Beatrice Concepcion @KidneyBea_n

Beatrice P. Concepcion  is a transplant nephrologist and newly appointed Associate Professor at the University of Chicago in the Department of Medicine, Section of Nephrology. She also serves as the Medical Director of the kidney transplant program. Her research interests include increasing access to kidney and pancreas transplantation and improving clinical and patient-centered outcomes of kidney transplant recipients.

Competitors for the Kidney Transplantation Region

Journey to the Wait List vs Organ Pool

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Kidney transplantation is the treatment of choice for patients with advanced kidney disease, providing superior survival and quality of life than remaining on the waiting list while offering cost savings to the healthcare system compared to chronic dialysis. Importantly, even “higher risk” candidates do better with a transplant than remaining on the waiting list. “Higher risk” candidates include those who are older, frail, obese, or those who have medical conditions such as amyloidosis or sickle cell disease.

Clearly, the major limitation to offering the treatment of choice to MOST patients in need is the limited supply of donor kidneys available for transplant. Not everyone who can potentially benefit from a transplant will receive one, or even be deemed a candidate. Candidates undergo a long and arduous pretransplant and evaluation process (Team Journey to the Waitlist) to determine if they will do well post-transplant. A significant number of patients will not make it because they are deemed “too high risk”. Some will make it to the waiting list but not to a transplant because the list is very long leading to prolonged waiting times. The median time to transplant from candidates has not been calculable for more than a decade.

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Expansion of the organ pool will not only shorten waiting time (and improve outcomes) for those on the waiting list, but also expand opportunities for patients who otherwise would not be offered transplant as an option. The Organ Pool scouting report provides an excellent summary on the topic. Below I provide additional commentary on a few important issues and initiatives:

• Removing disincentives and ensuring protection of living donors. Living donation rates in the United States have remained steady over the two years at approximately 6,000 transplants/year, after peaking in 2019 then dropping in 2020 (which was associated with the onset of the COVID-19 pandemic). A notable change in trends includes a rise in older donors (age >55 years), attributed to better understanding of long-term risks and individualized assessments of candidates. One of the best ways to increase the organ pool is to further expand living donation. In order to do so, we need to remove barriers to donation and ensure the protection of living donors. Currently, there is wide variability in existing state laws that protect living donors. There is an urgent need for the passage of the Living Donor Protection Act, introduced into both houses of Congress, and we as a kidney community need to continue advocating for it.

• Addressing the exceedingly high discard rate of deceased donor kidneys. In 2022, one in four kidneys (25%) procured for transplant was discarded. The reasons for this are numerous and complex and include inefficiencies in organ allocation leading to prolonged cold ischemia times, and risk aversion by transplant centers in taking “higher risk” kidneys.  Reducing discards is clearly a priority. I offer some of my thoughts on the issue here along with some thoughts on what we can do to mitigate the problem. There is a need to develop better tools that can help in organ offer decision-making.  The predictive analytics tool (now available through the OPTN) can hopefully help us better weigh risks and benefits when an organ offer for a waitlisted candidate becomes available in real time. We also need better tools to assess the quality of organs, with less reliance on procurement biopsy findings which lead to organ discards despite being shown to have no association with delayed graft function (DGF), primary non-function or death-censored graft survival. One potential assessment tool that needs to be investigated further is hypothermic machine perfusion, commonly called “pumping”. Although already utilized by many transplant centers, there remains a gap in knowledge as to which machine parameters are appropriate in assessing the viability of a kidney.

• Utilizing kidneys from donors with viral infections. These include kidneys from donors infected with hepatitis C, HIV, COVID, and Hepatitis B. Utilization of these kidneys provides additional transplant options for those in need.
  • • The Hepatitis C story is particularly worth telling again. In 2018, the THINKER and EXPANDER-1 pilot studies reported two single-center experiences of transplanting a total of 20 Hepatitis C-infected kidneys (HCV D+) into 20 uninfected recipients (HCV D-). Over the last 5 years, the practice of HCV D+/R- kidney transplantation has steadily increased and is now commonplace. In 2022, the discard rate of Hepatitis C kidneys equaled that of non-Hepatitis C kidneys. Reported 5-year graft outcomes from Hepatitis C-infected donors are excellent.
    • The HOPE trial reported outcomes on kidneys from HIV+ donors transplanted into HIV+ recipients with encouraging early results.
    • Kidneys from COVID-infected donors are also being utilized with success.
    • The utilization of kidneys from Hepatitis B viremic donors is in early stages and I foresee that there will soon be increased uptake in transplanting these kidneys.

• Emerging technologies may improve organ preservation. One of the biggest reasons for organ discard of “marginal kidneys”, such as kidneys from older donation after cardiac death (DCD) donors, is the fear of prolonged DGF and subsequent poor short-term outcomes. An organ preservation technique that could increase the quality and availability of kidneys from DCD donors is normothermic regional perfusion (NRP). NRP provides in situ perfusion of organs with oxygenated blood. Early experience, the largest study coming from Spain, has shown that NRP improves short-term outcomes including reduced rates of DGF and 1 year graft loss compared to standard recovery techniques. Barriers to widespread implementation of NRP include cost, logistical issues, and ethical concerns (which mainly surround thoraco-abdominal NRP). Nevertheless, this is a growing field and one that we will likely hear more about in the future.

• Progressing towards successful xenotransplantation. Xenotransplantation in my opinion represents the holy grail in the field. With the advancement in gene editing techniques, tremendous progress has been made leading to testing the safety and feasibility of transplanting porcine kidneys into a human brain-dead decedent for 3 days. As the field of xenotransplantation advances, many issues will need to be sorted out including which patient population should be included in live human trials. Let’s all stay tuned.

In conclusion, I believe ORGAN POOL is our Nephmadness 2023 winner. Let’s solve the organ shortage to provide patients with the best treatment option for advanced kidney disease!

– Guest Post written by Beatrice Concepcion @KidneyBea_n

As with all content on the AJKD Blog, the opinions expressed are those of the author of each post, and are not necessarily shared or endorsed by the AJKD Blog, AJKD, the National Kidney Foundation, Elsevier, or any other entity unless explicitly stated.

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