Renal Effects of Radiocontrast Agents in Rats: A New Model of Acute Renal Failure

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Abstract
The objectives of this study were first to develop a reproducible and reversible model of acute renal failure following contrast medium infusion in the rat; second to use that method to compare the nephrotoxicity of low- and high-osmolar contrast agents. Contrast media or saline were perfused in the aorta while a clamp was applied on the aorta just above the renal artery. Three minutes of renal ischemia with or without infusion of isotonic saline induced no change in serum creatinine and a slight and transient decrease in creatinine clearance at 24 h. Urinary N-acetyl glucosamidase (NAG) excretion was not modified in this control group. All 17 kidneys which were examined were normal. 2,100 mosm/kg hypertonic saline induced a significant increase in serum creatinine and a significant decrease in creatinine clearance (from 1.8 ± 0.1 to 0.8 ± 0.1 and 1.0 ± 0.2 ml/min at 24 and 48 h, respectively). Urinary NAG excretion increased from 23 ± 18 to 48 ± 20 and 8 ± 4 umol hrVmmol creatinine at 24 and 48 h, respectively (p _1/mmol creatinine at 24 and 48 h, respectively. Histologic examination of 7 kidneys revealed acute tubular necrosis (n = 4), tubular cytoplasmic vacuolization (n = 2), and no histologic abnormalities (n = 1). Ioxaglate and iopamidol induced no change in serum creatinine and a slight decrease in creatinine clearance comparable to that observed in the control group. Ioxaglate and iopamidol induced a significant increase in urinary NAG excretion at 24 h (ioxaglate: 31 ± 6 to 147 ± 31; iopamidol: 55 ± 20 to 123 ± 31 umol h_1/mmol creatinine) which was completely reversible at 48 h (ioxaglate: 31 ± 9; iopamidol: 41 ± 8). Histological analysis of 8 kidneys exposed to ioxaglate revealed tubular cytoplasmic vacuolisation (n = 7) and no histologic abnormalities (n = 1). Histological analysis of 10 kidneys exposed to iopamidol revealed tubular cytoplasmic vacuolization (n = 8) and no histologic abnormalities (n = 2). We have described a reproducible and reversible model of contrast-medium-induced acute renal failure in the rat. In this model, ionic and nonionic low-osmolar contrast agents are less nephrotoxic than high-osmolar contrast agents.

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