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

Peng ZG, Tian J.

Clinical Transplants 2014, Chapter 26

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 eatment for Ab post-transplant patients.