Why Waiting Time and HLA No Longer Fulfill the Ethical Tests

of Utility and Justice and DPI-EPTS is a Step in the Right Direction

Thomas Mone, MSCEO, OneLegacy

US Kidney Allocation: A Fundamental Problem

Remarkable waste of kidneys from older donors

Why Do We Discard So Many More Kidneys Than Europe?

• EuroTrans Old-for-Old System (65+ Donors to 65+ Recipients) prompts older recipients and their MDs to accept older donor kidneys.

• In the US, waiting time is the primary allocation determinant. A 65+ Recipient who is offered a kidney from a 65+ Donor will wait for an offer of a younger kidney within the next several weeks.

• Older kidneys are too frequently discarded or sometimes not even recovered.

How Did We Let This Waste Happen?

• When kidney allocation was first debated, efforts to identify predictors of graft survival were without adequate experiential data.

• Community opted for the predictive power of HLA matching to maximize graft survival to address the ethical concept of maximizing Utility.

• To ensure Justice, waiting time was chosen to ensure offers were fair across age, gender, race, and economic differences

What’s Wrong with HLA?

• Nothing really, except HLA is no longer the powerful predictor of graft survival nor patient survival it once was:– HLA was never all that powerful a predictor of graft survival, as it always

had limited value at 1-5 antigen matches and it was never paired with age factors so it allowed young donor kidneys to go to older recipients

– Advances in immunosuppression have made all HLA essentially non-predictive of graft and patient survival in all but zero-mismatch cases

– Adding DPI-EPTS supplements HLA and provides tremendous predictive power to maximize graft life (not as much as LYFT would have, but a dramatic improvement)

What’s Wrong with Waiting Time?

• Waiting Time may ensure equality of access within a region or a DSA, but

• Waiting Time can vary by 4-5 times and 5-10 years longer between regions and DSAs due to:– Widely disproportionate list sizes – Widely varied donor potential due to varying death and disease

rates – Moderate variation in donation consent rates

• This disparity is not addressed in this concept, but can be reduced if more older kidneys are transplanted

How Does DPI-EPTS Help?

• Maximizes graft survival– Reduces rejection, sensitization, re-transplant of

better-matched donors and recipients• Reduces CIT and resulting DGF– Less reliance on time-consuming subjective

assessment of donor-recipient compatibility– Less time wasted offering older organs to younger

patients

• Increase Organ Utilization– Older donor organs less likely to be bypassed

How Will DPI-EPTS Affect the Older Recipient Population?

• UNOS Data is inadequate to model due to high older donor discard and non-utilization rates

• German/EuroTransplant Data demonstrates the benefits: – First Year Study: “86% 1-Year Graft Survival vs 79% control; reduced

CIT”– Five Year Study: “Since initiation of the ESP (1999), availability of

elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7% vs. O/A 36.2%, p = 0.047) but 5-10% higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation.”

– Ten Year Study: waiting time for the recipient in the ESP program was shortened significantly by more than 1 year. Also the shipping time was to > 6 h significantly shorter.

EuroTrans Predicted Benefits of DPI-EPTS

• Increased Organ Availability +• More Transplants +• Decreased Waiting Times for old and young +• Decreased CIT +• Equivalent 1 year graft survival +• Decreased Younger Recipient Graft Loss +• Decreased Recipient Sensitization +• Increased Older Recipient 3-5 year Graft Failure –

Translating from the German Experience

• While the German Old-for-Old system is more extreme than DPI-EPTS, it reasonably predicts that we will see decreased discards, more transplants, increased overall graft survival, while DPI-EPTS broader age bands will limit the graft loss associated with the use of dramatically older organs

Ethical Implications of DPI-EPTS

• Utility Benefits – Increased utilization of older donor kidneys– Reduced CIT– Reduced waiting time– Improved prediction of graft function– Increased life years from transplant

Ethical Implications of DPI-EPTS

• Justice Benefits– Reduced graft loss, sensitization, and re-transplant

benefit younger recipients harmed by current system– Increased transplants and reduced waiting time for

older recipients offset the loss of access to younger donor organs

What Do Donor Families Have to Say?

• The question of DPI-EPTS hasn’t been asked of them, but when asked what they hope for when they choose to donate they offer:– Save as many lives as possible, for as long as possible– Keep my loved one’s organ functioning as long as possible

• DPI-EPTS fulfills these two goals– Transplants MORE organs– Reduces overall graft loss– Increases lives saved and years of organ function

Is DPI-EPTS the Ideal Solution?

• Will DPI-EPTS reduce discard rates as much as the German Old-for-Old? No, not as much but it can be predicted to decrease waiting time, reduce CIT, and lower discard rates.

• Will DPI-EPTS save as many lives, shorten waiting time, and maximize graft life as much as LYFT would, No, but…for a community that has an appropriate history of caution when fiddling with human lives, it is a meaningful incremental step that will extend graft life and save lives.

• Will DPI-EPTS end the demographic and geographic inequality? No, that will have to be another days work.

What’s the Bottom Line of this Debate?

… If the primary goals of the balancing of utility and justice in organ allocation are – (1) ending deaths on the waitlist– (2) increasing overall graft survival, and – (3) fulfilling and honoring the wishes of the donors and

donor families who make donation possible

… DPI-EPTS is a significant step forward and it is time to move it from concept to policy.

Bibliography• Hippen, et al; Risk, Prognosis, and Unintended Consequences in Kidney Allocation; New England Journal of Medicine 364;14 nejm.org April 7, 2011,

pg.1285• Leichtman, et al; Improving the Allocation System for Deceased-Donor Kidneys; New England Journal of Medicine 364;14 nejm.org April 7, 2011,

pg.1287• UNOS Kidney Concept Document; http://optn.transplant.hrsa.gov/SharedContentDocuments/KidneyConceptDocument.PDF; accessed 4/25/11• Smits, et al; Evaluation of the Eurotransplant Senior Program. The Results of the First Year; American Journal of Transplantation 2002; 2: 000-000• Smits et al; Urgency, chance of success, equal opportunities, principles and practice of distribution, gross donated organs in Germany; Intensivmed

42: 489-495 (2005) DOI 10.1007/s00390-005-0609-6• Schmidt; Distributive Justice in Kidney Allocation; Analyse & Kritij 23/2001; p.286-298• Kirste, et al; Organ Donation and Transplant in Germany; http://sysnews.multimodo.com/compoweb/590/File/DSO_JB2005_englisch.pdf; accessed

4/25/2011• Frei et al; Prospective Age-Matching in Elderly Kidney Transplant Recipients—A 5-Year Analysis of the Eurotransplant Senior Program; American

Journal of Transplantation 2008; 8: 50–57• Marckmann; The Eurotransplant Kidney Allocation Algorithm-Moral Consensus or Pragmatic Compromise; Analyse & Kritik 23/2001; p. 271-279• Glessing; 10 Year Eurotransplant Senior Program, Urologe 2009 · 48:1429–1437; DOI 10.1007/s00120-009-2155-5; Online publiziert: 11. November

2009; © Springer Medizin Verlag 2009• Hippen; The Kidney Allocation Score: Methodological Problems, Moral Concerns and Unintended Consequences; American Journal of Transplantation

2009; 9: 1507–1512• Scarantino; INDUCTIVE RISK AND JUSTICE IN KIDNEY ALLOCATION; Bioethics ISSN 0269-9702 (print); 1467-8519 (online), Volume 24 Number 8 2010

pp 421–430• Tong et al; Community Preferences for the Allocation of Solid Organs for Transplantation: A Systematic Review; Transplantation • Volume 89,

Number 7, April 15, 2010; pg 796• Rahmel; Impact of Different Kidney Allocation Systems;