Abstract
Glomerular filtration rate (GFR) is an essential parameter of kidney function which can be measured by dynamic contrast enhanced magnetic resonance imaging (MRI-GFR) and transcutaneous approaches based on fluorescent tracer molecules (optical-GFR). In an initial study comparing both techniques in separate measurements on the same animal, the correlation of the obtained GFR was poor. The goal of this study was to investigate if a simultaneous measurement was feasible and if thereby, the discrepancies in MRI-GFR and optical-GFR could be reduced. For the experiments healthy and unilateral nephrectomised (UNX) Sprague Dawley (SD) rats were used. The miniaturized fluorescent sensor was fixed on the depilated back of an anesthetized rat. A bolus of 5 mg/100 g b.w. of FITC-sinistrin was intravenously injected. For dynamic contrast enhanced perfusion imaging (DCE-MRI) a 3D time-resolved angiography with stochastic trajectories (TWIST) sequence was used. By means of a one compartment model the excretion half-life (t1/2) of FITC-sinistrin was calculated and converted into GFR. GFR from DCE-MRI was calculated by fitting pixel-wise a two compartment renal filtration model. Mean cortical GFR and GFR by FITC-sinistrin were compared by Bland-Altman plots and pair-wise t-test. Results show that a simultaneous GFR measurement using both techniques is feasible. Mean optical-GFR was 4.34±2.22 ml/min (healthy SD rats) and 2.34±0.90 ml/min (UNX rats) whereas MRI-GFR was 2.10±0.64 ml/min (SD rats) and 1.17±0.38 ml/min (UNX rats). Differences between healthy and UNX rats were significant (p<0.05) and almost equal percentage difference (46.1% and 44.3%) in mean GFR were assessed with both techniques. Overall mean optical-GFR values were approximately twice as high compared to MRI-GFR values. However, compared to a previous study, our results showed a higher agreement. In conclusion, the possibility to use the transcutaneous method in MRI may have a huge impact in improving and validating MRI methods for GFR assessment in animal models.
Highlights
Renal diseases can lead to terminal kidney failure that requires life-long dialysis or renal transplantation
We investigated the feasibility of simultaneously measuring glomerular filtration rate (GFR) by two non-invasive techniques, namely DCEMRI and transcutaneous Fluorescein isothiocyanate (FITC)-sinistrin clearance
This approach enables the validation of MRI methods for GFR assessment in animals and, for the first time, a clearance procedure comparable to classical sinistrin [12,13,14] that is independent of blood/ urine sampling or laboratory assays
Summary
Renal diseases can lead to terminal kidney failure that requires life-long dialysis or renal transplantation. It is important to monitor renal function closely in populations at high risk to develop kidney diseases [1]. Several tracers are available for GFR evaluation, including endogenous markers such as creatinine and cystatin C, or exogenous markers, including iothalamate [2] or inulin, which is accepted as gold standard for determination of renal function. Current techniques for the measurement of GFR, such as clearance of inulin or sinistrin, scintigraphy with radio-labeled markers, and creatinine clearance are limited. Either they are invasive, expensive, result in a radiation exposure, or are inaccurate, e.g. because of serum creatinine dependency on muscular tissue mass and nutritional factors [5,6]. At the present time, GFR is only approximated using approaches such as the Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) or Modification of Diet in Renal Disease (MDRD) [7,8]
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