Hemoglobin and Cholesterol Affect Apparent Tacrolimus Clearance in Pediatric Transplant Recipients – a Retrospective Cohort Study

Abstract

Introduction: Tacrolimus has a narrow therapeutic index with substantial inter- and intra-patient variability. Factors beyond genetic and developmental factors are poorly understood. Recent adult studies suggest that hemoglobin affects the apparent clearance (CL/F), whereas this and other potential factors in children are understudied. Methods: After ethics approval, we performed a single center retrospective cohort study of pediatric renal transplant recipients, who were followed between January 1st, 2004, and June 30th, 2018. Patients without tacrolimus therapy or concomitant sirolimus were excluded. The aim was to show the impact of hemoglobin, albumin, cholesterol and HDL on the apparent tacrolimus clearance (CL/F = Dose/AUC). Data were collected from electronic health record. We used 12-point pharmacokinetic (PK) profiles. Results: Thirty-three patients were included. Median age at transplantation was 10 years, 52% were female, the median tacrolimus area under the curve (AUC) was 133 ng*h/mL. CL/F mainly correlated with hemoglobin (n=1,257, 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). Conclusion: The present study suggests a moderate impact of the biochemical factors studied in the tacrolimus CL/F. Lower hemoglobin seems to increase it, while higher cholesterol decreases it. Physicians should be aware of this association during the TDM follow up.