Breaking Down The Kidney Transplant Landscape on National Donor Day

In light of National Donor Day, experts in the field highlight unmet needs in immunosuppression, newfound data regarding kidney transplantation outcomes, and explain the impact of donation on the future health of the donor.

In the nephrology landscape, National Donor Day can raise awareness about the unquestionable benefits of kidney transplantation in patients with chronic kidney disease (CKD), particularly with end-stage kidney failure (ESKD).1

“Transplantation is the treatment of choice for kidney failure,” said Janani Rangaswami, MD, FAHA, a nephrologist with expertise in cardiovascular- kidney medicine, professor of Medicine at George Washington University, Washington, DC, and co-chair of the Scientific Advisory Group of the AHA's presidential advisory on CKM Health.

While transplantation remains the ideal choice for kidney failure, it is a major undertaking for living donors and recipients, with individuals carefully weighing their predisposed health risks pre-surgery and needing to plan for annual checkups post-organ donation.

Kidney Failure and The State of Donation

Statistically, nephropathy is a widespread problem in the US, with 1 in 3 adults at risk for, and 1 in 7 living with, kidney disease. There are 90,000 individuals awaiting kidney transplants in the US alone, making up 86-87% of the national transplant waiting list.1,2

In 2025, the US achieved a record of organ transplants, with a 3% increase in individuals becoming living organ donors, according to data from the Organ Procurement and Transplantation Network. However, kidney transplants specifically declined by 102 transplants from 2024.2

Analysis of global data observed the possibility of successful pregnancies post transplantation, especially with careful monitoring, and observed a return in fertility quickly after surgery, although recommended ≥1 year before attempting conception. Furthermore, a cross-sectional study suggested kidney transplant recipients experienced a reduced risk of sleep disorders compared to those on maintenance dialysis.

Despite its widespread acknowledgement as a clinically superior treatment option for CKD, there are nuances to kidney transplant recipients’ outcomes.

According to a previous study, low exercise tolerance, defined as anaerobic threshold VO₂ < 11 mL/kg/min; peak VO₂ < 20 mL/kg/min, was associated with poor muscle recovery and sarcopenia. Additionally, psychological and behavioural factors, especially depression, significantly influenced immunosuppression medication adherence. Lastly, a recent investigation discovered a link between neighbourhood disadvantages and reduced kidney transplant access and waitlisting.

Most notably, living donor kidney transplants have been associated with increased long-term graft survival, decreased waiting time, and reduced risk of adverse health conditions from the donated allograft compared to deceased donor transplantation.4

Regardless, any form of kidney transplantation remains a significantly beneficial treatment option for patients with kidney failure.

“Every transplant that's done, somebody altruistically made it possible, a donor that's living or a deceased donor's family provided a gift for usually someone they don't know,” said Allan Kirk, MD, PhD, a transplant surgeon at Duke Kidney/Transplant Clinic, study investigator of a phase 2 pilot study of new immunosuupression, belatecept and dazodalibep. “Although living donor cases, it's frequently someone they do know. And I think that's very optimistic.”

The Impact of Kidney Donation on the Donor

For individuals who endeavour to donate a kidney, clinicians help provide insight into the impact of transplantation on their overall health.

“What happens to the donor's kidney health? You know, these are healthy people screened for eligibility to be suitable donors. Over time, as they age, they may develop other risk factors like hypertension or diabetes, and they themselves can go on and develop kidney disease,” said Rangaswami. “It's a very, very small number of patients that do that. Most donors do really well in terms of kidney outcomes and longevity, but it's so important for them to get screened frequently, at least annually.”

The risk to individuals who donate a kidney is relatively slight, with a low mortality risk and an estimated 4-6 week recovery period. In terms of long-term health, there is a <1% chance of developing kidney failure, a slight increase in high blood pressure, a 25-35% reduction in total kidney function, and a small risk of hernia. Additionally, if a kidney donor eventually needs a transplant after donation, they are given increased priority on the deceased donor waitlist.5,6

“And even if they develop some of those factors, we just have these amazing new therapies that are also applicable to protect their kidney health as well,” said Rangaswami.

The Future of Kidney Transplant Immunosuppresion

While kidney transplants offer clinical benefit to patients, long-term graft survival and immunosuppression strategies remain evolving.

Historically, immunosuppression for kidney transplant recipients has relied on tacrolimus as the standard of care. While this calcineurin inhibitor has been effective at preventing early acute rejection, its broad mechanism of action can contribute to nephrotoxicity, metabolic disturbances, and cardiovascular complications over time.5

“[Tacrolimus] is a great drug to control rejection, but it has a lot of unwanted side effects and patients are suffering,” said Eliezer Katz, Chief Medical Officer of Eledon Pharmaceutics. “When I talk to physicians, we know it's time to find a replacement. We need new drugs. It's a really unmet need, and we need to try to find something new.”

Costimulatory pathways have emerged as a focal point in efforts to refine immunosuppression following kidney transplantation. These pathways act upstream in T- and B-cell activation, offering potential to reduce chronic, low-grade immune activation without broadly suppressing the immune system.

Currently, tegoprubart, an investigational anti-CD40L monoclonal antibody, has exhibited safety and efficacy in phase 1b and 2 BESTOW trials, and is positioned as a potential immunosuppression to improve long-term graft survival.6

Additionally, a recent phase 2a, open-label trial of 23 patients receiving belatecept and dazodalibep was generally safe, well tolerated, and effective as the sole maintenance antirejection therapy. The dual-biologic regimen, belatecept and dazodalibep, are CD80/86 blockers, ​​specifically targets T-cell activation, potentially avoiding the nephrotoxicity associated with traditional, daily immunosuppressants.7

“It is truly one of the biggest landmark innovations in nephrology, and it should always be our endeavor to ensure that people with kidney failure have access and an opportunity to get transplanted, because it's the treatment of choice,” concluded Rangaswami.

Editor’s Note: Katz and Kirk report relevant disclosures with Eledon. Rangaswami reports relevant disclosures with Boehringer-Lily, Bayer, and others.

1. National Kidney Foundation. National Kidney Foundation. National Kidney Foundation. Published 2024. https://www.kidney.org/

2. U.S. surpasses 49,000 organ transplants while deceased organ donations dip | UNOS. UNOS. Published January 28, 2026. https://unos.org/media-resources/releases/u-s-surpasses-49000-organ-transplants-while-deceased-organ-donations-dip/

3. 90,000 people are waiting for a kidney. Here’s one way to get them a kidney faster. - UNOS. UNOS. Published January 27, 2025. https://unos.org/news/90000-people-are-waiting-for-a-kidney-heres-one-way-to-get-them-a-kidney-faster/

4. Murray J, Luke A, Wallace D, Callaghan C, Sharples LD. Comparison of outcomes after living and deceased donor kidney transplantation: UK national cohort study. British journal of surgery. 2025;112(8). doi:https://doi.org/10.1093/bjs/znaf162

5. National Kidney Foundation. Long-Term Risks of Living Donation. National Kidney Foundation. Published November 8, 2024. https://www.kidney.org/kidney-topics/long-term-risks-living-donatio‌

6. Wojciechowski D, Wiseman A. Long-Term Immunosuppression Management. Clinical Journal of the American Society of Nephrology. 2021;16(8):1264-1271. doi:https://doi.org/10.2215/cjn.15040920

7. ‌Vincenti F, Shoji J, Wojciechowski D, et al. Dual costimulation blockade with the CD154-specific fusion protein dazodalibep and belatacept for prophylaxis of kidney allograft rejection. American Journal of Transplantation. 2025;0(0). doi:https://doi.org/10.1016/j.ajt.2025.12.290