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Benjamin Hippen, M.D. Metrolina Nephrology Associates, P.A. and the Carolinas Medical Center Charlotte, North Carolina

University of Alberta Transplant Grand Rounds Conventional and Controversial Solutions to the Shortage of Kidneys. Benjamin Hippen, M.D. Metrolina Nephrology Associates, P.A. and the Carolinas Medical Center Charlotte, North Carolina. Declarations and Disclaimers.

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Benjamin Hippen, M.D. Metrolina Nephrology Associates, P.A. and the Carolinas Medical Center Charlotte, North Carolina

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  1. University of Alberta Transplant Grand Rounds Conventional and Controversial Solutions to the Shortage of Kidneys Benjamin Hippen, M.D. Metrolina Nephrology Associates, P.A. and the Carolinas Medical Center Charlotte, North Carolina

  2. Declarations and Disclaimers • I have received no funding from a pharmaceutical company or medical device manufacturer. • I will not discuss off-label use of any medication. • In the last 5 years, I have received fixed remuneration for services rendered from: • The American Enterprise Institute • The Cato Institute • Roche Organ Transplant Research Foundation • I have never been remunerated for any paper ultimately published in a peer-reviewed journal.

  3. Justice is when people receive what they are due – David Schmitz

  4. Learning Objectives Understand the magnitude, causes and implications of the shortage of transplantable kidneys. Become familiar with conventional and controversial solutions to the shortage, past and present, and the limitations of these solutions. Develop an informed basis for speculation on future trends in organ procurement policy

  5. Today - USA • 2006 – Total federal expenditures on ESRD = $22.7 billion • 5-year patient survival on dialysis = 35% • 2006 – Total federal expenditures on kidney transplantation = $ 2.2 billion • 5-year patient survival with a transplant = 75% • 2006 – Total federal expenditures on ESAs = $2 billion

  6. Projected Growth in the Waiting List for Deceased Donor Kidneys, and Projected Growth in Prevalent Dialysis Patients (712,000) Comb D&T (591,000) combined D&T (Predicted) ESRD Actual(Predicted) Wt list Aug ‘09 80,384 Sources: 2008 OPTN/SRTR Annual Report, Table 5.1. Predicted values for 2004-2010 based on slope of the line from 1994-2003, and JASN 12:2753, JASN 16:3736. Non-referred projections AJT 8(1):58.

  7. “Inactive” – The rest of the story • Delmonico & McDiarmid– Status 7 is • (a) Misleading with regard to organ demand • (b) Accounts for much of the vaunted “death on the list” • (c ) Imposes undue burdens on transplant centers • “The percentage of patients who died categorized as inactive on the kidney waiting list has also increased markedly from 31% (1,197) in 2003 to 52% (2,431) in 2007.” • Total deaths reported as such on Wt list 2007: 4,452 Transplantation: 86 (12) : 1678-1683

  8. “Inactive” – The rest of the story(2) Table 2 - Transplantation: 86 (12) : 1678-1683 • 2007 - 24,624 inactive candidates (32.8%) • 10,961 (45%) inactivated within 30 days of listing • Why should this be so? Data not illuminating • Candidates with GFR < 20, not ready for Tx • Accumulate time while completing evaluation • Insurance hold • Uncertainty about available/qualified living donors • Longer median waiting times

  9. Inactive 12/06 – Disposition 4/08 Table 4 - Transplantation: 86 (12) : 1678-1683 Total (Inactive 12/06) 20,334 Still Waiting/Inactive 9,797 (48.2%) Other Removal 3,330 (16.4%) Death 2,845 (14.0%) Still Waiting/Active 2,344 (11.5%) Deceased Donor Transplant 1,481 (7.3%) Living Donor Transplant 537 (2.6%)

  10. Reasons for removal (UNOS) • Total removal from list 2008: 26,673 • Deceased donor transplant 39.5% • Living donor transplant – 18.5% • Death – 17.5% • “Other” – 11.5% • “Too sick” - 7.2% • “Other” and “Too sick” are not counted as “Death” • Total removed, not transplanted = 9,252

  11. “Inactive” – The rest of the story(3) • Insinuation – Most patients “inactive” aren’t (ever) really candidates • Problem – Lack of granularity in data • Data doesn’t describe disposition of specific cohorts of patients listed inactive under specific conditions. • Doesn’t demonstrate substantial center variability in how Status 7 is used. • “Other” and “Too sick” confuses removals for death on both active and inactive list

  12. Projected Growth in the Waiting List for Deceased Donor Kidneys, and Projected Growth in Prevalent Dialysis Patients (712,000) Comb D&T (591,000) combined D&T (Predicted) ESRD Actual(Predicted) Wt list Aug ‘09 80,384 Sources: 2008 OPTN/SRTR Annual Report, Table 5.1. Predicted values for 2004-2010 based on slope of the line from 1994-2003, and JASN 12:2753, JASN 16:3736. Non-referred projections AJT 8(1):58.

  13. Unintended Consequences • Waiting time which exceeds median life span; • Older and sicker recipients, including young recipients with extended vintage on dialysis; • Increasing emotional pressure on any available living donor; • Increased reliance on extended criteria donors; • An upsurge in international organ trafficking; • Erosion of trust in the transplant community. Hippen, B. JMP 30:593

  14. Alternative solutions • “Prevention”; • Presumed consent; • Extended criteria donors; • Controlled donors after cardiac death; • Uncontrolled donors after cardiac death; • “Swaps” and list-paired donation; • Utility models – KPSAM/LYFT/KARS

  15. Hippen, B. Kidney International (2006) 70, 606–607. Preventive measures may not reduce the demand for kidney transplantation. NHANES III Data (2007) CKD 3 > 15,000,000 CKD 4 – 1,200,000 CKD 5 – 390,000 MMWR Weekly, 56(08);161-165

  16. Presumed consent • Existing presumed consent laws in Europe haven’t increased organ procurement rates. • Even 100% conversion wouldn’t solve the problem. • 10,500-13,800 potential BDD’s/year. • Weak vs. Strong versions • Weak opt-out versions more or less synonymous with tenacious solicitation; • Strong versions flirt with conflicts of interest; • Special problem of donation after cardiac death; Healy, K. Depaul Law Rev. 55:1017 Sheehy, E. NEJM 349:667.

  17. Healy, K. Depaul Law Rev. 55:1017.

  18. Extended criteria donors % of ECDs 56% 30% Schold, et.al. AJT 5:757

  19. Reasonable short-term outcomes from controlled DCD Bernat AJT 6:281 Table 5: Summary of adjusted kidney graft survival results by donor type and delayed graft function (DGF) Table 5: Summary of adjusted kidney graft survival results by donor type and delayed graft function (DGF)

  20. But… • Estimated number of controlled donors after cardiac death by 2013: (HRSA) 2,016

  21. Uncontrolled DCD – The signature solution of the IOM • Correctly identifying a candidate in the field; • IOM - 7.6% of all out-of-hospital cardiac arrests • Transfer to an ER with available personnel and capability for cardiopulmonary bypass within 90-120 minutes of cessation of CPR; • Limited knowledge regarding decedent’s medical history; • Identifying and evaluating recipient in short order; • Non-trivial cost of circulatory preservation with failed conversion; • (Forthcoming study in AJT – Testing the public’s trust?) • UCLA study – higher primary non-function and DGF; • (2.7% vs. 1.4, 51% vs. 25% P<0.0001) • Recent AIM study from Spain w/ better outcomes; Ganadeep AJT:1682, Sanchez-Fructuoso AIM 145:157

  22. Other issues with DCD • Scepticism about veracity of criteria for death by whole-brain criteria exacerbated by DCD • Alan Shewmon, Chronic "brain death": meta-analysis and conceptual consequences. Neurology 51(6):1538-1545, 1998. • Heterogeneous practices • How long to wait? Why? • IOM’s basis for 5 minute wait based on 6 small studies of autoresuscitation, from 1915 - present.

  23. Paired and List-paired Exchange Paired exchange: A1 B2 B1 A2 Potential for many iterations!

  24. Challenges of Paired Exchange • Standardization of immunologic evaluation • Transportation of organs from living donors • “Unbalanced” altruism • Donor age • Highly-sensitized or less physiologically robust recipient • New pressures on previously unavailable living donors • Too many O-recipients

  25. List-Paired Exchange A Waiting list Waiting Time B A1 C D E F […..]

  26. O Delmonico, F. AJT 4:1628 O-list – 550 days added over 3 years

  27. Utility Model – Maximize LYFT • Objective: • Maximize the total number of life-years saved of candidates on the waiting list for a deceased donor kidney • Survival Benefit: • Candidate survival with SCD transplant • minus • Candidate survival without a kidney transplant on the waiting list • KARS: Combination of LYFT and “Dialysis Years”

  28. Variables in Survival Benefit Model Center-specific data • Age • Time exposed to ESRD • Albumin • BMI • Diagnosis: • HTN • Polycystic • Diabetic • Other • Previous Transplant • Peak PRA • Ethnicity/Race • Angina • Peripheral Vascular Disease • Calendar Year of Listing • Gender • NYHA Functional Class • Primary Insurance Status • Drug Treated Hypertension • Type of Dialysis • DSA (Surrogate for Geography)

  29. Methodological criticisms of LYFT Wolfe RA, et.al. AJT 2008; 8 (Part 2): 997–1011 • No prospective testing of the model based entirely on retrospective data • Ability to correctly predict waitlist, patient and graft survival for individuals is poor: • IOC (index of concordance) 0.5 = chance • Waitlist survival = 0.6 • Patient survival = 0.68 • Graft survival = 0.57 • Zero granularity to diagnostic categories • Type II diabetes – 1 year = 35 years

  30. What we thought vs. What we now know Meier-Kriesche AJT 4:1289

  31. Moral Concerns • Which patients would be disadvantaged by the new system? • Balancing harms and benefits • Variability in interpersonal comparisons of utility • Competing claims for special dispensation • Unintended, forseeable consequences

  32. Moral Concerns (1) • Who loses ? • Utility involves benefits and harms • No assessment of harms to balance claims of benefit from LYFT • If LYFT-gains are a benefit, then surely additional time on dialysis and death is a harm. How to balance these harms with the purported benefits?

  33. Moral Concerns (2) • Interpersonal comparisons of utility • LYFT includes a discount QALY for time on dialysis, but otherwise a year = a year • Value of 15th -> 20th year off dialysis in a young recipient >> value of 0 -> 4th year off dialysis for an older recipient. • Don’t older recipients have some morally compelling claims about additional years at the end of their lives?

  34. Moral Concerns (3) Variability in interpersonal comparisons of utility is hard to measure There is good-faith disagreement about how charitably a crude, universal metric such as LYFT provides an answer to the question: “What is kidney transplantation for?” “We” will probably never agree on a single answer. Reference to “sound medical judgment,” “best use of resources,” etc. is an exercise is self-serving circularity.

  35. Unintended consequences (1) • Paradoxical effect of KAS on living donation trends (the pediatric exception lesson) • Homogenization of the waiting list • Raising the importance of previously minor variables, which encourages gaming

  36. The pediatric exception Groups with higher LYFT scores – Less living donor transplantation Groups with lower LYFT scores – More living donor transplantation

  37. Unintended consequences (2) • Homogenization of the waiting list • The youngest (18-34) cohort on the waiting list is small, and the incident rate is low • Eliminating a significant fraction of the 18-34 cohort will homogenize the LYFT scores of the remaining candidates • Narrow margins of error become important • Minor variables  Major variables • Gaming KAS at the margins to gain a crucial advantage

  38. Disparity between demand for and supply of transplantable organs; Unintended consequences of (1); Alternative solutions; The moral defensibility of incentives.

  39. Autonomy Engelhardt HT. Foundations of Bioethics, 2nd ed. • …as a primary value • Operational freedom is typically better for individuals and societies compared to the opposite • But not always – When and where that is the case is hotly disputed • ….as a side constraint • Given the vast moral pluralism of even stable, peaceful societies, valuing autonomy as a side-constraint on interference by others.

  40. Four side-constraints on incentives • The priority of safetyof the donor and recipient; • Transparencyregarding risks to the donor and recipient, and regarding institutional outcomes and follow-up care; • Institutional integritywith regard to establishing guidelines which broadly reflect the conditions under which institutions and individuals will participate • Operation undera rule of law providing enforceable redress. Hippen B. JMP 30:593

  41. Safety – Moral and market value • Moral value of safety • Non-maleficence • Market value of safety • Disincentive to engage in the risks of organ trafficking for organ sellers and recipients. • Organ markets may be safer than donation • Incentives to avoid short- and long-term harms; • Avoid emotional pressures to use marginal related living donors. Hippen B. JMP 30:593

  42. Transparency • Criteria for evaluation should apply equally to compensated and uncompensated donors. • Ample potential supply of potential living donors offers opportunity for even more stringent acceptance criteria • If donor compensation included a comprehensive health benefit  longitudinal outcomes studies. Hippen B. JMP 30:593

  43. Institutional integrity • Moral pluralism – Hallmark of a free society. • Institutions and individuals should not be obligated to participate in incentives. • The solidarity of moral communities: • Some donors will refuse compensation; • Some recipients will refuse to engage with compensated donors; • Some MDs, institutions will agree • “Centers of Authentic Altruism” • Free-rider “problem” – indirect beneficiaries of markets. Hippen B. JMP 30:593

  44. Rule of law • Productive function • Facilitates agreed-to arrangements between individuals and institutions • Protective function • Protects contractual and forebearance rights of all • Sample contracts • Mechanisms for adjudication and mediation • Standards for tort liability Hippen B. JMP 30:593

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