A Pilot Study to Assess the Feasibility of Transcutaneous Glomerular Filtration Rate Measurement Using Fluorescence-Labelled Sinistrin in Dogs and Cats

Abstract

In dogs and cats an assessment of renal function is often needed, however, existing methods including urine and plasma clearances are invasive, cumbersome and time consuming. This pilot study evaluated the feasibility of a transcutaneous glomerular filtration rate (GFR) measurement in dogs and cats. Additionally the optimal dose and location for the transcutaneous measurement device were investigated. Renal elimination of fluorescein-isothiocyanate-labelled sinistrin (FITC-S) was measured transcutaneously for 4 hours. The procedures were performed in awake, freely moving animals using escalating doses of FITC-S (10 mg/kg, 30 mg/kg, 50 mg/kg) with a wash-out period of at least 24 h in between. Multiple devices were placed on each animal. The resulting FITC-S disappearance curves were visually assessed to determine the most suitable location and the appropriate dose to reach an adequate transcutaneous peak signal for kinetic analysis. In both species 30 mg/kg were adequate for kinetic calculation. The most suitable place for the device was the lateral thoracic wall in dogs and the ventral abdominal wall in cats, respectively. Transcutaneous FITC-S clearance was then repeated using the optimal dose and location and in parallel with an additional plasma sinistrin clearance. Plasma elimination half-lives [min] were 26, 31 and 35, and corresponding transcutaneous elimination half-lives [min] were 26, 34 and 55, respectively in the dogs. Plasma elimination half-lives [min] were 51, 60 and 61, and corresponding transcutaneous elimination half-lives [min] were 75, 96 and 83, respectively in the cats. In conclusion, transcutaneous FITC-S clearance is a feasible method for the assessment of GFR in awake dogs and cats. It is noninvasive, well tolerated and easy to perform even in a clinical setting with results being readily available. A dose of 30 mg/kg of FITC-S seems adequate for kinetic assessment. Further studies are now needed to establish reference values and evaluate transcutaneous renal clearance in various conditions.

Transcutaneous Assessment of Renal Function in Conscious Rodents

“…This method to assess renal function has been already validated in different species by comparison with the traditional approach of plasma clearance 9,11,12 . Following the protocol exposed here, Schreiber et al demonstrated the validity of the technique in different mouse models, showing highly comparable results among the transcutaneous measurement and plasma clearance for all the groups studied (Table 1) 9 .…”

“…This adaptability of the method has already been confirmed by its successful application in different species of rodents and several types of strains with varied health conditions. In addition, the transcutaneous assessment of renal function has been recently validated in dogs and cats 12 with excellent results. Due to the undoubted differences between these animals and rodents, this study determined the appropriate dose of FITC-sinistrin for both, dogs and cats, and it performed a much longer measuring time, 4 hours instead of the 1 or 2 hours used in rodents.…”

Measuring Residual Renal Function in Hemodialysis Patients without Urine Collection

“…This technique allows noninvasive, real‐time monitoring of the elimination kinetics of an injected tracer to measure plasma clearance. These methods are currently under development and successful use of fluorescent GFR markers including carboystyril124‐DTPA‐europium and FITC‐sinistrin to measure kidney function in different animal models has been reported .…”

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

“…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. 74 Non-fluorescent sinistrin has been successfully used safely in humans with various levels of kidney function, including patients with augmented renal clearance.…”