Abstract
Accurate measurement of glomerular filtration rate (GFR) is essential for optimal decision making in many clinical settings of renal failure. We aimed to show that GFR can be accurately measured using compartmental tracer kinetic analysis of 18F-fluoride dynamic PET/CT. Twenty-three male Sprague-Dawley rats of three experimental groups (cyclosporine-administered [n = 8], unilaterally nephrectomized [n = 8], and control [n = 7]) underwent simultaneous 18F-fluoride dynamic PET/CT and reference 51Cr-EDTA GFR (GFRCrEDTA) test at day 0 and post-intervention day 3. 18F-fluoride PET GFR (GFRF-PET) was calculated by multiplying the influx rate and functional kidney volume in a single-tissue-compartmental kinetic model. Within-test repeatability and between-test agreement were evaluated by intraclass correlation coefficient (ICC) and Bland-Altman analysis. In the control group, repeatability of GFRF-PET was excellent (ICC = 0.9901, repeatability coefficient = 12.5%). GFRF-PET significantly decreased in the renally impaired rats in accordance with respective GFRCrEDTA changes. In the pooled population, GFRF-PET agreed well with GFRCrEDTA with minimal bias (−2.4%) and narrow 95% limits of agreement (−25.0% to 20.1%). These data suggest that the single-compartmental kinetic analysis of 18F-fluoride dynamic PET/CT is an accurate method for GFR measurement. Further studies in humans are warranted.
Highlights
The glomerular filtration rate (GFR) is a widely accepted measure of global renal function, and accurate measurement of GFR is essential for optimal decision making in many clinical settings of renal failure[1]
The repeatability of 18F-fluoride Positron emission tomography (PET) GFR (GFRF-PET) was excellent (ICC = 0.9901 [95% CI = 0.9501–0.9982], repeatability coefficient = 12.5%), whereas the repeatability of 51Cr-ethylenediamine-tetraacetic acid (EDTA) GFR (GFRCrEDTA) was slightly lower than that of GFRF-PET (ICC = 0.9372 [95% CI = 0.7155–0.9887], repeatability coefficient = 22.2%; Fig. 1)
We developed a compartmental tracer kinetic model for PET-based GFR measurement and applied it to 18F-fluoride, which is not a GFR tracer under the conventional concept of urinary or plasma clearance measurement
Summary
The glomerular filtration rate (GFR) is a widely accepted measure of global renal function, and accurate measurement of GFR is essential for optimal decision making in many clinical settings of renal failure[1]. Plasma clearance of a filtration marker, such as 51Cr-ethylenediamine-tetraacetic acid (EDTA), has been advocated for GFR measurement because of its acceptable accuracy without the necessity for tricky urine handling[3]. The previous 18F-fluoride dynamic PET/CT study reported a moderate correlation of fluoride clearance with a broad range of renal function parameters; the direct measurement of GFR was beyond the scope[13]. We hypothesized that because the compartmental modelling allows the separate quantification of influx and efflux rates, we might be able to quantify GFR using 18F-fluoride influx rate despite the presence of tubular reabsorption. We showed that GFR could be accurately measured in rats via compartmental modelling of dynamic 18F-fluoride PET/CT. Validity of the compartmental model was independently tested by calculating GFR using dynamic PET/CT scans of 68Ga-NOTA
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