Online feedback–controlled renal constant infusion clearances in rats

Schock-Kusch, Daniel; Shulhevich, Yury; Xie, Qing; Hesser, Juergen; Stsepankou, Dzmitry; Neudecker, Sabine; Friedemann, Jochen; Koenig, Stefan; Heinrich, Ralf; Hoecklin, Friederike; Pill, Johannes; Gretz, Norbert

doi:10.1038/ki.2012.117

Cited by 23 publications

(22 citation statements)

References 22 publications

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“…Hence, the repeatability of a transcutaneous method for GFR assessment was evaluated for the first time [14]. The method, allowing measurement in conscious, freely moving mice, is based on the transcutaneous measurement of the elimination kinetics of the exogenous GFR marker FITC-Sinistrin [2]–[4], [7], [8], [10], [14], [15].…”

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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Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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“…However, a number of different CIC protocols are described in rodent experimentation, without a single recognized optimized procedure enjoying widespread use. 46 The model we describe goes some way to addressing the problems encountered by Wang et al, 36 and additionally has several advantages over commonly used in vivo models. We are able to inflict a reproducible and severe renal IRI without excessive post-operative mortality, and by cannulating both ureters in a terminal procedure, are able to accurately calculate the GFR of each kidney by inulin clearance.…”

Section: Discussionmentioning

confidence: 99%

“…45,46 Many different experimental approaches have been used to calculate GFR, with constant infusion clearance (CIC) or bolus clearance techniques, widely accepted methods. Both approaches are based on the clearance of exogenous renal markers, with inulin clearance regarded as the 'gold standard.'…”

Section: Discussionmentioning

confidence: 99%

A novel rodent model of severe renal ischemia reperfusion injury

et al. 2016

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Renal ischemia reperfusion injury (IRI) is a major problem, currently without treatments in clinical use. This reflects the failure of animal models to mimic the severity of IRI observed in clinical practice. Most described models lack both the ability to inflict a permanent reduction in renal function and the sensitivity to demonstrate the protective efficacy of different therapies in vivo. To test novel cell-based therapies, we have developed a model of renal IRI in Fisher 344 rats. Animals were subjected to 120 min of unilateral warm ischemia, during which they underwent an intra-renal artery infusion of therapeutic agents or vehicle. At either 2 or 6 weeks post-surgery, animals underwent terminal glomerular filtration rate (GFR) studies by inulin clearance to most accurately quantify renal function. Harvested kidneys underwent histological analysis. Compared to sham operations, saline treated animals suffered a long-term reduction in GFR of &50%. Histology revealed short-and long-term disruption of renal architecture. Despite the injury severity, postoperative animal losses are 55%. This model produces a severe, consistent renal injury that closely replicates the pathological processes encountered in clinical medicine. Renal artery infusion mimics the route likely employed in clinical transplantation, where the renal artery is accessible. Inulin clearance characterizes GFR, allowing full assessment of therapeutic intervention. This model is useful for screening therapeutic agents prior to testing in a transplant model. This reduces animal numbers needed to test drugs for clinical transplantation and allows for refinement of dosing schedules.

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“…Sinistrin, a derivative of inulin with increased solubility, and FITC-sinistrin has been used in bolus and continuous infusion studies in rats. 67,68,72 These later studies were accomplished using a transcutaneous fluorescence excitation emitter and an emission monitor that detects ECF fluorescence through the skin. Transcutaneous detection of fluorescent sinistrin has also been used in cats and dogs 73 , and a detector that allows continuous monitoring has been developed for use in awake mice.…”

Section: Translating Fluorescence Measurements Into Clinical Observatmentioning

confidence: 99%

Rethinking CKD Evaluation: Should We Be Quantifying Basal or Stimulated GFR to Maximize Precision and Sensitivity?

Molitoris

2017

American Journal of Kidney Diseases

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Chronic kidney disease (CKD) remains an increasing clinical problem. Although clinical risk factors and biomarkers for development and progression of CKD have been identified, there is no commercial surveillance technology to definitively diagnose and quantify the severity and progressive loss of glomerular filtration rate (GFR) in CKD. This has limited the study of potential therapies to late stages of CKD when FDA-registerable events are more likely. Since patient outcomes, including the rate of CKD progression, correlate with disease severity, and effective therapy may require early intervention, being able to diagnose and stratify patients by their level of decreased kidney function early on is key for translational progress. In addition, renal reserve, defined as the increase in GFR following stimulation, may improve the quantification of GFR based solely on basal levels. Various groups are developing and characterizing optical measurement techniques utilizing new minimally invasive or non-invasive approaches for quantifying basal and stimulated kidney function. This development has the potential to allow widespread individualization of therapy at an earlier disease stage. Therefore, the purposes of this review are to suggest why quantifying stimulated GFR, by activating renal reserve, may be advantageous in patients and review fluorescent technologies to deliver patient-specific GFR.

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Online feedback–controlled renal constant infusion clearances in rats

Cited by 23 publications

References 22 publications

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

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

A novel rodent model of severe renal ischemia reperfusion injury

Rethinking CKD Evaluation: Should We Be Quantifying Basal or Stimulated GFR to Maximize Precision and Sensitivity?

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