Can intravenous immunoglobulin and simvastatin solve the problem of sensitization in renal transplant candidates?

Abstract

The value of intravenous immunoglobulin (IVIG) and simvastatin as potential modalities for the treatment of sensitized patients was evaluated by testing the efficacy of these agents on a relatively large cohort of adult hemodialysis patients (11) who were waiting for renal allotransplantation at our center. The patients had persistently positive crossmatches with their living related donors and a panel reactive antibody titer of more than 20%. All patients received IVIG (500 mg/kg per day on alternate days for a total of six doses); panel reactive antibody (PRA) titer and crossmatch testing were carried out after each dose and before each subsequent one. Two months after the last dose, eight patients received simvastatin (20 mg/day) for a period of 2 months; PRA titer and crossmatch testing were carried out every two weeks. Only four patients showed an insignificant reduction of PRA activity (P = 0.36); no patient attained a negative crossmatch. Simvastatin also resulted in an insignificant reduction of anti-human leukocyte antigen (HLA) antibodies in three patients (P = 0.32). We propose that IVIG or simvastatin alone can not effectively inhibit preformed anti-HLA antibodies to allow successful renal transplantation. Further trials on the use of IVIG and simvastatin with other modalities of treatment to desensitize these patients may be warranted.

Intravenous human immunoglobulin treatment of serum from HLA-sensitized patients in kidney transplantation

“…28 In addition, the unresponsiveness to IVIG treatment could be also explained, in accordance with some evidences, by a higher sensitization due to an increase of received blood units or to more pregnancies. [30][31][32] In conclusion, our data reveal that the variable effect of IVIG on reducing PRA in the HLA-sensitized patients could be attributed to a different inhibitory effect on complement, likely due to the type and the titre of anti-HLA antibodies. Similarly, Wassmuth et al showed that the immunomodulatory capacity is largely caused by the IgM/IgA fraction of IVIG when analyzed by lymphocytotoxicity.…”