Barbara Elmståhl

Nephrotoxicity after renal angiography using iodine and gadolinium contrast media in pigs with renal damage

Iodine contrast medium (I-CM) induced nephrotoxicity is recognized for many years and is especially frequent in patients with pre-existing renal insufficiency alone or combined with diabetes mellitus. The use of non-ionic low osmolar contrast media (LOCM) has reduced the risk of renal injury after X-ray arteriography in patients with renal impairment (1). The importance of nephrotoxicity may increase in the future, due to an anticipated higher number of examinations of elderly subjects, who often have impaired renal function. Furthermore, interventional radiology uses large doses of contrast media (CM). These risk factors make it necessary to adopt some strategies to overcome the problems with nephrotoxicity associated with CM administration in patients with renal damage, for instance the use of non-ionic LOCM (1) and adequate

Iodixanol 320 results in better renal tolerance and radiodensity than do gadolinium-based contrast media: arteriography in ischemic porcine kidneys.

PURPOSE To prospectively compare nephrotoxicity and radiodensity of plasma hyperosmotic gadolinium chelates (attenuation-osmotic ratio of 1:1) with those of plasma iso-osmotic iodine-based contrast media (attenuation-osmotic ratio of 3:1 or 6:1) after renal arteriography in ischemic porcine kidneys. MATERIALS AND METHODS The local animal care committee approved this study. The following contrast media were used: (a) iodixanol (150 mg of iodine per milliliter and 320 mg I/mL, 0.29 osm/kg H(2)O), (b) iopromide (150 mg I/mL, 0.34 osm/kg), (c) 0.5 mol/L gadodiamide (0.78 osm/kg), and (d) 1.0 mol/L gadobutrol (1.6 osm/kg). After left-sided nephrectomy, contrast media (3 mL per kilogram of body weight) were injected (20 mL/min) in a noncrossover design into the right renal artery of pigs during a 10-minute ischemic period. There were eight pigs in each group and one group for each contrast medium. We compared histomorphology, radiographic contrast medium excretion, subjective radiodensity of nephrograms (70 kVp) at the end of injection, and contrast medium plasma half-life elimination times 1-3 hours after injection. Longer elimination times resulted in lower glomerular filtration rates. RESULTS Gadobutrol caused extensive tubular necrosis and moderate glomerular necrosis; gadodiamide and iopromide, minimal to mild tubular necrosis; and iodixanol, no necrosis. Gadobutrol was the only contrast medium to show no sign of excretion, and its plasma half-life elimination time (median, 1103 minutes; P < .001) was significantly longer than that of other contrast agents. Gadodiamide had a significantly longer plasma half-life elimination time (median, 209 minutes; P = .01) than did iodine-based contrast media (median, 136-142 minutes). The 320 mg I/mL dose of iodixanol had the highest radiodensity, whereas gadodiamide had the lowest radiodensity. The radiodensity of the 320 mg I/mL dose of iodixanol was greater than that of the 150 mg I/mL dose of iodixanol, which was equal to the radiodensities of the 150 mg I/mL dose of iopromide and 1.0 mol/L gadobutrol, which in turn were greater than that of 0.5 mol/L gadodiamide. CONCLUSION Plasma iso-osmotic iodine-based contrast media used at commercially available concentrations have superior attenuation and nephrotoxic profiles compared with equal volumes of hyperosmotic nonionic 0.5-1.0 mol/L gadolinium-based contrast media when performing renal arteriographic procedures.

Abdominal plain film findings in acute ischemic bowel disease differ with age

Purpose: To evaluate the use and findings of abdominal plain film in acute ischemic bowel disease (AIBD) in different age subsets, and to correlate the clinical findings. Material and Methods: Eighty-nine radiographically examined patients with AIBD at Malmö University Hospital, Sweden between 1987 and 1996. Results: In 89%, the plain film displayed pathologic signs. Bowel dilatation was more common in the elderly. Of 68 patients aged ⩾71 years, 19 (28%) had colon gas/fluid levels with/without colon dilatation, and of 19 patients >84 years 16 (84%) had small-bowel dilatation. Of 20 patients aged <71 years, 1 (5%) had colon gas/fluid levels with/without colon dilatation, and 11 (55%) small-bowel dilatation (P<0.05; P<0.05). Gasless abdomen was more common in the younger age group, noted in 5 of 20 (25%) patients aged <71 years, compared to 2 of 68 (3%) patients aged ⩾71 years (P = 0.001). Of the patients with diarrhea, 13 of 33 (40%) had colon gas/fluid levels with/without colon dilatation compared to 2 of 29 (7%) without (P = 0.003). In the elderly (⩾71years), 48 of 53 (91%) patients with bowel dilatation on plain film died, compared to 11 out of 16 (69%) without this finding (P<0.05). Conclusion: Abdominal plain film findings differed with age. Bowel dilatation was more frequent in the elderly with AIBD, whereas gasless abdomen was more common in younger patients. The radiographic findings were associated with clinical symptoms and mortality.

Histomorphological Changes after Renal X-Ray Arteriography Using Iodine and Gadolinium Contrast Media in an Ischemic Porcine Model.

Background: Gadolinium contrast media (Gd-CM) are regarded as non-nephrotoxic or considerably less nephrotoxic than iodine contrast media (I-CM), and have therefore come to be used as a substitute for I-CM in patients with renal insufficiency in a variety of radiographic examinations. Purpose: To investigate renal histomorphological changes caused by Gd-CM in comparison with I-CM after renal X-ray arteriography in an ischemic porcine model, and to evaluate these changes in relation to the nephrotoxicity of the CM used. Material and Methods: Test solutions: gadopentetate, gadodiamide, iohexol, gadobutrol, iopromide, iodixanol, mannitol, and saline. The experiments were performed on 152 animals. Each pig was randomized to receive one test solution injected into the balloon-occluded (10 min) right renal artery. The kidneys were evaluated histomorphologically. The severity of histomorphological changes was graded subjectively: 1 = minimal, 2 = mild, 3 = moderate, and 4 = marked. Results: The main histological changes were 1) proximal tubular and glomerular necrosis, 2) hemorrhage/congestion of the cortex, medulla, and glomeruli, 3) proximal tubular vacuolation, and 4) protein-filled tubules in the cortex and medulla. Necrosis and hemorrhage/congestion were more frequent after injections with gadopentetate, mannitol solution iso-osmotic to gadopentetate, and gadobutrol compared to all other groups (P<0.001). The degree of necrosis and hemorrhage/congestion was related to the degree of impairment of renal function, but inversely related to vacuolation and tubular protein filling. Conclusion: In ischemic porcine kidneys, the histomorphological changes caused by Gd-CM are similar to those caused by I-CM. Vacuolation appears to be independent of the osmolality and viscosity of the CM, and does not seem to be an indicator of renal impairment. “High-osmolal” Gd-CM are more nephrotoxic than “low- and iso-osmolal” I-CM when compared in equal volumes of concentrations, resulting in equal X-ray attenuation.

A case of hyperoxaluria Radiological aspects

Purpose: Oxalosis is an unusual pathological condition with calcium oxalate deposits in soft tissue and bone, recognized as osteosclerosis on radiography. Osteosclerotic bone changes in patients treated with hemodialysis are in most cases due to secondary hyperparathyroidism, but several other diagnoses have to be considered Material, Methods and Results: We describe the case of a young woman with advanced renal failure treated with hemodialysis since her youth. She had skeletal pain and radiological examination showed: osteosclerosis with sclerotic vertebral bodies; irregular sclerosis and unsharp periostal outline in the tubular bones of the extremities; and acrolysis and calcifications of vascular and soft tissue in the hands. Histological examination showed changes typical of oxalosis. A liver biopsy excluded primary oxalosis type I, and she probably had a secondary oxalosis due to renal failure. This condition (as opposed to primary oxalosis) can be treated with renal transplantation Conclusion: Oxalosis is a rare condition but it should be considered in patients with radiological skeletal changes and chronic renal failure and should not be misinterpreted as renal osteodystrophy. the classification of oxalosis as primary or secondary is important for further treatment

Iodine contrast media doses equal-attenuating with gadolinium chelates at CT-aortography may have less risk of contrast-induced nephropathy and no risk of nephrogenic systemic fibrosis in azotaemic patients!

Dear Editor: European Radiology recently published a paper by Esteban et al. [1] on the use of 1.0 M gadobutrol as contrast medium for CT aortography in patients with contraindications to iodine contrast media (I-CM) including renal impairment. They should be complimented for obtaining “excellent to adequate” visualisation of the aorta in all patients using a 16-detector-row CT scanner after injecting a mean dose of only 30 mL 1.0 M gadobutrol (0.37mmol/kg), a non-ionic gadolinium contrast medium (Gd-CM) primarily intended for magnetic resonance imaging. However, in the Discussion (page 2398), they express some inconsistencies about the risk of contrast-mediuminduced nephropathy (CIN) and how to interpret equal-attenuating doses of Gdand I-CM that may confuse the readers. Firstly we do not share the opinion that “dimeglumine gadopentetate has low nephrotoxicity” when Esteban et al. at the same time cite a study [2] with a reported 3.5% incidence of oliguria or anuria, among patients with chronic renal insufficiency who received a lower average gadopentetate dose (0.28 mmol/kg) than in the study by Esteban et al. Secondly, the cited statement [2] that “gadolinium-based contrast agents appear approximately 20 times safer than iodinated agents in patients with impaired renal function” completely lacks scientific evidence. On the contrary, when comparing both equal-attenuating and equal-molecular doses, Gd-CM appears to be more nephrotoxic than modern I-CM following injections into porcine renal arteries [3, 4]. Thirdly, Esteban et al. state that “there is no need to use gadolinium at the same attenuating dose as iodine to obtain diagnostic, and even excellent, CTA exams using a 16-channel scanner”. This declaration is an insidious argumentative pirouette referring to our statement [3, 5] and that of others [6, 7] that comparisons between Gdand I-CM regarding CIN must be made at doses with equal attenuation of the X-rays. The point made by us and the other authors was that if the same volumes of I-CM in concentrations that are equal-attenuating with 0.5–1.0 M Gd-CM are used, the patients may be exposed to a considerably lower number of potentially nephrotoxic molecules and also a lower renal osmotic load. The vast majority of studies have shown that a 0.5 M Gd-CM dose is roughly equalattenuating with 110 mg I/mL at 120 kVp CT [4, 5]. Thus, in the study of Esteban et al. the equal attenuating dose of I-CMwould be 30 mL of about 220 mg I/mL, i.e. 6.6 g iodine, a substantially less nephrotoxic risk than that of conventional CT doses of I-CM, which usually range from 30 to 45 g iodine (100–150 mL 300 mg I/mL). A 6.6-g iodine dose of iodixanol would imply a renal osmotic load of only 8.7 mmol iodixanol molecules; i.e. less U. Nyman (*) Department of Diagnostic Radiology, Lasarettet Trelleborg, University of Lund, SE-231 85 Trelleborg, Sweden e-mail: ulf.nyman@skane.se Fax: +46-410-15983

Low Carotid Calcium Score Is Associated With Higher Levels of Glycosaminoglycans, Tumor Necrosis Factor-Alpha, and Parathyroid Hormone in Human Carotid Plaques

Background and Purpose— Computed tomography (CT) is used to study coronary artery plaques, but little is known about its potential to characterize plaque composition. This study assesses the relation between carotid calcium score (CCS) by CT and plaque composition, namely extracellular matrix, inflammatory mediators, and calcium metabolites. Methods— Thirty patients with significant carotid stenosis underwent preoperative CT. CCS was quantified by Agaston calcium score. Plaque components were studied histologically and biochemically (collagen, elastin, and glycosaminoglycans). Fraktalkine, interferon-&ggr;, interleukin-10, interleukin-12 p70, interleukin-1&bgr;, interleukin-6, monocyte chemoattractant protein-1, platelet-derived growth factor-AB/BB, RANTES and tumor necrosis factor-&agr;, and parathyroid hormone were measured using Luminex technology. Results— Plaques with CCS ≥400 had more calcium (P=0.012), less glycosaminoglycan (P=0.002), tumor necrosis factor-&agr; (P=0.013), and parathyroid hormone (P=0.028) than those with CCS <400. CCS correlated with plaque content of calcium (r=0.62; P<0.001) and inversely with glycosaminoglycan (r=−0.49; P=0.006) and tumor necrosis factor-&agr; (r=−0.56; P=0.001). Conclusions— Human carotid plaques with high CCS are richer in calcium and have lower amounts of glycosaminoglycan, parathyroid hormone, and tumor necrosis factor-&agr;, which is one of the main proinflammatory cytokines involved in atherosclerosis. This suggests that CCS not only reflects the degree of calcification, but also other important biological components relevant for stability such as inflammation.

Gadolinium contrast media for DSA in azotemia: are they really safer than iodinated agents?

Iodinated contrast media (I-CM) may result in contrast medium induced nephropathy (CMN) (1). Gadolinium(Gd)-CM, intended as an intravenous CM for magnetic resonance imaging (MRI), is regarded as non-nephrotoxic (2). Therefore it has been recommended to replace I-agents with Gd-CM in azotemic patients undergoing X-ray angiography (XRA) with digital subtraction technique (DSA) for endovascular diagnostic and therapeutic purposes (3–5). The aim of this review was to evaluate the scientific support for this recommendation.

The dogma that gadolinium contrast media are less nephrotoxic than iodine agents for X-ray angiography is a misconception

In the seemingly endless number of human experiments on substituting gadolinium (Gd) for iodine contrast media (ICM) for X-ray examinations on patients at risk of contrastinduced nephropathy (CIN), yet another one was recently published in Heart and Vessels. Barcin et al. compared the nephrotoxicity of a mixture of 2/3 of gadodiamide and 1/3 of iohexol (350 mg I/ml) with that of equal volumes of “pure” iohexol 350 mg I/ml during coronary angiography. None of the 21 patients in the gadodiamide–iohexol group developed CIN, while 23% (5/21) in the pure iohexol group did. Though these results may seem “encouraging” at fi rst sight we feel inclined to strongly discourage such use for several reasons including pharmacolegal issues: