft outcomes and reduced toxicity (Transplantation. 1980;29(4):287-89) . . Their findings were subsequently supported by by Peter Morris and colleagues in Oxford in an RCT comparing high and low dose steroid regimens (Lancet. 1982 Mar 6;1(8271):525-7).
The single most transformative development in maintenance immunosuppression after azathioprine was the introduction of the first calcineurin inhibitor, cyclosporin (originally known as cyclosporin A). Remarkably a major role in the development of both azathioprine and cyclosporin was played by one UK transplant surgeon, Roy Calne. Once established in clinical practice cyclosporin was transformative taking one year graft survival to more than 80%. Nevertheless, its first clinical use in Cambridge produced major unforeseen challenges. Calne had used dogs (as he did for azathioprine) for the first experimental use of cyclosporin in mammals; it was highly effective in preventing rejection. However, cyclosporin was not nephrotoxic in dogs, and when the same doses were first applied in human transplants there was not only anuria because of nephrotoxicity, but also in some patients significant vasoconstrictive effects including digital ischaemia. Eventually a much lower dosing regimen, suitable for human use, emerged.
Once in wide clinical use, the step benefit of cyclosporin became obvious; median 1 year graft survival immediately increased from 60% with azathioprine to over 80%.
The 1990s produced another wave of maintenance immunosuppressive agents, as the pharmaceutical industry began to invest in the field, realising that the lifelong therapy required by solid organ transplant patients meant potential for substantial commercial benefit, even if patient numbers were relatively small. Each of these new agents gave some incremental improvement in transplant outcomes, but no further step changes as had been delivered by azathioprine and cyclosporin.
Tacrolimus gradually replaced cyclosporin as the CNI of first choice. Mycophenolate mofetil became the preferred antimetabolite rather than azathioprine. Sirolimus also proved useful in selected patients.
The narrow therapeutic index of CNI’s (between efficacy and nephrotoxicity) required the introduction of routine drug level monitoring, which had only ever been used before in transplantation in a research setting. Local arrangements varied and assays for cyclosporin, and later tacrolimus, were established in either clinical biochemistry or H&I labs. A minority of centres also monitored mycophenolate levels.
Lower numbers of acute rejection episodes remained the conventional parameter for immunosuppressive success. The net effect of the changes just described was a gradual increase in the potency of maintenance immunosuppression. And thus, through the 1990s the reduced risk of adverse effects achieved with lower dose steroid regimens was being outweighed by the addition of induction agents and a gradual intensification in maintenance immunosuppression. This was never achieved without the disadvantages of adverse effects including infection and malignancy. CMV infection remained a problem, BK virus emerged as an important cause of graft dysfunction, lymphoid malignancy continued to be a concern.
Induction of tolerance obviating the need for maintenance immunosuppression has been a goal for transplant immunologists since the 1970s but has proved extremely difficult to achieve reliably in clinical transplantation despite success with many experimental protocols. A rare clinical example of tolerance occurs when there has been prior bone marrow transplantation from the same donor.
Tolerance is also exposed when stable transplant recipients (most commonly young adults) decide against advice to stop their maintenance immunosuppression. Many reject, a few maintain graft function and are thus tolerant. But no clinical or laboratory evaluation can yet reliably distinguish between the two.
Throughout the 1970s and 1980s only a small minority of transplants used live related donors (LRD), usually first-degree relatives. Indeed, a small number in the transplant community thought at time that LRD transplantation was unethical when there was the possibility of accessing a deceased donor kidney. But through the 1990s and into the 21st century there was a surge in LRD numbers. Several factors were at play:
Each of the factors described above has contributed to incremental progressive improvement in transplant outcomes over the last four decades. Now that 1 year graft survival has reached 95% for deceased donor transplants and 98% for living donor transplants it has become increasingly difficult whether by RCT or using registry data to show if there is real benefit from any specific alterations in care.
Authorship: Neil Turner, John Feehally
First published March 2022
Last Updated on June 7, 2026 by John Feehally