Nine‐yr experience of 700 hand‐assisted laparoscopic donor nephrectomies in Japan Clinical Transplantation Volume 26, Issue 5, pages 797-807, 26 MAR 2012

Nine yr experience of 700 hand assisted laparoscopic donor nephrectomies in Japan‐ ‐

Clinical TransplantationVolume 26, Issue 5, pages 797-807, 26 MAR 2012 DOI: 10.1111/j.1399-0012.2012.01617.xhttp://onlinelibrary.wiley.com/doi/10.1111/j.1399-0012.2012.01617.x/full#ctr1617-fig-0001

http://onlinelibrary.wiley.com/doi/10.1111/ctr.2012.26.issue-5/issuetoc

http://onlinelibrary.wiley.com/doi/10.1111/j.1399-0012.2012.01617.x/full%23ctr1617-fig-0001

Organ Transplantation

Lloyd E Ratner MD MPHDepartment of Surgery

Columbia UniversityNew York-Presbyterian Hospital

New York, NY

http://www.nyp.org/

Disclaimer:I am a transplant surgeon, not an ethicist

Topics• Brain death• Allocation• Transplant center interests versus patient interests

– Patient selection

• Living Donation– Risk acceptance/aversion– Misattributed paternity– Kidney paired donation

• Compatible pair participation• Organ equity• Donor safety oversight

– Living donor list exchange– Living organ donation in terminally ill patients– Donor/Recipient risk/benefit ratio

• Utilization of vulnerable populations as donors– Transplant commercialism– Transplant tourism– Prisoners as donors

• Living • Executed

– Children as donors• Deceased donor experimentation

Brain Death: History• 1954 Murray kidney transplant from an identical twin• 1962 Murray first successful cadaveric kidney transplant• 1963 Starzl first human liver transplant• 1963 Hardy first lung transplant• 1967 Barnard first heart transplant• Brain death donor was brought to the OR, ventilator was

stopped and everyone waited for the donors heart to stop, therefore these donors were not brain death at the time of organ retrieval

Brain Death: History cont.• 1959 Wertheimer et al. characterized the death of the nervous system• 1959 Mollaret and Goulon coined the term “coma depasse” (beyond coma) for and

irreversible state of coma and apnea• June 3,1963 Guy Alexandre introduced the first set of Brain Death Criteria based

on description of coma depasse and performed the first kidney transplantation from a heart beating brain death donor

• The recipient, who was maintained on PD, died of sepsis on post op day 87• 1968 Ad hoc Committee at HMS defined irreversible coma and transplantation

from brain death donors begins in the US• 1970’s only 20 stated had adopted the criteria• 1981 the presidents commission for the study of ethical problems in medicine and

biomedical and behavioral research published its guidelines adopting “whole brain” formulation

• All 50 states accepted these guidelines

Brain Death• Harvard Ad Hoc Committee 1968

– “ With its pioneering interest in organ transplantation, I believe the faculty of Harvard Medical School is better equipped to elucidate this area than any other single group” – Dean Robert Ebert

– 13 Members• Technological progress

– “Life” support (e.g. mechanical ventillation)– Diagnostics (e.g. EEG)– Cardiac arrest & cardiopulmonary bypass in cardiac surgery

• Transplantation’s need for organs– 1st heart transplant 1967– Kidney procurement from heart beating donors 1960s

• Public distrust of the medical profession– Fear of premature burial (ancient fear)

• Resource utilization of “comatose” patients• Benefit to the donor

“Any modification of the means of diagnosing death to facilitate transplantation will cause the

whole procedure to fall into disrepute…….”

Discussion regarding establishing brain death criteria 1966

Defining Brain Death:

4 Major Questions 1. Under what circumstances, if ever, shall extraordinary means of support be

terminated, with death to follow? (Answer: When the criteria of irreversible coma described above have been fulfilled.)

2. From the earliest times the moment of death has been recognized as the time the heartbeat ceased. Is there adequate evidence now that the "moment of death" should be advanced to coincide with irreversible coma while the heart continues to beat? (Answer: Yes.)

3. When, if ever, and under what circumstances is it right to use for transplantation the tissues and organs of a hopelessly unconscious patient? (Answer: When the criteria of irreversible coma described above have been fulfilled.)

4. Can society afford to discard the tissues and organs of the hopelessly unconscious patient when they could be used to restore the otherwise hopelessly ill but still salvageable individual? (Answer: No.)

Renewal: Finds Living Kidney Donors In the Orthodox

Jewish Community

Directed Donation• Donor or decedent’s family stipulate who the

organs will go to– Individual– Specific group of people

• Race, Religion, Ethnic group, Geographic location, etc

• Non-directed donation• Living donor giving purely altruistically without a

connection to any individual recipient

Organ Allocation

Structuring

• Analytic discussion that spells out a variety of conflicting ethical principles in order to isolate and ultimately clarify the pivotal concepts involved in the decision

Rationing

Goal: Maximize # of lives saved1 Produce the greatest benefit2 Give the most deserving3 Give to those who make the greatest

contribution to society4 Give to individuals who have the greatest

responsibility to others5 Assign by random choice6 (Select those willing to pay the most)

Distributive Justice

Goal: Maximize quality-adjusted life years saved1 Utility (length & quality of life produced)2 Neutral queuing (first-in-first-out)3 Principle of rescue

– Absolute – save life above all else– Modified – triage for expected length of survival

or quality related issues– Modified Utility Principle

Value-Based System

1 Urgency– Pro or Con– Saving the most lives vs Longest possible

functional period per organ

2 Loyalty to patient– Influences judgement

3 Fairness

Medical Considerations

• Age• Potential for recurrent disease• Retransplantation• Non-adherence• Immunologic compatibility• Waiting time

United States Organ Allocation

• National Organ Transplant Act– Sponsored by Al Gore

• Governed by OPTN – UNOS is the OPTN contractor

• Membership organization– Transplant centers

• Public members (e.g. patients, organ donors, etc.)

• Organ specific differences in allocation

• Sickest patients prioritized– Liver – Heart – Lung

• Post-transplant outcomes not included in allocation

• Kidney largely based on waiting time & longevity matching

United States Organ Allocation

Over time, waiting time has become the primary driver of kidney allocation Histocompatibility components have diminished over time

This overreliance led to a system that does not accomplish any goal other than transplanting the candidate waiting the longest Doesn’t recognize that not all can wait the same length of time Fails to acknowledge different needs for different candidates (e.g., speed

over quality)

Unbalanced System Components

Make the most of every donated kidney without diminishing access

Promote graft survival for those at highest risk of retransplant

Minimize loss of potential graft function through better longevity matching

Improve efficiency and utilization by providing better information about kidney offers

Proposed Policy Objectives

Provide comprehensive data to guide transplant decision making

Reduce differences in access for ethnic minorities and sensitized candidates

Proposed Policy Objectives

Kidney Donor Profile Index (KDPI)

KDPI Variables

•Donor age•Height•Weight•Ethnicity•History of Hypertension•History of Diabetes•Cause of Death•Serum Creatinine•HCV Status•DCD Status

KDPI values now displayed with all organ offers in DonorNet®

Sequence AKDPI <=20%

Sequence BKDPI >20% but <35%

Sequence CKDPI >=35% but

<=85%

Sequence DKDPI>85%

Highly Sensitized0-ABDRmm (top 20% EPTS)Prior living donorLocal pediatricsLocal top 20% EPTS0-ABDRmm (all)Local (all)Regional pediatricsRegional (top 20%)Regional (all)National pediatricsNational (top 20%)National (all)

Highly Sensitized0-ABDRmmPrior living donorLocal pediatricsLocal adultsRegional pediatricsRegional adultsNational pediatricsNational adults

Highly Sensitized0-ABDRmmPrior living donorLocal RegionalNational

Highly Sensitized0-ABDRmmLocal + Regional National *all categories in Sequence D are limited to adult candidates

Estimated Post-Transplant Survival Candidate age, time on dialysis, prior organ transplant, diabetes status

Top 20% of candidates by EPTS to receive kidneys matched on longevity

Applies only to kidneys with KDPI scores <=20% not allocated for multi-organ, very highly sensitized, or pediatric candidates

Proposed Classification: Longevity Matching




<=85%

Sequence DKDPI>85%





Propose

d

Longe

vity

matching

Candidates with CPRA >=98% face immense biological barriers

Current policy only prioritizes sensitized candidates at the local level.

Proposed policy would give following priority

To participate in Regional/National sharing, review & approval of unacceptable antigens will be required

Proposed Classifications: Very Highly Sensitized

CPRA=100% NationalCPRA=99% RegionalCPRA=98% Local




<=85%

Sequence DKDPI>85%





New

categories

for highly

sensitized

candidates

Prior living organ donors receive the same level of priority as current policy

Requirements remain the same for registering a prior living organ donor Policy proposal to allow priority with subsequent registrations to be

considered by Board in November 2012

Proposed policy will base qualification on date of procurement not date of transplant Would provide priority for prior donors whose organs were removed but not

transplanted

Unmodified Classification: Prior Living Organ Donor




<=85%

Sequence DKDPI>85%





Continued priority for prior living donors

Current policy prioritizes donors younger than 35 to candidates listed prior to 18th birthday

Proposed policy would Prioritize donors with KDPI scores <35% Eliminate pediatric categories for non 0-ABDR KPDI >85%

Provides comparable level of access while streamlining allocation system

Modified Classification: Pediatric




<=85%

Sequence DKDPI>85%



Highly Sensitized0-ABDRmmPrior living organ donorLocal RegionalNational


Continued

priority

pediatric

candidates

(now based

on KDPI)

KDPI >85% kidneys would be allocated to a combined local and regional list

Would promote broader sharing of kidneys at higher risk of discard

DSAs with longer waiting times are more likely to utilize these kidneys than DSAs with shorter waiting times

Modified Classification: Local + Regional for High KDPI Kidneys




<=85%

Sequence DKDPI>85%

Highly Sensitized0-ABDRmm (top 20% EPTS)Prior living organ donorLocal pediatricsLocal top 20% EPTS0-ABDRmm (all)Local (all)Regional pediatricsRegional (top 20%)Regional (all)National pediatricsNational (top 20%)National (all)

Highly Sensitized0-ABDRmmPrior living organ donorLocal pediatricsLocal adultsRegional pediatricsRegional adultsNational pediatricsNational adults

Highly Sensitized0-ABDRmmPrior living organ donorLocal RegionalNational


Proposed

Regional

Sharing

Organ Allocation – Other Countries

• Old for old (some European countries)• Israel: Prioritization given to those individuals

who are designated organ donors• Japan: Little acceptance of brain death,

therefore minimal deceased donation

Transplant Center Interests Versus Patient Interests

Transplant Center Interests Versus Patient Interests

• Patient selection– Transplant center performance metrics

• Patient safety– Use of hemostatic clips in living donor

nephrectomy• Cost savings• FDA contra-indication in US but not elsewhere• Continued use in other countries

Transplant Volume Declined in Centers With Low Performance

Schold JD et al: AJT 2013, 13(1):67-75

Living Donation

Living Donation• Risk acceptance/aversion• Misattributed paternity• Potential donor’s desire to back out• Kidney paired donation

– Compatible pair participation– Organ equity– Donor safety oversight

• Living donor list exchange• Living organ donation in terminally ill patients• Donor/Recipient risk/benefit ratio

Living Donation:Risk Acceptance/Aversion

• Who determines the degree of risk a donor should take?– Paternalism?– Opportunity to do good

• What risk?– Operative risk– Long term risk

• Absolute minimal risk versus risk assessment and stratification?• Risk based on what comparator group?• Should the relationship between donor & recipient influence risk

tolerance?– Coercion?

• Liver versus Kidney donation

LIVE DONOR MORTALITY RATES

Segev

Trotter/Ringe

Truthfulness?• Misattributed paternity

– Medical implications– Relationship dynamics– Legal implications

• Potential donor’s desire to back out– Coercion– Medical excuse

• Ability to donate at a later date

ABO CompatibilityRandom Pairs of Individuals

ABO Identical39%

ABO Compatible 25%

A to O 21%

B to O 4%AB to O 1.3%AB to A 1.1%

B to A 5%

A to B 3%AB to B 0.6%

Kidney Paired Donation

History of Kidney Paired Donation• 1986

– Rapaport first proposes KPD to overcome immunologic incompatibility with live kidney donors• 1991

– Establishment of KPD program at Yonsei Univ in S. Korea • 1995

– First Laparoscopic Donor Nephrectomy – Johns Hopkins Univ.• 1998

– Successful use of Plasmapheresis/IVIg to overcome immunologic incompatibility – Johns Hopkins Univ. – February– First international presentation of Korean PKE Program – ASTP - May

• 2000– First KPD in U.S. NEOB

• 2001– First KPD Johns Hopkins U – Legal Dept. requirement to anesthetize donors simultaneously

• 2003– Establishment of Dutch “Crossover Transplantation Program”

• 2004– Antibody Working Group 3rd Meeting – Focus on KPD to overcome immunologic incompatibility

• 2007– Rees removes logistical constraint of simultaneous operations with Nonsimultaneous, Extended, Altruistic-Donor

Chain– Utilization of compatible donor/recipient pairs to facilitate KPD for incompatible donor/recipient pairs

• 2008– National Kidney Registry established

• 2010 – UNOS Pilot Project commences

A Conventional Paired Exchange

Donor 1Blood Group A

Donor 2Blood Group B

Recipient 1Blood Group B

Recipient 2Blood Group A

X

X

An Unconventional Paired Exchange

Donor 1Blood Group 0



(DSA)

Recipient 2Blood Group B

X

X

Positive Crossmatch

ABO Incompatibility

A Nonsimultaneous, Extended, Altruistic-Donor ChainBrief Report:Michael A Rees, Jonathan E Kopke, Ronald P Pelletier, Dorry L Segev, et al. The New England Journal of Medicine. Boston: Mar 12, 2009. Vol. 360, Iss. 11; pg. 1096

Compatible Pair Participation

Compatible Pair Participation:

Background• Living Kidney Donor:

– a private resource for the recipient since first LD Tx in 1954

• “Good Samaritan” or “Undirected” Donors:– Used with increasing frequency– Public resource (center limited?)

• Kidney Paired Donation (KPD):– Incompatible donors are relinquished

• Compatible Pair Participation (CPP):– Compatible donors exchanged to enable more

incompatible patients to be transplanted


Donor 1Blood Group 0



Recipient 2Blood Group BX

Compatible

ABO Incompatibility


• Major paradigm shift: donor from private resource to public or shared resource

• Potential large impact on organ supply• Regional or national sharing networks not necessary

to achieve AUPKEs• Easily performed at any center• Ross et al – ethical concerns due to potentially

coercive nature– Transplantation. 2000 Apr 27;69(8):1539-43.

Altruistic Kidney ExchangeLive Donor Renal Transplants Columbia University

January 2005 – July 2006n = 163

DonorRecip

A B O AB

A 29 2 21 0

B 3 9 6 0

O 9 4 74 0

AB 2 2 2 0

THE POTENTIAL FOR 2005-2006DONOR A B O AB

RECIPIENT A X X 868

B X X 403 O X X X AB 78 55 43

Total # of Living Donor Transplants in the UNOS data base 2005-2006: 6,565Total # of Transplants that had the Potential to Participate in AUPKE: 1,447 (22%) Blood group O donors:

1314 (90.8%)


Areas of Ethical Concern• Coercion

Opportunity to Participate in AUPKE Would Place Unwanted Pressure

Strongly Disagree

Disagree

Neither Agree Nor Disagree

Agree

Strongly Agree

Nu

mb

er o

f P

atie

nts

Res

po

nd

ing

0

2

4

6

8

10

12

14

16

18

20

RecipientDonor

Coercion

• Recipient: opportunity to obtain an organ with likelihood of a superior outcome

• Donor: primary goal of altruism fulfilled by facilitating more transplants

Altruistic Unbalanced Paired Kidney Exchange:

Areas of Ethical Concern• Coercion• Donor equity or “trading up”


Areas of Ethical Concern• Coercion• Donor equity or “trading up”• Donor/recipient age matching


Areas of Ethical Concern• Coercion• Donor equity or “trading up”• Donor/recipient age matching• Disparity in donor/recipient attitudes

Disparity in Donor/Recipient Attitudes Towards CPP

Donor - Yes Donor - No

Recipient - Yes Yes/Yes Yes/No

Recipient – No No/Yes No/No

Donor & Recipient Attitudes Towards Decision Making Responsibility for Participation in AUPKE

Strongly Disagree

Disagree

Neither Agree Nor DisagreeAgree

Strongly Agree

Donor-Recipient Decision

Recipient-Recipient Decision

Donor-Donor Decision

Recipient-Donor Decision

Donor-Joint Decision

Recipient-Joint Decision

Potential Recipients' Willingness to Participate in an AUPKE

Likert Scale

0 1 2 3 4 5 6

# o

f R

ecip

ien

ts R

esp

on

din

g

0

5

10

15

20

25

30

35

No advantageBetter matchOther recipient a relativeDonor strongly supports AUPKE

Potential Donors' Willingness to Participate in AUPKE

Likert Scale

0 1 2 3 4 5 6

# o

f D

on

ors

Res

po

nd

ing

0

5

10

15

20

25

30

No advantageAdvantage to the recipientYounger donorBetter matchOther recipient someone I knewOther recipient a relativeOther recipient a childRecipient strongly supports AUPKE


Areas of Ethical Concern• Coercion• Donor equity or “trading up”• Donor/recipient age matching• Disparity in donor/recipient attitudes • Donor selection based on willingness to

participate in AUPKE


Areas of Ethical Concern• Coercion• Donor equity or “trading up”• Donor/recipient age matching• Disparity in donor/recipient attitudes • Donor selection based on willingness to

participate in AUPKE• Anonymity

Anonymity

• Dislike• Coercion• Poor outcomes

First Compatible Pairs Participation

Columbia University 8/30/07Recipient Donor Relationship

O AB

AAB

OA

Spouse

Acquaintance

Spouse

X

Compatible Pairs Participation:Complex Exchange

Recipient Donor Relationship

AB O

BO

ABB

Spouse

Daughter

Brother

X

X

Ethical ConsiderationsCUMC Ethics Committee &

University of Pisa Symposium:

Ethically Sound & Acceptable


• Definition of :– Compatible – Incompatible

• Immunologically incompatible • Blood type• Donor specific antibodies

– Quasi-compatible• Some advantage may be obtained in either survival (patient

or graft) or risk if participate in KPD• Age• Serology

Safety Oversight in KPD

• What responsibility does the recipient center have to the donor?

• What responsibility does the donor center have to the recipient?

• Each patient has their own physicians to assess and counsel regarding risk

• What if different centers have different risk tolerances?

• What if organ is lost or damaged in transport?

Living Donor List Exchange

• Deceased donor organ is used to initiate a KPD chain

• Opportunity to increase the number of transplants by utilizing more live donors

• Some patients advantaged while other disadvantaged– Blood group O patients without live donor are

disadvantaged– Blood group A patients will be advantaged

ABO CompatibilityRandom Pairs of Individuals

ABO Identical39%

ABO Compatible 25%

A to O 21%

B to O 4%AB to O 1.3%AB to A 1.1%

B to A 5%

A to B 3%AB to B 0.6%

Living Organ Donation In Terminally Ill Patients

• Question has come up in patients with ALS (Lou Gehrig’s Ds)

• More and better quality organs for transplantation if taken from living donor

• Able to give informed consent and express individual’s wishes

• Decision for withdrawal of life support and subsequent donation

Utilization Of Vulnerable Populations As Donors

• Transplant commercialism– Black market– Regulated system (Iran)

• Transplant tourism• Prisoners as donors

– Living – Executed

• Children as donors– Child conceived as donor for ill sibling– Court as guardian

Transplant Commercialism• US NOTA prohibits “valuable consideration” for organs• Regulated system of organ sales

– Government establishes non-negotiable price and pays donors– Proposal for US $100,000– Iran only country with this system

• Black market• How to prevent in US?• What is the role of the transplant center/physician?

– Suspicion– No investigative powers

Transplant Tourism Definition:Declaration of Istanbul

“Travel for transplantation is the movement of organs, donors, recipients or transplant professionals across jurisdictional borders for transplantation purposes.

Travel for transplantation becomes transplant tourism if it involves organ trafficking and/or transplant commercialism or if the resources (organs, professionals and transplant centers) devoted to providing transplants to patients from outside a country undermine the country's ability to provide transplant services for its own population.”

Transplant Tourism

• Stewardship of a scarce resource• Potential for exploitation of vulnerable

populations• Poor follow-up care• Transplant service may not be available in all

localities (countries)

Prisoners As Donors• Living prisoners

– Mississippi case– Free will and informed consent?– Quid pro quo?

• Executed prisoners– Ethics of capital punishment?– Main source of donated organs in China– Justice of the legal system– Consent– Donor donation part of repaying debt to society– Transplant tourism in China

Children As Donors• Ability to give informed consent• Coercive nature of parental relationship• 18 yo age of consent

– Mature 17 yo• Independent• Understands risks and consequences

• Child conceived as donor for ill sibling• Court serves as guardian for decision

Deceased Donor Experimentation

Deceased Donor Experimentation

• Necessary to move the field of transplantation forward– Organ supply

• Number of organs per donor• Quality of organs

• Multiple potential recipients with competing needs– When in relation to organ allocation– Consent?– Which organ takes priority?

• Who provides oversight?

ht

Summary & Conclusions• Finite resource (organs) brings transplantation to

the fore for ethical considerations• Everyday part of transplantation• Plethora of interesting and vexing ethical issues • Acceptance of various ethical issues in

transplantation have evolved and will continue to do so

• As demand increasing and technology advances we can expect new challenging issues

Documents

Nine‐yr experience of 700 hand‐assisted laparoscopic donor nephrectomies in Japan Clinical Transplantation Volume 26, Issue 5, pages 797-807, 26 MAR 2012