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

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.