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Published in: European Radiology 12/2006

01-12-2006 | Contrast Media

Gadolinium contrast media are more nephrotoxic than iodine media. The importance of osmolality in direct renal artery injections

Authors: Barbara Elmståhl, Ulf Nyman, Peter Leander, Chun-Ming Chai, Klaes Golman, Jonas Björk, Torsten Almén

Published in: European Radiology | Issue 12/2006

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Abstract

A study was undertaken of the role of osmotoxicity in gadolinium (Gd) and iodine contrast media (CM) nephrotoxicity in ischemic porcine kidneys. Test solutions: mannitol iso-osmotic to 0.5 M gadopentetate (1.96 Osm/kg H2O), 0.5 M gadodiamide (0.78 Osm/kg H2O) and 0.5 M iohexol (190 mg I/ml, 0.42 Osm/kg H2O). Each solution was injected [3 ml/kg body weight (BW)] into the balloon-occluded (10 min) renal artery of eight left-sided nephrectomized pigs. The plasma half-life of a glomerular filtration rate (GFR) marker was used to compare their effects on GFR 1–3 h post-injection. The median half-lives of the GFR marker after injection of gadopentetate (1,730 min) and mannitol 1.96 Osm/kg H2O (2,782 min) did not differ statistically (P=0.28), but were significantly longer than after all other solutions (P<0.001). There was no significant difference (P=0.06) between gadodiamide (218 min) and mannitol 0.82 Osm/kg H2O (169 min), while there was (P=0.03) between iohexol (181 min) and mannitol 0.43 Osm/kg H2O (148 min). The difference between gadodiamide and iohexol was significant (P=0.01). Reduction in GFR, as a marker of nephrotoxicity, induced by gadopentetate correlated with its high osmolality, while the effect of gadodiamide and iohexol may include chemotoxicity. Iohexol molecules were less nephrotoxic than the Gd-CM molecules and contain three-times the number of attenuating atoms per molecule.
Literature
1.
go back to reference Spinosa DJ, Matsumoto AH, Angle JF, Hagspiel KD (1998) Use of gadopentetate dimeglumine as a contrast agent for percutaneous transluminal renal angioplasty and stent placement. Kidney Int 53:503–507PubMedCrossRef Spinosa DJ, Matsumoto AH, Angle JF, Hagspiel KD (1998) Use of gadopentetate dimeglumine as a contrast agent for percutaneous transluminal renal angioplasty and stent placement. Kidney Int 53:503–507PubMedCrossRef
2.
go back to reference Spinosa DJ, Matsumoto AH, Hagspiel KD, Angle JF, Hartwell GD (1999) Gadolinium-based contrast agents in angiography and interventional radiology. AJR Am J Roentgenol 173:1403–1409PubMed Spinosa DJ, Matsumoto AH, Hagspiel KD, Angle JF, Hartwell GD (1999) Gadolinium-based contrast agents in angiography and interventional radiology. AJR Am J Roentgenol 173:1403–1409PubMed
3.
go back to reference Sarkis A, Badaoui G, Azar R, Sleilaty G, Bassil R, Jebara VA (2003) Gadolinium-enhanced coronary angiography in patients with impaired renal function. Am J Cardiol 91:974–975PubMedCrossRef Sarkis A, Badaoui G, Azar R, Sleilaty G, Bassil R, Jebara VA (2003) Gadolinium-enhanced coronary angiography in patients with impaired renal function. Am J Cardiol 91:974–975PubMedCrossRef
4.
go back to reference Ailawadi G, Stanley JC, Williams DM, Dimick JB, Henke PK, Upchurch GR Jr (2003) Gadolinium as a nonnephrotoxic contrast agent for catheter-based arteriographic evaluation of renal arteries in patients with azotemia. J Vasc Surg 37:346–352PubMedCrossRef Ailawadi G, Stanley JC, Williams DM, Dimick JB, Henke PK, Upchurch GR Jr (2003) Gadolinium as a nonnephrotoxic contrast agent for catheter-based arteriographic evaluation of renal arteries in patients with azotemia. J Vasc Surg 37:346–352PubMedCrossRef
5.
go back to reference Strunk HM, Schild H (2004) Actual clinical use of gadolinium-chelates for non-MRI applications. Eur Radiol 14:1055–1062PubMedCrossRef Strunk HM, Schild H (2004) Actual clinical use of gadolinium-chelates for non-MRI applications. Eur Radiol 14:1055–1062PubMedCrossRef
6.
go back to reference Erly WK, Zaetta J, Borders GT et al (2000) Gadopentetate dimeglumine as a contrast agent in common carotid arteriography. AJNR Am J Neuroradiol 21:964–967PubMed Erly WK, Zaetta J, Borders GT et al (2000) Gadopentetate dimeglumine as a contrast agent in common carotid arteriography. AJNR Am J Neuroradiol 21:964–967PubMed
7.
go back to reference Chryssidis S, Davies RP, Tie ML (2002) Gadolinium-enhanced computed tomographic aortography. Australas Radiol 46:97–100PubMedCrossRef Chryssidis S, Davies RP, Tie ML (2002) Gadolinium-enhanced computed tomographic aortography. Australas Radiol 46:97–100PubMedCrossRef
8.
go back to reference Rémy-Jardin M, Dequiedt P, Ertzbischoff O et al (2005) Safety and effectiveness of gadolinium-enhanced multi-detector row spiral CT angiography of the chest: preliminary results in 37 patients with contraindications to iodinated contrast agents. Radiology 235:819–826PubMed Rémy-Jardin M, Dequiedt P, Ertzbischoff O et al (2005) Safety and effectiveness of gadolinium-enhanced multi-detector row spiral CT angiography of the chest: preliminary results in 37 patients with contraindications to iodinated contrast agents. Radiology 235:819–826PubMed
9.
go back to reference Nyman U, Elmståhl B, Leander P, Nilsson M, Golman K, Almén T (2002) Are gadolinium-based contrast media really safer than iodinated media for digital substraction angiography in patients with azotemia? Radiology 223:311–318PubMed Nyman U, Elmståhl B, Leander P, Nilsson M, Golman K, Almén T (2002) Are gadolinium-based contrast media really safer than iodinated media for digital substraction angiography in patients with azotemia? Radiology 223:311–318PubMed
10.
go back to reference Elmståhl B (2006) Are gadolinium contrast media really less nephrotoxic than iodine agents in radiographic examinations? A comparison in relation to their ability to attenuate X-rays in a pig model. In: Lund University Faculty of Medicine. Doctoral Dissertation Series 2006:9, Lund, Sweden Elmståhl B (2006) Are gadolinium contrast media really less nephrotoxic than iodine agents in radiographic examinations? A comparison in relation to their ability to attenuate X-rays in a pig model. In: Lund University Faculty of Medicine. Doctoral Dissertation Series 2006:9, Lund, Sweden
11.
go back to reference Spinosa DJ, Matsumoto AH, Angle JF et al (1998) Gadolinium-based contrast and carbon dioxide angiography to evaluate renal transplants for vascular causes of renal insufficiency and accelerated hypertension. J Vasc Interv Radiol 9:909–916PubMedCrossRef Spinosa DJ, Matsumoto AH, Angle JF et al (1998) Gadolinium-based contrast and carbon dioxide angiography to evaluate renal transplants for vascular causes of renal insufficiency and accelerated hypertension. J Vasc Interv Radiol 9:909–916PubMedCrossRef
12.
go back to reference Morcos SK (1999) Contrast medium-induced nephrotoxicity. In: Dawson P, Cosgrove DO, Grainger RG (eds) Textbook of contrast media. Isis Medical Mediad, Oxford pp 135–148 Morcos SK (1999) Contrast medium-induced nephrotoxicity. In: Dawson P, Cosgrove DO, Grainger RG (eds) Textbook of contrast media. Isis Medical Mediad, Oxford pp 135–148
13.
go back to reference Heyman SN, Reichman J, Brezis M (1999) Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia. Invest Radiol 34:685–691PubMedCrossRef Heyman SN, Reichman J, Brezis M (1999) Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia. Invest Radiol 34:685–691PubMedCrossRef
14.
go back to reference Garber GL, Read RC (1961) Red cell factor in renal damage from hypertonic solutions. Proc Soc Exp Biol Med 107:472–475 Garber GL, Read RC (1961) Red cell factor in renal damage from hypertonic solutions. Proc Soc Exp Biol Med 107:472–475
15.
go back to reference Katzberg RW, Schulman G, Meggs LG, Caldicott WJ, Damiano MM, Hollenberg NK (1983) Mechanism of the renal response to contrast medium in dogs. Decrease in renal function due to hypertonicity. Invest Radiol 18:74–80PubMedCrossRef Katzberg RW, Schulman G, Meggs LG, Caldicott WJ, Damiano MM, Hollenberg NK (1983) Mechanism of the renal response to contrast medium in dogs. Decrease in renal function due to hypertonicity. Invest Radiol 18:74–80PubMedCrossRef
16.
go back to reference Morris TW, Katzberg RW, Fischer HW (1978) A comparison of the hemodynamic responses to metrizamide and meglumine/sodium diatrizoate in canine renal angiography. Invest Radiol 13:74–78PubMedCrossRef Morris TW, Katzberg RW, Fischer HW (1978) A comparison of the hemodynamic responses to metrizamide and meglumine/sodium diatrizoate in canine renal angiography. Invest Radiol 13:74–78PubMedCrossRef
17.
go back to reference Törnquist C, Almén T, Golman K, Holtås S, (1984) Renal function following nephroangiography with diatriozoate Effects of saline, mannitol and diatrizoate on renal blood flow, glomerular permeability and filttration rate and diuresis in dogs. Acta Radiol 25:343–350 Törnquist C, Almén T, Golman K, Holtås S, (1984) Renal function following nephroangiography with diatriozoate Effects of saline, mannitol and diatrizoate on renal blood flow, glomerular permeability and filttration rate and diuresis in dogs. Acta Radiol 25:343–350
18.
go back to reference Morcos SK, Thomsen HS, Webb JA (1999) Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR). Eur Radiol 9:1602–1613PubMedCrossRef Morcos SK, Thomsen HS, Webb JA (1999) Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR). Eur Radiol 9:1602–1613PubMedCrossRef
19.
go back to reference Grainger RG, Thomas AMK (1999) History of the development of radiological contrast media (1985–1996). In: Dawson P Cosgrove DO, Grainger RG (eds) Textbook of contrast media. Isis Medical Media, Oxford, pp 3–14 Grainger RG, Thomas AMK (1999) History of the development of radiological contrast media (1985–1996). In: Dawson P Cosgrove DO, Grainger RG (eds) Textbook of contrast media. Isis Medical Media, Oxford, pp 3–14
20.
go back to reference Elmståhl B, Nyman U, Leander P, Chai Ch-M, Frennby B, Almén T (2004) 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 pigs. Acad Radiol 11:1219–1228PubMedCrossRef Elmståhl B, Nyman U, Leander P, Chai Ch-M, Frennby B, Almén T (2004) 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 pigs. Acad Radiol 11:1219–1228PubMedCrossRef
21.
go back to reference de Haën C, Morisetti A, Bertani F, Tirone P (1994) The factor time in acute intravenous toxicity studies of contrast media. Invest Radiol 29 (Suppl 2):S108–S110PubMed de Haën C, Morisetti A, Bertani F, Tirone P (1994) The factor time in acute intravenous toxicity studies of contrast media. Invest Radiol 29 (Suppl 2):S108–S110PubMed
22.
go back to reference Weinmann HJ (1999) Gadolinium chelates: physico-chemical properties, formulation and toxicology. In: Dawson P Cosgrove DO, Grainger RG (eds) Textbook of contrast media. Isis Medical Media, Oxford, pp 297–318 Weinmann HJ (1999) Gadolinium chelates: physico-chemical properties, formulation and toxicology. In: Dawson P Cosgrove DO, Grainger RG (eds) Textbook of contrast media. Isis Medical Media, Oxford, pp 297–318
23.
go back to reference Almén T, Frennby B, Sterner G (1999) Trends in contrast media. Determination of glomerular filtration rate with contrast media. In: Thomsen HS, Muller RN, Mattrey RF (eds) Medical radiology. Diagnostic imaging and radiation oncology. Springer, Berlin Heidelberg New York, pp 81–94 Almén T, Frennby B, Sterner G (1999) Trends in contrast media. Determination of glomerular filtration rate with contrast media. In: Thomsen HS, Muller RN, Mattrey RF (eds) Medical radiology. Diagnostic imaging and radiation oncology. Springer, Berlin Heidelberg New York, pp 81–94
24.
go back to reference Greenblatt DJ, Shader RI (1985) Pharmacokinetics in clinical practice. W.B. Saunders, Philadelphia, pp 1–40 Greenblatt DJ, Shader RI (1985) Pharmacokinetics in clinical practice. W.B. Saunders, Philadelphia, pp 1–40
25.
go back to reference Dean RE, Andrew JH, Read RC (1964) The red cell factor in renal damage from angiographic media; perfusion studies of the in situ canine kidney with cellular and acellular perfusates. JAMA 187:27–31PubMed Dean RE, Andrew JH, Read RC (1964) The red cell factor in renal damage from angiographic media; perfusion studies of the in situ canine kidney with cellular and acellular perfusates. JAMA 187:27–31PubMed
26.
go back to reference Katzberg RW, Morris TW, Burgener FA, Kamm DE, Fischer HW (1977) Renal renin and hemodynamic responses to selective renal artery catheterization and angiography. Invest Radiol 12:381–388PubMedCrossRef Katzberg RW, Morris TW, Burgener FA, Kamm DE, Fischer HW (1977) Renal renin and hemodynamic responses to selective renal artery catheterization and angiography. Invest Radiol 12:381–388PubMedCrossRef
27.
go back to reference Törnquist C, Almén T, Golman K, Holtas S (1985) Renal function following nephroangiography with metrizamide and iohexol. Effects on renal blood flow, glomerular permeability and filtration rate and diuresis in dogs. Acta Radiol Diagn (Stockh) 26:483–489 Törnquist C, Almén T, Golman K, Holtas S (1985) Renal function following nephroangiography with metrizamide and iohexol. Effects on renal blood flow, glomerular permeability and filtration rate and diuresis in dogs. Acta Radiol Diagn (Stockh) 26:483–489
28.
go back to reference Deray G, Baumelou B, Martinez F, Brillet G, Jacobs C (1991) Renal vasoconstriction after low and high osmolar contrast agents in ischemic and non ischemic canine kidney. Clin Nephrol 36:93–96PubMed Deray G, Baumelou B, Martinez F, Brillet G, Jacobs C (1991) Renal vasoconstriction after low and high osmolar contrast agents in ischemic and non ischemic canine kidney. Clin Nephrol 36:93–96PubMed
29.
go back to reference Lund G, Einzig S, Rysavy J et al (1984) Role of ischemia in contrast-induced renal damage: an experimental study. Circulation 69:783–789PubMed Lund G, Einzig S, Rysavy J et al (1984) Role of ischemia in contrast-induced renal damage: an experimental study. Circulation 69:783–789PubMed
30.
go back to reference Aspelin P (1979) Effect of ionic and non-ionic contrast media on red cell deformability in vitro. Acta Radiol 20:1–11 Aspelin P (1979) Effect of ionic and non-ionic contrast media on red cell deformability in vitro. Acta Radiol 20:1–11
31.
go back to reference Aspelin P, Nilsson PE, Schmid-Schonbein H, Schroder S, Simon R (1987) Effect of four non-ionic contrast media on red blood cells in vitro. III. Deformability. Acta Radiol Suppl 370:89–91 Aspelin P, Nilsson PE, Schmid-Schonbein H, Schroder S, Simon R (1987) Effect of four non-ionic contrast media on red blood cells in vitro. III. Deformability. Acta Radiol Suppl 370:89–91
32.
go back to reference Almén T, Bergentz S-E, Törnquist K, Öystese B (1985) Selective nephroangiography in the dog causing renal plateletaggregation and irregutar nephrographic phase. Acta Radiol 26:627–634 Almén T, Bergentz S-E, Törnquist K, Öystese B (1985) Selective nephroangiography in the dog causing renal plateletaggregation and irregutar nephrographic phase. Acta Radiol 26:627–634
33.
go back to reference Morcos SK, Brown PW, Oldroyd S, el Nahas AM, Haylor J (1995) Relationship between the diuretic effect of radiocontrast media and their ability to increase renal vascular resistance. Br J Radiol 68:850–853PubMedCrossRef Morcos SK, Brown PW, Oldroyd S, el Nahas AM, Haylor J (1995) Relationship between the diuretic effect of radiocontrast media and their ability to increase renal vascular resistance. Br J Radiol 68:850–853PubMedCrossRef
34.
go back to reference Katzberg RW (1997) Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity. Radiology 204:297–312PubMed Katzberg RW (1997) Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity. Radiology 204:297–312PubMed
35.
go back to reference Barrett BJ (1994) Contrast nephrotoxicity. J Am Soc Nephrol 5:125–137PubMed Barrett BJ (1994) Contrast nephrotoxicity. J Am Soc Nephrol 5:125–137PubMed
36.
go back to reference Hardiek K, Katholi RE, Ramkumar V, Deitrick C (2001) Proximal tubule cell response to radiographic contrast media. Am J Physiol Renal Physiol 280:F61–F70PubMed Hardiek K, Katholi RE, Ramkumar V, Deitrick C (2001) Proximal tubule cell response to radiographic contrast media. Am J Physiol Renal Physiol 280:F61–F70PubMed
37.
go back to reference Heinrich MC, Kuhlmann MK, Grgic A, Heckmann M, Kramann B, Uder M (2005) Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro. Radiology 235:843–849PubMed Heinrich MC, Kuhlmann MK, Grgic A, Heckmann M, Kramann B, Uder M (2005) Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro. Radiology 235:843–849PubMed
38.
go back to reference Thomsen HS (2004) Gadolinium-based contrast media may be nephrotoxic even at approved doses. Eur Radiol 14:1654–1656PubMed Thomsen HS (2004) Gadolinium-based contrast media may be nephrotoxic even at approved doses. Eur Radiol 14:1654–1656PubMed
39.
go back to reference Thomsen HS, Almén T, Morcos SK (2002) Contrast Medai Safety Committee of The European Society of Urogenital Radiology (ESUR). Gadolinium-containing contrast media for radiographic examinations: a position paper. Eur Radiol 12:2600–2605PubMed Thomsen HS, Almén T, Morcos SK (2002) Contrast Medai Safety Committee of The European Society of Urogenital Radiology (ESUR). Gadolinium-containing contrast media for radiographic examinations: a position paper. Eur Radiol 12:2600–2605PubMed
40.
go back to reference Barrett BJ, Carlisle EJ (1993) Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 188:171–178PubMed Barrett BJ, Carlisle EJ (1993) Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 188:171–178PubMed
41.
go back to reference Rudnick MR, Goldfarb S, Wexler L et al (1995) Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a randomized trial. The Iohexol Cooperative Study. Kidney Int 47:254–261PubMed Rudnick MR, Goldfarb S, Wexler L et al (1995) Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a randomized trial. The Iohexol Cooperative Study. Kidney Int 47:254–261PubMed
42.
go back to reference Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ (2003) Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 348:491–499PubMedCrossRef Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ (2003) Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 348:491–499PubMedCrossRef
43.
go back to reference Olsson B, Aulie Å, Sveen K, Andrew E (1983) Human pharmacokinetics of iohexol a new nonionic contrast medium. Invest Radiol 18:177–182PubMedCrossRef Olsson B, Aulie Å, Sveen K, Andrew E (1983) Human pharmacokinetics of iohexol a new nonionic contrast medium. Invest Radiol 18:177–182PubMedCrossRef
44.
go back to reference Weinmann HJ, Laniado M, Mutzel W (1984) Pharmacokinetics of GdDTPA/dimeglumine after intravenous injection into healthy volunteers. Physiol Chem Phys Med NMR 16:167–172PubMed Weinmann HJ, Laniado M, Mutzel W (1984) Pharmacokinetics of GdDTPA/dimeglumine after intravenous injection into healthy volunteers. Physiol Chem Phys Med NMR 16:167–172PubMed
45.
go back to reference Van Wagoner M, Worah D (1993) Gadodiamide injection. First human experience with the nonionic magnetic resonance imaging enhancement agent. Invest Radiol 28(Suppl 1):S44–S48PubMedCrossRef Van Wagoner M, Worah D (1993) Gadodiamide injection. First human experience with the nonionic magnetic resonance imaging enhancement agent. Invest Radiol 28(Suppl 1):S44–S48PubMedCrossRef
46.
go back to reference Terris JM (1985) Swine as a model in renal physiology and nephrology: an overview. Swine in biomedical research. In: Tumbleson, ME (ed) Swine in Biomedical Research, Vol. II, pp 1673–1690 Terris JM (1985) Swine as a model in renal physiology and nephrology: an overview. Swine in biomedical research. In: Tumbleson, ME (ed) Swine in Biomedical Research, Vol. II, pp 1673–1690
47.
go back to reference Idée JM, Bonnemain B (1996) Reliability of experimental models of iodinated contrast media-induced acute renal failure. From methodological considerations to pathophysiology. Invest Radiol 31:230–241PubMedCrossRef Idée JM, Bonnemain B (1996) Reliability of experimental models of iodinated contrast media-induced acute renal failure. From methodological considerations to pathophysiology. Invest Radiol 31:230–241PubMedCrossRef
Metadata
Title
Gadolinium contrast media are more nephrotoxic than iodine media. The importance of osmolality in direct renal artery injections
Authors
Barbara Elmståhl
Ulf Nyman
Peter Leander
Chun-Ming Chai
Klaes Golman
Jonas Björk
Torsten Almén
Publication date
01-12-2006
Publisher
Springer-Verlag
Published in
European Radiology / Issue 12/2006
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-006-0357-4

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