Immunosuppression Minimization in Belatacept-Treated Kidney Transplant Recipients Guided by Combined Cell-Free DNA...

This study examined whether the combined use of donor-derived cell-free DNA (cfDNA) and gene expression profile testing can facilitate immunosuppression minimization in belatacept-treated kidney transplant recipients.

Patients at least one year out from transplant with stable renal function, no history of rejection, negative donor-specific antibodies (DSA), urine protein/creatinine ratio <0.5 g/g, cfDNA <1% and negative gene expression profile at baseline were eligible. Mycophenolate (MMF), mTOR inhibitors and steroids were tapered off and stopped over 10 months. Belatacept dosing was not changed. During a 24-month follow-up period, cfDNA and gene expression tests were performed monthly.

Out of 13 participants, 8 were weaned to belatacept monotherapy. In the remaining patients, immunosuppression was only partially reduced. Three had repeated gene expression test quality control failures (all after the first MMF dose reduction), one experienced a transient decrease in eGFR with a rejection ruled out by kidney biopsy and one patient developed transient proteinuria >0.5 g/g. There were no results suggesting (sub)clinical rejection or any other safety signals for these patients throughout the remainder of follow-up.

These novel immune monitoring tools can help identify patients in a likely state of immunologic quiescence, who may be eligible for reductions in immunosuppressive therapy.