Correlation between insulin-like growth factor 1 levels and tacrolimus dose in pediatric liver recipients

Abstract

Introduction. To prevent post-transplant complications associated with unbalanced immunosuppression, objective indicators reflecting the state of the immune system and associated with the immunosuppressant dose are required. In pediatric liver transplantation, an important indicator of hepatocellular function and restoration of anthropometric characteristics is insulin-like growth factor 1 (IGF-1), which exhibits both nonspecific and selective immunomodulator properties.Objective: to assess the correlation between growth hormone and IGF-1 levels and tacrolimus dose and blood concentrations in pediatric liver recipients and to determine the possibility of using the IGF-1 level in selecting the drug dose required to achieve its target concentration in the blood. Materials and methods. We examined 156 children aged from 2 to 105 (median – 8) months with liver cirrhosis of various etiology, who received liver from a living related donor. The concentration of growth hormone and IGF-1 was determined in blood plasma before, one month, and one year after transplantation using the enzyme-linked immunosorbent assay. Tacrolimus residual concentration was measured in the patient’s whole blood by immunochemical method.Results. Growth hormone levels in the blood of pediatric liver recipients did not correlate with the dose or concentration of immunosuppressant tacrolimus one month or one year after transplantation, whereas the IGF-1 content was directly related to tacrolimus dose one year later (r = 0.41, p = 0.001), but not a month after surgery. The correlation coefficient was higher in uncomplicated post-transplant recipients (r = 0.51, p = 0.002) than in those with complications (r = 0.26, p = 0.17). The diagnostic efficiency of the IGF-1 level as an objective criterion for selecting the tacrolimus dose required to achieve its target blood concentration was 0.80 ± 0.11; 95% CI [0.58–1.00] (p = 0.007). In recipients with blood IGF-1 levels ≥115.7 ng/mL, the probability of prescribing a tacrolimus dose ≥0.25 mg/kg/day was 14 times higher than in children with lower blood IGF-1 levels. The estimated accuracy of the test was 83%, positive predictive value was 71%, and negative predictive value was 85%.Conclusion. The IGF-1 level was found to correlate with tacrolimus dose in liver transplant recipients one year after transplantation. The diagnostic efficiency of IGF-1 as a potential indicator for choosing the tacrolimus dose required to achieve its target blood concentration is 80%, which suggests further study of the test to assess the effectiveness of immunosuppression and selection of an individual immunosuppressant dose.

Keywords

• living-donor liver transplantation
• congenital biliary tract diseases
• biomarker
• effectiveness of immunosuppression