Follow-up biopsies identify high rates of persistent rejection in pediatric kidney transplant recipients after treatment of T cell-mediated rejection

Background: Incomplete resolution of T cell-mediated rejection (TCMR) after treatment may not be detected with serum creatinine monitoring and is associated with donor-specific antibodies and chronic rejection. We evaluate the utility of follow-up biopsies (FUB) to identify and characterize rates of persistent TCMR after treatment in pediatric kidney transplant patients. Methods: Patients from two pediatric transplant centers performing standard of care FUB at 1.5-2 months after treatment for TCMR were included. FUB were evaluated for extent of rejection resolution (complete vs. incomplete) and grade. Clinical data at time of FUB and later were reported, where available. Results: Fifty-eight patients underwent FUB, at mean of 1.7 months (SD 0.7) post-index biopsy. Rejection grade on index biopsy was Banff borderline (>= i1t1 and = 1A (>= i2t2) in 41%. Acute rejection was persistent in 32 (55%) of FUB. Borderline rejection had higher rates of complete resolution of rejection compared to grade >= 1A (53% vs. 33%, p =.033). Incomplete resolution of rejection on FUB was re-treated in 25 (78%) of cases. Change in eGFR from index to FUB did not differ between those with complete and incomplete resolution (5.7 +/- 32.2 vs. 13.1 +/- 51.3, p =.28) and was not a sensitive marker of identifying persistent rejection. Conclusions: FUB were effective at detecting persistent rejection, which was common among pediatric transplant patients after standard TCMR treatment. Until more effective rejection treatments or sensitive biomarkers are available, FUB may be effectively utilized to identify patients with ongoing rejection who would benefit from further treatment.