Higher Serum Trough Levels of Tacrolimus Increase 5-Year Allograft Survival in Antibody Positive Renal Transplant Patients.

Abstract

Background: The presence of human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related gene-A (MICA) antibodies after transplantation is correlated with rejection episodes, proteinuria, and renal allografts loss. We assessed the clinical value of high-dose tacrolimus on post-transplant HLA and MICA antibodies and proteinuria after renal transplantation.

Methods: Post-transplant sera of 310 renal transplantation patients who were negative for antibodies prior to transplant were tested by Luminex flow cytometry for HLA antibodies and MICA antibodies posttransplant. Once a patient was found to be antibody positive (Ab+), tacrolimus was dosed at two different concentrations: high tacrolimus Ab+ group (11 ± 1.36 ng/mL average tacrolimus trough) or low tacrolimus Ab+ group (7 ± 1.28 ng/mL average tacrolimus trough). Antibody negative (Ab-) patients were also studied and were given comparable tacrolimus doses to the low tacrolimus Ab+ group (7 ± 1.28 ng/mL average tacrolimus trough). Proteinuria was measured using the pyrogallol method. All patients were followed for 5 years after renal transplantation. Associations between tacrolimus, proteinuria, and survival were analyzed.

Results: In the HLA or MICA Ab+ patients, proteinuria decreased after 5 years in the high tacrolimus Ab+ group unlike the low tacrolimus Ab+ group. Allograft survival in the high tacrolimus Ab+ group was significantly higher than the low tacrolimus Ab+ group and was similar to that of the Ab- group.

Conclusions: High-dose tacrolimus might play a role in improving allograft survival in HLA or MICA Ab+ post-transplant patients. Increasing tacrolimus concentration might be a plausible treatment for Ab+ post-transplant patients.