Optimal sampling strategies to assess inulin clearance in children by the inulin single-injection method

Abstract

Background: Glomerular filtration rate in patients can be determined by estimating the plasma clearance of inulin with the single-injection method. In this method, a single bolus injection of inulin is administered and several blood samples are collected. For practical and convenient application of this method in children, it is important that a minimal number of samples are drawn. The aim of this study was to develop and validate sampling strategies with fewer samples for reliable prediction of inulin clearance in pediatric patients by the inulin single-bolus-injection method.

Methods: Complete inulin plasma concentration-time curves of 154 patients were divided into an index (n = 100) and a validation set (n = 54). A population pharmacokinetic model was developed for the index set. Optimal sampling times were selected based on D-optimality theory. For the validation set, Bayesian estimates of clearance were generated using the derived population parameters and concentrations at two to four sampling times. Bayesian estimates of clearance were compared with the individual reference values of clearance.

Results: The strategies with samples taken at 10/30/90/240 min, 10/30/240 min, 10/90/240 min, 30/90/240 min, and 90/240 min allowed accurate prediction of inulin clearance (bias <3% and not significantly different from 0; imprecision <15%).

Conclusions: Strategies involving two to four samples, including a sample at 240 min after administration of inulin, in the inulin single-injection method allow accurate prediction of inulin clearance in pediatric patients. Even one blood sample at 240 min showed acceptable performance. The proposed strategies are practical and convenient to children, and reduce repetitive blood sampling without compromising accuracy.