Average Tacrolimus Trough Level in the First Month After Transplantation May Predict Acute Rejection.
BACKGROUND
Although tacrolimus is one of the essential drugs used for the prevention of rejection in kidney recipients, target trough levels are not well established. In this study, we aimed to investigate the association between average tacrolimus trough levels (TTLs) of the first month after transplantation and biopsy-proven acute rejection (BPAR) during the first 12 months after transplant.


METHODS
A total of 274 patients who underwent kidney-alone transplantation between 2002 and 2014 were enrolled in the study. Average TTLs of the first month were assessed by means of receiver operating characteristic (ROC) curve analysis to discriminate patients with and those without BPAR. Univariate and multivariate Cox proportional hazards models were used to determine the effect of average TTLs of the first month on BPAR.


RESULTS
According to ROC curve analysis, the highest area under the curve (AUC) was obtained from 8 ng/mL (AUC = 0.73 ± 0.11; 95% confidence interval [CI], 0.62-0.84). Forty-two (31.8%) of the 132 patients with average TTLs <8 ng/mL and 13 (9.1%) of 142 patients with ≥8 ng/mL had BPAR during the first 12 months after transplant (P < .001). In univariable analysis, average TTLs of the first month <8 ng/mL were associated with higher risk of BPAR (P < .001), and the significance remained in Cox multivariable analysis (hazard ratio, 2.79; 95% CI, 1.76-3.82; P = .001). No significant differences were observed in the glomerular filtration rate, cytomegalovirus, BK viremia, or BK nephropathy between groups at post-transplant month 12.


CONCLUSIONS
Keeping the average TTLs of the first month after transplantation at ≥8 ng/mL not only prevents BPAR occurrence but also minimizes the toxic effects of the use of a single-trough level.
Department of Nephrology, Ankara University School of Medicine, Ankara, Turkey. Electronic address: serkan.akturkmd@gmail.com.
S
S
Aktürk
Department of Nephrology, Ankara University School of Medicine, Ankara, Turkey.
Ş
Ş
Erdoğmuş
Department of Nephrology, Ankara University School of Medicine, Ankara, Turkey.
G
G
Kumru
Department of Biostatistics, Ankara University School of Medicine, Ankara, Turkey.
A H
AH
Elhan
Department of Nephrology, Ankara University School of Medicine, Ankara, Turkey.
Ş
Ş
Şengül
Department of General Surgery, Ankara University School of Medicine, Ankara, Turkey.
A
A
Tüzüner
Department of Nephrology, Ankara University School of Medicine, Ankara, Turkey.
K
K
Keven
D000328:Adult; D001706:Biopsy; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000175:diagnosis* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012372:ROC Curve; D016559:Tacrolimus / Q000097:blood* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016559:Tacrolimus