Live Donor Kidney Transplantation:
Updates in Paired Kidney Exchange
Miguel Tan, MD, FRCSC
Surgical Director, Kidney & Pancreas Transplantation
Piedmont Transplant Institute
Outline
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Current statistics for kidney transplantation in the United States
Living donor outcomes
Paired exchange, impact, logistics and challenges
Patients on the waiting list on December 31
of the year (active listings only)
Organ supply continues to be a
problem in kidney transplantation
Almost 100 000 patients on waiting list
Average waiting time to transplant 4- 5
years
4% of potential recipients die while
waiting on list annually
Transplants performed during the year (adult & pediatric
combined)
Deceased kidney donation rates
Organ discard rate for organs recovered for
transplantation
Possible reasons for lack of growth of supply include
-lack of education on donation options ie. living donation, paired exchange, desensitization
-Increasing rate of morbid obesity and diabetes resulting poorer quality of organs
Advantages of Live Donor Kidney Transplant
To address the issue of long wait times and organ shortage there has been an effort to increase
living donation
Advantages:
If recipient has living donor there is no wait time
Quality of organs and long term outcome are superior
Allows opportunity for desensitization in highly sensitized recipients
eg. plasmapheresis, biologic agents( bortezomib, rituximab)
Advantages of Live Donor Kidney Transplant
Death-censored graft failure within 90 days among adult kidney transplant recipients
Delayed graft function among adult kidney transplant recipients
Incidence of first acute rejection among adult patients receiving a kidney transplant in
2005–2009
Long Term Deceased Donor Transplant Outcomes
Long Term Living Donor Transplant Outcomes
Half-lives for adult kidney transplant recipients
Paired Exchange
It is clear that living kidney donation is superior to deceased donor transplant from an outcomes standpoint
A third of intended donor recipient pairs are incompatible
Paired exchange allows transplants to occur for ABO incompatible and highly sensitized patients by ‘swapping’
for an ABO compatible donor or a donor that the recipient is not as highly sensitized
Paired exchange transplants are fastest growing source of transplantable kidneys over the last decade
Paired Exchange
Example of simple 2 way paired exchange.
Logistically complex if more than 2 pairs as all cases need to happen simultaneously
Resource intensive
–need multiple OR
-multiple surgeons and OR staff
-coordinating OR between multiple
hospitals in different geographic
regions difficult
Domino chain transplantation
Requires an altruistic or non-directed donor (NDD)
Advantagescases need to occur in sequence but not necessarily
at same time
- easier to manage from a resource standpoint
- chains can last indefinitely with use of a bridge
donor
Longest chain on record is 30 transplants - 17
hospitals across 11 states over 4 months (NKR chain
124)
Open Chain or Non-simultaneous extended altruistic donor (NEAD) chain
History of Paired Exchange
Felix Rapaport first advocated for a “living emotionally related international kidney-donor
exchange registry “ in 1986
First donor exchange program was initiated in Korea in 1991
–
–
Single center
129 transplants in 11 years
Netherlands paired exchange program first to use computer algorithms in 2004
- 7 centers
- 128 transplants in 5 years
US, Canada, United Kingdom, Netherlands and Korea have multi center paired exchange registries
In the United States there are 7 active multicenter paired exchange registries plus many single
center programs
US Paired Exchange Programs
Alliance for Paired Donation
(APD)
74 centers (30 states)
National Kidney Registry (NKR) 50 centers (20 states)
UNOS Kidney Pilot Program
North Central Donor Exchange
Cooperative
Washington Regional
Transplant Community
Johns Hopkins Paired
Exchange Program
North American Paired
Donation Network
130 centers
Exchange programs in the US are fragmented
Ideally, a national program with a single pool would allow maximum exposure of patients to
potential donors
Kidney Paired Donation Pilot Program (UNOS-KPD) was started by UNOS in 2010 in order to unify
and standardize the process of paired kidney donation
How does the paired exchange process work?
Optimization
Optimization is a branch of applied mathematics
“In the simplest case, an optimization problem consists of maximizing or minimizing a real
function by systematically choosing input values from within an allowed set and computing the
value of the function. “
Optimization algorithms are used for airline scheduling, medical school and residency matching,
online dating services, artificial intelligence research…
Alvin Roth (Nobel Memorial Prize in Economic Science 2012)
developed the algorithms that are used by a number of paired
exchange registries including Alliance for Paired Donation
Photo: U. Montan
In the context of KPD, the main problem is how to optimize for maximum number of transplants
or how to transplant the most highly sensitized patients, or some combination of both
Optimization Example
Schematic of incompatible pairs and reciprocal
compatibility shows 2-way paired donation possibilities.
Each numbered circle represents a transplant
candidate/incompatible donor pair. A connecting line is
shown if the donor from each pair can donate to the
candidate of the other pair.
Optimal matching. The bold lines denote optimal matching of
incompatible pairs for 2-way paired donations; for example, pair 1
matches with pair 15. Using an appropriate mathematical
algorithm guarantees that the largest number of transplants or
best set of transplants using some other criterion will be chosen.
For instance, if incompatible pair 1 and incompatible pair 3 were
matched for paired donation, neither pair 14 nor pair 15 could
undergo transplant
Paired exchange logistics
After match run is completed, participating centers review medical histories or donor and
recipient as well as crossmatch data
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Age matching
CMV status
Willingness of donor to travel
Size match
OR times, surgeons, resources need to be coordinated amongst centers
- can be very tricky in simultaneous paired exchange with multiple pairs
Currently, payment and financial issues need to be coordinated between centers on a case by
case basis
For donor convenience and comfort, many donors stay at local center and kidney is shipped
Segev et al (AJT 2011) demonstrated that cold ischemia time less than 14 hours does not
adversely affect rate of delayed graft function (3.5% vs 3.6% for nonshipped kidneys)
Donor travels
Kidney Shipped
Adv
Disadv
Adv
Disadv
Eliminates complex logistics
of shipping organs
Travel is costly for donor
Generally not covered by
recipient insurance (although
GTF covers up to $500)
Less costly for donor
Potential for extended
coldtime especially when
traversing time zones
Minimizes cold ischemia time
Donor in unfamiliar
hospital/environment
Away from support network
Donor stays in familiar
environment and support
Potential for missed
flights/delays/ lost organs
Reduced billing/financial
complexities related to
shipping organs
Follow up care can be
challenging
Cost $$$
Surgery often needs to be
done off hours
Kidneys removed by
unfamiliar donor teams
creates anxiety especially if
technically complex
At the end of the day, we need to do what is best for the donor.
Potential impact of Paired Exchange
Each year up to 3500 potential living donors cannot donate to intended recipient due to
incompatibility
Hopkins study using mathematical simulation based on probability data and the UNOS database
(Segev DL et al JAMA 2005, 293: 1883) to predict impact of KPD
In an efficiency national program 4000 pairs but be enrolled with 750 added per year
Rees et al AJT 2012 suggest that an well implemented standardized KPD program could yield an
additional 1000 live donor transplants at a cost savings of 250-500 million to the healthcare
system
Various models predict 2-10% increase in overall kidney transplant volumes
Domino chain donation is particularly interesting (Segev et al AJT 2009;9:1330)
Using monte carlo simulations* comparing altruistic donors donating directly to waitlist vs
donating to a domino paired exchange yields 20% more transplants. Open ended chains even
more efficient and leads to more sensitized patients receiving transplant.(Ashlagi et al . AJT, 2011(11,)5:
984
*Monte Carlo methods are a broad class of computational algorithms that rely on
repeated random sampling to obtain numerical results; i.e., by running simulations
many times over in order to calculate those same probabilities heuristically just like
actually playing and recording your results in a real casino situation: hence the
name.
JAMA 2005
Current Challenges in KPD
from The 2012 KPD consensus conference
Donor Evaluation and Care
How Do we ensure health and safety of the living kidney donor?
All potential NDDs should be informed about KPD as an option prior to initiating evaluation
The medical and psychosocial evaluation of an NDD should be guided by the “Evaluation of the Living Kidney Donor—a Consensus
Document from the AST/ASTS/NATCO/UNOS Joint Societies Work Group” recommendations
NDDs should undergo preliminary (i.e. screening) assessment by a mental health professional before the medical evaluation is
initiated
The National Living Donor's Assistance Center should be used provide travel and lodging expenses to the NDDs
In addition to the standard informed consent donor nephrectomy, KPD donor informed consent should include these additional
elements: risks and benefits of non-KPD donation options, kidney transport, possible kidney redirection due to unforeseen
circumstances, and the inability to provide information about the actual recipient
Donor privacy should be strictly protected. Specific consent should be obtained from the donor if their name is released to the
press
The donor center evaluation processes and procedures at which the donor nephrectomy takes place should be followed
All evaluative studies should be completed before registering a donor in KPD and repeated after 12 months. Anatomical
imaging, however, does not need to be routinely repeated
Histocompability recommendations for KPD
How do we account for lab-to-lab variation and KPD acceptance criteria between centers ?
HLA typing should be done using molecular methods
Ab analysis should be done by using at least 2 methods and specificity confirmed using HLA
single antigen assay. Both assays should be reported to allow other centers to compare data
with center specific ranges of positive reactivity.
2 levels of Ab “unacceptibility” should be defined.
- absolute contra-indication with high prob of +x-match
- relative contra-indication that may yield +x-match
HLA lab directors/staff need to be involved in clinical decision making on a full time basis
KPD registry members need to communicate effectively
Labs should strive to achieve 95% accuracy in KPD x-match predictions
Geographic Barriers
Increasing size of KPD pools results in pairs that are geographically distant
How do we balance achieving higher transplant rates with these larger pools while limiting complexity and
costs of geographic expansion?
Recommended policies to overcoming geographic barriers to KPD
Donors should have the option to travel to the recipient center and to choose to where they
are willing to travel. Donors should never be required to travel (unless extenuating
circumstance)
KPD centers should be willing to transport kidneys, both to and from the center
A standard format for sharing patient information and medical records should be defined
Payers should cover donor travel and lodging costs when a donor travels for KPD.
OPO support/guidance should be used for packaging, labeling and transportation
Direct surgeon-to-surgeon communication is recommended prior to and immediately after KPD
donor nephrectomy
All kidney transport should follow chain-of-custody principles
- detailed documentation of kidney location and parties responsible until delivery
When traveling by commercial plane, all flights should be designated “lifeguard status” .Kidneys
on long distance routes should be accompanied by a tracking device. Kidneys on routes
involving any layovers should be accompanied by a courier
-”lifeguard” -request to waive standard lockout for tendering and expedited
loading/unloading and priority takeoff and landing
Financial Challenges
KPD incurs unique financial costs that are challenging to recover under current reimbursement
practices
Evaluation of potential KPD donors
Evaluation of NDDs
HLA testing
KPD administration
Donor travel or kidney transport
Facility/professional fees for donor nephrectomy (big issue dealing with out of network payers)
Donor complications/follow up
Financial Challenges
Currently these issues are negotiated on a center-to-center and case by case basis which is
problematic as there is too much variability.
Standardizing payments is desirable as it would allow simpler administration by eliminating
individual negotiations, guarantees payment for all involved parties, provides predictability from
payer standpoint and allows them to predictably underwrite their transplant risk portfolio
The current solution is to develop a national KPD Standard Acquisition Charge (SAC)
Alliance for Paired Donation has received a grant from AHRQ to develop this model
Financial Challenges
In order to be viable the following criteria need to be addressed
Donor expenses must be paid by recipient center r
Must be predictable, minimizing center-to-center variability in donor costs
Must be portable, minimize barriers to professional reimbursement for donor nephrectomy
posed by recipient payer contracts
Full recovery of costs of donor eval, surgery, follow up, and complications treatment incurred
by donor center
Compliance with CMS rules
Financial Challenges
Proposed National KPD-SAC would:
Aggregate all costs associated with donor evaluation and be paid out by a single administrative
center
Geographic difference in cost accounted for by multiplying a predetermined CMS approved rate
by a factor accounting for cost-of-care differences among hospitals and regions.
Aggregated national costs would then be used to derived a KPD SAC charged to recipient centers
at the time of transplant. Recalculated annually
KPD Implementation Strategies
Implementing KPD protocols can be difficult and problems amplified in multicenter exchanges
How do we establish and operate a successful KPD program?
Each center should identify a KPD champion to lead a KPD team that includes an HLA expert
and dedicated coordinators
Programs should be encouraged to enter NDDs into KPD registries to benefit the most number
of patients
Strategies should be identified to reduce preventable late stage match failures that disrupt
large exchanges
- donor w/u should be complete prior to listing
- updated annual work up and reported in a standardized format that other centers can use
- user friendly database interfaces with automated histocompatibility data transfer
Prompt responses to match offers should be a priority
Effective communication with other centers
- ALL donor evaluation records need to be sent to recipient center
- prior to planned transplant a “logistics” call should be made to confirm dates, OR times,
details of transport
- donor surgeon should communicate with recipient surgeon 24 hrs prior to case and
immediately after nephectomy
- coordinators should communicate within 24hrs after transplant to exchange donor/recipient
status updates
- any potential transmissible disease in donor within 2 years post donation should be
reported to recipient center, registry and UNOS
Summary
 Living kidney donation is an important modality to address the stagnant rate
of kidney transplantation
 Paired exchange allows transplantation of otherwise incompatible or hard to
match pairs and an increasingly important source of transplantable kidneys
and has the potential to increase overall kidney transplant volumes
 A unified national program will maximize exposure to pairs registered in KPD
this is in the initial stages with the UNOS pilot program
 There is economic value to paired exchange with some estimates suggesting a
benefit to the overall healthcare system of 250-500 million annually
References
1. Serur, D and Charlton, M. Kidney Paired Donation 2011. Progress in Transplant 21(3) :215
2. Gentry, S Montgomery RA, Segev DL. Kidney Paired Donation: Fundamentals, Limitations, and Expansions.
AJKD 2011;57(1): 144
3. Gentry SE, Montgomery RA, Swihart BJ, Segev DL. The Roles of Dominos and Nonsimultaneous Chains in
Kidney Paired Donation. AJT 2009;9:1330
4. Rees MA et al. Call to Develop a Standard Acquisition Charge Model for Kidney Paired Donation. AJT 2012;
12: 1392
5.Melcher ML et al. Dynamic Challenges Inhibiting Optimal Adoption of Kidney Paired Donation: Findings of a
Consensus Conference. AJT 2013;13:851
6. Segev DL, Gentry SE, Warren DS, Reeb B, Montgomery RA. Kidney Paired Donation and Optimizing the Use of
Live Donor Organs . JAMA 2005, 293(15):1883