Kidney transplantation: How we can do better for patients in need
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It has been almost 70 years since the first successful living donor kidney transplant between identical twin brothers was performed at the Peter Bent Brigham Hospital in Boston.
Since then, tremendous advances have been made in the specialty, particularly in overcoming immunologic barriers to transplantation, including modern-day immunosuppression.
Short-term outcomes significantly improved in the 1980s through the 1990s and have largely remained unchanged today, with acute rejection rates at less than 10% and graft survival at greater than 95% in the first posttransplant year.
Longer-term outcomes have also gradually improved in the years, although not as dramatically, with 5-year graft survival rates in the United States at 72% and 85% for deceased and living donor transplants, respectively.
In a letter recently published in KI Reports, Daan Kremer, MD, and colleagues report on a recipient who has had a functioning deceased donor kidney for 50 years. This is a remarkable achievement and an outcome beyond what is currently expected.
Nonetheless, it is certainly one that we would hope to achieve for all patients. Unfortunately, cumulative effects of current day immunosuppression, immunologic insults to the allograft, cardiovascular disease, infectious complications and posttransplant malignancy continue to limit both graft and patient survival in 2023.
Treatment of choice
Despite these challenges, kidney transplantation remains the treatment of choice for most patients with advanced kidney disease, conferring not only a longer lifespan and a better quality of life compared to chronic dialysis, but also offering cost savings to the health care system.
The reality, however, is that despite the advances made in kidney transplantation and its benefits for patients, most patients with advanced kidney disease will never receive a transplant. In the United States, more than 90,000 patients are waiting for a kidney transplant and there are tens or hundreds of thousands more, depending on which population you select, who could potentially benefit from a transplant but are never referred or listed. Among those waitlisted, approximately 10% are removed from the list or die while waiting on the list each year.
Equity for transplants
In February 2022, the National Academy of Sciences, Engineering, and Medicine (NASEM) issued a report entitled “Realizing the promise of equity in the organ transplantation system,” and called for the need to increase the number of donated organs used for transplant and to improve equity within the organ donation and transplantation system. The NASEM report included recommendations to develop national performance goals, modernize the information technology infrastructure for organ procurement, allocation and distribution, and increase transparency and accountability for organ offer declines, among others.
Deceased donor kidney procurement, allocation and transplantation involves a complex interplay among organ procurement organizations (OPOs), the Organ Procurement and Transplantation Network (OPTN) and transplant centers. All three entities must be accountable in improving performance and partnership to increase the supply of deceased donor kidney transplants and meet the needs of patients with advanced kidney disease.
Efficiencies
The current Kidney Allocation System 250 circle-based allocation system was implemented in March 2021 to reduce geographic disparities in access to kidney transplantation. Unfortunately, alongside broader sharing comes greater complexity in the allocation process and longer distances that kidneys must travel. This leads to longer cold ischemic times and ultimately, organ discards.
The kidney discard rate in 2022 was an astonishing 25%, an increase from 21% prior to the allocation policy change. A new system of organ allocation, continuous distribution, is set to take effect in 2024 and will replace the current system. Currently, it is difficult to predict what effect it will have on the efficiency of organ allocation.
Regardless, utilization by transplant centers of organ offer filters will facilitate placement of kidneys. Improvements to the mechanism and logistics by which organs are transported is another achievable aim which can reduce travel delays. Finally, improved communication and partnership between transplant centers and OPOs is key to avoiding unnecessary delays in the allocation process.
Acceptance practices
There is great variability in organ acceptance practices among transplant centers, resulting in a wide range of transplant rates across the country and even among transplant centers located close to each other in the same donor service area. In addition, even within a transplant center there is variability in provider acceptance practices. There is risk aversion for kidneys that are deemed marginal, such as those from donors who have a Kidney Donor Profile Index greater than 85%, are a donor after cardiac death, or have AKI.
Many kidneys are turned down due to procurement biopsy findings, even if data show these findings do not correlate with outcomes. Several factors lead to risk aversion in organ acceptance practices including fear of poor outcomes due to regulatory pressure, lack of expertise or infrastructure in caring for recipients with a complicated postoperative course, and suboptimal expertise in utilizing marginal kidneys.
OPO performance
OPOs have been subject to recent scrutiny due to significant variability in performance and lack of appropriate metrics to track performance. In 2020, CMS issued a final rule that changed the conditions for coverage that OPOs must meet to receive payment. Changes were instituted to key metrics and performance benchmarks were introduced. A study by Karp and colleagues published in JAMA Surgery earlier this year compared two OPOs and noted that ratios of actual donors to potential donors varied widely, raising concern regarding vast differences in OPO performance across the country and the large number of potential donors that are being missed.
The new metrics instituted by the federal government, along with data collection and sharing, will hopefully increase OPO transparency and accountability, and ultimately improve OPO performance.
Living kidney donation
Although much attention has been given to increasing the deceased donor organ pool, one cannot stress enough the importance of expanding living kidney donation. Living donor transplants in the United States have remained relatively stable during the last 2 years after peaking in 2019 at 6,867 donors. In the last several years, an individualized approach to assessing risks for living kidney donors has led to an increase in living donors older than 55 years.
Support from the National Living Donor Assistance Center allows eligible living donors to recoup travel expenses, lost wages and dependent care expenses. Continued work and advocacy to remove disincentives and barriers to living donation is of utmost importance, including passage of the Living Donor Protection Act at both the state and federal levels.
Future
Technology, such as normothermic regional perfusion, already utilized by some centers to improve organ preservation, holds promise in improving outcomes of marginal kidneys, particularly those from donors after cardiac death. If this technology proves to be beneficial and becomes widely available, the number of viable kidneys for transplantation can increase significantly and potentially alleviate the organ shortage.
Looking at the longer term, xenotransplantation utilizing porcine kidneys holds the promise of solving the organ shortage altogether and completely changing the transplantation landscape.
Although kidney transplantation provides the best outcomes for most patients with advanced kidney disease, only a minority of those in need will make it to a transplant and reap its benefits. Solving the organ shortage is of critical importance to provide patients with the best outcomes possible.
- References:
- Hariharan S, et al. N Engl J Med. 2021;doi:10.1056/NEJMra2014530.
- Johnson W, et al. JAMA Surg 2023;doi:10.1001/jamasurg.2022.7853.
- Kremer D, et al. KI Reports. 2023;doi:10.1016/j.ekir.2023.03.006.
- Lentine KL, et al. Am J Transplant. 2022; Suppl 2:21-136.
- www.healio.com/news/nephrology/20230113/new-record-set-for-annual-organ-transplants-in-us.
- For more information:
- Beatrice Concepcion, MD, is medical director of the kidney transplant program at the University of Chicago, She is also an Associate Editor on the Editorial Advisory Board for Healio Nephrology. She can be reached at beatrice.concepcion@bsd.uchicago.edu.
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