Kidney Transplant Breakthrough: Ditch the Pills, Embrace Immunotherapy

A nascent clinical investigation suggests a potential paradigm shift for individuals undergoing kidney transplantation, moving from a daily regimen of multiple oral medications to a more manageable monthly treatment. This novel therapeutic approach also holds the promise of mitigating adverse effects and extending the viability of the donated renal organ.

Currently, recipients of kidney transplants are prescribed a lifelong daily regimen of pharmaceutical agents. These essential immunosuppressants serve to prevent the recipient’s immune system from mounting an attack against the foreign organ. However, with prolonged use, these medications can degrade renal function and diminish in their efficacy over time.

Furthermore, conventional immunosuppressive therapies are implicated in the development of diabetes, hypertension, and elevated cholesterol levels. They also engender a spectrum of side effects that frequently lead transplant recipients to deviate from their prescribed dosing schedules, as highlighted by the study’s lead investigator, Flavio Vincenti, MD, a professor of medicine and surgery within the Division of Nephrology at UC San Francisco. Additional reported sequelae encompass profound fatigue, diminished muscular strength, sexual impairment, alopecia, and insomnia.

In the context of a Phase 2 exploratory study, a cohort of 23 participants were administered intravenous infusions of belatacept and dazodalibep. These agents, functioning as proteins, serve to impede the immune system’s assault on the transplanted organ without adversely impacting non-immune cells, a distinction from the mechanism of action of standard treatments.

The renal functionality experienced a notable enhancement across all participants who concluded the study, maintaining parity even in instances where organ rejection had occurred. Notably, no participant developed rejection mediated by antibodies produced by the immune system, a primary instigator of transplant failure. The findings from this research were disseminated on February 3rd in the esteemed publication, the American Journal of Transplantation.

We anticipate a marked improvement in medication adherence with the novel protocol, given its liberation from the daily ingestion of multiple pharmaceuticals.

Flavio Vincenti, MD, professor of medicine and surgery, Division of Nephrology, UC San Francisco

Initially, study participants received conventional immunosuppressants, which were subsequently withdrawn by day 28 to facilitate the commencement of infusions for the remaining duration of the 48-week trial.

Among the initial three participants, two experienced episodes of organ rejection. These events were effectively managed, leading to the reversal of the rejection process. Subsequently, adjustments were made to the drug frequency and dosage for the subsequent participants, 13 of whom successfully completed the study. Seven individuals discontinued their participation due to acute renal rejection, adverse reactions, or for undisclosed reasons.

The subsequent phase of this investigation will be dedicated to ascertaining whether these preliminary observations are corroborated within a larger patient population, according to senior author Allan D. Kirk, MD, PhD, a professor of surgery at Duke University School of Medicine.

“Our aspiration is to spare the majority of patients from the deleterious effects of immunosuppressants, reserving their use for individuals presenting with specific high-risk profiles,” stated Dr. Kirk.