Optimal Sampling Strategies to Assess Inulin Clearance in Children by the Inulin Single-Injection Method

L. K. van Rossum
2003 Clinical Chemistry  
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
more » ... ction 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 Doptimality 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 ac-curate 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. Measurement of renal function, i.e., glomerular filtration rate (GFR), 3 is essential for evaluating suspected renal diseases and for studying changes in renal function in patients with renal failure. The ideal marker is freely filtered by the glomerulus; not reabsorbed, secreted, or metabolized by the kidney; physiologically inert; and does not alter renal function. Inulin, an exogenous marker, is such a marker, and its renal clearance during continuous intravenous infusion is regarded as the gold standard for measuring GFR in children (1 ). This method, however, is complex, time-consuming, invasive, and requires urine collection. For these reasons, renal inulin clearance is not routinely used in the clinical setting. An alternative method, which can be performed without collection of urine, is the determination of plasma clearance of inulin. Plasma clearance of inulin can be measured by use of either a continuous intravenous infusion or a single bolus injection. The former method is more accurate, but is time-consuming because a steady-state situation has to be achieved (1 ). With the latter method, a bolus injection of inulin is administered, and 10 to 12 serial blood samples are collected for the construction of a plasma concentration-time decay curve. Adequate results have been reported with this method in adults (2, 3 ), but for practical and convenient application in children, it is
doi:10.1373/49.7.1170 pmid:12816915 fatcat:j3awz5ix2jhf3fp2va3qwawjea