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

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 < 0.05). Histologic analysis of 5 kidneys revealed acute tubular necrosis (n = 3) and no histologic abnormalities (n = 2). Diatrizoate induced an acute and reversible renal failure. Creatinine clearance decreased from 1.6 ± 0.1 to 0.4 ± 0.1 and 0.8 ± 0.1 ml/min at 24 and 48 h, respectively (p < 0.01). Urinary NAG excretion increased also significantly from 43 ± 9 to 352 ± 79 and 64 ± 23 umol h^_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.

Gadolinium contrast media are more nephrotoxic than a low osmolar iodine medium employing doses with equal x-ray attenuation in renal arteriography: An experimental study in pigs1

“…Our results regarding the effect on renal function seems to be in accordance with another series of experiments (34,35). In an ischemic rat model it was found that intra-aortic injections of gadopentetate and diatrizoate, both with an osmolality of about 2.0 osmol/kg water, caused a similar decrease in GFR measured as creatinine clearance.…”

“…In an initial pilot study, we did not notice any effect on renal function when the CM were injected into patent renal arteries as had been found in an earlier canine study from our laboratory (44). Therefore, an ischemic period was added to the experiment, a well-established procedure to potentiate the nephrotoxic effect of CM (35,40,45,46). It is well known from both clinical and experimental studies that prior preconditioning is often necessary to make living species susceptible to CM-induced renal failure.…”

Are Gadolinium-based Contrast Media Really Safer than Iodinated Media for Digital Subtraction Angiography in Patients with Azotemia?

“…However, the dose of iodine atoms appears to have been 10 times that of gadolinium atoms, according to the following: The osmolality of the gadopentetate dimeglumine solution used was reported to be 1,900 mosm/kg and "very close to diatrizoate." These statements, as well as a previous report from the same research group (25), indicate that a 0.5 mol/L gadopentetate dimeglumine solution and a 76% diatrizoate solution (0.97 mmol/mL diatrizoate molecules; Table 1) were used. Thus, only 0.75 mmol (1.5 mL ϫ 0.5 mmol/mL) of gadopentetate dimeglumine molecules (0.75 mmol of gadolinium atoms) seems to have been injected, compared with 2.5 mmol (2.6 mL ϫ 0.97 mmol/mL) of diatrizoate molecules (3 ϫ 2.5 ϭ 7.5 mmol of iodine atoms).…”

Urinary Fructose-1,6-Bisphosphatase (FBP-1,6) and N-Acetyl-β-Hexosaminidase (HEX) in Monitoring Kidney Transplantation - Literature Review

“…The only objection to that results is the short time of determination of HEX urinary excretion after application of ioxaglate, as another researchers (Wellwood et al, 1978) observed increase in urinary HEX excretion three days after administration of gentamycine. However, it was found on the rat model, that ioxaglate induced a smaller increase in urinary HEX excretion than diatrizoate sodium meglumine (Deray et al, 1990). It was reported that PenToXifylline (PTX) seemed to be temporarily effective in reducing proteinuria and stabilizing renal graft function in more t h a n h a l f o f p a t i e n t s a t t h e e n d o f 6 m o n t h f o l l o w -u p i n Chronic Allograft Nephropathy(CAN) (Shu et al, 2007).…”