Antibody-mediated rejection and treatment in pediatric patients: one center's experience

Exp Clin Transplant. 2013 Oct;11(5):404-7. doi: 10.6002/ect.2012.0242.

Abstract

Objectives: Antibody-mediated rejection is a rare complication that often results in the loss of the kidney graft. Treatment options include plasmapheresis, intravenous immunoglobulin, and use of rituximab.

Materials and methods: We retrospectively evaluated the data files from 86 pediatric renal transplant patients over the last 5 years. A biopsy was taken for each rejection episode.

Results: Seven patients (7.7%) developed antibody-mediated rejection. All patients with antibody-mediated rejection had histologic evidence of severe acute humoral rejection and extensive C4d staining in peritubular capillaries. Staining was diffuse (involving > 50% of peritubular capillaries) for 4 biopsies, and it was focal (involving < 50% of peritubular capillaries) for 3 biopsies. Twelve biopsies demonstrated at least 1 histologic feature associated with acute humoral rejection. Donor-specific antibodies were evaluated in recipients. The mean peak panel reactive antibody class 1 was 7.16% (range, 0%-86%). The mean time between rejection episodes and the transplant was 16.9 ± 13.5 months. All patients were treated with high-dose intravenous methylprednisolone and intravenous immunoglobulin. Three patients recovered renal function rapidly after this treatment. Donor-specific antibodies were negative in these patients. Five sessions of plasmapheresis were used simultaneously in these 4 patients. In 3 resistant patients, rituximab was prescribed after plasmapheresis and intravenous immunoglobulin. The presence of donor-specific antibodies was demonstrated in 4 patients. Two patients were refractory to antibody-mediated rejection treatment and lost their transplants. One patient had interstitial fibrosis and tubular atrophy during the 16th month after her antibody-mediated rejection. Graft survival in patients with antibody-mediated rejection at the end of 1 year was 71.4%.

Conclusions: Early diagnosis and treatment with plasmapheresis, intravenous immunoglobulin, and rituximab may resolve antibody-mediated rejection. Although effective therapy is available for acute antibody-mediated rejection, the allograft remains at risk for chronic antibody-mediated rejection and shortened survival.

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Biomarkers / analysis
  • Biopsy
  • Child
  • Complement C4b / analysis
  • Early Diagnosis
  • Female
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • Graft Rejection / mortality
  • Graft Rejection / therapy
  • Graft Survival* / drug effects
  • Humans
  • Immunity, Humoral* / drug effects
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Isoantibodies / blood*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / mortality
  • Male
  • Methylprednisolone / therapeutic use
  • Peptide Fragments / analysis
  • Plasmapheresis
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Factors
  • Rituximab
  • Time Factors
  • Treatment Outcome
  • Turkey

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers
  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents
  • Isoantibodies
  • Peptide Fragments
  • Rituximab
  • Complement C4b
  • complement C4d
  • Methylprednisolone