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European Radiology

, Volume 16, Issue 12, pp 2712–2720 | Cite as

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

  • Barbara ElmståhlEmail author
  • Ulf Nyman
  • Peter Leander
  • Chun-Ming Chai
  • Klaes Golman
  • Jonas Björk
  • Torsten Almén
Contrast Media

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.

Keywords

Angiography Computed tomography Contrast media Osmolality Renal impairment Gadolinium 

Notes

Acknowledgement

This study was financed in part by GE Healthcare.

References

  1. 1.
    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 53:503–507PubMedCrossRefGoogle Scholar
  2. 2.
    Spinosa DJ, Matsumoto AH, Hagspiel KD, Angle JF, Hartwell GD (1999) Gadolinium-based contrast agents in angiography and interventional radiology. AJR Am J Roentgenol 173:1403–1409PubMedGoogle Scholar
  3. 3.
    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 91:974–975PubMedCrossRefGoogle Scholar
  4. 4.
    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 37:346–352PubMedCrossRefGoogle Scholar
  5. 5.
    Strunk HM, Schild H (2004) Actual clinical use of gadolinium-chelates for non-MRI applications. Eur Radiol 14:1055–1062PubMedCrossRefGoogle Scholar
  6. 6.
    Erly WK, Zaetta J, Borders GT et al (2000) Gadopentetate dimeglumine as a contrast agent in common carotid arteriography. AJNR Am J Neuroradiol 21:964–967PubMedGoogle Scholar
  7. 7.
    Chryssidis S, Davies RP, Tie ML (2002) Gadolinium-enhanced computed tomographic aortography. Australas Radiol 46:97–100PubMedCrossRefGoogle Scholar
  8. 8.
    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 235:819–826PubMedGoogle Scholar
  9. 9.
    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 223:311–318PubMedGoogle Scholar
  10. 10.
    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, SwedenGoogle Scholar
  11. 11.
    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 9:909–916PubMedCrossRefGoogle Scholar
  12. 12.
    Morcos SK (1999) Contrast medium-induced nephrotoxicity. In: Dawson P, Cosgrove DO, Grainger RG (eds) Textbook of contrast media. Isis Medical Mediad, Oxford pp 135–148Google Scholar
  13. 13.
    Heyman SN, Reichman J, Brezis M (1999) Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia. Invest Radiol 34:685–691PubMedCrossRefGoogle Scholar
  14. 14.
    Garber GL, Read RC (1961) Red cell factor in renal damage from hypertonic solutions. Proc Soc Exp Biol Med 107:472–475Google Scholar
  15. 15.
    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 18:74–80PubMedCrossRefGoogle Scholar
  16. 16.
    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 13:74–78PubMedCrossRefGoogle Scholar
  17. 17.
    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 25:343–350Google Scholar
  18. 18.
    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 9:1602–1613PubMedCrossRefGoogle Scholar
  19. 19.
    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 3–14Google Scholar
  20. 20.
    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 11:1219–1228PubMedCrossRefGoogle Scholar
  21. 21.
    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–S110PubMedGoogle Scholar
  22. 22.
    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 297–318Google Scholar
  23. 23.
    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 81–94Google Scholar
  24. 24.
    Greenblatt DJ, Shader RI (1985) Pharmacokinetics in clinical practice. W.B. Saunders, Philadelphia, pp 1–40Google Scholar
  25. 25.
    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 187:27–31PubMedGoogle Scholar
  26. 26.
    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 12:381–388PubMedCrossRefGoogle Scholar
  27. 27.
    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) 26:483–489Google Scholar
  28. 28.
    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 36:93–96PubMedGoogle Scholar
  29. 29.
    Lund G, Einzig S, Rysavy J et al (1984) Role of ischemia in contrast-induced renal damage: an experimental study. Circulation 69:783–789PubMedGoogle Scholar
  30. 30.
    Aspelin P (1979) Effect of ionic and non-ionic contrast media on red cell deformability in vitro. Acta Radiol 20:1–11Google Scholar
  31. 31.
    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 370:89–91Google Scholar
  32. 32.
    Almén T, Bergentz S-E, Törnquist K, Öystese B (1985) Selective nephroangiography in the dog causing renal plateletaggregation and irregutar nephrographic phase. Acta Radiol 26:627–634Google Scholar
  33. 33.
    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 68:850–853PubMedCrossRefGoogle Scholar
  34. 34.
    Katzberg RW (1997) Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity. Radiology 204:297–312PubMedGoogle Scholar
  35. 35.
    Barrett BJ (1994) Contrast nephrotoxicity. J Am Soc Nephrol 5:125–137PubMedGoogle Scholar
  36. 36.
    Hardiek K, Katholi RE, Ramkumar V, Deitrick C (2001) Proximal tubule cell response to radiographic contrast media. Am J Physiol Renal Physiol 280:F61–F70PubMedGoogle Scholar
  37. 37.
    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 235:843–849PubMedGoogle Scholar
  38. 38.
    Thomsen HS (2004) Gadolinium-based contrast media may be nephrotoxic even at approved doses. Eur Radiol 14:1654–1656PubMedGoogle Scholar
  39. 39.
    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 12:2600–2605PubMedGoogle Scholar
  40. 40.
    Barrett BJ, Carlisle EJ (1993) Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 188:171–178PubMedGoogle Scholar
  41. 41.
    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 47:254–261PubMedGoogle Scholar
  42. 42.
    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 348:491–499PubMedCrossRefGoogle Scholar
  43. 43.
    Olsson B, Aulie Å, Sveen K, Andrew E (1983) Human pharmacokinetics of iohexol a new nonionic contrast medium. Invest Radiol 18:177–182PubMedCrossRefGoogle Scholar
  44. 44.
    Weinmann HJ, Laniado M, Mutzel W (1984) Pharmacokinetics of GdDTPA/dimeglumine after intravenous injection into healthy volunteers. Physiol Chem Phys Med NMR 16:167–172PubMedGoogle Scholar
  45. 45.
    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–S48PubMedCrossRefGoogle Scholar
  46. 46.
    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 1673–1690Google Scholar
  47. 47.
    Idée JM, Bonnemain B (1996) Reliability of experimental models of iodinated contrast media-induced acute renal failure. From methodological considerations to pathophysiology. Invest Radiol 31:230–241PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Barbara Elmståhl
    • 1
    Email author
  • Ulf Nyman
    • 2
  • Peter Leander
    • 1
  • Chun-Ming Chai
    • 3
  • Klaes Golman
    • 4
  • Jonas Björk
    • 5
  • Torsten Almén
    • 1
  1. 1.Department of Diagnostic RadiologyMalmö University Hospital, Lund UniversityMalmöSweden
  2. 2.Department of RadiologyLasarettet TrelleborgTrelleborgSweden
  3. 3.Department of Experimental ResearchMalmö University Hospital, Lund UniversityMalmöSweden
  4. 4.GE HealthBiosciencesMalmöSweden
  5. 5.Competence Center for Clinical ResearchUniversity Hospital, Lund UniversityLundSweden

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