Questions regarding abo-incompatible kidney transplantation in children.

Abstract

We read with interest the article by Shishido et al. (1) describing the efficacy and safety of ABO-incompatible kidney transplantation in children. They concluded that the long-term graft outcome of ABO-incompatible living-donor kidney transplantation was comparable with that of ABO-compatible living-donor kidney transplantation. We have drawn the same conclusion, as reported previously (2). It becomes clear from both studies that transplantation across a major ABO barrier can be successful with adequate removal of isoagglutinin, adequate immunosuppression, and splenectomy. We have four questions for Dr. Shishido about their study. First, 10 of 16 cases in their series had rebound increase in isoagglutinin titers to greater than 1:64 or predepletion levels within 10 days after transplantation. In our study of 10 ABO-incompatible pediatric recipients, posttransplant isoagglutinin titers never exceeded 1:32, except in one patient. We wonder what caused this difference. We measured isoagglutinin titers by the saline method, indirect Coombs’ method, and bromelin method with macroscopic evaluation. We would like to know the methods they used for this measurement. Second, did the increases early in the posttransplant course lead to humoral rejection? In our series, acute rejection episodes occurred 11 times in 6 patients. Four of nine biopsy-proven episodes were grade IIb according to Banff classification, which is cellular rejection accompanied by humoral rejection. On the contrary, Shishido et al. (1) reported that nine patients experienced renal dysfunction in association with the rebound increases in anti-A/B antibodies, and three acute rejection episodes verified by allograft biopsy were grade Ia, or mild cellular rejection without humoral rejection. Was the increase found in their series directly associated with rejection episodes? Third, the initial immunosuppressive regimen in their series consisted of cyclosporine, methylprednisolone, cyclophosphamide (CPM), and anti-lymphocyte globulin in combination with preoperative plasmapheresis and intraoperative splenectomy. CPM was switched to azathioprine at 2 months after transplantation, probably for fear of side effects associated with long-term usage. On the other hand, mycophenolate mofetil has been approved for the prevention of renal allograft rejection (3). Mycophenolic acid selectively suppresses T and B lymphocytes and antibody formation and decreases glycosylation and expression of adhesion molecules, which interferes with the binding of activated lymphocytes to activated endothelial cells. These immunologic events play important roles in the rejection episode of ABO-incompatible transplantation. Therefore, we recommend regimens containing mycophenolate mofetil as a substitution for CPM or azathioprine. Takahashi (4) proposed introducing mycophenolate mofetil into ABO-incompatible kidney transplantation in a recently published book. What is the authors’ opinion regarding this proposal? Fourth, we are concerned that persistent stimulation of vascular endothelial cells by a high level of isoagglutinin after transplantation may result in chronic rejection in spite of accommodation, and we suspect that the patients should be continuously followed, especially for late allograft dysfunction. We would like to know what the authors think about this possibility. Toshiyuki Ohta1 Hiroshi Kawaguchi Kazunari Tanabe Motoshi Hattori Hiroshi Shiraga Katsumi Ito