A reduced dose of immunosuppression did not affect outcomes in kidney transplantation in patients who were age 65 years and older compared to standard immunosuppression, according to results of a randomized clinical trial conducted mainly in the Netherlands. 

The key takeaway is that it's possible to safely reduce immunosuppression in this patient population, said co-principal investigator Stefan P. Berger, MD, nephrologist with University Medical Center Groningen in the Netherlands. Berger presented the latest data from the study at Kidney Week 2025: American Society of Nephrology’s Annual Meeting.

The results were simultaneously published online in the Journal of the American Society of Nephrology. 

More than 30% of kidney transplant recipients in the Netherlands are older than age 65 years. These patients have lower rejection rates than younger patients; however, they have higher rates of malignancy and infection-related mortality, and increased susceptibility to nephrotoxicity of calcineurin inhibitors (CNIs) in kidneys from older donors, Berger and colleagues explained. 

“Hence, it is pivotal to shift the focus from prevention of rejection to preservation of graft function and prevention of over-immunosuppression in the elderly,” they write. 

The researchers therefore hypothesized that an immunosuppressive regimen aiming to reduce CNI toxicity and infectious burden would specifically have an advantage in older recipients.

Optimizing Immunosuppression

The OPTIMIZE trial was a randomized, multicenter, international, open-label, interventional trial conducted between July 2019 and April 2025 at six transplant centers in the Netherlands and one in Belgium. 

Researchers enrolled a total of 379 patients aged 65 years and older, receiving a kidney from a deceased donor older than 65 (stratum A, n = 198) or receiving a kidney either from a live donor or a younger deceased donor (stratum B, n = 181). Patients from both strata were randomly assigned to receive either the standard immunosuppressive regimen with standard-dose tacrolimus, mycophenolate, and prednisolone, or a regimen of low-dose tacrolimus, everolimus, and prednisolone. 

The primary endpoint was being alive with a functioning graft with an estimated glomerular filtration rate (eGFR) above a predefined threshold at 2 years post-transplantation: 30 mL/min/1.73 m² for stratum A, and 45 mL/min/1.73 m² for stratum B.

There was no significant difference in the primary outcome, or in patient survival at 2 years, which was 89% in both arms (P =.95), Berger reported. In addition, graft survival and kidney function were similar between both immunosuppression groups. 

The rejection rates were low in both arms (11% in stratum A vs 8% in stratum B) after 2 years. There was a 95% graft survival rate in both arms. They also found that “low-dose tacrolimus, everolimus, and prednisolone did not result in a higher rate of successful transplantation in these older recipients, and it also did not result in better kidney function or less infectious events, despite the COVID pandemic hitting right into our trial,” Berger said. 

“While we were pleased to see that the lower-dose regimen was indeed safe, it was somewhat surprising that it did not result in fewer complications or better kidney function,” said Berger. 

As tacrolimus levels were clearly lower in the low-dose tacrolimus arm with a mean of 3.3 ng/mL at 2 years vs 6.4 ng/mL in the standard dose arm, “we would have at least expected a tendency toward improved kidney function,” he told Medscape Medical News. 

“On the other hand, outcomes were so good that it may be difficult to improve these in the short term, and beneficial effects may need more time to become apparent,” he added.

“I think the point we want to make [with this study] is that maybe we can stratify [patients] beforehand and try to individualize treatments at an earlier phase, not when the trouble starts,” said Berger. 

Nephrologist Suphamai Bunnapradist, MD, from UCLA School of Medicine in Los Angeles, said more studies are warranted to verify whether these lower-dose regimens are better than the standard regimen. 

In addition, the low-dose tacrolimus-based regimen used basiliximab induction, and more than 90% of the patients were White, she said. Therefore, further studies need to be conducted in the United States, where the population demographic and the use of primarily thymoglobulin induction are different. 

The study was partially supported by the Dutch organization for Health Research and Development. Berger and Bunnapradist disclosed no relevant financial relationships. 

John Schieszer, MA, is an award-winning national journalist and podcast broadcaster of The Medical Minute. He can be reached at medicalminutes@gmail.com.