EXPERIMENTAL AND CLINICAL TRANSPLANTATION

In 2014, there is unanimous agreement that kidney transplant is the optimal treatment for most patients who have end-stage renal failure. Increasing organ shortage is the main obstacle that delays transplant and might even cause death while the patient is on the waiting list for kidney transplant. Many innovations have been proposed to increase the number of organs for transplant in different countries such as increasing awareness about organ donation, based on different cultures and religions. Support of religious and faith leaders exists for procurement of organs for transplant from patients with brain death or circulatory death. In the past decade, use of marginal and expanded-criteria deceased-donor transplant has been very helpful to expand the kidney donor pool. Dual kidney transplant is another procedure that may minimize the waiting list. The 1977 transport of kidneys from Minneapolis to Tehran helped change the life of a 15-year-old girl. At that time, we had the potential to change a life across 2 continents, even though our techniques were new. This should have provided the impetus to develop such a program. Presently, with progress in science, techniques, and organ shipment, it is our responsibility to reach across the globe to change the lives of many more young and adult patients waiting for kidney transplant. There are many countries in which kidneys from patients with brain or cardiac death are being discarded because of the unavailability of a transplant program in these countries, or because these countries have young transplant programs and very limited resources. If a global registry could be organized under the observation of the International Society of Nephrology and The Transplantation Society Sister Transplant Center Program, transplant teams would be able to use kidneys from patients with brain or cardiac death, with strict regulation of organ donation in accordance with World Health Organization guidelines.

Key words : Brain death donor, Cardiac death donor, Transplant commercialism, Transplant tourism, Xenotransplant

The idea about transplant existed in ancient Iran. A griffin still exists in Persepolis that shows that the idea of xenotransplant had been present in ancient times (Figure 1). In 2014, there is unanimous agreement that kidney transplant is the optimal treatment for most patients who have end-stage renal failure. Increasing organ shortage is the main obstacle that delays transplant and might even cause death while the patient is on the waiting list for kidney transplant.

Many innovations have been proposed to increase the number of organs for transplant in different countries such as increasing awareness about organ donation, based on the different cultures and religions. Support of religious and faith leaders exists for procurement of organs for transplant from patients with brain death or circulatory death. In the past decade, use of marginal and expanded-criteria deceased-donor transplant has been very helpful to expand the kidney donor pool. Dual kidney transplant is another procedure to minimize the waiting list.

With living-donor kidney allografts, the most important step is to reassure and encourage relatives to donate their kidney. Another helpful policy has been the use of paired kidney donors. In addition, living-unrelated donors constitute transplant commercialism.

Since 1988 in Iran, when deceased-donor transplant was not possible, the government funded regulated living–unrelated-donor transplant, which is being replaced by transplant from brain dead donors. In 2013, forty-eight percent of the transplants in Iran were from brain dead donors. Despite these tactics to provide organs, the waiting list still is expanding.

In July 2013, there has been some promising news that partially may satisfy the shortage of organs for all types of transplant including kidney allografts. The first good news was about the development of a new national policy for organ donation and transplant in China.^1,2 The promise was that the new national policy will improve the disturbing situation in China. It was disappointing to observe daily demonstrations of Chinese people in front of Transplant Week in San Francisco in July 2014 asking for help from Participants of the 2014 World Transplant Congress to join and support their struggle to stop “a crime against humanity” such as, slaughtering of bodies of prisoners to provide organs for transplant in China, and that “this barbaric human rights abuse must be stopped” (Figures 2 and 3).

At the Fourteenth Congress of the Middle East Society of Organ Transplantation on September 10, 2014, a pamphlet was circulated by Doctors Against Forced Organ Harvesting to promote ethics in medicine in China. In March 2014, Chinese officials stated that China will continue using organs from prisoners, and organs will be accounted for and entered in the newly designed Computerized Organ Transplant Registry System. These unpleasant facts proved that, regretfully, the first good news was not trustworthy or reliable.

The second promising news was the Human Transplantation Bill of Wales. The Welsh assembly proposed a new system of presumed consent, in which individuals are presumed to have consented to donate their organs after death unless they have specifically opted out.³ This bill will become enforced in Wales in 2015, and hopefully this will increase the number of available organs for transplant after 2015.

Increased mortality on the transplant waiting list is a multidimensional disaster. Another extremely disturbing outcome, beyond increased mortality as a result of the organ shortage, is organ trafficking and transplant tourism, which are shameful for the medical profession. The struggle to overcome this unwanted outcome was addressed in the 2008 Istanbul Declaration, which has had continuous follow-up by responsible, dedicated scientists who are involved in transplant.⁴

There are few other solutions considered by physicians involved in transplant to overcome the organ shortage for transplant. In China, part of problem contributing to the shortage of deceased donors is cultural, because brain death criteria are not widely accepted.⁵ Global collaboration between scientific, general, and renal health care organizations is required to decrease the organ shortage for transplant and stop transplant tourism and commercialism.

I propose a new project to address the increasing shortage of organs for transplant for the future, based on our experience in Iran during the past 55 years.

In 1968, the first deceased-donor kidney transplant was performed in Shiraz, Iran, and this was the first deceased-donor kidney transplant performed in the Middle East.⁶ In the early 1960s, the art of renal replacement therapy was young throughout the world including Iran. Gradually, by expanding dialysis units and the numbers of patients under maintenance hemodialysis, the need for transplant became more obvious.

In the Middle East and Iran during that decade, there were a few trained renal doctors. There were few institutes to train experts in the field. The field of renal replacement therapy was young and unknown to the public. Therefore, the need for renal replacement therapy, dialysis, and transplant was not adequately appreciated, and the pace of expansion of the field of transplant was very slow. Only a few of the patients who had end-stage renal disease and who were being dialyzed in Tehran had adequate financial support and related donors, and those patients often would travel to the United Kingdom for transplant.

There were few patients who had end-stage renal disease and who had transplant performed in Tehran and Shiraz. In 1975, several trained nephrologists, urologists, and general surgeons familiar with kidney transplant returned to Iran. The result was an increased performance of living-related donor transplant per year in 3 universities and Ministry of Health hospitals in Tehran: Dariush Kabir, Beh Avar, and Tajrish Shohada Hospitals.

With the expansion of dialysis units, increased numbers of end-stage renal disease patients, and higher knowledge of the public about the advantages of organ transplant, the demand for kidney transplant gradually increased. The shortage of experts, facilities, and suitable volunteer donors still were major obstacles to meet the demand.

Before the April 5, 2000, the 1985 Brain Death Act was not approved by the Iranian parliament, and there were no transplants from living-unrelated donors; the so-called Regulated living-unrelated donors paid by Iranian government was not yet accepted. From mid-‘s 1975, a committee known as The National Dialysis and Transplant Committee was established, composed of experts from the national blood bank, interested nephrologists, and surgeons. This committee contributed to the expansion of transplant facilities. The human leukocyte antigen profile of all patients undergoing maintenance dialysis was detected by the Iranian national blood bank. Therefore, a small national registry was created.

To expand the transplant program, the committee contacted colleagues at Euro Transplant in Leyden, Holland, and provided them the human leukocyte antigen profiles of patients waiting to be transplanted in Iran. This cooperation had phenomenal outcome. From 1975 to 1980, there were 14 deceased-donor kidneys sent to Tehran, Iran via Euro Transplant. The most impressive was a kidney flown from Hennepin County, Minneapolis via Chicago and Frankfurt, to Tehran. This story was published in the Eugene Register-Guard, April 18, 1977 (Figure 4):

Incidentally, I was the doctor from the National Dialysis Committee. At that time, I was in charge of the committee and practicing as a nephrologist at Beh Avar Hospital of the Ministry of Health where the transplant was performed. A photograph showed me in the operating room taking those kidneys out of preservative solution on ice (Figure 5).

When the transplant team in Beh Avar Hospital and the Iranian national blood bank registry were informed that 2 kidneys with ABO group AB+ were flown from Frankfurt to Tehran, a search revealed 2 patients listed in the Iranian national blood bank registry that had ABO group AB+, including a 15-year-old girl who was receiving maintenance dialysis in Kerman, a city in southern Iran, for 11 months.

The 15-year-old girl who had end-stage renal failure was evaluated for transplant. Her father previously had been evaluated for kidney donation to his daughter. The father and daughter were haplotype-identical for human leukocyte antigen but a positive reaction was observed in the mixed lymphocyte culture, so it was decided that the father would not be a suitable donor. We called her to come to Tehran from Kerman, and she arrived at Tehran Mehrabad airport at the same time as the kidney from Frankfurt. Both kidney and recipient moved quickly to Beh Avar Hospital and the transplant was performed successfully by an urologist and vascular surgeon, with immediate postoperative recovery of renal function. The recipient was maintained only with prednisolone and azathioprine.

After transplant, the 15-year-old recipient was followed regularly in my office. Her main problem was hypertension, which was poorly controlled with methyldopa. Her serum creatinine was < 1.5 mg/dL until 1983, when it started to rise slowly. In 1985, at 8 years after kidney transplant, the recipient developed chest pain. She was evaluated and had 3-vessel coronary artery disease that led to her death 14 years after transplant, when her serum creatinine was 4.3 mg/dL.

This recipient had been transplanted with a kidney after almost 70 hours of cold ischemia. The kidney had been rejected by a German transplant team because the transportation was not ideal. Although we had much less facilities and resources in Iran, the transplant was performed with a good outcome.

I am reporting this unusual case to cast hope for the future. The lesson to be learned from the journey of that kidney is that possibilities would be much greater when we start worldwide cooperation and a global registry. Many more patients across the world would benefit from cross-continent transplants, and we could decrease the organ shortage problem, even if just slightly.

At present there are many countries in which kidneys from patients who die from brain or cardiac death are discarded because of the unavailability of a transplant program in these countries, or because they have young transplant programs and very limited resources. If a global registry could be organized under the observation of the International Society of Nephrology and The Transplantation Society Sister Transplant Center Program, the transplant teams would be able to use these kidneys, with strict regulation of organ donation in accordance with World Health Organization guidelines.

I am certain that it would take time to develop such a system adequately. This may seem like a cumbersome initiative, with an unknown or possibly small effect on the shortage of kidneys for transplant. However, when fully developed, it would have a tremendous effect on the lives of end-stage renal disease patients across the globe.

Another important aspect of this plan would be that it will leave no room for transplant commercialism and tourism, and would halt organ trafficking. Our experience in Iran during the past 3 decades showed that increasing the numbers of transplants from brain death donors was an effective barrier to the sale of kidneys.⁷

In addition, globalization of the organ registry and transplant may help reach underserved and underdeveloped programs that are run by our dedicated colleagues across the globe in areas with poor facilities and resources. This, in turn, would help improve reciprocity, education, and growth of these programs across the globe and increase organ procurement and efficiency.

The 1977 transport of the kidneys from Minneapolis to Tehran helped to change the life of a 15-year-old girl and provided hope for that young girl. At that time, we were so inexperienced in our techniques, but we had the potential to change a life across 2 continents. This should have provided the impetus to develop such a program. Now that science, techniques, and organ shipment have progressed, it is our responsibility to advance programs across the globe to change the lives of many more young and adult patients who need a renal transplant.

Volume: 13 Issue: 1 April 2015 - Supplement - 1

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