Acute cellular rejection treatment outcomes stratified by Banff grade in pediatric kidney transplant

Abstract

Introduction There are limited data to guide optimal treatment strategies for acute cellular rejection (ACR) based on Banff grade for pediatric kidney transplant recipients. This report reviews a large pediatric transplant center's experience with ACR. Materials and Methods A retrospective analysis of pediatric kidney transplant recipients at our center from 2007 to 2014 was performed. Primary outcomes were incidence of graft failure and graft function one year following ACR based on Banff grade and treatment received. Results A total of 204 patients were reviewed, of which 65 received rejection treatment with either an oral steroid cycle (n = 16), intravenous steroid pulse (n = 28), or anti‐thymocyte globulin (rATG, n = 21). Overall, patients received rATG for treatment of more severe rejection associated with impaired graft function and as a group experienced statistically significant improvements in eGFR over the year following treatment, though most did not regain baseline graft function. Discussion Our data suggest that rATG is partially effective in treating ACR, but our study was underpowered to determine the effect of different treatments based on Banff grade. Since there is limited literature to guide clinical treatment of ACR in children, large transplant centers should collaborate to evaluate outcomes and establish evidence‐based practice.

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

“…Despite that it is generally accepted that inadequately treated rejection is adversely associated with allograft function and patient survival, 1,5,37–40 there is limited evidence on the optimal treatment for TCMR in children 10,28 . Our study demonstrates that the standard treatment for rejection is ineffective.…”

“…Good evidence is particularly lacking in borderline TCMR, resulting in inconsistencies of treatment approaches among and within centers, which range from no treatment to increasing maintenance immunosuppression alone to high-dose IV steroids. 1,2,9,10,41 In this study, 85% of borderline TCMR cases were treated, which may reflect a bias toward treatment in the two participating centers with an expressed commitment to FUB. In addition, the standard practice at each center was to persistently treat refractory rejection until it was completely resolved on subsequent FUB, which may explain the lack of difference in long-term graft outcome in those who were initially refractory to treatment on the first FUB.…”

“…To improve treatment for rejection, high‐quality clinical trials evaluating alternative therapies are needed, and must include biopsy confirmation to determine response. Good evidence is particularly lacking in borderline TCMR, resulting in inconsistencies of treatment approaches among and within centers, which range from no treatment to increasing maintenance immunosuppression alone to high‐dose IV steroids 1,2,9,10,41 . In this study, 85% of borderline TCMR cases were treated, which may reflect a bias toward treatment in the two participating centers with an expressed commitment to FUB.…”

“…Lymphocyte depleting therapies such as ATG are often used in more severe rejection forms in conjunction with IV steroids; however, there is not a standard approach for when it should be used. 10,42,43 In a 2017 systematic review and meta-analysis, the use of depleting antibody therapy for the treatment of TCMR was found to be 50% more effective at reversing rejection and 20% more effective at preventing graft loss than steroid treatment alone, but at the expense of greater side effects. 44 However, in our study, only 17% of patients with grade ≥1A TCMR and one patient with borderline TCMR received ATG.…”

Considerations and controversies of pharmacologic management of the pediatric kidney transplant recipient

“…Antithymocyte globulin antibody therapies, including eATG and rATG, demonstrated improved reversal of ACR compared with steroids for treatment of first rejection episode, but considerations need to be made regarding the negative sequelae of eATG or rATG administration. A recent single center analysis also reinforced the efficacy of rATG at improving renal function during ACR episodes in the pediatric KTR population 149 …”