nine‐yr experience of 700 hand‐assisted laparoscopic donor nephrectomies in japan clinical...
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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
Organ Transplantation
Lloyd E Ratner MD MPHDepartment of Surgery
Columbia UniversityNew York-Presbyterian Hospital
New York, NY
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.)
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
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
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
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
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
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
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
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
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 organ donorLocal RegionalNational
Highly Sensitized0-ABDRmmLocal + Regional National *all categories in Sequence D are limited to adult candidates
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
Sequence AKDPI <=20%
Sequence BKDPI >20% but <35%
Sequence CKDPI >=35% but
<=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
Highly Sensitized0-ABDRmmLocal + Regional National *all categories in Sequence D are limited to adult candidates
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
• 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
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
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%
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
Donor 2Blood Group A
Recipient 1Blood Group A
(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:
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
Compatible Pair Participation
Donor 1Blood Group 0
Donor 2Blood Group A
Recipient 1Blood Group A
Recipient 2Blood Group BX
Compatible
ABO Incompatibility
Compatible Pair Participation
• 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%)
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”
Compatible Pair Participation:
Areas of Ethical Concern• Coercion• Donor equity or “trading up”• Donor/recipient age matching
Compatible Pair Participation:
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
Compatible Pair Participation:
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
Compatible Pair Participation:
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
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
Compatible Pair Participation
• 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
• 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?
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