Sequential measurements of glomerular filtration rate in conscious rats by a bolus injection of iodixanol and a single blood sample

• Published in: Journal of applied toxicology 2011-05, Vol.31 (4), p.360-365
• Main Authors: Katayama, Rieko, Watanabe, Kanji, Yamagishi, Norio, Abe, Sumito, Satoh, Hiroshi, Furuhama, Kazuhisa
• Format: Article
• Language: English
• Subjects: Aging - blood; Animal Use Alternatives; Animals; Biological and medical sciences; Chromatography, High Pressure Liquid; Contrast Media; contrast medium; Glomerular Filtration Rate; HPLC; Injections, Intravenous; Kidney Diseases - blood; Kidney Diseases - chemically induced; Male; Medical sciences; nephropathy; rat; Rats; Rats, Inbred F344; Toxicology; Triiodobenzoic Acids - blood
• ISSN: 0260-437X; 1099-1263; 1099-1263
• DOI: 10.1002/jat.1619

ABSTRACT To estimate the glomerular filtration rate (GFR) sequentially in conscious rats, we validated a single‐blood‐sample method using a bolus injection of the nonionic contrast medium iodixanol as a tracer. First, to clarify basal age‐related GFR profiles, iodixanol was intravenously administered once weekly at 1500 mg kg−1 I to clinically healthy male F344 rats from 6 to 15 weeks of age. The blood sample was collected 120 min later, and serum iodixanol concentration was measured by HPLC. GFR values decreased gradually by 9 weeks, presumably due to rapidly increased body weights, and then remained constant from 10 weeks onward. When converting the GFR from body weight to body surface area, the reference range (40–60 ml min−1 m−2) in the latter was much more stable than that (6–11 ml min−1 kg−1) in the former. For nephropathy rats induced by cisplatin (3.75–7.5 mg kg−1, i.v., single dose), bromoethylamine hydrobromide (BEA, 250–500 mg kg−1, i.v., single dose) or puromycin aminonucleoside (PAN, 15 mg kg−1 day−1, s.c., 10 days), GFR decreased or tended to decrease before increasing in serum urea nitrogen (UN) and creatinine concentrations. Accordingly, serum UN and creatinine concentrations became elevated when the GFR decreased to 50–60% of the basal value. This method without urine collection contributes to the reduction of animal numbers because of repeated application to the same animals. Copyright © 2011 John Wiley & Sons, Ltd. To estimate GFR sequentially in conscious rats, we validated a single‐blood‐sample method using a bolus injection of the nonionic contrast medium iodixanol as a tracer. Iodixanol was intravenously administered once weekly at 1500 mg kg−1 I to clinically healthy male F344 rats from 6 to 15 weeks of age. The blood sample was collected 120 min later, and serum iodixanol concentration was measured by HPLC. This method without urine collection contributes to the reduction in animal numbers.