title: Indicators of treatment responsiveness to rituximab and plasmapheresis in antibody-mediated rejection after kidney transplantation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Institute for Transfusion Medicine, Hannover Medical School, Hannover, Lower Saxony, Germany. 2 Institute of Pathology, Hannover Medical School, Hannover, Lower Saxony, Germany. 3 Clinic for Nephrology and Hypertension, Hannover Medical School, Hannover, Lower Saxony, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Immenschuh
authors.forename: Eva
authors.initials: E
authors.lastname: Zilian
authors.forename: Max E
authors.initials: ME
authors.lastname: Dämmrich
authors.forename: Anke
authors.initials: A
authors.lastname: Schwarz
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gwinner
authors.forename: Jan Ulrich
authors.initials: JU
authors.lastname: Becker
authors.forename: Cornelia A
authors.initials: CA
authors.lastname: Blume
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D018579:Patient Selection; D010956:Plasmapheresis / Q000009:adverse effects; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000097:blood / Q000276:immunology; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000069283:Rituximab