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.

Cisplatin Binding and Inactivation of Mitochondrial Glutamate Oxaloacetate Transaminase in Cisplatin-Induced Rat Nephrotoxicity

“…Cisplatin was administered intraperitoneally at 45 mg/m 2 , corresponding to 7.5 mg/kg (FDA-CDER Guidance 2005), to groups of six 8-week-old SD rats, as described in our previous reports. 31,32) Our previous studies indicated that intraperitoneally administration of cisplatin at 22.5 mg/m 2 slightly induced nephrotoxicity. We also found that administration of cisplatin at 45 mg/m 2 moderately induced the nephrotoxicity.…”

“…We noted marked increases in SUN and CRE with decreased body weight and extensive tubular necrosis, loss of the epithelial brush-border, pyknosis in the renal proximal epithelia, and the presence of cysts in the lumen on day 5, as found previously. 31,32) Renal mitochondrial GOT and MDH activities in cisplatin-induced nephrotoxicity…”

Validation of a routine two-sample iohexol plasma clearance assessment of GFR and an evaluation of common endogenous markers in a rat model of CKD

“…; Levey ; Katayama et al. ). Despite their limitations, endogenous biomarkers of kidney function, such as creatinine and urea, are widely used to evaluate kidney function in experimental models.…”