Fluorescence-Enhanced Europium-Diethylenetriaminepentaacetic (DTPA)-Monoamide Complexes for the Assessment of Renal Function

Chinen, Lori K.; Galen, Karen P.; Kuan, K. T.; Dyszlewski, Mary; Ozaki, Hiroaki; Sawai, Hiroaki; Pandurangi, Raghootama S.; Jacobs, Frederick G.; Dorshow, Richard B.; Rajagopalan, Raghavan

doi:10.1021/jm070842+

Cited by 36 publications

(28 citation statements)

References 32 publications

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“…[4][5][6][7][8][9] Recently, Wang et al 9 introduced a ratiometric fluorescent technique based on the measurement of a reporter and a marker substance using a fluorescent microscope and a two compartment mathematical model in anesthetized rats. The use of a ratiometric technique to overcome movement artifacts is of high interest especially in measurements in freely moving animals.…”

Section: Comparison To Other Approachesmentioning

confidence: 99%

Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves

Schock-Kusch

Xie

Shulhevich

et al. 2011

Kidney International

121

103

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Determination of the urinary or plasma clearance of exogenous renal markers, such as inulin or iohexol, is considered to be the gold standard for glomerular filtration rate (GFR) measurement. Here, we describe a technique allowing determination of renal function based on transcutaneously measured elimination kinetics of fluorescein isothiocyanate (FITC)-sinistrin, the FITC-labeled active pharmaceutical ingredient of a commercially available marker of GFR. A low cost device transcutaneously excites FITC-sinistrin at 480 nm and detects the emitted light through the skin at 520 nm. A radio-frequency transmission allows remote monitoring and real-time analysis of FITC-sinistrin excretion as a marker of renal function. Due to miniaturization, the whole device fits on the back of freely moving rats, and requires neither blood sampling nor laboratory assays. As proof of principle, comparative measurements of transcutaneous and plasma elimination kinetics of FITC-sinistrin were compared in freely moving healthy rats, rats showing reduced kidney function due to unilateral nephrectomy and PKD/Mhm rats with cystic kidney disease. Results show highly comparable elimination half-lives and GFR values in all animal groups. Bland-Altman analysis of enzymatically compared with transcutaneously measured GFR found a mean difference (bias) of 0.01 and a -0.30 to 0.33 ml/min per 100 g body weight with 95% limit of agreement. Thus, with this device, renal function can be reliably measured in freely moving rats eliminating the need for and influence of anesthesia on renal function.

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Section: Comparison To Other Approachesmentioning

confidence: 99%

Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves

Schock-Kusch

Xie

Shulhevich

et al. 2011

Kidney International

121

103

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“…Several approaches for the transcutaneous measurement of glomerular filtration rate (GFR) in laboratory animals have been developed based on fluorescent markers [1]–[13].…”

Section: Introductionmentioning

confidence: 99%

Reliability of Transcutaneous Measurement of Renal Function in Various Strains of Conscious Mice

et al. 2013

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Measuring renal function in laboratory animals using blood and/or urine sampling is not only labor-intensive but puts also a strain on the animal. Several approaches for fluorescence based transcutaneous measurement of the glomerular filtration rate (GFR) in laboratory animals have been developed. They allow the measurement of GFR based on the elimination kinetics of fluorescent exogenous markers. None of the studies dealt with the reproducibility of the measurements in the same animals. Therefore, the reproducibility of a transcutaneous GFR assessment method was investigated using the fluorescent renal marker FITC-Sinistrin in conscious mice in the present study. We performed two transcutaneous GFR measurements within three days in five groups of mice (Balb/c, C57BL/6, SV129, NMRI at 3–4 months of age, and a group of 24 months old C57BL/6). Data were evaluated regarding day-to-day reproducibility as well as intra- and inter-strain variability of GFR and the impact of age on these parameters. No significant differences between the two subsequent GFR measurements were detected. Fastest elimination for FITC-Sinistrin was detected in Balb/c with significant differences to C57BL/6 and SV129 mice. GFR decreased significantly with age in C57BL/6 mice. Evaluation of GFR in cohorts of young and old C57BL/6 mice from the same supplier showed high consistency of GFR values between groups. Our study shows that the investigated technique is a highly reproducible and reliable method for repeated GFR measurements in conscious mice. This gentle method is easily used even in old mice and can be used to monitor the age-related decline in GFR.

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“…Alternative strategies using fluorescent markers have been adopted in experimental animals [26,27,28]. Some of these fluorescent markers are chelates of europium with DTPA [29], but they may have some drawbacks due to their nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Simplified Method to Measure Glomerular Filtration Rate by Iohexol Plasma Clearance in Conscious Rats

Carrara¹,

Azzollini²,

Nattino³

et al. 2016

Nephron

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Background/Aims: Glomerular filtration rate (GFR) is the best index for evaluating renal function. We aimed to develop a simplified iohexol plasma clearance procedure for GFR measurement in rats without urine collection, animal catheterization or anesthesia, with limited sampling and requiring blood instead of plasma, to further reduce the sample volume and improve animal welfare. Methods: After iohexol injection (129.4 mg), samples were drawn according to 2-compartment kinetics and analyzed by high performance liquid chromatography. Healthy male Lewis rats were used to find a correction factor (CF) to obtain the ‘reference clearance' from the simplified 1-comparment model. This approach was validated using male or female (Lewis, Sprague-Dawley) rats and animals with renal mass reduction (RMR). In additional rats, different simplified approaches were evaluated. Results: Iohexol concentrations in blood and plasma strongly correlated (r = 0.9784, p < 0.0001). A CF of 0.90 enabled the calculation of the reference GFR. Validation results in male Lewis rats were 0.99 ± 0.27 for the reference GFR and 1.03 ± 0.29 ml/min/100 g for the simplified approach. Results in female Sprague-Dawley rats confirmed the suitability of the proposed method. In RMR rats, GFR was 0.14 ± 0.05 and 0.14 ± 0.04 ml/min/100 g for the reference and simplified model, respectively. Conclusion: The procedure we set up to measure GFR in conscious rats was proven to be reliable, required a small volume of blood at only 4 selected time points, without the need to collect urine or catheterize the animals, was applicable to rats from different strains and sexes, both healthy and with renal function impairment. Moreover, the procedure enables the monitoring of GFR changes over time in the same animal, thereby reducing the number of animals to be used.

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Fluorescence-Enhanced Europium-Diethylenetriaminepentaacetic (DTPA)-Monoamide Complexes for the Assessment of Renal Function

Cited by 36 publications

References 32 publications

Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves

Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves

Reliability of Transcutaneous Measurement of Renal Function in Various Strains of Conscious Mice

Simplified Method to Measure Glomerular Filtration Rate by Iohexol Plasma Clearance in Conscious Rats

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