Efficacy of Acute Cellular Rejection Treatment According to Banff Score in Kidney Transplant Recipients: A Systematic Review

Lamarche, Caroline; Côté, Jean-Maxime; Senécal, Lynne; Cardinal, Héloïse

doi:10.1097/txd.0000000000000626

Cited by 33 publications

(37 citation statements)

References 20 publications

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“…Identifying different rejection subtypes is important as the underlying biological drivers are likely different, and effective resolution of each type of rejection episode requires disparate treatments. Treatment of CMR is well defined with the use of corticosteroids and T cell depleting agents ( 16 ), but effective treatments for AMR remain to be identified, despite some efficacy for AMR resolution from plasmapheresis, intravenous immune globulin, and B cell depletion ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Novel Non-Histocompatibility Antigen Mismatched Variants Improve the Ability to Predict Antibody-Mediated Rejection Risk in Kidney Transplant

et al. 2017

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Transplant rejection is the critical clinical end-point limiting indefinite survival after histocompatibility antigen (HLA) mismatched organ transplantation. The predominant cause of late graft loss is antibody-mediated rejection (AMR), a process whereby injury to the organ is caused by donor-specific antibodies, which bind to HLA and non-HLA (nHLA) antigens. AMR is incompletely diagnosed as donor/recipient (D/R) matching is only limited to the HLA locus and critical nHLA immunogenic antigens remain to be identified. We have developed an integrative computational approach leveraging D/R exome sequencing and gene expression to predict clinical post-transplant outcome. We performed a rigorous statistical analysis of 28 highly annotated D/R kidney transplant pairs with biopsy-confirmed clinical outcomes of rejection [either AMR or T-cell-mediated rejection (CMR)] and no-rejection (NoRej), identifying a significantly higher number of mismatched nHLA variants in AMR (ANOVA—p-value = 0.02). Using Fisher’s exact test, we identified 123 variants associated mainly with risk of AMR (p-value < 0.001). In addition, we applied a machine-learning technique to circumvent the issue of statistical power and we found a subset of 65 variants using random forest, that are predictive of post-tx AMR showing a very low error rate. These variants are functionally relevant to the rejection process in the kidney and AMR as they relate to genes and/or expression quantitative trait loci (eQTLs) that are enriched in genes expressed in kidney and vascular endothelium and underlie the immunobiology of graft rejection. In addition to current D/R HLA mismatch evaluation, additional mismatch nHLA D/R variants will enhance the stratification of post-tx AMR risk even before engraftment of the organ. This innovative study design is applicable in all solid organ transplants, where the impact of mitigating AMR on graft survival may be greater, with considerable benefits on improving human morbidity and mortality and opens the door to precision immunosuppression and extended tx survival.

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Section: Introductionmentioning

confidence: 99%

Novel Non-Histocompatibility Antigen Mismatched Variants Improve the Ability to Predict Antibody-Mediated Rejection Risk in Kidney Transplant

et al. 2017

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“…A limitation of creatinine-based definitions of treatment response is their important variation across studies. 5 , 6 , 25 , 28 Even though kidney function was back to baseline after treatment, 15% of our respondents were still unsure that acute rejection had been sufficiently treated, 5% were somewhat doubtful, and 3% were not confident. This may explain why 30% of respondents assessed histological response to treatment independent of changes in kidney function.…”

Section: Discussionmentioning

confidence: 85%

“…Older studies performed in patients with vascular (Banff 2-3) or corticosteroid-resistant Banff grade 1 rejections showed poor correlation between the reversal of serum creatinine and histological clearance of rejection on a posttreatment protocol biopsy. 26 , 27 While maintenance immunosuppressive protocols have since changed, 20 we have recently reviewed the literature 5 and found no recent data reporting on the value of changes in serum creatinine to predict histological reversal.…”

Section: Discussionmentioning

confidence: 99%

“…A major problem inhibiting reliable comparison of novel treatments in multisite clinical trials is the absence of a uniform standardized protocol to treat TCMR in Canada. Given the weak strength of the evidence on which clinical guidelines are based 2 and the heterogeneity of existing literature, 5 there is also no uniformly accepted clinical conduct related to the use of surveillance biopsies, the treatment of subclinical acute rejection, the definition of response to treatment, and how it should be monitored. 2 , 5 , 6 Hence, the aim of this study was to gather clinicians’ views and practice patterns on the diagnosis, treatment, and monitoring of acute TCMR in Canada.…”

Section: Introductionmentioning

confidence: 99%

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Practice Patterns in the Treatment and Monitoring of Acute T Cell–Mediated Kidney Graft Rejection in Canada

Leblanc

Subrt²,

Paré

et al. 2018

Can J Kidney Health Dis

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Background:One of the goals of the Canadian National Transplant Research Program (CNTRP) is to develop novel therapies for acute rejection that could positively affect graft outcomes with greater efficacy or less toxicity. To develop innovative management strategies for kidney graft rejection, new modalities need to be compared with current clinical practices. However, there are no standardized practices concerning the management of acute T cell–mediated rejection (TCMR).Objectives:To describe clinicians’ practice patterns in the diagnosis, treatment, and monitoring of acute TCMR in Canada.Design:Survey.Setting, Patients/Participants:Canadian transplant nephrologists and transplant surgeons involved in the management of acute TCMR.Methods and Measurements:We developed an anonymous, web-based survey consisting of questions related to the diagnosis, treatment, and monitoring of TCMR. The survey was disseminated on 3 occasions between June and October 2016 through the Canadian Society of Transplantation (CST) kidney group electronic mailing list.Results:Forty-seven respondents, mostly transplant nephrologists (97%), originating from at least 18 of the 25 Canadian centers offering adult or pediatric kidney transplantation, participated in the study. Surveillance biopsies were used by 28% of respondents to screen for kidney graft rejection. High-dose steroids were used by most of the respondents to treat clinical and subclinical Banff grade 1A and 1B rejections. Nine percent (95% confidence interval [CI]: 1-17) of practitioners used lymphocyte-depleting agents as the first-line approach for the treatment of Banff grade 1B acute rejection. Eighteen percent (95% CI: 7-29) and 36% (95% CI: 8-65) of respondents reported that they would not use high-dose steroids for treating clinical and subclinical borderline rejections, respectively. Seventy percent (95% CI: 54-83) of respondents answered that there was no indication to assess histological response to treatment independent of the change in kidney function.Limitations:The limitations of this study are its limited sample size and the low representation of pediatric specialists.Conclusions:There is heterogeneity regarding the use of surveillance biopsies, treatment of borderline rejection, and modalities to monitor treatment response among transplant physicians. Our results illustrate the current state of practice patterns across Canada and can be used to inform the design of future trials.

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“…Death-censored allograft survival was comparable for aTCMR I, aTCMR II+III, ABMR and mixed-type rejection. Surprisingly, kidney function after 12 months in patients with aTCMR grade II+III was superior to those with aTCMR grade I. Allograft survival rates according to Banff grade rejection have been described by others [ 29 , 30 ] and showed better allograft survival in patients with aTCMR I than in patients with aTCMR II and III. Our surprising finding may have resulted from a longer interval between pulse glucocorticoids and rATG in patients with aTCMR grade I.…”

Section: Discussionmentioning

confidence: 72%

The Efficacy of Rabbit Anti-Thymocyte Globulin for Acute Kidney Transplant Rejection in Patients Using Calcineurin Inhibitor and Mycophenolate Mofetil-Based Immunosuppressive Therapy

et al. 2018

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BackgroundT cell depleting antibody therapy with rabbit anti-thymocyte globulin (rATG) is the treatment of choice for glucocorticoid-resistant acute kidney allograft rejection (AR) and is used as first-line therapy in severe AR. Almost all studies investigating the effectiveness of rATG for this indication were conducted at the time when cyclosporine A and azathioprine were the standard of care. Here, the long-term outcome of rATG for AR in patients using the current standard immunosuppressive therapy (i.e., tacrolimus and mycophenolate mofetil) is described.Material/MethodsBetween 2002 to 2012, 108 patients were treated with rATG for AR. Data on kidney function in the year following rATG and long-term outcomes were collected.ResultsOverall survival after rATG was comparable to overall survival of all kidney transplantation patients (P=0.10). Serum creatinine 1 year after rATG was 179 μmol/L (interquartile range (IQR) 136–234 μmol/L) and was comparable to baseline serum creatinine (P=0.22). Early AR showed better allograft survival than late AR (P=0.0007). In addition, 1 year after AR, serum creatinine was lower in early AR (157 mol/L; IQR 131–203) compared to late AR (216 mol/L; IQR 165–269; P<0.05). The Banff grade of rejection, kidney function at the moment of rejection, and reason for rATG (severe or glucocorticoid resistant AR) did not influence the allograft survival.ConclusionsTreatment of AR with rATG is effective in patients using current standard immunosuppressive therapy, even in patients with poor allograft function. Early identification of AR followed by T cell depleting treatment leads to better allograft outcomes.

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Efficacy of Acute Cellular Rejection Treatment According to Banff Score in Kidney Transplant Recipients: A Systematic Review

Abstract: Supplemental digital content is available in the text.

Cited by 33 publications

References 20 publications

Novel Non-Histocompatibility Antigen Mismatched Variants Improve the Ability to Predict Antibody-Mediated Rejection Risk in Kidney Transplant

Novel Non-Histocompatibility Antigen Mismatched Variants Improve the Ability to Predict Antibody-Mediated Rejection Risk in Kidney Transplant

Practice Patterns in the Treatment and Monitoring of Acute T Cell–Mediated Kidney Graft Rejection in Canada

The Efficacy of Rabbit Anti-Thymocyte Globulin for Acute Kidney Transplant Rejection in Patients Using Calcineurin Inhibitor and Mycophenolate Mofetil-Based Immunosuppressive Therapy

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