Innovations in kidney transplantation: End-chain kidney paired donation

At the Penn Transplant Institute (PTI), end-chain kidney paired donation (KPD) is an increasingly important part of living donor kidney transplantation. A type of kidney paired exchange, end-chain KPD begins with a single donor and connects through a chain that ends with a candidate on the kidney transplant list.

Living donor kidney transplantation has been performed at the PTI for almost 60 years, and today remains the optimal kidney replacement therapy for individuals with kidney failure. KPDs have historically allowed incompatible potential donors to consider donating on behalf of their intended recipient through simple 2-way or multi-chain exchanges.

More recently, the scope of KPDs has expanded through innovations such as advanced kidney donation and voucher donations. Non-directed donation (wherein the donor and recipient are unknown to one another) has also been a major driver for increasing living kidney donor transplantation through paired exchanges.

At the Penn Transplant Institute, growth in living kidney transplantation has been augmented by these innovations, and we have become the leading transplant center in paired kidney exchanges, performing over 100 paired kidney exchanges in 2024.

Kidney paired donation

The basics

First proposed in 1986, KPD was initially implemented in transplant center-specific kidney-paired exchange programs.

More recently, with computer algorithm-based registries and infrastructure for logistics and care coordination using the Alliance for Paired Donation and the National Kidney Registry, KPD has extended beyond site-specific pairing to include trans-continental paired exchanges (American Journal of Kidney Diseases, 2011). Now, over half of US transplant centers perform KPD transplants (American Journal of Transplantation, 2024).

Advantages of KPD include both recipient and donor benefits. For recipients, KPD provides increased access to living donor kidney transplants with reduced reliance on desensitization protocols for ABO incompatibility, shorter waiting times, and improved outcomes compared to deceased donor kidney transplants. In addition, KPD promotes a broader pool of potential candidates, thus increasing the likelihood of finding compatible matches for complex cases. For living donors, this process empowers donation by eliminating the need for direct donation and provides additional resources through KPD programs such as reimbursement for lost wages and prioritization for living donor transplantation.

The benefits of KPD also include overcoming immunologic incompatibilities (for example, blood type or HLA mismatch). In addition, biological mismatch of age or kidney volume can be more tailored to allow improved outcomes for recipients. Comparison of short- and longer-term outcomes of kidney paired exchange recipients showed no difference in graft failure or mortality at 5-year and 7-year marks in comparison with living donor kidney transplant recipients of other types of living donor kidney transplant (Clinical Journal of the American Society of Nephrology, 2020).

With the addition of non-directed donors and advanced kidney donation, downstream chains can conclude with an ‘end-chain kidney’.

The end-chain kidney is allocated to an individual who does not have a living donor who has entered the donor pool. The donor who initiates the chain may be a non-directed donor (a donor willing to give to anyone), an incompatible donor, or an advanced donor.

In advanced donation, there is a time incompatibility between donor and recipient, wherein donors donate in advance of their intended recipient’s need. Whatever the donor’s circumstances, the result of the end-chain kidney paired exchange is that an individual receives a living donor kidney transplant who would otherwise be waiting for a deceased donor kidney transplant. (See Figure 2).

The assignment of an end-chain kidney recipient is determined by the transplant center.

Different approaches to the assignment of end-chain kidneys have been considered, including adherence to the kidney allocation system, which identifies an eligible candidate at the top of the waiting list, maximizing the longevity of the living donor kidney transplant, or prioritizing high-risk candidates (American Journal of Transplantation, 2024).

Unlike deceased kidney donation, end-chain kidney transplants do not occur immediately after a match is identified, so there is time to ensure appropriate recipient selection and recipient readiness. Thus, recipient readiness is a key factor in receipt of endchain kidney transplantation.

End-chain kidney donation at Penn Medicine

There is a substantial benefit to end-chain kidney transplant allocation, as it allows increased access to living kidney donation.

From July 2023 to July 2024, for example, the PTI received 64 end-chain kidneys. This represented approximately 45% of the living donor kidney transplant volume in this time frame. Within the end-chain kidney donor population at Penn, the mean recipient age was 55, and individuals were predominantly male (66%) and black (62.5%). Additional benefits of end-chain kidney donation include timely allocation of kidneys donated from non-directed donors. This may increase interest among potential living donors because of more control and certainty over timing of a surgery.

At Penn Medicine, we have found that numerous patients who are ready for transplantation can receive an end-chain living donor kidney and experience excellent outcomes with substantially shortened waiting list times.

Conclusions and key takeaways

End-chain paired kidney donation at Penn Transplant Institute has substantially increased living donor kidney transplant volume. Innovations in kidney transplantation, such as kidney-paired exchange programs, have the potential to increase access to living kidney donation across the nation. The success of KPD programs highlights the importance of collaboration and innovation in transplantation across healthcare centers.

Referring to the Penn Transplant Institute kidney transplant program

To refer a patient to the PTI Kidney Transplant Program, please call 800-789-7366.

Kidney transplant surgeons

• Peter L. Abt, MD
• Samir Abu-Gazala, MD - Surgical Director, Living Donor Kidney Transplant
• Kyle Jackson, MD, PhD
• Matthew H. Levine, MD, PhD
• James F. Markmann, MD, PhD - Vice-President, Transplant Services
• Ronald Parsons, MD - Surgical Director of Kidney and Pancreas Transplant
• Elizabeth Sonnenberg, MD

Kidney transplant nephrologists

• Melissa B. Bleicher, MD
• Roy D. Bloom, MD - Medical Director of Kidney and Pancreas Transplantation
• Gaia Coppock, MD*
• Simin Goral, MD
• Meera Harhay, MD
• Sabiha Hussain, MD
• Mary Ann Lim, MD
• Amanda Leonberg-Yoo, MD* - Medical Director, Living Donor Kidney Program
• Vishnu Potluri, MD
• Ghazal Quinn, MD*
• Karthik Rangana, MBA, MD
• Nay Seif, MD
• Salma Shaikhouni, MD
• Srijan Tandukar, MD

*Living Donor nephrologists