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In View: People in Transplantation

Francis L. Delmonico, MD

The Science of Organ Donation

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doi: 10.1097/TP.0000000000001306
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Transplantation: The discrepancy between demand and supply is one of the most pressing current problems in transplantation. What can we do to solve this problem?

FLD: The Declaration of Istanbul has highlighted the importance of reducing the demand for organ transplantation by stating that “National governments, working in collaboration with international and nongovernmental organizations, should develop and implement comprehensive programs for the screening, prevention and treatment of organ failure.”

This sensible and essential recommendation has not been accomplished through a collaboration of professional societies with government and other insurance providers that pay for the treatment of renal failure. A Consensus Conference of all stakeholders is therefore long overdue. The National Kidney Foundation, to its credit, attempted a pilot project to detect and treat patients with renal dysfunction to forestall kidney failure. Blood pressure monitoring and urine analysis for protein and glycosuria—as done, for example, successfully in Cuba, represent an effective and cost efficient approach.

Moreover, changing demographics of patient populations that are driving the demand for kidney transplants must be addressed in the United States and in populous regions of Asia and the Gulf Countries.

Examining UNOS data of waitlist additions and the proportion of patients undergoing kidney transplantation provide important information: In the past 20 years, the proportion of patients (> 50 years) undergoing kidney transplantation has increased from 35% to now 60%! Patients older than 65 years receiving transplants have tripled (from 6% in 1995—to almost 18% in 2015).1 Thus, we clearly have a demand that is not going to be solved unless a focus to prevent kidney failure is accomplished.

Transplantation: Comparing the utilization and discard rates of organ transplants, Eurotransplants appears to be using many more kidneys that are considered suboptimal in the United States. Are we overassessing the quality of kidneys?

FLD: The quality of deceased donor kidneys before transplantation is not being evaluated correctly. The routine practice to biopsy kidneys in an attempt to determine the likelihood of either immediate function or long-term outcome is not entirely evidence based. Biopsy results are not a criterion of the kidney donor profile index (KDPI) that predicts outcome by 1 and 3 years after transplantation.

The reliance on information based on biopsies findings is a major disparity with Eurotransplant that does not perform histological evaluations in a comparable way. Of note, the absence of biopsies in Eurotransplant does not appear to alter outcomes after kidney transplantation.

Indeed, the frequency of biopsies has become absurd without data to support its routine use.2,3 The biopsy rate in the United States has doubled since 2012 (from 27% to >50%). Of note, while only 16% of non-ECD donor kidneys had been biopsied in 2000, this rate has increased to 40% in 2012. Moreover, in the age group of donors 18 t o 34 years, biopsy rates have increased 4-fold (from 6% in 2000 to 24% in 2012) (Darren Stewart, personal communication).

Routine biopsies engender the risk of unnecessary kidney discards, a process that has also received increased public attention.4

Regulatory bodies in transplantation such as UNOS and the Centers for Medicare and Medicaid Services (CMS) in the United States have emphasized thus far on monitoring transplant outcomes when assessing transplant center performance. Consequently, a risk adverse approach has evolved that does not justify declining organ offers because those organs may benefit patients when compared to the increased mortality when staying on dialysis.5 Thus, both quality control combined with an encouragement to reduce organ wastage may be able to achieve to optimize outcomes.

Transplantation: Organs procured from donors after circulatory arrest (DCD) are utilized more frequently for transplantation. Can we use more DCD organs in the future?

DCD donation has greatly increased the availability of organs. Over a 5-year period, the New England Organ Bank NEOB had almost 500 DCD donors, representing 30% of overall deceased donors. Only 17% did not become actual DCD donors while 16% progressed to brain death.6

In 2014, 82% of kidneys recovered from 1291 DCD donors in the US were transplanted (with a discard rate of 18%). During the same year, 86% of kidneys recovered from 87 NEOB DCD donors were transplanted. DCD activity contributed to an average of 15% in deceased donation in the US in 2014, but varied by region, with 11 DSAs at greater than 25% and 18 DSAs less than 10%. Of note, in the United States, there are still OPOs that do not have a DCD program, perhaps, in part, because no transplant center within that donor service area (DSA) has interest. That deficiency is a loss of transplant opportunity for the patients of that DSA.

Transplantation: How do you suggest that we use kidneys of compromised quality, those from donors that used to be called “expanded criteria donors,” now termed in the United States as donors with a KDPI > 85 best?

FLD: Assessing demographics of those dying on the waiting list by age, duration of waiting time, functional status and cause of death may help determining whether a kidney of suboptimal quality would have impacted their survival.7,8

Transplantation: UNOS was established in 1984, at a time when the discrepancy between demand and supply was not as pronounced as today. What can be done to encourage the utilization of marginal grafts?

FLD: Implementing performance metrics that will encourage the utilization of available organs represents a timely change and may reduce organ discard.

CMS and the OPTN have a responsibility to foster kidney transplantation because of the survival benefit; thus, kidney transplants with a KDPI that predicts an outcome that is comparatively reduced to kidneys transplanted with an excellent KDPI should still be used. Centers should not be discouraged in performing such transplants because of outcome metrics.

Transplantation: Novel organ preservation and perfusion techniques have come a long way. How do you envision that those techniques will contribute to an increased utilization of organs?

FLD: By establishing that the organ that has been perfused ex vivo has achieved a threshold of function that will predictably enable the successful use. For example, kidneys with a high KDPI that are regularly discarded may be assessed perfusion characteristics (resistance and flow), and ultimately on the production of urine (under a normothermic conditions with blood).

Transplantation: Self-sufficiency is the proclaimed goal that will help preventing transplant tourism and organ-trafficking. How can we achieve this goal worldwide?

FLD: Only by government engagement with ministries of health accepting their responsibility to provide organs for the people of their country. Governments enable transplant tourism. Patients traveling from Africa or the Middle East may have no other recourse because their own governments have not established a program of deceased donation within their country. The Declaration of Istanbul Custodian Group (DICG) is in the midst of developing guidelines for professionals confronted with transplant tourists—either in advance or upon return from the foreign destination. The DICG will also seek the support of the World Health Organization in developing a resolution to curtail transplant tourism consistent with the Council of Europe Convention against Organ Trafficking.

Transplantation: We have been delighted to learn that you have recently been appointed to the Pontifical Academy of Sciences (PAS). This is an outstanding honor for you, personally, and for the greater transplantation community! Could you share some of the academy’s responsibilities, your role, and the potential for organ donation and the overall transplant community with us?

FLD: The agenda of the Pontifical Academy of Sciences (PAS) is international in scope, multi-ethnic in composition, and nonsectarian in its choice of members. The work of the Academy comprises these major areas: Science and technology of global significance representing in particular challenges in the developing world, scientific policies, bioethics and aspects of epistemology. I hope to follow in the footsteps of Dr. Joseph Murray, who had been a member of PAS in contributing information regarding our field of organ donation and transplantation.

Transplantation: What fascinates you in transplantation?

FLD: The emerging possibility to repair organs prior to transplantation to expand their availability from deceased donors and the notion that organ replacement can restore health and productivity.

I would hope that the emerging success of ex-vivo repair can attract young individuals to reinvigorate the field of organ donation and transplantation.

Transplantation: What excites you outside of work?

FLD: The creativity of woodworking—morticing mahogany and oak into personalized boxes, the precision and patience of jig saw puzzles of Impressionist paintings by Monet, Renoir Cezanne and others, the diversion to play the piano and the pride to watch my grandchildren grow up.

REFERENCES

1. Organ Procurement and Transplantation Network. National Data. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/Updated2016. Accessed April, 10th, 2016.
2. Wang CJ, Wetmore JB, Crary GS, et al. The donor kidney biopsy and its implications in predicting graft outcomes: a systematic review. Am J Transplant. 2015;15:1903–1914.
3. Kasiske BL, Stewart DE, Bista BR, et al. The role of procurement biopsies in acceptance decisions for kidneys retrieved for transplant. Clin J Am Soc Nephrol 2014 ;9:562–571.
4. Yasinski E. When Donated Organs Go to Waste. http://www.theatlantic.com/health/archive/2016/02/when-donated-organs-go-to-waste/470838/. Published February 24th, 2016. Accessed, April, 10th, 2016.
5. Organ Procurement and Transplantation Network. Final Rule. https://optn.transplant.hrsa.gov/governance/about-the-optn/final-rule/. Published 2004. Accessed, April, 10th, 2016.
6. Nelson HM, Glazier AK, Delmonico FL. Changing patterns of organ donation: brain dead donors are not being lost by donation after circulatory death. Transplantation. 2016;100:446–450.
7. Reese PP, Shults J, Bloom RD, et al. Functional status, time to transplantation, and survival benefit of kidney transplantation among wait-listed candidates. Am J Kidney Dis. 2015;66:837–845.
8. Hellemans R, Stel VS, Jager KJ, et al. Do elderly recipients really benefit from kidney transplantation? Transplant Rev (Orlando). 2015;29:197–201.
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