Treatment of C4d-positive acute humoral rejection with plasmapheresis and rabbit polyclonal antithymocyte globulin

Transplantation. 2004 May 15;77(9):1399-405. doi: 10.1097/


Background: Alloantibody-mediated acute rejection is a major cause of renal allograft loss despite aggressive therapy. Patients with humoral rejection can be identified with high sensitivity and specificity by the presence of peritubular capillary C4d staining on renal biopsy and donor-specific anti-human leukocyte antigen antibodies. Standard therapy for acute humoral rejection (AHR) has been removal of donor-specific antibodies by plasmapheresis (PPH) in conjunction with intravenous immunoglobulin therapy. We describe a series of seven patients with C4d positive AHR who received combined therapy with PPH and polyclonal rabbit antithymocyte globulin (rATG).

Methods: PPH (1.4 volume exchange) was initiated on diagnosis of AHR on an alternate day basis for a mean number of 6.8 treatments, in conjunction with rATG (0.75 mg/kg/day 5-10 days) until the serum creatinine returned to 120% of nadir.

Results: The nadir posttreatment creatinine was significantly lower than pretreatment creatinine (1.0+/-1.2 vs. 2+/-1.4, P <0.007) with only one episode of graft loss. On follow-up there was no difference in renal allograft survival between the AHR group and the 60 patients without AHR who underwent transplantation during the same period. We describe the ability of rATG to induce apoptosis in vitro peripheral blood and activated B cells.

Conclusion: Combination therapy using PPH and rATG is an effective means of reversing AHR in renal allografts.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adult
  • Animals
  • Antibody Formation
  • Antilymphocyte Serum / therapeutic use*
  • Apoptosis / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Combined Modality Therapy
  • Complement C4 / immunology*
  • Complement C4b*
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / therapy*
  • Humans
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Plasmapheresis*
  • Rabbits
  • Treatment Outcome


  • Antilymphocyte Serum
  • Complement C4
  • Peptide Fragments
  • Complement C4b
  • complement C4d