Higher Serum Trough Levels of Tacrolimus Increase 5-Year Allograft Survival in Antibody Positive Renal Transplant Patients.
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.
Zhi-Guo
ZG
Peng
Jun
J
Tian
D000328:Adult; D015415:Biomarkers / Q000097:blood; D065095:Calcineurin Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006680:HLA Antigens / Q000097:blood*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000276:immunology / Q000517:prevention & control; D016559:Tacrolimus / Q000097:blood* / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D065095:Calcineurin Inhibitors; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016559:Tacrolimus