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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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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


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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.



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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


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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


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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.


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“Inactive” – The rest of the story Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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


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“Inactive” – The rest of the story(2) Kidneys, and Projected Growth in Prevalent Dialysis Patients

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


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Inactive 12/06 – Disposition 4/08 Kidneys, and Projected Growth in Prevalent Dialysis Patients

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%)


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Reasons for removal (UNOS) Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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


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“Inactive” – The rest of the story(3) Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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


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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.


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Unintended Consequences Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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


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Alternative solutions Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • “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


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Hippen, B. Kidneys, and Projected Growth in Prevalent Dialysis Patients 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


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Presumed consent Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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.


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Healy, K. Depaul Law Rev. 55:1017. Kidneys, and Projected Growth in Prevalent Dialysis Patients


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Extended criteria donors Kidneys, and Projected Growth in Prevalent Dialysis Patients

% of ECDs

56%

30%

Schold, et.al. AJT 5:757


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Reasonable short-term outcomes from controlled DCD Kidneys, and Projected Growth in Prevalent Dialysis Patients

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)


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But… Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • Estimated number of controlled donors after cardiac death by 2013: (HRSA)

    2,016


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Uncontrolled DCD – The signature solution of the IOM Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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


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Other issues with DCD Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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.


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Paired and List-paired Exchange Kidneys, and Projected Growth in Prevalent Dialysis Patients

Paired exchange:

A1 B2

B1 A2

Potential for many iterations!


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Challenges of Paired Exchange Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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


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List-Paired Exchange Kidneys, and Projected Growth in Prevalent Dialysis Patients

A Waiting list

Waiting Time

B A1

C

D

E

F […..]


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O Kidneys, and Projected Growth in Prevalent Dialysis Patients

Delmonico, F. AJT 4:1628

O-list – 550 days added over 3 years


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Utility Model – Maximize LYFT Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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”


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Variables in Survival Benefit Model Kidneys, and Projected Growth in Prevalent Dialysis Patients

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)


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Methodological criticisms of LYFT Kidneys, and Projected Growth in Prevalent Dialysis Patients

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


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What we thought vs. What we now know Kidneys, and Projected Growth in Prevalent Dialysis Patients

Meier-Kriesche AJT 4:1289


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Moral Concerns Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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


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Moral Concerns (1) Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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?


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Moral Concerns (2) Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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?


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Moral Concerns (3) Kidneys, and Projected Growth in Prevalent Dialysis Patients

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.


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Unintended consequences (1) Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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


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The pediatric exception Kidneys, and Projected Growth in Prevalent Dialysis Patients

Groups with higher LYFT scores – Less living donor transplantation

Groups with lower LYFT scores – More living donor transplantation


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Unintended consequences (2) Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • 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


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Disparity between demand for and supply of transplantable organs;

Unintended consequences of (1);

Alternative solutions;

The moral defensibility of incentives.


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Autonomy organs;

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.


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Four side-constraints on incentives organs;

  • 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


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Safety – Moral and market value organs;

  • 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


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Transparency organs;

  • 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


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Institutional integrity organs;

  • 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


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Rule of law organs;

  • 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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“Valuable consideration” organs;

  • Compensation need not be limited to money

    • Lifetime health insurance and drug benefit

  • Meaning of exchange not reduced to cash-value

    • Contribution to charity, retirement, college ed.;

    • Proscribed consideration limits fungibility: HSAs, 401k, 529

    • Reimbursement for otherwise noble endeavors: Firefighters and soldiers still get paid.

Gaston RS. AJT 6:2548


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Other advantages of incentives for organs organs;

  • Reduce economic support for international organ trafficking;

  • Permits altruistic donors to donate free of emotional and psychological pressures;

  • Increase in pre-emptive transplantation;

  • Fewer complications, shorter hospital stays, better outcomes;

  • The leisure and safety value of time;

  • More chances for highly-sensitized recipients.


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Per-patient break-even and cost-effectiveness costs of incentives for organs

$134,659

$47,290

Matas A. AJT 4:216


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Objections to a regulated organ market incentives for organs

  • Damage to living and deceased donation

    • The lessons of organ trafficking – harm to sellers

      • Chicken or Egg - Shortage leads to economic support for organ trafficking.

    • “Crowding out” – Richard Titmuss and his descendents

      • Authentic altruism will not be crowded out, but inauthentic altruism might be.

  • Corrosive to the virtue of altruism

    • Current system is damaging altruism – “Tyranny of the Gift”

    • Markets can (and should) coexist with donation

    • Markets clarify altruism – That which can be sold can also be donated.


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Objections to a regulated organ market incentives for organs

  • Exploitation of the poor

    • Excluding the poorest among us for other reasons

      • Poverty as a risk for CKD

    • Vending/Donating as a right of forebearance

    • Organ markets versus organ trafficking

  • Commercialization as offensive to human dignity

    • Little consensus as to what constitutes “human dignity”

    • Even less consensus on whether human dignity should represent a supervenient political concept (moral pluralism)

    • Few proponents draw out these consequences entirely

      • Well-remunerated athletes, entertainers, runway models

      • The whole of non-reconstructive cosmetic surgery

      • A wide array of commonplace market arrangements.



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Long term recipient outcomes incentives for organs

Graft survival rates in HLA-identical, one HLA-haplotype match and living unrelated renal transplant in Hahemi Nehad Hospital, Tehran from 1986 to 2000

Ghods, A. J. Nephrol. Dial. Transplant. 2002 17:222-228


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Trafficking – Recipient outcomes incentives for organs

“It remains likely, however, that with the severe organ shortage and ever-increasing waiting times

for an organ, a greater number of patients will present to Canadian transplant centers in this manner.”

Prasad GVR. Transplantation 82:1130


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Vendor outcomes incentives for organs

  • Mixed, anecdotal data….but very worrisome

  • Malakoutian, et.al.

    • 91% “satisfied with the exchange”

    • 53% “would recommend vending to others”

  • Zargooshi – a different story

    • 38% lost job from post-op complications

    • 39% “severe social ostracism”

    • 84% “difficulty securing employment”

    • 60% “fully expected to be dialysis-dependent”



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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.


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What if Kidneys, and Projected Growth in Prevalent Dialysis Patientsnothing happens?

  • Policy

    • More pressure to revise allocation policies

    • More efforts to revise “demand” downward

    • More pressure to push ethical boundaries with donors

  • Organ trafficking may evolve into equilibrium

    • Centers may improve on recipient outcomes out of pure self-interest, even if incentives to improve donor outcomes not robust.

  • Is this already happening?


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Iran? Kidneys, and Projected Growth in Prevalent Dialysis Patients

1967-1985 – 100-110 transplants

1988 – Legalization of market in organs from living vendors

1999 – Elimination of the waiting list for kidneys in Iran


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How it works Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • Recipient counseled that LRD the best option

  • If no LRD willing/available:

    • Waiting list for deceased donor organ

    • If not available, or > 6 months waiting -> Vendor

  • Separation of responsibilities

    • Vendor candidates identified by patient-run charity – initial screening done as well

    • Responsibility for evaluation and approval of vendor candidacy rests with transplant center


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How it works (2) Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • Vendors remunerated in two ways:

    • Fixed compensation from State = $1200 US

    • Negotiated compensation from recipient/family = $2300-$4600 US

    • If recipient impoverished, second payment negotiated and paid by patient-run charity

  • Vendors receive health coverage for 1 year, only for conditions related to organ procurement


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Vendor Demographics Kidneys, and Projected Growth in Prevalent Dialysis Patients

  • Caveat – Studies of vendors are paltry

  • Ghods, et.al. 500 vendors, random:

    • 90.2% male

    • 84% “poor,” 16% “middle class”

    • 6% “illiterate,” 24% “elementary education”

  • Zargooshi, et.al. 301 vendors:

    • 71% male; 27% unemployed; 18% “confined to home duties”; 35% illiterate; 25% elementary education


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Long-term vendor outcomes Kidneys, and Projected Growth in Prevalent Dialysis Patients

?