Introduction: Traditional methods of monitoring the response to treatment of acute rejection (AR) in kidney transplant recipients (KTR) include creatinine based eGFR and quantification of proteinuria. Routinely obtaining a kidney biopsy following AR treatment is controversial and not commonly performed. Our center obtains follow-up biopsies to assess resolution of AR and we hypothesize these results better guide subsequent treatment compared to traditional monitoring strategies.
Methods: We performed a retrospective chart review of pediatric KTR who had a kidney biopsy diagnosing acute T-cell mediated rejection (TCMR) or antibody mediated rejection (AMR) from January, 2015 to August, 2022 using Banff criteria interpreted by local pathologists. Those included had a follow-up kidney biopsy 3 to 6 months after the rejection diagnosis. Treatment for TCMR included IV pulse steroids or escalation in oral steroid dose followed by a taper. Anti-thymocyte globulin was added in severe cases. AMR treatment included IV immune globulin, rituximab, and/or therapeutic plasma exchange in some cases. The primary endpoint was resolution of rejection (follow-up biopsy without activity or Banff scores < i1t1 and v=0 for TCMR or g+ptc < 2 for AMR). The secondary endpoint was change in eGFR from time of AR diagnosis to follow-up biopsy (utilizing Modified Schwartz or CKD-EPI).
Results: We identified 18 patients who had a follow-up biopsy 3 to 6 months following diagnosis of AR (9 TCMR, 7 AMR, and 2 cases of mixed AMR/TCMR). Overall, 11 (61%) of children had resolution of AR on follow-up biopsy (8 of 9 TCMR, 2 of 7 AMR, and 1 of 2 mixed rejection). AR resolution was significantly more likely in TCMR compared to AMR or mixed rejection, p = 0.04. The two cases of mixed rejection both had resolution of TCMR but showed ongoing chronic active AMR. Five of 7 cases of AMR (71%) showed chronic active rejection.
Those who did not have resolution of AR on follow-up biopsy were significantly more likely to have recurrent episodes of AR or ongoing chronic active rejection seen on future biopsies (p < 0.01). The median change in eGFR was not significantly different between those who had chronic active findings or AR recurrence (-2 mL/min/1.73m2, IQR -6 to 29) and those who did not (5 mL/min/1.73m2, IQR -2 to 12), p = 0.35. There were no instances of graft loss.
Conclusion: Follow-up biopsies after AR detected many cases of unresolved AR and subclinical inflammation that would not otherwise be identified. These cases often required additional treatment to control ongoing rejection and preserve graft function. There was no difference in the median change in eGFR between those who had resolution of AR and those with ongoing activity, supporting the hypothesis that traditional measures of graft function are not sensitive enough to determine the adequacy of AR treatment. While larger studies are needed, clinicians should consider implementing a follow-up biopsy protocol to guide management in KTR.