Impact of choice of kinetic model for the determination of transcutaneous FITC-sinistrin clearance in rats with streptozotocin-induced type 1 diabetes.

Abstract

Transcutaneous assessment of fluorescein isothiocyanate (FITC)-sinistrin clearance using an optical device was recently validated for determination of glomerular filtration rate (GFR) in conscious animals. In the current study, we compared four available kinetic models for calculating FITC-sinistrin clearance, to provide further insight into whether the choice of model might influence findings generated using this device. Specifically, we calculated the excretion half-life of FITC-sinistrin (minutes), rate constant (minute-1 ) and GFR indexed to bodyweight in control rats and rats with streptozotocin-induced diabetes across a 4-week experimental period using standard one-compartment (1-COM), two-compartment (2-COM) and three-compartment (3-COM) kinetic models (1-COM), and a three-compartment kinetic model with baseline correction (3-COMB). Glomerular hyperfiltration was detected in STZ-induced diabetic rats with the 2-COM or 3-COMB at day 14 and with the 3-COM at day 3 and 14 after induction of diabetes, but not at any time point using the 1-COM. From a theoretical perspective, we reasoned that the 3-COMB model provides a better estimate of t1/2 than the other models. Linear regression analysis of data generated using the 3-COMB showed a significant relationship between blood glucose and calculated GFR at the day 14 (P=.004) and day 28 (P=.01) time points, and a strong tendency for a relationship at the day 3 time point (P=.06). We conclude that hyperfiltration is an early and sustained characteristic of STZ-induced diabetes in rats. Furthermore, we propose that the 3-COMB model provides the most valid t1/2 for estimation of GFR via transcutaneous detection of FITC-sinistrin clearance.