Validation of non‐invasive transcutaneous measurement for glomerular filtration rate in lean and obese C57BL/6J mice. Issue 7 (29th March 2020)

• Record Type: Journal Article
• Authors: Mullins, Thomas P.; Tan, Wei Sheng; Carter, David A.; Gallo, Linda A.
• Is Part Of: Nephrology. Volume 25:Issue 7(2020)
• Page Start: 575
• Page End: 581
• Publication Date: 2020-03-29
• Subjects: kidney -- obesity -- renal function -- rodents -- technique; Nephrology -- Periodicals; Kidneys -- Diseases -- Periodicals; Nephrologists -- Periodicals; 616.61; 616.61
• DOI: 10.1111/nep.13713
• Languages: English
• ISSNs: 1320-5358

Abstract

Abstract: Aim: The measurement of glomerular filtration rate (GFR) in experimental rodents is pivotal to understanding the progression of kidney disease and benefits of treatment strategies. A non‐invasive clearance device has been developed, which measures transcutaneous decay of injected FITC‐sinistrin in conscious rodents. The technique was validated against the well‐established plasma clearance method in the same mice, but on consecutive days, using only models of uninephrectomy and polycystic kidney disease. We aimed to validate this widely used technique in the same lean or obese mice, at the same time. Methods: Five‐week‐old male C57BL/6J mice were randomised to a high fat diet (n = 12) or normal diet (n = 11) for 10 weeks. Transcutaneous and plasma clearance of FITC‐sinistrin were measured simultaneously in each mouse. Results: In lean mice, there was a positive correlation between transcutaneous and plasma derived GFR ( P < .01, R 2 = .704), although there was an approximate 40% underestimation by the transcutaneous method ( P < .0001). In obese mice, no correlation was observed between transcutaneous and plasma derived GFR, nor elimination half‐life which removes any effect of the conversion factor and injected dose. The limits of agreement in a Bland‐Altman plot were narrower when we used new conversion factors derived from mice in the current study and, in lean mice, a generic conversion factor which assumes 20% extracellular volume. Conclusion: The non‐invasive clearance device may be useful for serial GFR measurements in lean and healthy mice, provided validation studies have been carried out, but its utility in obesity requires further study. SUMMARY AT A GLANCE: This article shows that the transcutaneous GFR method may be useful for serial GFR measurements in lean and healthy mice but may be impractical in obese mice.