Are Anemic Patients More Sensitive to Calcineurin Inhibitors?

Abstract

A calcineurin inhibitor (CNI) is characterized by high affinity binding to red blood cells. There is a possibility that hematocrit levels might affect the immunosuppressive effects of cyclosporine (CsA). The purpose of this study was to examine whether the treatment with CNI was more effective in preventing acute rejection in anemic compared with nonanemic patients and to find a suitable method to monitoring immunosuppression. Ninety-five living donor renal transplant recipients who were treated with CsA were divided into five groups depending on their Ht levels. The incidences of biopsy-proven acute rejection were 1/8 (12.5%), 8/31 (25.8%), 6/28 (21.4%), 10/22 (45.5%), and 2/6 (33.3%) for Ht ≤ 25%, 25% < Ht ≤ 30%, 30% < Ht ≤ 35%, 35% < Ht ≤ 40%, and 40% < Ht, respectively. In vitro IL-2 mRNA inhibition tests were performed to evaluate lymphocyte function after stimulation of whole-blood with phorbol myristate acetate and Ca-ionophore in the presence of various concentrations of CsA. Whole blood CsA levels causing 50% inhibition of IL-2 mRNA (IC50) were 256, 310, 175, and 55 ng/mL for Ht 50%, 40%, 30%, and 20%, respectively. It is speculated that plasma concentrations of CsA may increase at low Ht levels, because lower incidences of acute rejection and lower IC50 values of CsA were observed in the anemic state. When the dosage of CsA was adjusted to its whole-blood concentration, the anemic state is likely to enhance the immunosuppressive effect of CsA. A pharmacodynamic study, such as the IL-2 mRNA inhibition test, is preferable for CsA monitoring.