K. Golman

Urine profiles and kidney histology after intravenous injection of ionic and nonionic radiologic and magnetic resonance contrast media in normal rats

RATIONALE AND OBJECTIVESnPrevious studies showed that both high-osmolality and low-osmolality iodinated contrast media cause temporary albuminuria and enzymuria (presence of enzymes in urine) in normal rats. Whether the same is true with ionic high-osmolality and nonionic low-osmolality magnetic resonance (MR) contrast media is unknown. We studied urine profiles and histology after intravenous injection of four types of contrast media in rats with normal kidneys.nnnMETHODSnUrine profiles were monitored 4, 24, 48, and 72 hr after intravenous injection of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide (4.59 mmol/kg of body weight) in normal rats. Each group included 20 male rats. After sacrifice, both kidneys were removed for examination by light microscopy (LM) and electron microscopy (EM).nnnRESULTSnAll four contrast agents caused a temporary (< 22 hr) increase in the excretion of albumin (2-5 times) and of cytoplasmic (30-100 times) and brush border (10-100 times) renal enzymes when compared with saline. The degree of albuminuria correlated well (r = 0.90) with the osmolality of the injected media, whereas the increased level of enzymuria was unrelated to the osmolality. No major differences in the enzymuric effects of the four agents were noted. LM revealed vacuoles in all kidneys exposed to radiologic contrast media but not in kidneys exposed to MR contrast media or saline. Slight vacuolation was revealed by EM after the use of MR contrast media, and significant vacuolation was evident via EM after the use of radiologic contrast media. No difference between ionic and nonionic media within each drug group was detected by either LM or EM.nnnCONCLUSIONSnTransient renal effects are induced by both ionic and nonionic high-osmolality and low-osmolality radiologic and MR contrast media in normal rats. Both osmotic (e.g., albuminuria) and chemotoxic (e.g., enzymuria) mechanisms seem to be involved. From a morphologic point of view, the chemotoxic mechanisms seem to be of major importance.

Contrast Medium Induced Nephropathy: Animal Experiments

Contrast medium induced nephropathy may be defined as an acute impairment of renal function that follows exposure to radiographic contrast materials, and for which alternative etiologies have been excluded. Acute renal insufficiency has been reported following exposure to contrast media administered by intravenous and intra-arterial routes. Contrast media may account for as many as 12% of episodes of hospital-acquired acute renal failure, thus exceeding aminoglycoside antibiotics in nephrotoxic potential (Hou et al. 1983). The incidence of contrast medium induced nephropathy is difficult to establish with certainty from the literature, since incidence figures in various reports vary depending on the population studied, the definition of acute renal failure, and differences in methodology (Jevnikar et al. 1988). Furthermore, the true incidence of nonoliguric contrast medium induced nephropathy is not known because it is not routine to systematically monitor renal function following contrast medium administration. Clinically, the glomerular filtration rate is usually assessed indirectly by measuring serum creatinine concentrations or, more precisely, by measuring creatinine clearance. This operational definition may greatly underestimate toxicity that is not severe enough to affect these rather insensitive markers of renal function. Serum creatinine concentration, the measure most often used as indicator of renal dysfunction, may not be elevated above the normal range until glomerular filtration rate falls below 50% of normal values because of its nonlinear relation to glomerular filtration rate.

Urine profiles and kidney histology after ionic and nonionic radiologic and magnetic resonance contrast media in rats with cisplatin nephropathy

RATIONALE AND OBJECTIVESnThe nephrotoxic drug cisplatin has been used successfully in treating some cancers. Patients with suspected carcinoma frequently undergo examinations with contrast media. We examined whether ionic and nonionic radiologic and magnetic resonance contrast media would have any effect on cisplatin nephropathy in rats.nnnMETHODSnUrine and serum profiles were monitored for 24 days after intravenous (i.v.) injections of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide in high doses (4.59 mmol/kg body weight) in rats that received a weekly intraperitoneal (i.p.) injection of cisplatin (1 mg/kg) for 10 weeks. There were 10 rats in each group. Another 10 rats injected with both i.p. and i.v. saline served as control subjects. After euthanization, rats kidneys were removed for examination by light microscopy and electron microscopy.nnnRESULTSnLight and electron microscopy showed severe morphologic changes, including tubular dilatation, atrophy, and necrosis induced by cisplatin; however, the contrast media did not induce any additional morphologic changes. Gadopentetate dimeglumine, diatrizoate, and iohexol significantly increased (3-20 times) albuminuria compared with i.v. saline in cisplatin nephropathy, whereas gadodiamide did not. Albuminuria was highest after diatrizoate injection. All four contrast media caused an immediate and transient significant increase in the excretion of the brush border enzymes alkaline phosphatase and gamma-glutamyltransferase (125-500 times) and the cytoplasmatic enzymes alanine aminopeptidase and lactate dehydrogenase (16-100 times). Compared with saline, the ionic agents significantly increased the excretion of both glucose (two times) and sodium (three to five times), whereas the nonionic agents did not.nnnCONCLUSIONnHigh doses of radiologic and magnetic resonance contrast agents cause temporary dysfunction in rats with cisplatin nephropathy. Gadodiamide caused the least dysfunction and diatrizoate the most.

One or Two Samples for Determination of Total Plasma Clearance of a Nonionic Contrast Medium in Patients Undergoing Enhanced CT

Plasma clearance of nonionic iopamidol (300 mg I/ml) was measured in 50 patients in connection with enhanced CT. Before injection of either 50 or 100 ml of the contrast medium, S-creatinine and urine osmolality were measured. Employing Renalyzer PRX 90, the plasma concentration of iodine was determined in blood samples drawn approximately 3 and 4 h after injection of iopamidol. The glomerular filtration rate was calculated by the Renalyzer using 2 different formulas, one requiring only a single sample, and one requiring at least 2 samples (standard). Both the 3- and 4-h single sample values correlated well with the glomerular filtration rate expressed by the standard sample value. The result was independent of whether 50 or 100 ml had been administered and whether or not water soluble contrast medium had been given orally before CT. As could be expected S-creatinine and urine osmolality correlated poorly with the clearance values. It is concluded that in patients receiving either 50 or 100 ml contrast medium for enhanced CT, the glomerular filtration rate can be determined in a single sample as well as with 2 samples taken between 3 and 4 h after contrast medium injection.

Nephrotoxicity of cyclosporin A and contrast media. A comparison between diatrizoate and iohexol in rats.

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of the cyclosporin A solution (placebo) and saline injected intravenously served as controls. The effect of iohexol and saline on the albumin excretion was similar, whereas diatrizoate increased it significantly. Both contrast media caused significantly increased excretion of all three enzymes. The contrast media had no effect on the excretion of glucose and sodium. Except for the fact that the excretion of NAG was significantly higher following iohexol than following diatrizoate 24 to 46 h after injection no significant differences between the two media were found from 24 h after injection among the rats given cyclosporin A. No contrast medium related changes were found by light microscopy of the kidneys. Neither iohexol nor diatrizoate potentiate acute cyclosporin A nephrotoxcity.

Low Sodium Diet, Indomethacin, and Contrast Media: A comparison between renal effects of diatrizoate and iohexol in rats

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol, or saline in 30 adult Wistar rats, which received a low sodium diet for 14 days, and indomethacin intravenously 2 hours and immediately before contrast medium or saline injection. A control group of 10 rats, which also received low sodium diet, got saline alone and no indomethacin or contrast medium. Diatrizoate increased albuminuria during the first 22 hours after its injection whereas iohexol did not have any significant effect on albuminuria. Both contrast media caused tubular dysfunction, but there was significant difference between them during the first 2 hours after injection. Compared to the effect of saline, iohexol but not diatrizoate caused increased excretion of lactate dehydrogenase and N-acetyl-beta-glucosaminidase for 2 days. Iodine measurements showed delayed excretion of both media. Light microscopy showed focal location of dilated tubular profiles with hydrophia, which were only present in kidneys exposed to contrast media. It is concluded that in rats fed on a low sodium diet administration of indomethacin in relation to iohexol has a greater tubular cell effect than diatrizoate, which in turn has a greater effect on the glomerular permeability. The excretion of both media is delayed.

Gentamicin nephropathy and contrast media

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol or saline in 30 rats, where a tubulointerstitial nephropathy was induced by gentamicin given over a 14-day period. Another 10 rats who had an injection of saline served as controls. Iohexol increased the excretion of lactate dehydrogenase significantly more than both saline and diatrizoate for the first 3 days, whereas diatrizoate had no effect. Both media caused significantly increased excretion of L-gamma-glutamyltransferase compared with saline, but iohexol significantly more than diatrizoate. Compared with saline S-creatinine was significantly increased following iohexol at 24 h, 3 and 9 days, and following diatrizoate only at 9 days. Among rats having gentamicin light microscopy revealed more severe changes in kidneys exposed to iohexol than to either diatrizoate or saline 3 days after their injection. Six days later no obvious differences were found between the 3 groups. in conclusion, iohexol induced mo...

Gentamicin nephropathy and contrast media. A comparison between diatrizoate and iohexol in rats.

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol or saline in 30 rats, where a tubulointerstitial nephropathy was induced by gentamicin given over a 14-day period. Another 10 rats who had an injection of saline served as controls. Iohexol increased the excretion of lactate dehydrogenase significantly more than both saline and diatrizoate for the first 3 days, whereas diatrizoate had no effect. Both media caused significantly increased excretion of L-gamma-glutamyltransferase compared with saline, but iohexol significantly more than diatrizoate. Compared with saline S-creatinine was significantly increased following iohexol at 24 h, 3 and 9 days, and following diatrizoate only at 9 days. Among rats having gentamicin light microscopy revealed more severe changes in kidneys exposed to iohexol than to either diatrizoate or saline 3 days after their injection. Six days later no obvious differences were found between the 3 groups. In conclusion, iohexol induced more renal dysfunction than diatrizoate in this animal model of gentamicin induced nephropathy.

Adriamycin Nephrosis and Contrast Media A Comparison between Diatrizoate and Iohexol in Rats

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 9 days after intravenous injection of either diatrizoate, iohexol, or saline in 27 Wistar rats with nephrosis induced by Adriamycin 42 days before. Another 9 rats exposed to neither Adriamycin nor contrast media served as controls. None of the contrast media caused further increased albuminuria of significance, whereas both induced significantly increased excretion of all 5 tubular components. The excretion of NAG and sodium was significantly higher following diatrizoate than following iohexol. From 24 h post injection there was no significantly greater excretion of any of the components after either diatrizoate or iohexol than after saline among the rats given Adriamycin. At the end of day 9 after contrast medium injection neither serum sodium, potassium, glucose, urea, creatinine, nor albumin revealed any contrast media related changes. Kidney histology showed quantitatively larger lesions in kidneys exposed to Adriamycin and contrast media than in kidneys exposed to Adriamycin and saline. There were no differences between the two contrast media groups. It is thus concluded, that both high osmolar ionic and low osmolar non-ionic contrast media cause temporary tubular dysfunction but no further glomerular dysfunction in rats with nephrosis induced by Adriamycin. The histologic findings indicate that both media may worsen non-reversible renal lesions.

Low Sodium Diet, Indomethacin, and Contrast Media

Urine profiles were followed for 3 or 9 days after intravenous injection of diatrizoate, iohexol, or saline in 30 adult Wistar rats, which received a low sodium diet for 14 days, and indomethacin intravenously 2 hours and immediately before contrast medium or saline injection. A control group of 10 rats, which also received low sodium diet, got saline alone and no indomethacin or contrast medium. Diatrizoate increased albuminuria during the first 22 hours after its injection whereas iohexol did not have any significant effect on albuminuria. Both contrast media caused tubular dysfunction, but there was significant difference between them during the first 2 hours after injection. Compared to the effect of saline, iohexol but not diatrizoate caused increased excretion of lactate dehydrogenase and N-acetyl-beta-glucosaminidase for 2 days. Iodine measurements showed delayed excretion of both media. Light microscopy showed focal location of dilated tubular profiles with hydrophia, which were only present in ki...