Contrast-induced nephrotoxicity: Clinical landscape
2006; Elsevier BV; Volume: 69; Linguagem: Inglês
10.1038/sj.ki.5000366
ISSN1523-1755
AutoresRichard W. Katzberg, Christlieb Haller,
Tópico(s)Muscle and Compartmental Disorders
ResumoOver 80 million doses of iodinated intravascular contrast media (CM) were administered in the most recent tabulations of 2003, corresponding to approximately 8 million liters, making it one of the highest volume medical drugs used compared to any other pharmaceutical. The evolution of CM has focused on minimizing adverse events by eliminating ionicity, increasing hydrophilicity, lowering osmolality and increasing the number of iodine atoms per molecule. Contrast media are classified into three general categories based on their osmolality relative to blood: high osmolar (5 times or greater than blood), low osmolar (2–3 times blood) and iso-osmolar (the same as blood). All imaging modalities that employ CM, especially computerized tomography (CT), have shown rapid growth. In the last two decades, the use of CT scanning has increased by 800%. From 1979 to 2002, the number of cardiac catheterization procedures in the USA increased by 390% and in Europe from 1992 to 1999 by 112%. There is a general consensus that renal insufficiency and diabetes are major risk factors for contrast-induced nephropathy (CIN), particularly when co-existing. The US Renal Data System documents a ‘relentless’ increase in kidney failure, projecting a 90% increase by 2010. Diabetes affects 194 million people worldwide and the number is anticipated to increase by 75% by 2025. The unavoidable conclusion is that patient exposure and prevalence of risk factors for CIN will continue to increase. Over 80 million doses of iodinated intravascular contrast media (CM) were administered in the most recent tabulations of 2003, corresponding to approximately 8 million liters, making it one of the highest volume medical drugs used compared to any other pharmaceutical. The evolution of CM has focused on minimizing adverse events by eliminating ionicity, increasing hydrophilicity, lowering osmolality and increasing the number of iodine atoms per molecule. Contrast media are classified into three general categories based on their osmolality relative to blood: high osmolar (5 times or greater than blood), low osmolar (2–3 times blood) and iso-osmolar (the same as blood). All imaging modalities that employ CM, especially computerized tomography (CT), have shown rapid growth. In the last two decades, the use of CT scanning has increased by 800%. From 1979 to 2002, the number of cardiac catheterization procedures in the USA increased by 390% and in Europe from 1992 to 1999 by 112%. There is a general consensus that renal insufficiency and diabetes are major risk factors for contrast-induced nephropathy (CIN), particularly when co-existing. The US Renal Data System documents a ‘relentless’ increase in kidney failure, projecting a 90% increase by 2010. Diabetes affects 194 million people worldwide and the number is anticipated to increase by 75% by 2025. The unavoidable conclusion is that patient exposure and prevalence of risk factors for CIN will continue to increase. It has been over a half century since the first episode of contrast-induced nephrotoxicity (CIN) was reported by Bartls et al.,1..Bartels E.D. Brun G.C. Gammeltoft A. Gjorup P.A. Acute anuria following intravenous pyelography in a patient with myelomatosis.Acta Med Scand. 1954; 150: 297-302Crossref PubMed Scopus (104) Google Scholar a case report associated with multiple myeloma following intravenous pyelography using 20 ml Diodrast 50%. Since then, there have been several thousand clinical reports, the rate of which accelerated appreciably in the mid-1970s.2..Mudge G.H. Nephrotoxicity of urographic radiocontrast drugs.Kidney Int. 1980; 18: 540-552Abstract Full Text PDF PubMed Scopus (84) Google Scholar Iodinated contrast media (CM) are among the most commonly prescribed medications in the history of modern medicine, with approximately 80 million doses being administered in 2003 worldwide corresponding to approximately 8 million liters.3..Persson P.D. Editorial: contrast medium-induced nephropathy.Nephrol Dial Transplant. 2005; 20: ilGoogle Scholar The general indication for the use of iodinated CM is to create an X-ray attenuation differential in tissues in order to increase the visualization of disease processes. Proven clinical efficacy in clinical trials has been shown by one or more of the following criteria: percent lesion enhancement (i.e. contrast-to-noise ratio); number of lesions detected; level of diagnostic information and confidence in diagnosis.4..Runge V.M. Armstrong M.R. Barr R.G. et al.A clinical comparison of the safety and efficacy of MultiHance (gadobenate dimeglumine) and Omniscan (gadodiamide) in magnetic resonance imaging in patients with central nervous system pathology.Invest Radiol. 2001; 36: 65-71Crossref PubMed Scopus (50) Google Scholar As CM have no therapeutic effects, the ideal agent should provide optimal quality without substantial adverse effects.5..McClennan B.L. Ionic and nonionic iodinated contrast media: evolution and strategies for use.Am J Roentgenol. 1990; 155: 225-233Crossref PubMed Scopus (69) Google Scholar, 6..Morris T.W. X-ray contrast media: Where are we now and where are we going?.Radiology. 1993; 188: 11-16Crossref PubMed Scopus (40) Google Scholar The major driving forces in the development of CM have been to eliminate systemic and central nervous system toxicities.5..McClennan B.L. Ionic and nonionic iodinated contrast media: evolution and strategies for use.Am J Roentgenol. 1990; 155: 225-233Crossref PubMed Scopus (69) Google Scholar, 6..Morris T.W. X-ray contrast media: Where are we now and where are we going?.Radiology. 1993; 188: 11-16Crossref PubMed Scopus (40) Google Scholar, 7..Eloy R. Corot C. Belleville J. Contrast media for angiography: physicochemical properties, pharmacokinetics and biocompatibility.Clin Mater. 1991; 7: 89-97Crossref PubMed Scopus (104) Google Scholar, 8..Katzberg R.W. State of the Art. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity.Radiology. 1997; 204: 297-312Crossref PubMed Scopus (162) Google Scholar, 9..Stacul F. Current iodinated contrast media.Eur Radiol. 2001; 11: 690-697Crossref PubMed Scopus (44) Google Scholar Indeed, with the advent of non-ionic, low-osmolality CM (LOCM) in the 1980s, most adverse events are relatively mild and require no medical treatment.10..Idée J.-M. Pinès E. Prigent P. Corot C. Allergy-like reactions to iodinated contrast agents. A critical analysis.Fund Clin Pharmacol. 2005; 19: 263-281Crossref PubMed Scopus (80) Google Scholar Severe or life-threatening reactions to non-ionic monomeric CM occur in association with approximately 4 in 10 000 exams and with a mortality rate estimated to be approximately 1 in 170 000 exams, a remarkable safety profile.10..Idée J.-M. Pinès E. Prigent P. Corot C. Allergy-like reactions to iodinated contrast agents. A critical analysis.Fund Clin Pharmacol. 2005; 19: 263-281Crossref PubMed Scopus (80) Google Scholar, 11..Katayama H. Yamaguci K. Kozuka T. et al.Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on safety of contrast media.Radiology. 1990; 175: 621-628Crossref PubMed Scopus (1266) Google Scholar All currently used X-ray CM are based on the tri-iodinated benzene ring, acetrizoate being the parent tri-iodinated contrast medium first in clinical use.8..Katzberg R.W. State of the Art. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity.Radiology. 1997; 204: 297-312Crossref PubMed Scopus (162) Google Scholar, 12..Wallingford V. The development of organic iodine compounds as x-ray contrast media.J Am Pharm Assoc. 1953; 42: 721-729Abstract Full Text PDF Scopus (32) Google Scholar Strategies to improve efficacy and safety can be best demonstrated by showing modifications of acetrizoate. As a first principle, it was suggested by Lasser et al.13..Lasser E. Farr R.S. Fujimagari T. Tripp W. The significance of protein binding of contrast media in roentgen diagnosis.Am J Roentgenol. 1962; 87: 338-360Google Scholar that the presence of a hydrogen atom at the tri-iodinated benzene ring give a higher degree of protein binding than when the hydrogen atom has been substituted. It was hypothesized that an increase in protein binding is a factor that incited anaphylactoid reactions. Indeed, in diatrizoates the unsubstituted hydrogen of acetrizoate has been exchanged for another acetamido unit; this has led to a higher biologic tolerance, as indicated by a median lethal dose of 5 g of iodine per kilogram with acetrizoate versus 5–10 g of iodine per kilogram with diatrizoate.14..Almén T. Visipaque: a step forward – a historical review.Acta Radiol. 1995; 36: S2-S18Google Scholar Further strategies to decrease general toxicity have been to decrease both osmotoxicity and ionicity by replacing the ionizing carboxyl group (i.e. COO-Na+ and COO-Meg+) with hydrophilic structures that can be covalently bound to the benzene ring to derive a non-dissociating (non-ionic) water-soluble contrast medium molecule.5..McClennan B.L. Ionic and nonionic iodinated contrast media: evolution and strategies for use.Am J Roentgenol. 1990; 155: 225-233Crossref PubMed Scopus (69) Google Scholar, 8..Katzberg R.W. State of the Art. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity.Radiology. 1997; 204: 297-312Crossref PubMed Scopus (162) Google Scholar, 9..Stacul F. Current iodinated contrast media.Eur Radiol. 2001; 11: 690-697Crossref PubMed Scopus (44) Google Scholar, 15..Spataro R.F. Newer contrast agents fro urography.Radiol Clin North Am. 1984; 22: 365-380PubMed Google Scholar, 16..Sovak M. The Harry W. Fischer lecture: Contrast media – a meandering look.Acad Radiol. 1996; 3: S241-S247Abstract Full Text PDF PubMed Google Scholar, 17..Idée J.-M. Jachman I. Port M. et al.Iodinated contrast media: from non-specific to blood-pool agents.Top Curr Chem. 2002; 222: 153-171Google Scholar The first major breakthrough along these lines was the historic introduction by Almén18..Almèn T. Contrast agent design: some aspects of synthesis of water-soluble contrast agents of low osmolality.J Theor Biol. 1969; 24: 216-226Crossref PubMed Scopus (150) Google Scholar of the first ratio 3 non-ionic monomer, metrizamide. The new generation of LOCM now in clinical use includes iohexol (OMNIPAQUE®, GE Healthcare, Piscataway, NJ, USA), ioversol (OPTIRAY®, Tyco Healthcare-Medical Imaging, Hazelwood, MO, USA), iopamidol (ISOVUE, Bracco Diagnostics Inc., Princeton, NJ, USA; IOPAMIRO, Bracco SpA, Italy), iopromide (UTRAVIST®, Schering AG, Germany), iobitridol (XENETIX®, Guerbet, France), iomeprol (IOMERON, Bracco SpA, Italy) and ioxilan (OXILAN®, Guerbet, France). However, the first LOCM in clinical use was ioxaglate (HEXABRIX®, Guerbet, France), a low osmolar ionic agent. This is a somewhat unusual class of agent, since it is both ionic and also the first dimer in clinical use. Mechanisms to diminish subarachnoid toxicity, besides decreasing osmolality and eliminating ionicity, include increasing the number of hydroxyl groups and distributing the hydroxyl groups more evenly around the CM molecule.14..Almén T. Visipaque: a step forward – a historical review.Acta Radiol. 1995; 36: S2-S18Google Scholar Proof of principle is evidenced by the fact that the newer LOCM have median lethal doses and subarachnoid toxicities superior to that of metrizamide. Iohexol has six hydroxyl groups evenly distributed around the molecule compared to metrizamide, which has only four hydroxyl groups clustered at one end of the molecule on the glucosamide moiety. In the 1980s and 1990s, there has been an ongoing development of non-ionic isotonic ratio 6 dimers to include iodixanol (VISIPAQUE®, GE Healthcare, UK) and iotrolan (ISOVIST®, Schering AG, Germany).5..McClennan B.L. Ionic and nonionic iodinated contrast media: evolution and strategies for use.Am J Roentgenol. 1990; 155: 225-233Crossref PubMed Scopus (69) Google Scholar, 6..Morris T.W. X-ray contrast media: Where are we now and where are we going?.Radiology. 1993; 188: 11-16Crossref PubMed Scopus (40) Google Scholar, 7..Eloy R. Corot C. Belleville J. Contrast media for angiography: physicochemical properties, pharmacokinetics and biocompatibility.Clin Mater. 1991; 7: 89-97Crossref PubMed Scopus (104) Google Scholar, 8..Katzberg R.W. State of the Art. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity.Radiology. 1997; 204: 297-312Crossref PubMed Scopus (162) Google Scholar, 9..Stacul F. Current iodinated contrast media.Eur Radiol. 2001; 11: 690-697Crossref PubMed Scopus (44) Google Scholar, 14..Almén T. Visipaque: a step forward – a historical review.Acta Radiol. 1995; 36: S2-S18Google Scholar, 15..Spataro R.F. Newer contrast agents fro urography.Radiol Clin North Am. 1984; 22: 365-380PubMed Google Scholar, 16..Sovak M. The Harry W. Fischer lecture: Contrast media – a meandering look.Acad Radiol. 1996; 3: S241-S247Abstract Full Text PDF PubMed Google Scholar, 17..Idée J.-M. Jachman I. Port M. et al.Iodinated contrast media: from non-specific to blood-pool agents.Top Curr Chem. 2002; 222: 153-171Google Scholar These agents are a consequence of further applications of principles to eliminate ionicity, increase hydrophilicity, lower osmotoxicity and increase the number of iodine atoms per molecule. The concept of non-ionic isotonic dimers is, however, of some small compromise, since the self-assembly in a solution of molecules containing six, rather than three, iodines gives low osmolality, but results in higher viscosity and greater resistance to catheter injection.8..Katzberg R.W. State of the Art. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity.Radiology. 1997; 204: 297-312Crossref PubMed Scopus (162) Google Scholar By adding small amounts of calcium ions to solutions of the non-ionic monomers, even further improvement in neural and cardiac tolerance has been achieved. The combination of sodium and calcium ions decreases CM effects on cardiac contractility and the risk of ventricular fibrillation.6..Morris T.W. X-ray contrast media: Where are we now and where are we going?.Radiology. 1993; 188: 11-16Crossref PubMed Scopus (40) Google Scholar, 7..Eloy R. Corot C. Belleville J. Contrast media for angiography: physicochemical properties, pharmacokinetics and biocompatibility.Clin Mater. 1991; 7: 89-97Crossref PubMed Scopus (104) Google Scholar The pH of the solution is made neutral since a low pH leads to vasodilatation, a possible factor leading to hypotension in some circumstances. Calcium disodium ethylenediaminetetraacetic acid, an additional additive, sequesters both Fe and Cu, which catalyze de-iodination that can occur during contrast medium sterilization.12..Wallingford V. The development of organic iodine compounds as x-ray contrast media.J Am Pharm Assoc. 1953; 42: 721-729Abstract Full Text PDF Scopus (32) Google Scholar, 14..Almén T. Visipaque: a step forward – a historical review.Acta Radiol. 1995; 36: S2-S18Google Scholar Calcium disodium ethylenediaminetetraacetic acid does not chelate plasma calcium, a characteristic that might otherwise result in greater cardiotoxicity. Some unusual characteristics of the ratio six dimers are that the increased viscosity has been shown to lead to a more prolonged decrease in single-nephron glomerular filtration rate (GFR) and a decrease in oxygen tension in the medulla of the kidney when compared to either high-osmolar CM (HOCM) or LOCM.19..Ueda J. Effect of contrast media on single nephron functions. Thesis. Uppsala University, Uppsala, Sweden1991Google Scholar, 20..Liss P. Effects of contrast media in renal microcirculation and oxygen tension: an experimental study in the rat. Thesis. Uppsala University, Uppsala, Sweden1996Google Scholar, 21..Jakobsen J.Å. Lundby B. Kristoffersen D.T. et al.Evaluation of renal function with delayed CT after injection of nonionic monomeric and dimeric contrast media in healthy volunteers.Radiology. 1992; 182: 419-424Crossref PubMed Scopus (71) Google Scholar, 22..Dobrota M. Powell C.J. Holtz E. et al.Biochemical and morphological effects of contrast media on the kidney.Acta Radiol. 1995; 36: 196-203PubMed Google Scholar Furthermore, the iso-osmolar CM are pinocytized into the tubular cells with sustained renal retention and density to a greater extent than LOCM. There is also concern for an increase in delayed systemic and cutaneous reactions.9..Stacul F. Current iodinated contrast media.Eur Radiol. 2001; 11: 690-697Crossref PubMed Scopus (44) Google Scholar Owing to these characteristics, there has been an interest in a further evolution of CM to non-ionic, ratio 6 compact dimers with smaller size in vivo and lower viscosity.16..Sovak M. The Harry W. Fischer lecture: Contrast media – a meandering look.Acad Radiol. 1996; 3: S241-S247Abstract Full Text PDF PubMed Google Scholar, 23..Petta M. Raynal I. Bourrinet P. et al.Nonionic compact dimers: a new generation of isomolar iodinated contrast media with low viscosity.Acad Radiol. 1998; 5: 41-45Abstract Full Text PDF PubMed Scopus (5) Google Scholar CM are classified as ionic or non-ionic and as monomers or dimers.5..McClennan B.L. Ionic and nonionic iodinated contrast media: evolution and strategies for use.Am J Roentgenol. 1990; 155: 225-233Crossref PubMed Scopus (69) Google Scholar, 6..Morris T.W. X-ray contrast media: Where are we now and where are we going?.Radiology. 1993; 188: 11-16Crossref PubMed Scopus (40) Google Scholar, 7..Eloy R. Corot C. Belleville J. Contrast media for angiography: physicochemical properties, pharmacokinetics and biocompatibility.Clin Mater. 1991; 7: 89-97Crossref PubMed Scopus (104) Google Scholar, 8..Katzberg R.W. State of the Art. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity.Radiology. 1997; 204: 297-312Crossref PubMed Scopus (162) Google Scholar, 9..Stacul F. Current iodinated contrast media.Eur Radiol. 2001; 11: 690-697Crossref PubMed Scopus (44) Google Scholar, 14..Almén T. Visipaque: a step forward – a historical review.Acta Radiol. 1995; 36: S2-S18Google Scholar, 15..Spataro R.F. Newer contrast agents fro urography.Radiol Clin North Am. 1984; 22: 365-380PubMed Google Scholar, 16..Sovak M. The Harry W. Fischer lecture: Contrast media – a meandering look.Acad Radiol. 1996; 3: S241-S247Abstract Full Text PDF PubMed Google Scholar, 17..Idée J.-M. Jachman I. Port M. et al.Iodinated contrast media: from non-specific to blood-pool agents.Top Curr Chem. 2002; 222: 153-171Google Scholar, 24American College of Radiology Manual on Contrast Media Version 5.0 Retrieved 29 August 2005, from http://www.acr.orgGoogle Scholar Ionic media dissociate in water; the iodinated benzene ring contains the ionizing carboxyl group (valence, -1) with a cation (valence, +1), usually sodium or meglumine. Non-ionic contrast agents have the desirable property of being water-soluble (hydrophilic) and yet do not dissociate in solution. The ratio of iodine atoms to dissolved particles is an important characteristic of CM and is a commonly used term in the literature. This describes the important relationship between the imaging effect (attenuation of X-rays) and the osmotoxic effect of the media. Since the ratio represents the number of iodine atoms divided by the number of particles of CM in solution, a higher ratio is desirable, since more iodine means better opacification and fewer particles of contrast medium means a lower osmotoxic effect. Agents with a ratio of 1.5 are HOCM, agents with a ratio of 3 LOCM and agents with a ratio of 6 iso-osmolar CM. CM are generally classified by osmolality, which is defined by the number of osmotically active particles per kg of solvent.5..McClennan B.L. Ionic and nonionic iodinated contrast media: evolution and strategies for use.Am J Roentgenol. 1990; 155: 225-233Crossref PubMed Scopus (69) Google Scholar, 8..Katzberg R.W. State of the Art. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity.Radiology. 1997; 204: 297-312Crossref PubMed Scopus (162) Google Scholar, 9..Stacul F. Current iodinated contrast media.Eur Radiol. 2001; 11: 690-697Crossref PubMed Scopus (44) Google Scholar, 15..Spataro R.F. Newer contrast agents fro urography.Radiol Clin North Am. 1984; 22: 365-380PubMed Google Scholar, 24American College of Radiology Manual on Contrast Media Version 5.0 Retrieved 29 August 2005, from http://www.acr.orgGoogle Scholar This value is further determined by the size of the CM molecule and the number of particles in solution. First-generation CM were ionic monomers with an ionic carboxyl group attached to the first carbon of the iodine-containing benzene ring. With HOCM, for every three iodine atoms, two particles are present in solution (i.e. a ratio of 3:2). The osmolality in solution for this class of agents ranges from 1500–1800 mOsm/kg, whereas that of human plasma is 290 mOsm/kg. LOCM are classified as (1) non-ionic monomers and (2) ionic dimers. These second-generation CM have approximately half the osmolality of the HOCM. As the non-ionic monomers lack a carboxyl group, they do not ionize in solution; therefore, for every three iodine atoms only one particle is present in solution (i.e., a ratio of 3:1). Their iodine concentrations range from 300 to 370 mg/ml and they have an osmolality of 600–700 mOsm/kg, more than twice that of blood. The ionic dimers have a slightly lower osmolality in solution than the non-ionic monomers. They dissociate in solution and there are six iodine atoms for two particles, also giving a ratio of 3. Third-generation CM iso-osmolar dimers that consist of two molecules of CM linked together by a shared side chain have a higher viscosity than the previous generation of agents. This is a ratio 6 class of agent, since there are six iodine atoms for each particle in solution. In clinical use, one should consider that the larger molecular size and higher viscosity may reduce flow velocity, especially in small vessels. The pharmacokinetics of all the currently used iodinated agents are similar.5..McClennan B.L. Ionic and nonionic iodinated contrast media: evolution and strategies for use.Am J Roentgenol. 1990; 155: 225-233Crossref PubMed Scopus (69) Google Scholar, 6..Morris T.W. X-ray contrast media: Where are we now and where are we going?.Radiology. 1993; 188: 11-16Crossref PubMed Scopus (40) Google Scholar, 7..Eloy R. Corot C. Belleville J. Contrast media for angiography: physicochemical properties, pharmacokinetics and biocompatibility.Clin Mater. 1991; 7: 89-97Crossref PubMed Scopus (104) Google Scholar, 8..Katzberg R.W. State of the Art. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity.Radiology. 1997; 204: 297-312Crossref PubMed Scopus (162) Google Scholar, 14..Almén T. Visipaque: a step forward – a historical review.Acta Radiol. 1995; 36: S2-S18Google Scholar, 17..Idée J.-M. Jachman I. Port M. et al.Iodinated contrast media: from non-specific to blood-pool agents.Top Curr Chem. 2002; 222: 153-171Google Scholar, 25..Bourin M. Jolliet P. Ballereau F. An overview of the clinical pharmacokinetics x-ray contrast media.Clin Pharmacokinet. 1997; 32: 180-191Crossref PubMed Scopus (102) Google Scholar All of these agents have very low lipid solubility, extremely low chemical activity with bodily fluids, relatively small molecular weights, a half-time in patients with normal renal function of approximately 1–2 h, and are in a class of compounds termed ‘extracellular tracers’ with a bi-exponential decay curve. With the exception of the iso-osmolar CM agents, they are osmotic diuretics. The general characteristics of iodinated CM that have significant biological implications include osmolality, ionicity, hydrophilicity viscosity and the unique chemical structure.26..Katzberg R.W. The Contrast Media Manual. Williams and Wilkins, Baltimore, MD1992Google Scholar The systemic effect of CM, predominately due to their increased osmolality, is to increase the plasma volume, decrease the hematocrit, decrease peripheral vascular resistance, increase blood flow, and decrease systemic blood pressure. There is a transient decrease in the GFR due to osmotic effects, a physiologic response seen with non-specific osmotic diuretics such as mannitol.8..Katzberg R.W. State of the Art. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity.Radiology. 1997; 204: 297-312Crossref PubMed Scopus (162) Google Scholar, 27..Mudge G.H. The maximum urinary concentration of diatrizoate.Invest Radiol. 1980; 15: S67-S78Crossref PubMed Scopus (21) Google Scholar It is perhaps necessary to keep in mind that the risks for CM-induced morbidity and mortality are significantly different in comparing the clinical experiences between the daily radiology usage of CM versus percutaneous cardiac procedures and interventions. Growth rates in CM utilization will be discussed separately between the two disciplines. There are several interesting milestones in the radiological perception of CM utilization that may be of interest. In the early 1970s, with the advent of computerized tomography (CT), many radiologists felt that there would be a decreased need for iodinated CM because of the excellent soft-tissue discrimination of CT technology. However, exactly the opposite has transpired. A similar concern was felt for the growth of CT (and thus CM, again) in the 1980s with the advent of magnetic resonance. This also has proven to be just the opposite. Another milestone occurred in 1995 with the seminal publication in Radiology by Smith et al.28..Smith R.C. Rosenfield A.T. Choe K.A. et al.Acute flank pain: comparison of non-contrast-enhanced CT and intravenous urography.Radiology. 1995; 194: 789-794Crossref PubMed Scopus (601) Google Scholar ‘Acute flank pain: comparison of non-contrast enhanced CT and intravenous urography’. This has led to a true epitaph for the urogram as predicted and articulated in 1999 by Amis Jr,29..Amis Jr, E.S. Editorial. Epitaph for the urogram.Radiology. 1999; 213: 639-640Crossref PubMed Scopus (65) Google Scholar ‘Epitaph for the urogram’, an editorial also published in Radiology. Before the advent of CT, intravenous urography and angiography were the major indications for CM. In the pre-CT era, most radiologists were utilizing 30–50 ml HOCM and with hand injection rates of less than 1 ml/s for urography. This is in comparison to the average CM dose for CT of approximately 100–150 ml and with power injection rates of up to 3–4 ml/s. The first CT scan was performed on a 41-year-old woman on 1 October 1971, taking 15 h of scanning time using the first clinical CT instrument developed by the Nobel Prize Laureate Sir Godfrey Neobold Houndsfield.30..Kalra M.K. Maher M.M. Toth T.L. et al.Multidetector computed tomography technology. Current status and emerging developments.J Comput Assist Tomogr. 2004; 28: S2-S6Crossref PubMed Scopus (73) Google Scholar Spiral CT introduced in the early 1990s led to reduced scan times of 0.75–0.8 s of rotation time.30..Kalra M.K. Maher M.M. Toth T.L. et al.Multidetector computed tomography technology. Current status and emerging developments.J Comput Assist Tomogr. 2004; 28: S2-S6Crossref PubMed Scopus (73) Google Scholar, 31..Rubin G.D. Shiau M.C. Schmidt A.J. et al.Computed tomographic angiography: historical prospective and new state-of-the-art using multi detector-row helical computed tomography.J Comput Assist Tomogr. 1999; 23: S83-S90PubMed Google Scholar, 32..Flohr T.G. Schaller S. Stierstorfer K. et al.Multi-detector row CT systems and image-reconstruction techniques.Radiology. 2005; 235: 756-773Crossref PubMed Scopus (288) Google Scholar Acquisition of volume data without misregistration established the basis for applications such as CT angiography and three-dimensional displays. Multidetector-row CT introduced in the late 1990s with further reduced scan times (0.5 s) enabled breath-hold acquisitions in multiple phases of contrast enhancement. There is the expectation for a continual rapid growth in CT angiography, functional imaging of multiple organ systems with CM, coronary artery imaging and others.32..Flohr T.G. Schaller S. Stierstorfer K. et al.Multi-detector row CT systems and image-reconstruction techniques.Radiology. 2005; 235: 756-773Crossref PubMed Scopus (288) Google Scholar There are now 25 000 CT scanners in the world and in the last two decades the use of CT scanning has increased by 800%.30..Kalra M.K. Maher M.M. Toth T.L. et al.Multidetector computed tomography technology. Current status and emerging developments.J Comput Assist Tomogr. 2004; 28: S2-S6Crossref PubMed Scopus (73) Google Scholar There has been a 10% annual growth rate in global CT and it has been estimated that over 50 million CT procedures were performed in the last year. Over 50% of CT procedures employ iodinated CM and now with near-universal use of LOCM and iso-osmolar CM. Vascular indications have shown a growth rate by 235%, cardiac by 145%, abdominal, pelvic, thoracic, each by 25%, head and neck by 7%, and there is a projected 122% continued increase in CT procedures for 2002–2008. Even with the advent of magnetic resonance and rapid growth of magnetic resonance of the head and neck, data from the Medicare part B data over the last 6 years show a 17% increase in cranial CT.33..Health Care Financing Administration 1999 HCFA Statistics. US Government Printing Office, Washington, DC2000Google Scholar, 34..Maitino A.J. Levin D.C. Parker L. et al.Nationwide trends in rates of utilization of noninvasive diagnostic imaging among the Medicare population between 1993 and 1999.Radiology. 2003; 227: 113-117Crossref PubMed Scopus (100) Google Scholar This is very likely to increase even more rapidly, with the advent of multidetector-row CT, CT angiography, and the potential for functional imaging of various organ systems. Diagnostic imaging is now a $100 billion a year industry in the US and is the fastest growing type of physician service expenditure, according to the 2004 Medicare Payment Advisory Commission report to Congress.35Medicare Payment Advisory Commission (MedPAC) Report to Congress, 17 March 2005 (Imaging Services 1999–2002)Google Scholar Growth in all imaging services is 46% compared to growth of all physician services of 22%. All modalities that employ iodinated CM have shown continued rapid growth rates. According to the Heart Disease Stroke Statistics – 2005 Update of the American Heart Association, 1 463 000 inpatient cardiac catheterizations were performed in the US in 2000 (US population approximately 300 million).36..Heart Disease and Stroke Statistics Update. American Heart Association, 2005Google Scholar From 1979 to 2002, the number of cardiac catheterization procedures increased by 390%. In total, 657 000 percutaneous transluminal coronary angioplasties were performed in 640 000 patients in the US in 2002. The number of percutaneous transluminal coronary angioplasties increased by 324% from 1987 to 2002. In 2002, 50% were performed in people ≥65 years old. Coronary stent insertions increased by 150% between 1996 and 2000. There were an estimated 1 806 238 cardiac catheterization procedures performed in Europe in 2001 (29 countries, population about 550 million).37..Togni M. Balmer F. Pfiffner D. et al.Percutaneous coronary interventions in Europe 1992–2001.Eur Heart J. 2004; 25: 1208-1213Crossref PubMed Scopus (94) Google Scholar From 1992 to 1999, the number of cardiac catheterizations increased by 112%. In 2001, 617 176 percutaneous transluminal coronary angioplasties were performed in Europe, an increase of 205% from that in 1992–1999.38..Rotter M. Pfiffner D. Maier W. et al.Interventional cardiology in Europe 1999.Eur Heart J. 2003; 24: 1164-1170Crossref PubMed Scopus (34) Google Scholar In summary, there are continued dramatic increases in patient exposure to iodinated CM, probably beyond anyone's imagination even 10 years ago. There is general consensus that renal insufficiency and diabetes are major risk factors for CIN, particularly when coexisting.24American College of Radiology Manual on Contrast Media Version 5.0 Retrieved 29 August 2005, from http://www.acr.orgGoogle Scholar, 39..Parfrey P.S. Griffiths S.M. Barrett B.J. et al.Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both.N Eng J Med. 1989; 320: 143-149Crossref PubMed Scopus (891) Google Scholar, 40..Gleeson T.G. Bulugahapitiya S. Review: contrast-induced nephropathy.Am J Roentgenol. 2004; 183: 1673-1689Crossref PubMed Scopus (321) Google Scholar The major focus of this overview will be on these primary clinical factors. The good news is that the US adult population has an expectation to live to a record 77.6 years of age.41..National Center for Health Statistics Annual Mortality Report. Center for Disease Control (CDC), Atlanta, GA2005Google Scholar This is still less than Japan (highest at 81.9 years), Switzerland, Australia, Austria, Belgium, France, Germany, Italy, Norway, Spain and the UK. The US Census Bureau estimates that there will be 40 million Americans ≥65 years old by 2010.41..National Center for Health Statistics Annual Mortality Report. Center for Disease Control (CDC), Atlanta, GA2005Google Scholar, 42..American Heart Association Heart Disease and Stroke Statistics – Update. American Heart Association, Dallas, TX2005Google Scholar In 2003 the Centers of Disease Control reported that the two largest killers of Americans showed a decrease in death rates from heart disease of 240.8/100 000 in 2002 to 232.1 (-4%) in 2003 and from cancer 193.3–189.9/100 000 (-2%). The bad news is that death rate from hypertension increased by 5.7% and kidney disease by 2.1%. The aging of the population will undoubtedly result in an increase in incidence of chronic diseases such as coronary artery disease, heart failure, stroke, renal disease, diabetes and hypertension, among others.42..American Heart Association Heart Disease and Stroke Statistics – Update. American Heart Association, Dallas, TX2005Google Scholar The US Renal Data System has documented a ‘relentless’ increase in kidney failure requiring dialysis therapy or transplantation to 347 000 patients in 1999 and a projected 651 000 patients in 2010 (91% increase).43..US Renal Data System USRDS 2001 Annual Data Report. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD2001Google Scholar, 44..Xue J.L. Ma J.Z. Louis T.A. Collins A.J. Forecast of the number of participants with end-stage renal disease in the United States to the year 2010.J Am Soc Nephrol. 2001; 12: 2753-2758PubMed Google Scholar Utilizing the Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (2002) guidelines, the prevalence of chronic kidney disease estimated from a larger representative sample of US adults from the third National Health and Examination Survey III was approximately 11% of the US adult population (20 million persons from 1988 to 1994). Chronic kidney disease is defined as either kidney damage or decreased kidney function (decreased GFR) for 3 or more months. The prevalence of early stages of kidney disease (stages 1–4, 10.8%) is more than 100 × greater than the prevalence of kidney failure (stage 5; 0.1%). Stage 1 of chronic kidney disease is kidney damage with normal or increased GFR (≥90 ml/min), stage 2 kidney damage with mild decreased GFR (60–89 ml/min), stage 3 moderate decreased GFR (30–59 ml/min), stage 4 severe decreased GFR (15–24 ml/min) and stage 5 kidney failure, GFR<15 ml/min or dialysis.45..National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification.Am J Kidney Dis. 2002; 39: S1-S266PubMed Google Scholar, 46..Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical practice guidelines for CKD.Am J Kidney Dis. 2004; 43: S10PubMed Google Scholar Also, because GFR declines with age, the prevalence of chronic kidney disease increases with age; approximately 31.2% of persons older than 60 years have a GFR <60 ml/min/1.73 m2.47..Coresh J. Astor B.C. Greene T. et al.Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Examination Survey.Am J Kidney Dis. 2003; 41: 1-12Abstract Full Text Full Text PDF PubMed Scopus (2301) Google Scholar, 48..Levey A.S. Coresh J. Balk E. et al.National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Ann Intern Med. 2003; 139: 137-147Crossref PubMed Scopus (3671) Google Scholar, 49..Coresh J. Astor B.C. Mintner P.M. et al.Estimates of glomerular filtration rate in the United States population. Third National Health and Nutrition Examination Survey (NHANES III).J Am Soc Nephrol. 2001; 12: A1025Google Scholar, 50..Baumelou A. Bruckert E. Bagnis C. Deray G. Renal disease in cardiovascular disorders: an under-recognized problem.Am J Nephrol. 2005; 25: 95-105Crossref PubMed Scopus (18) Google Scholar The prevalence of types of chronic kidney disease include diabetes (types I and II) (33%); vascular (including hypertension) (21%); glomerular (19%); cystic disease (6%) and tubulointerstitial (4%).46..Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical practice guidelines for CKD.Am J Kidney Dis. 2004; 43: S10PubMed Google Scholar According to the International Diabetes Federation, diabetes is the fourth or fifth leading cause of death in most developed countries.51Diabetes International Diabetes Federation Retrieved 29 August 2005 from http://www.eatlas.idf.orgGoogle Scholar Diabetes affects 194 million people worldwide and the number could rise by 75% (to 333 million) by 2025 (90% type I and 10% type II).52..Rigalleau V. Lasseur C. Perlemoine C. et al.Estimation of glomerular filtration rate in diabetic subjects. Cockroft formula or modification of diet in renal disease study equation?.Diabetes Care. 2005; 28: 838-843Crossref PubMed Scopus (179) Google Scholar Diabetic nephropathy affects 25–40% of diabetic patients and diabetes is the leading cause of end-stage renal disease.53..Parving H.H. Renoprotection in diabetes: genetic and non-genetic risk factors and treatment.Diabetologia. 1998; 41: 745-759Crossref PubMed Scopus (140) Google Scholar Mainly because of the high prevalence and increased expectancy of type II diabetic patients, the proportion of patients with both diabetes and end-stage renal disease is dramatically growing in developed countries.54..Ritz E. Orth S.R. Nephropathy in patients with type 2 diabetes mellitus.N Engl J Med. 1999; 341: 1127-1133Crossref PubMed Scopus (656) Google Scholar, 55..Ritz E. Rychlik I. Wahl P. Michael C. End-stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimension.Am J Kidney Dis. 1999; 34: 795-808Abstract Full Text Full Text PDF PubMed Scopus (696) Google Scholar Obesity is a modern epidemic. Since 1991 the prevalence of obesity has increased by 75% and nearly 7 of 10 US adults are overweight and about 3 of 10 are obese (body mass index ≥30 kg/m2; weight (kg)/height in m2 or about 30 pounds over the average weight).42..American Heart Association Heart Disease and Stroke Statistics – Update. American Heart Association, Dallas, TX2005Google Scholar ‘Diabesity’ is also a modern epidemic. From 1991 to 2000, there has been a 10% increase in US adults who are both obese and diabetic. For each 1 kg increase in weight the risk of diabetes increases by 5–9%.56..Resnik H. Valsaria P. Hallor J. Lin X. Relation of weight gain and weight loss on subsequent diabetes risk in overweight adults.J Epidemiol Commun Health. 2000; 54: 596-602Crossref PubMed Scopus (243) Google Scholar, 57..Mokdad A.H. Bowman B.A. Ford E.S. et al.The continuing epidemics of obesity and diabetes in the United States.JAMA. 2001; 286: 1195-1200Crossref PubMed Scopus (2247) Google Scholar The unavoidable conclusion is that the prevalence of risk factors and exposure for CIN will continue to increase.
Referência(s)