In Partnership with CSL Behring
In recent decades, huge strides have occurred in every aspect of transplant, from surgical techniques to immunosuppressive drugs. However, as demand for organs rises, organ supply has not increased to match this demand. This problem has fueled an innovation explosion in many fields like policy, bioengineering, and computer science; extraordinary scientific ideas are under way for addressing issues from the waitlist to all the way through improving post-transplant kidney function. Three notable approaches include: increasing the donor kidney supply, decreasing demand for organs, and increasing donated kidney duration.
In part 1 of this innovation series, we will focus on increasing donor kidney supply:
Currently, there is a shortage of viable, transplantable organs, resulting in lengthy wait times and diminished quality of life for patients with chronic illnesses. There are varied levels of investigation in increasing kidney supply, ranging from innovations in making suboptimal kidneys usable, to advances in creating new kidneys. Increasing the supply of donor kidneys is a multifaceted issue that requires collaboration between the fields of science and policy.
One avenue of increasing donor kidney supply is through policy changes that expand the donor pool, like expanded criteria donor systems (ECD). This means allowing suboptimal kidneys, like those from geriatric donors, to be transplanted. Due to the extant, rigorous standards for organ donation, many organ donors are refused and kidneys that are suboptimal, even if they are functional, are discarded[1].
Leveraging Technology in Donor Chains
Another innovation in kidney transplantation is leveraging technology to match donors and recipients in “donor chains.” Often, a patient necessitating a kidney transplant has a relative or loved one who is willing to donate a kidney, but their kidney is incompatible. Donor chains and paired kidney donations match patients with incompatible living donors, to allow a kidney “swap.” One of the longest chains, Chain 124, had 60 operations, 30 donated kidneys, in 17 hospitals across 11 states, initiated by the altruistic donation by Mr. Ruzzamenti, who gave his kidney expecting nothing in return[2]. As matching systems, surgical techniques, and organ shipping technology improves, donor chains can greatly improve the allocation of kidney supply.
Beyond policy changes and incremental upgrades to increase supply, there are some groundbreaking ideas and extraordinary science behind alternative sources for kidney transplants. While these innovations are currently far from being standard of care or accessible to everyone seeking a transplant, exciting progress is increasing kidney supply to match the rising demand.
Xenotransplantation
Xenotransplantation is cross-species organ transplantation, where genetically engineered pigs are the kidney donors rather than humans. The very first nonhuman kidney was transplanted in 2021 at NYU Langone Health to a deceased donor. So far, there have been no signs of rejection[3]. Barriers to xenotransplantation are steadily being overcome, but a primary barrier is our immune system’s response to a “foreign” object in our body. Even with human-to-human transplants, careful genetic matching and immunosuppressant drugs are necessary to stop our body from rejecting the new kidney. For xenotransplantation to work, the donor pig is genetically engineered to remove a gene that causes this rejection. A gland from the pig is also transplanted with the donated kidney. As genetic engineering and our understanding of the immune system improves, xenotransplantation may be a promising way to combat the current organ shortage[4].
Organ Cloning and Repair
Innovations in tissue engineering and regenerative medicine have resulted in cutting-edge ideas for cloning organs and repairing damaged organs. The process works by taking tissue from a person, bioengineering it, and implanting it back into the person. Although the kidneys are currently too complex to do this[5], promising results have already been found with bladders, vessels, and urethras. As the scientific community continues to innovate, bioengineered organs have considerable potential in the future of transplantation.
The grand vision of tissue engineer in transplantation is 3D printed organs. Using a patient’s own cells, researchers are hoping to create technology similar to conventional 3D printing. This innovation would not only increase organ supply, but eliminate the need for immunosuppression, as the organ would be printed from the patient’s own cells. However, this technology is decades away and currently quite costly. Particularly for solid organs, like kidneys and hearts, the complexity of the internal structure may take decades until 3D printing is a viable option[6].
[1] Reese PP, Harhay MN, Abt PL, Levine MH, Halpern SD. New solutions to reduce discard of kidneys donated for transplantation. Journal of the American Society of Nephrology. 2016 Apr 1;27(4):973-80.
[2] Sack K. 60 lives, 30 kidneys, all linked. New York Times. 2012 Feb 16;18.
[3] Cooper DK, Hara H. “You cannot stay in the laboratory forever”*: Taking pig kidney xenotransplantation from the laboratory to the clinic. EBioMedicine. 2021 Sep 1;71:103562.
[4] Cooper DK, Hara H, Iwase H, Yamamoto T, Jagdale A, Kumar V, Mannon RB, Hanaway MJ, Anderson DJ, Eckhoff DE. Clinical pig kidney xenotransplantation: how close are we?. Journal of the American Society of Nephrology. 2020 Jan 1;31(1):12-21.
[5] Madariaga ML, Ott HC. Bioengineering kidneys for transplantation. InSeminars in nephrology 2014 Jul 1 (Vol. 34, No. 4, pp. 384-393). WB Saunders.
[6] Kyung YS, Kim N, Jeong IG, Hong JH, Kim CS. Application of 3D printed kidney model in partial nephrectomy for predicting surgical outcomes: a feasibility study. Clinical Genitourinary Cancer. 2019 Oct 1;17(5):e878-84.
In Partnership with CSL Behring
In recent decades, huge strides have occurred in every aspect of transplant, from surgical techniques to immunosuppressive drugs. However, as demand for organs rises, organ supply has not increased to match this demand. This problem has fueled an innovation explosion in many fields like policy, bioengineering, and computer science; extraordinary scientific ideas are under way for addressing issues from the waitlist to all the way through improving post-transplant kidney function. Three notable approaches include: increasing the donor kidney supply, decreasing demand for organs, and increasing donated kidney duration.
In part 2 of this innovation series, we will focus on decreasing demand:
Creating new organs and increasing organ supply sounds like something out of science fiction (see part 1 of this series to learn more). However, a very real alternative, or complement to increasing supply, is to decrease the number of people with chronic diseases like end stage renal disease (ESRD) that require transplantation. While organ supply innovations continue, it is necessary to address issues like rising demand for organs, the disparity between organs needed and organs available, and the quality of life of those awaiting transplants. Focusing on slowing disease progression and increasing access to programs for early prevention or treatment are crucial.
The key to decreasing demand is preventing kidney failure. Diabetes and hypertension are two common diseases that account for more than 70% of cases that end in ESRD and require transplant. Thus, early education and lifestyle change in patients with diabetes and patients with hypertension can dramatically reduce long term complications, and delay onset of renal failure[1].
Medications for kidney failure are also a major area of advancement, hoping to reduce the loss of kidney function and slow the progression of disease. Initiatives like KidneyX, an innovation accelerator, and the 2019 Advancing Kidney Care Health Executive Order, which helps accelerate the development of therapies, are pushing for better drugs and therapies for people with kidney disease[2]. As kidney disease is better understood, and new diagnostic technologies, biomarkers, and signaling pathways are discovered, therapeutic development may be a promising avenue to reduce kidney demand and improve quality of life.
Finally, many people awaiting a kidney transplant need dialysis. While dialysis is a lifesaving, it can have major effects on one’s quality of life, finances, environment, and overall wellbeing[3]. For example, conventional dialysis machines are heavy, requiring people to be stationary, and generally require multiple sessions per week at a clinic. One innovative approach to dialysis is “wearable artificial kidneys”, which is a smaller, more portable device.[4]
[1] Stephan A. Organ shortage: can we decrease the demand?. Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation. 2017 Feb 1;15(Suppl 1):6-9.
[2] Watnick S. The kidney accelerator: Innovation wanted, nephrologists needed. Clinical Journal of the American Society of Nephrology. 2018 Nov 7;13(11):1750-2.
[3] Himmelfarb J, Vanholder R, Mehrotra R, Tonelli M. The current and future landscape of dialysis. Nature Reviews Nephrology. 2020 Oct;16(10):573-85.
[4] Himmelfarb J, Ratner B. Wearable artificial kidney: problems, progress and prospects. Nature Reviews Nephrology. 2020 Oct;16(10):558-9.
In Partnership with CSL Behring
In recent decades, huge strides have occurred in every aspect of transplant, from surgical techniques to immunosuppressive drugs. However, as demand for organs rises, organ supply has not increased to match this demand. This problem has fueled an innovation explosion in many fields like policy, bioengineering, and computer science; extraordinary scientific ideas are under way for addressing issues from the waitlist to all the way through improving post-transplant kidney function. Three notable approaches include: increasing the donor kidney supply, decreasing demand for organs, and increasing donated kidney duration.
In part 3 of this innovation series, we will focus on preserving donated kidneys:
Donated kidneys can last a long time, especially with lifestyle changes and compliance with the immunosuppressive drugs. Deceased donor kidneys last on average 8-12 years, and living donor kidneys can last on average 12-20 years. If you would like to learn more about complications or rejection after transplant, see the TransplantLyfe article here. However, there may be transplant complications, or the donated kidney reaches the end of its lifespan, resulting in the need for a second transplant. Some estimate that almost 30% of patients on the transplant waiting list are waiting for a second transplant[1]. Thus, innovations in preserving donated kidney function are crucial, especially as demand for first kidney transplants rise.
The first step, better matching donor and recipient to ensure the best compatibility, is underway. This helps prevent rejection and other complications from the donor’s immune system. Sometimes, patients are not given kidneys that are optimal matches, due to lack of availability, geography, or timing. A transplant team at John Hopkins has developed a machine to continuously pump blood through a donor organ, increasing its endurance and transplant viability[2]. Improved computer matching and advances in treating ESRD also ensure patients’ ability to receive an optimal kidney[3].
The next avenue of major innovation in preserving transplanted kidney function is in immunosuppression. After receiving a kidney transplant, a strict immunosuppressive regimen of drugs is used to prevent the patient’s immune system from attacking the donor kidney. However, there is a delicate balance between prescribing these drugs to prevent the immune system from being too strong and harming the new kidney, and ensuring that the patient isn’t vulnerable to the outside world without an immune system to protect them from infections. Furthermore, these drugs have a wide range of side effects, which can negatively affect quality of life, or even cause patients to cease medication compliance. Ideally, advances in research will lead to therapeutic interventions which would have minimal side effects, and only suppress the parts of the immune system that would attack the donated kidney, leaving the rest of the immune system free to function normally. As our understanding of the immune system improves, researchers and drug companies are discovering new therapeutic avenues for drug development, and are working to reduce side effects and improve targeted immunosuppression[4]. Furthermore, as clinicians and transplant specialists gain more experience with transplant recipients, there will be innovations in treating kidney transplant recipients, whether in designing a personalized drug regimen based on how the patient is matched or mismatched with the donor or in recognizing and treating complications earlier.
Conclusion:
As demand for organs rises, researchers, clinicians, policymakers, and companies are developing different innovations to improve transplantation and the experience of transplant recipients. There are many grand ideas, from 3D printing organs (see part 1 of this series to learn more) to creating wearable dialysis machines (see part 2 of this series to learn more), as well as small, practical changes that are already implemented and are impacting the transplantation field. As the mystery of transplantation is further unraveled, extraordinary scientific ideas from diverse fields like tissue engineering and computer science are being applied. The future of transplantation, even the near future, may look very different than it does today.
[1] Wong G, Chua S, Chadban SJ, Clayton P, Pilmore H, Hughes PD, Ferrari P, Lim WH. Waiting time between failure of first graft and second kidney transplant and graft and patient survival. Transplantation. 2016 Aug 1;100(8):1767-75.
[2] Markmann JF, Abouljoud MS, Ghobrial RM, Bhati CS, Pelletier SJ, Lu AD, Ottmann S, Klair T, Eymard C, Roll GR, Magliocca J. Impact of portable normothermic blood-based machine perfusion on outcomes of liver transplant: the OCS Liver PROTECT randomized clinical trial. JAMA surgery. 2022 Mar 1;157(3):189-98.
[3] Kaplan I, Houp JA, Leffell MS, Hart JM, Zachary AA. A computer match program for paired and unconventional kidney exchanges. American Journal of Transplantation. 2005 Sep;5(9):2306-8.
[4] Salvadori M, Tsalouchos A. Innovative immunosuppression in kidney transplantation: A challenge for unmet needs. World Journal of Transplantation. 2022 Mar 18;12(3):27.