Indicators of treatment responsiveness to rituximab and plasmapheresis in antibody-mediated rejection after kidney transplantation

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Stephan Immenschuh
  • Eva Zilian
  • Max E. Dämmrich
  • Anke Schwarz
  • Wilfried Gwinner
  • Jan Ulrich Becker
  • Cornelia A. Blume

External Research Organisations

  • Hannover Medical School (MHH)
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Details

Original languageEnglish
Pages (from-to)56-62
Number of pages7
JournalTRANSPLANTATION
Volume99
Issue number1
Publication statusPublished - 15 Jan 2015
Externally publishedYes

Abstract

Background. Treatment of patients with antibody-mediated rejection (AMR) after kidney transplantation by rituximab and plasmapheresis is ambiguous. Because of its unknown efficiency and serious side effects, biomarkers, which are predictive for responsiveness to this treatment in AMR patients, are required.

Methods. Twenty renal transplant patients were included in this retrospective study. Selection was based on Renal Index Biopsies, classified according to Banff within 3 months before treatment. Patients were categorized into responders (R) and nonresponders (NR) depending on whether they returned to dialysis within 6 months after initiation of rituximab treatment. Clinical, histopathologic (Banff classification) and serologic parameters were compared between both groups by t test, Mann-Whitney U test, or likelihood ratio chi-square test.

Results. In comparisons between the groups, the R group showed a 1.5-fold higher level of estimated glomerular filtration rate and a fourfold lower level of proteinuria. By contrast, there were no differences in the histologic scores for chronic transplant lesions between the groups. The t and i scores were higher in NRs, whereas Banff-C4d scores of peritubular capillaries were increased in the Rs. Transplant biopsies in the Rs exhibited more CD138+ cell infiltrates. Serologic determination of human leukocyte antigen antibodies showed higher positivity for human leukocyte antigen class II donor-specific antibodies in the R group. No significant differences in other clinical criteria were found.

Conclusion. Increased proteinuria, decreased graft function, and a higher grade of tubulitis and inflammation in AMR are negative predictors for responsiveness to rituximab therapy. Rituximab therapy therefore should be initiated in an early phase of AMR.

ASJC Scopus subject areas

Cite this

Indicators of treatment responsiveness to rituximab and plasmapheresis in antibody-mediated rejection after kidney transplantation. / Immenschuh, Stephan; Zilian, Eva; Dämmrich, Max E. et al.
In: TRANSPLANTATION, Vol. 99, No. 1, 15.01.2015, p. 56-62.

Research output: Contribution to journalArticleResearchpeer review

Immenschuh S, Zilian E, Dämmrich ME, Schwarz A, Gwinner W, Becker JU et al. Indicators of treatment responsiveness to rituximab and plasmapheresis in antibody-mediated rejection after kidney transplantation. TRANSPLANTATION. 2015 Jan 15;99(1):56-62. doi: 10.1097/TP.0000000000000244
Immenschuh, Stephan ; Zilian, Eva ; Dämmrich, Max E. et al. / Indicators of treatment responsiveness to rituximab and plasmapheresis in antibody-mediated rejection after kidney transplantation. In: TRANSPLANTATION. 2015 ; Vol. 99, No. 1. pp. 56-62.
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abstract = "Background. Treatment of patients with antibody-mediated rejection (AMR) after kidney transplantation by rituximab and plasmapheresis is ambiguous. Because of its unknown efficiency and serious side effects, biomarkers, which are predictive for responsiveness to this treatment in AMR patients, are required.Methods. Twenty renal transplant patients were included in this retrospective study. Selection was based on Renal Index Biopsies, classified according to Banff within 3 months before treatment. Patients were categorized into responders (R) and nonresponders (NR) depending on whether they returned to dialysis within 6 months after initiation of rituximab treatment. Clinical, histopathologic (Banff classification) and serologic parameters were compared between both groups by t test, Mann-Whitney U test, or likelihood ratio chi-square test.Results. In comparisons between the groups, the R group showed a 1.5-fold higher level of estimated glomerular filtration rate and a fourfold lower level of proteinuria. By contrast, there were no differences in the histologic scores for chronic transplant lesions between the groups. The t and i scores were higher in NRs, whereas Banff-C4d scores of peritubular capillaries were increased in the Rs. Transplant biopsies in the Rs exhibited more CD138+ cell infiltrates. Serologic determination of human leukocyte antigen antibodies showed higher positivity for human leukocyte antigen class II donor-specific antibodies in the R group. No significant differences in other clinical criteria were found.Conclusion. Increased proteinuria, decreased graft function, and a higher grade of tubulitis and inflammation in AMR are negative predictors for responsiveness to rituximab therapy. Rituximab therapy therefore should be initiated in an early phase of AMR.",
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T1 - Indicators of treatment responsiveness to rituximab and plasmapheresis in antibody-mediated rejection after kidney transplantation

AU - Immenschuh, Stephan

AU - Zilian, Eva

AU - Dämmrich, Max E.

AU - Schwarz, Anke

AU - Gwinner, Wilfried

AU - Becker, Jan Ulrich

AU - Blume, Cornelia A.

N1 - Publisher Copyright: Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2015/1/15

Y1 - 2015/1/15

N2 - Background. Treatment of patients with antibody-mediated rejection (AMR) after kidney transplantation by rituximab and plasmapheresis is ambiguous. Because of its unknown efficiency and serious side effects, biomarkers, which are predictive for responsiveness to this treatment in AMR patients, are required.Methods. Twenty renal transplant patients were included in this retrospective study. Selection was based on Renal Index Biopsies, classified according to Banff within 3 months before treatment. Patients were categorized into responders (R) and nonresponders (NR) depending on whether they returned to dialysis within 6 months after initiation of rituximab treatment. Clinical, histopathologic (Banff classification) and serologic parameters were compared between both groups by t test, Mann-Whitney U test, or likelihood ratio chi-square test.Results. In comparisons between the groups, the R group showed a 1.5-fold higher level of estimated glomerular filtration rate and a fourfold lower level of proteinuria. By contrast, there were no differences in the histologic scores for chronic transplant lesions between the groups. The t and i scores were higher in NRs, whereas Banff-C4d scores of peritubular capillaries were increased in the Rs. Transplant biopsies in the Rs exhibited more CD138+ cell infiltrates. Serologic determination of human leukocyte antigen antibodies showed higher positivity for human leukocyte antigen class II donor-specific antibodies in the R group. No significant differences in other clinical criteria were found.Conclusion. Increased proteinuria, decreased graft function, and a higher grade of tubulitis and inflammation in AMR are negative predictors for responsiveness to rituximab therapy. Rituximab therapy therefore should be initiated in an early phase of AMR.

AB - Background. Treatment of patients with antibody-mediated rejection (AMR) after kidney transplantation by rituximab and plasmapheresis is ambiguous. Because of its unknown efficiency and serious side effects, biomarkers, which are predictive for responsiveness to this treatment in AMR patients, are required.Methods. Twenty renal transplant patients were included in this retrospective study. Selection was based on Renal Index Biopsies, classified according to Banff within 3 months before treatment. Patients were categorized into responders (R) and nonresponders (NR) depending on whether they returned to dialysis within 6 months after initiation of rituximab treatment. Clinical, histopathologic (Banff classification) and serologic parameters were compared between both groups by t test, Mann-Whitney U test, or likelihood ratio chi-square test.Results. In comparisons between the groups, the R group showed a 1.5-fold higher level of estimated glomerular filtration rate and a fourfold lower level of proteinuria. By contrast, there were no differences in the histologic scores for chronic transplant lesions between the groups. The t and i scores were higher in NRs, whereas Banff-C4d scores of peritubular capillaries were increased in the Rs. Transplant biopsies in the Rs exhibited more CD138+ cell infiltrates. Serologic determination of human leukocyte antigen antibodies showed higher positivity for human leukocyte antigen class II donor-specific antibodies in the R group. No significant differences in other clinical criteria were found.Conclusion. Increased proteinuria, decreased graft function, and a higher grade of tubulitis and inflammation in AMR are negative predictors for responsiveness to rituximab therapy. Rituximab therapy therefore should be initiated in an early phase of AMR.

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