The SHR as a small animal model for radiocontrast renal failure. Relation of nephrotoxicity to animal's age, gender, strain, and dose of radiocontrast.
The male spontaneously hypertensive rat (SHR), as it ages, suffers many of the renal and cardiovascular complications that are recognized in humans as risk factors for radiocontrast (RC) agent induced renal failure (RF). Knowledge of this led us to test this strain of rats as a small animal model for RC-induced renal failure (RC-RF). Functional studies demonstrated a significant fall in GFR in the recovery period after RC administration. In addition, histopathologic evaluation of the kidneys was done in this study. Our results are based on assigning separate scale values to the histopathological evaluation of the (a) glomeruli, (b) tubules, (c) interstitium, and (d) arteries and arterioles of the kidneys. Saline (S) was administered to one group and the RC agent Hypaque-76 (diatrizoate meglumine sodium) to paired groups of 5-, 8-, 10-, 12-, and 14-month-old male SHR. The results indicated that younger animals (5 and 8 months old) were resistant to the nephrotoxic effects of the RC, but developed susceptibility at 10 months of age, when spontaneous renal pathology became manifest. Both spontaneous renal pathology and RC-induced renal damage (RC-RD) increased as the animals aged. In addition, when the administered dose of RC was repeated after a short interval of only 6 h, the degree of RC-RD increased greatly. In parallel control studies of the influence of gender and strain on the response to RC in 12-month-old rats, neither hypertensive female SHR nor male normotensive Wistar-Kyoto (WKY) rats demonstrated significant spontaneous renal pathology or the marked susceptibility to RC nephrotoxicity shown by their male SHR counterparts. This small animal model for RC-RD, the mature male SHR, has the distinct advantage that risk factors for RC-RD, similar to those characterized in humans for RC-RF, develop spontaneously without requiring any special treatment or surgical intervention.
Duarte
C G
CG
Food and Drug Administration, Division of Cardio-Renal Drug Products, Rockville, MD 20857, USA. DUARTE@cder.fda.gov@internet
Zhang
J
J
Ellis
S
S
D000367:Age Factors; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D003973:Diatrizoate / Q000008:administration & dosage / Q000009:adverse effects*; D003974:Diatrizoate Meglumine / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D005919:Glomerular Filtration Rate; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000473:pathology; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000473:pathology; D012307:Risk Factors; D012737:Sex Factors; D013045:Species Specificity
D003287:Contrast Media; D004338:Drug Combinations; D003973:Diatrizoate; D003974:Diatrizoate Meglumine; C027278:urovision