A new pilot study points to a future where kidney transplant patients may swap daily pills for a monthly infusion, potentially reducing toxic side effects and protecting donor organs. Researchers now plan larger trials to confirm the early results.
For people living with a kidney transplant, life often revolves around a strict schedule of daily pills that keep their immune systems from attacking the donated organ. A new study suggests that one day, many of those pills might be replaced by a monthly treatment that could be easier to manage and gentler on the body.
Researchers tested a new combination therapy that uses two infused proteins instead of the standard mix of daily immunosuppressant drugs. In a small Phase 2 pilot study, they found that kidney function improved in all patients who completed the trial, and none experienced a type of rejection driven by antibodies, a major cause of transplant failure.
The approach is designed to tackle one of the biggest challenges in transplant medicine: how to prevent the immune system from rejecting a donor organ without causing serious long-term harm.
Today, kidney transplant recipients typically take several immunosuppressant medications every day for the rest of their lives. These drugs are effective at blocking immune attacks on the new kidney, but they can damage kidney function over time and become less effective. They are also linked to diabetes, high blood pressure, high cholesterol and a long list of side effects, including fatigue, muscle weakness, sexual dysfunction, hair loss and trouble sleeping.
Those burdens make it hard for many patients to stick to their treatment plans, according to first author Flavio Vincenti, a professor of medicine and surgery in the Division of Nephrology at the University of California San Francisco. Missed doses can raise the risk of rejection and shorten the life of the transplanted kidney.
“We would hope to see better medication compliance with the new regimen since it does not involve taking multiple medications every day,” Vincenti said in a news release.
In the study, 23 kidney transplant patients were enrolled to receive infusions of two proteins, belatacept and dazodalibep. These proteins are designed to interfere with the immune system’s attack on the transplanted organ without affecting non-immune cells the way standard drugs do.
All patients started out on conventional immunosuppressant pills, but those medications were stopped by day 28. From that point through the end of the 48-week study, patients were maintained on the infusion-based regimen instead.
The early experience was not without setbacks. Two of the first three patients experienced acute organ rejection. Those episodes were treated successfully, and the rejection was reversed. In response, the research team adjusted the drug dosing and frequency for the remaining participants.
Of the 23 patients, 13 completed the full study. Seven withdrew because of acute kidney rejection, side effects or reasons that were not specified. Among those who stayed in the trial, kidney function improved and remained strong, even in patients who had experienced rejection. Importantly, no patient developed rejection driven by antibodies, which is a common and especially damaging form of transplant failure.
The findings, published Feb. 3 in the American Journal of Transplantation, are far from the final word. The study was small, and the revised dosing strategy needs to be tested in many more people before doctors can know how well it works and which patients are most likely to benefit.
The next phase of research will take on that challenge by enrolling a larger group of transplant recipients, according to senior author Allan D. Kirk, a professor of surgery at Duke University School of Medicine.
“We hope that most patients can be spared the toxic effects of immunosuppressants, which would be reserved for those with certain high-risk factors,” Kirk added.
If future trials confirm the early promise, the new regimen could reshape life after kidney transplant. A once-a-month infusion, delivered in a clinic, might be easier for many patients to manage than a complex daily pill schedule. Reducing exposure to toxic drugs could also help donor kidneys last longer and lower the risk of serious complications like diabetes and cardiovascular disease.
Kidney transplantation is often the best treatment for people with end-stage kidney disease, offering better quality of life and survival than long-term dialysis. But the success of a transplant depends heavily on lifelong immune control. Researchers around the world are searching for ways to fine-tune that control so that patients can keep their organs functioning for decades without sacrificing their overall health.
The new study, led by UCSF in collaboration with Duke University and other centers, is one step in that direction. Co-authors included investigators from Cedars-Sinai Medical Center, the University of Texas Southwestern Medical Center, the University of Southern California and Amgen, which funded the trial and provided grant support.
For now, the infusion therapy remains experimental, and standard daily immunosuppressant pills will continue to be the norm for transplant patients. But the pilot results offer a glimpse of a future in which protecting a donated kidney might not require such a heavy daily toll.