A 32-year-old woman with a history of blood transfusions and one pregnancy underwent a living-donor renal transplant three weeks prior to presentation. Creatinine on discharge was 98 µmol/L. Her next blood test three days later shows a creatinine of 240 µmol/L. You suspect she has antibody-mediated rejection.
What are the findings on renal biopsy that suggest acute humoral rejection? How would you treat her?
The hallmark of acute humoral rejection is positive staining for C4d, a complement degradation product. Other histologic features vary by organ. In kidney transplants, these include peritubular capillaritis and glomerulitis. In addition, documentation of donor-specific antibodies (DSA) and typical morphologic changes on allograft biopsies are expected.
Treatment of acute humoral rejection requires removal of circulating donor-specific antibodies as well as suppression of the antibody-producing cells (plasma cells) producing them. Conventional immunosuppression has only limited effect in humoral rejection, although steroids and thymoglobulin do have some activity against B cells. Conventional maintenance immunosuppression is still required, as control of T-cell activity is required to control B-cell activation and proliferation.
Rapid removal of antibodies can be achieved by plasmapheresis. Intravenous immunoglobulin (IVIg) has multiple effects, among them the suppression of antibody production. Rituximab has been used to eliminate B cells. More recently, there is interest in using newer agents such as eculizumab (an inhibitor of terminal complement activation) and bortezomib (a proteasome inhibitor).