Xenotransplantation can bring hope to patients waiting for a kidney
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To stay alive, Americans with kidney failure have made the common choice to be tethered to a machine three times a week in an outpatient dialysis clinic for several hours at a time.
More than 80% of patients choose this method; the dialysis machine clears the body of toxins but not as efficiently or effectively as an actual organ, a kidney.
In the intervening hours that patients are not tethered to a machine, they endure the repeated insults of toxins slowly building up in their bodies. Fluid overload exacts injury to their hearts, minds and physical capacities – it is as though the body is a coastline slowly eroding as waves batter the shore.
The statistics are staggering; 47% of patients newly diagnosed with end-stage kidney disease are alive 5 years later. For perspective, a 40-year-old patient with ESKD statistically has a remaining life expectancy of 10 years compared with 40 years for similar-aged counterparts without kidney failure.
Life-saving power
With the life-saving power of kidney transplantation, 83% to 93% of kidney transplant recipients are still alive at 5 years and a kidney transplant provides a 40-year-old patient with kidney failure a remaining life expectancy of 30 years.
Transplantation can offer patients hope for a future that had been uncertain; grief turns to thoughts of celebration, worry to joy, and new dreams emerge.
Yet every day, 12 Americans die on the national kidney waitlist, expecting, trusting and waiting for a transplant that may never come. It is a humbling reminder to the transplant community and federal regulators of the unmitigated crisis that is the organ shortage. This is a crisis that is impactful, refractory and in need of a radical solution.
Xenotransplantation
Xenotransplantation – the transplant of a genetically edited pig kidney into a human – fits the bill and is proving to be the solution our patients have been waiting for.
Xenotransplantation is quickly catapulting from bench to bedside, based on the following advances:
- The Nobel Prize-winning discovery of clustered regularly interspaced short palindromic repeats-associated protein (CRISPR/CAS) has facilitated genetic editing.
- The introduction of novel therapeutics has proven effective for inhibiting complement.
- The development of a novel pre-clinical human decedent model builds on non-human primate work, filling knowledge gaps by answering key safety questions.
These developments have created multiple, viable, genetically edited pig constructs; identified optimal FDA-approved immunosuppression regimens ideal for human xenograft recipients; demonstrated the ability of a pig kidney to clear endogenous and exogenous substrates; and provide physiologic homeostasis for a human. These laid the foundation for the first successful pig-to-human kidney xenotransplant in a living person – performed at the Massachusetts General Hospital – under a compassionate use indication from the FDA.
Our work, however, is not done. We must move quickly to bring xenotransplantation from the realm of experimental to the realm of reality, where any patient with kidney failure has access to hope. While exciting and exhilarating to see this first transplant, it is also a call to action for the transplant community and federal regulators alike. Remember, our patients are expecting and trusting us to deliver hope.
- References:
- Cozzolino M, et al. Nephrol Dial Transplant. 2018;doi:10.1093/ndt/gfy174.
- End-stage renal disease: Cardiovascular disease in patients with ESRD. In: 2020 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. Volume 2, Chapter 8. https://usrds-adr.niddk.nih.gov/2020/end-stage-renal-disease/8-cardiovascular-disease-in-patients-with-esrd. NIH, National Institute of Diabetes and Digestive and Kidney Diseases.
- Gupta R, et al. Semin Vasc Surg. 2021;doi:10.1053/j.semvascsurg.2021.02.010.
- Lentine K, et al. OPTN/SRTR 2021 Annual Data Report: Kidney. https://srtr.transplant.hrsa.gov/annual_reports/2021/Kidney.aspx. Accessed April 17, 2024.
- NKF. Be an organ donor. https://www.kidney.org/transplantation/beadonor#:~:text=Of%20the%20123%2C000%20Americans%20currently,die%20waiting%20for%20a%20kidney. Accessed April 17, 2024.
- For more information:
- Jayme E. Locke MD, MPH, is professor of surgery and the Arnold G. Diethelm, MD, Endowed Chair in Transplant Surgery at the University of Alabama at Birmingham Heersink School of Medicine. She can be reached at jlocke@uabmc.edu.
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