Hemoglobin and Cholesterol Affect Apparent Tacrolimus Clearance in Pediatric Transplant Recipients-A Retrospective Cohort Study.

Abstract

Background: Tacrolimus has a narrow therapeutic index with substantial inter- and intra-patient variability, requiring therapeutic drug monitoring (TDM). Influences beyond genetic and developmental factors need to be better understood. Recent studies among adult patients suggest that hemoglobin affects the apparent clearance (CL/F) of tacrolimus, whereas this and other potential factors in children are under-investigated.

Methods: After ethics approval, we performed a single-center retrospective cohort study of pediatric renal transplant recipients between January 1, 2004, and June 30, 2018. Patients without tacrolimus therapy or those with concomitant sirolimus were excluded. Apparent clearance (CL/F) was predicted for this analysis using a regression equation derived from 12-point pharmacokinetic (PK) profiles. The equation allowed for the estimation of the area under the curve (AUC) from trough levels, which were then used to calculate CL/F. Data were collected from electronic health records, and univariate and multivariate mixed-effect regression analyses were performed to evaluate the impact of hemoglobin, albumin, cholesterol, and HDL on CL/F.

Results: Thirty-three patients were included. The median age at transplantation was 10 years, 52% were female, and the median tacrolimus AUC was 133 ng•h/mL. CL/F correlated with hemoglobin (n = 1257, r = -0.3767, p < 0.0001), HDL-cholesterol (n = 236, r = -0.3973, p < 0.0001), and total cholesterol (n = 373, r = -0.1821, p = 0.0004). In multivariate mixed-effect regression, hemoglobin and cholesterol remained significant predictors of CL/F.

Conclusions: The present study suggests a moderate impact of hemoglobin and cholesterol on tacrolimus CL/F. Lower hemoglobin appears to increase CL/F, while higher cholesterol reduces it. These findings highlight the potential value of integrating biochemical parameters into dosing strategies to optimize TDM in pediatric kidney transplant recipients.