Background: The advantage of histological endpoints in rejection trials may explain the inadequate therapeutic response. Graft histology early after treatment is a critical endpoint for the therapeutic success of rejection therapy and is crucial in correlating long-term graft survival. The sequence and timing of the resolution of the cellular and vascular changes of rejection are incompletely understood. Thus, we aimed to find the best time to assess for complete histological reversal of renal allograft rejection.
Methods: A total of 105 patients with acute TCMR who were diagnosed between 1998-2015 were included in the study. PRA, DSA, and C4d expressions were negative in all recipients. Totally 562 follow-up biopsies, which were performed after index biopsy, were re-examined.
All Banff grades were treated with high-dose corticosteroids. Lymphocyte-depleting agents were used in steroid-resistant AR patients.
Results: The mean follow-up time was 103,4 ± 4,9 months. Among 105 recipients, 12 had borderline, 27 had grade 1A, 23 had grade 1B, 29 had grade 2A, and 14 had grade 2B acute TCMR. The steroid treatment was successful in 43 (41%) patients. But the remaining 62 did not respond to steroid therapy. Of 62 patients with steroid-resistant AR, 20 received OKT3, and 42  received ATG. The highest steroid response was observed in the borderline and grade 1A groups, with 91% and 55% rates, respectively. But, only 26% of grade 1B and 34% of grade 2A patients have shown steroid response, while only 7% of grade 2B AR cases respond to the steroid.   The mean time between the index biopsy and the follow-up biopsy with the histological response after steroid therapy was one month for borderline, grade 1A, and grade 1B patients. It was 1,68 months for grade 2A and three months for grade 2B patients. Only 63% of cases with steroid-resistant TCMR showed a response to lymphocyte-depleting agents at a mean time of  3,58 months. While all individual Banff scores affected the steroid response, only glomerular and vascular scores affected the treatment response in the lymphocyte-depleting treatment groups. TCMRs with a sum score less than 5 are most likely reversible and responsive to steroid and lymphocyte-depleting agents. A sum score greater than six is associated with an increased steroid resistance or irreversibility of the rejection. Only Glomerular and vascular scores showed a significant association with serum creatinine levels. Banff histological scores significantly influence 10-year allograft survival and IFTA development in the first 36 months after transplantation.
Conclusion: We determined that the histological response after steroid treatment was one month. Additionally, steroid-resistant TCMRs under lymphocyte-depleting treatment went to complete histological resolution about 3.5 months after index biopsy. Thus we can suggest that the most appropriate time for the biopsy for complete histological reversal of AR after treatment is between one to four months.