Live Donor Kidney Transplantation

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Transcript Live Donor Kidney Transplantation

Live Donor Kidney Transplantation: Updates in Paired Kidney Exchange

Miguel Tan, MD, FRCSC Surgical Director, Kidney & Pancreas Transplantation Piedmont Transplant Institute

Outline 1.



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)

Advantages cases 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 130 centers North Central Donor Exchange Cooperative Washington Regional Transplant Community Johns Hopkins Paired Exchange Program North American Paired Donation Network

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 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 – 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

Adv Eliminates complex logistics of shipping organs Minimizes cold ischemia time Reduced billing/financial complexities related to shipping organs Disadv Travel is costly for donor Generally not covered by recipient insurance (although GTF covers up to $500) Donor in unfamiliar hospital/environment Away from support network Follow up care can be challenging

Kidney Shipped

Adv Less costly for donor Donor stays in familiar environment and support Disadv Potential for extended coldtime especially when traversing time zones Potential for missed flights/delays/ lost organs 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


 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


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