How Should Acute T-cell Mediated Rejection of Kidney Transplants Be Treated: Importance of Follow-up Biopsy

Abstract

Background. Limited published data exist to guide patient monitoring after the treatment of T-cell mediated rejection (TCMR) of kidney allografts. Methods. We reviewed the kidney function and histological outcomes after treatment of 163 first episodes of biopsy-proven TCMR between January 1‚ 2015‚ and July 31‚ 2020. Results. Of the 146 patients treated with steroid pulse alone, complete histological response was seen in 83% of patients with borderline rejection, 82.5% with grade 1A, 67% with grade 1B, and 50% with grade IIA. Of the 17 patients treated with steroids plus antithymocyte globulin, the complete histological response rate was 100% with grade 1A, 75% with grade 1B, 100% with grade IIA, and 57% with grade IIB. Among the patients with complete response as assessed by kidney function, 14% only had a partial or no response histologically. Among patients with no kidney function response, 68% had a complete response histologically. Conclusion. We thus find that responses based on kidney function alone do not correlate well with histological responses. If further treatment had been based solely on changes in estimated glomerular filtration rate, a significant number of patients would have been subsequently undertreated or overtreated. These results support the use of protocol follow-up biopsies after the treatment of TCMR.

How Should Acute T Cell–mediated Rejection of Kidney Transplants be Treated: Importance of Follow-up Biopsy From Kidney Transplantation

“…Although our data represent for-cause biopsy, rather than protocol biopsy, they reemphasize the data from Aziz et al 1 and Ho et al 2 Irrespective of the improvement in creatinine, a repeat biopsy showed complete resolution of histology in only 40% to 53% of patients at a median of 2 wk after the first biopsy.…”

“…Aziz et al 1 in Wisconsin published their experience with protocol repeat biopsies in 163 episodes of T cell–mediated rejection (TCMR) between 2015 and 2020. Among their patients with a complete response as assessed by kidney function, 14% had a partial or no response histologically.…”

The Histological Spectrum and Clinical Significance of T Cell–mediated Rejection of Kidney Allografts

“…Most recently, Aziz et al compared functional with histological responses of 163 patients with acute TCMRs (47% BL) that were predominantly on maintenance tacrolimus and MMF and had a follow-up biopsy approximately 3 mo later. 91 Of 146 treated with steroids alone, complete histologic response rates were 83% for BL, 82.5% for grade IA, 67% for grade IB, and 50% for grade II. Of the 17 treated with steroids plus antithymocyte globulin, the respective rates were 100% (grade IA), 75% (IB), 100% (IIA), and 57% (IIB).…”

Immune monitoring in pediatric kidney transplant

“…As early as 1999, there was evidence showing that two-thirds of 'clinically successful' rejection treatments had residual inflammation on biopsy, 17 and a 2022 cohort study of 163 adults with TCR similarly demonstrated that 14% of those with complete clinical response had only partial or no improvement in their inflammation histologically. 18 In children, rates of persistent rejection are even higher; Landsberg et al 19 reported persistent TCR in 55% of follow-up biopsies at a mean of 1.7 months after the original diagnosis.…”

“…In addition to the diagnosis of rejection, there is increasing evidence for the use of biopsy for follow up of treated rejection episodes. As early as 1999, there was evidence showing that two‐thirds of ‘clinically successful’ rejection treatments had residual inflammation on biopsy, 17 and a 2022 cohort study of 163 adults with TCR similarly demonstrated that 14% of those with complete clinical response had only partial or no improvement in their inflammation histologically 18 . In children, rates of persistent rejection are even higher; Landsberg et al 19 .…”