Contrast Media—Different

Types of Contrast Media,

Their History, Chemical
Properties, and Relative
Nephrotoxicity
Sadichhya Lohani, MD*, Michael R. Rudnick, MD

KEYWORDS
 Contrast-induced nephropathy  Contrast media  High osmolar  Low osmolar  Iso-osmolar
 Contrast-induced acute kidney injury

KEY POINTS
 The hypothesis of osmolality as a cause of injection pain led to the discovery of low-osmolar
contrast media (LOCM) and iso-osmolar contrast media (IOCM) and discontinuation of earlier
high-osmolar contrast media (HOCM).
 The evidence from many clinical studies has failed to support initial claims that IOCM is less
nephrotoxic than LOCM.
 The lack of significant difference in CIN with IOCM and LOCM led to the concepts that
osmolality is likely not the only cause of CIN and that other chemical properties like viscosity
also contribute to the risk.
 In vivo and in vitro model results do not necessarily translate into human toxicity, as shown by
results of clinical studies.

INTRODUCTION isotonic fluids are important preventative

measures.
Contrast-induced nephropathy (CIN) is defined
as acute kidney injury (AKI) caused by the iodin- HISTORY AND CHEMICAL PROPERTIES OF
ated contrast media (CM) within 48 hours to CONTRAST MEDIA
72 hours after CM administration. Chronic kid-
ney disease (CKD), with an estimated glomerular In 1896, Wilhelm Roentgen invented radio-
filtration rate (GFR) less than 30 mL/min/1.73 m2 graphs.1,2 Shortly thereafter, Hashek and Lin-
to 45 mL/min/1.73 m2, and diabetes mellitus denthal used calcium and mercury compounds
(DM) are the most predictive CIN risk factors, to perform the first angiography in an ampu-
regardless of the CM used. The history and evo- tated hand.3 Initial investigators realized that el-
lution of chemical and osmolar characteristics of ements with high atomic numbers would
different CM are important in understanding the enhance tissue on x-ray images. Bismuth, lead,
pathophysiology and prevention of CIN. Avoid- barium salts, and other elements initially were
ance of high-osmolar CM (HOCM), use of lowest evaluated as CM but all were abandoned due
volume of CM, and volume optimization with to toxicity.1,4–6

Renal-Electrolyte and Hypertension Division, Penn Presbyterian Medical Center, Perelman School of Medicine, Uni-
versity of Pennsylvania, 51N 39th Market Street, Suite 240, Philadelphia, PA 19104, USA
* Corresponding author.
E-mail address: [email protected]
Twitter: @LohaniSadichhya (S.L.); @MichaelRudnick7 (M.R.R.)

Intervent Cardiol Clin 9 (2020) 279–292

https://doi.org/10.1016/j.iccl.2020.02.008
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280 Lohani & Rudnick

A solution of sodium iodide was first used by classified as a monomer.13,17,20,21 The first
Cameron in 1918.2,7 In the early 1920s, Osborne LOCM developed in 1970s was metrizamide
and colleagues8 noted that urine of syphilis pa- (Amipaque) but its use was limited because it
tients treated with iodine compounds was radi- precipitated at high sterilization tempera-
opaque. Uroselectan and diodrast, iodinated tures.4,13 This problem resolved with subsequent
derivatives of iodopyridine (a 5-carbon ring formulations of LOCM. The LOCM iohexol
molecule), were the earliest CM used world- (Omnipaque), iopamidol (Isovue) (Fig. 2A), and
wide.4,9,10 In 1933, Wallingford produced the ioxaglate (Hexabrix) (Fig. 2B) were Food and
iodine pyridine derivative, para-aminohippuric Drug Administration (FDA) approved in 1985 fol-
acid, incorporating up to 3 iodine atoms per lowed by the approval of ioversol (Optiray) in
molecule.4,11,12 Wallingord and Swick next intro- 1988 and iopromide (Ultravist) in 2002.22 Ioxa-
duced a 6-carbon benzene ring as the iodine car- glate (Hexabrix) is unique in that although it is
rier leading to the development of acetrizoate an ionic CM, it is still able to be grouped with
(Urokon) in 1951, the first true iodinated benzoic the LOCM because each molecule contains 2
acid derivative.13 In 1953, diatrizoic acid (Hypa- benzene rings (a dimer), with a total of 6 iodine
que) as the sodium or meglumine salt was devel- atoms.
oped, followed by the development of In order to reduce osmolality further, a new
iothalamate and metrizoate (Fig. 1).1,11,14 These class of CM was developed by attaching 2
early CM were ionic, containing a sodium or nonionic benzene rings to produce a dimer,
meglumine atom that dissociated in aqueous so- each containing 3 atoms of iodine, resulting in
lution from a benzene ring molecule carrying 3 each osmotically active molecule having 6 iodine
iodine atoms. Because these ionic CM required atoms.23 Due to the reduction in molecules
2 osmotically active particles to deliver 3 iodine needed to deliver the optimal iodine concentra-
atoms, this resulted in extremely high osmolality tion, the osmolality of this CM was reduced and
of approximately 2000 mOsm/L; thus, these CM is iso-osmolar (290 mOsm/kg H2O) to plasma,
have been termed, HOCM.15 HOCM remained termed, iso-osmolar CM (IOCM). This reduction
in use until late 1980s but are used uncommonly in osmolality, however, comes with the price of
today for intravascular imaging due to increased increased viscosity.24 The only IOCM approved
nephrotoxicity, injection pain, and high adverse by the FDA (approval 1996) is iodixanol (Visipa-
reactions.4,16,17 Diatrizoic sodium and meglu- que) (Fig. 3).25
mine (Gastrografin) are still used as oral CM.18 To summarize, CM vary in terms of osmolality,
Almén suggested that the high osmolality of viscosity, and ionic/nonionic properties. The dif-
the then current CM could be reduced by ferences in the number of atoms per unit volume
substituting the ionized carboxyl radical in the between an object and its surroundings creates
benzene ring with a nonionized amide an object contrast.1 Iodine content in relation
(CONH2) radical, reducing the osmolality of the to osmotic particle per molecule is important in
CM molecule by 50%.13,17,19,20 CM developed attenuation.13,21,26 The CM ratio is the number
from this concept are now termed, nonionic of iodine atoms divided by number of particles
low-osmolar CM (LOCM), and, because they in a solution—the higher the ratio, the lower
have a single nonionic benzene ring, also are the osmolality of the CM.1,13,21 Table 1 is a sum-
mary of the various CM and their properties.

EMERGENCE OF LOW-OSMOLAR
CONTRAST MEDIA AND IMPACT ON
NEPHROTOXICITY
CM was first reported to cause AKI in 1954 when
Bartels and colleagues27 reported a patient who
developed anuria after intravenous pyelography.
Later, more reports on AKI after CM administra-
tion during coronary angiography began to be
published and the term, CIN, was defined. The
Fig. 1. Structures of HOCM iothalamate and sodium
diatrizoate. HOCM have an iodine-to-molecule ratio American College of Radiology (ACR) has sug-
of 1.5: 1. (From Solomon R. Contrast media: are there gested replacing the term, CIN, with the term,
differences in nephrotoxicity among contrast media? contrast-induced AKI (CI-AKI). The ACR intro-
BioMed research international. 2014;2014:934947; duced the term, postcontrast AKI (PC-AKI), for
with permission.) AKI after CM exposure in which it is uncertain

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 Contrast Media 281

Fig. 2. Structures of LOCM. (A)

Chemical structure of LOCM,
nonionic, and monomer (iohexol,
ioversol, and iopamidol). LOCM
have an iodine-to-molecule ratio of
3:1. (B) Structure of LOCM ionic
dimer (Ioxaglate). (From Solomon
R. Contrast media: are there differ-
ences in nephrotoxicity among
contrast media? BioMed research in-
ternational. 2014;2014:934947; with
permission.)

if the CM caused the AKI.28 CIN results in signif- nephrotoxic than LOCM.37 LOCM cause less
icant morbidity and mortality in hospitalized pa- reduction in renal blood flow,38–43 albumin-
tients and has been observed to be the third uria,41,44–46 enzymuria,46,47 GFR,37,41,47 and his-
leading cause of hospital-acquired AKI.29,30 As tologic damage.40,47–49 Based on these
discussed previously, HOCM were the standard experimental observations of reduced nephro-
CM until LOCM were introduced in 1980s, with toxicity, the introduction of LOCM into clinical
the latter eventually replacing HOCM due to practice was quickly followed by the hope that
the reduced incidence of adverse events and LOCM would be less nephrotoxic than HOCM.
cost.17,31 Initial clinical studies on this issue, however,
The primary mechanisms by which CM cause failed to demonstrate a difference in the inci-
AKI are by causing renal ischemia and by direct dence of nephrotoxicity between HOCM and
tubular epithelial cell toxicity.32 CM reduce the LOCM.50–56 These studies were limited, howev-
oxygen tension in the medulla, as a result of er, by small number of high-risk patients for
increased work of active transport in response CIN, that is, patients with preexisting CKD with
to an osmotic diuresis from hyperosmolar agents or without DM. Based on these limitations, it
as well as the release of vasoconstrictive com- was not possible to assess the relative nephro-
pounds, such as endothelin.33 In addition, this toxicity between the LOCM and HOCM groups
contrast-induced medullary hypoxic injury is in these initial studies.57
exacerbated by the blockade of vasodilatory Subsequently, a randomized prospective
compounds, such as nitrous oxide (NO) and study comparing the CIN incidence between
prostaglandins.33 These hypoxic injuries result the LOCM iohexol and the HOCM diatrizoate
in reactive oxygen species, which mediate AKI. was performed in a large patient population
Experimental observations suggest that the (1196) undergoing coronary angiography. This
hyperosmolality and ionic composition of CM study included both low-risk (normal renal func-
play roles in the pathogenesis of CIN.34–36 Ani- tion without DM [30.4%] and with DM [26.6%])
mal studies suggested HOCM were much more and high-risk (CKD without DM [24.9%] and
with DM [18.1%]) patients.57 The iohexol was
associated with significantly less nephrotoxicity
than the diatrizoate in high-risk azotemic pa-
tients.57 In nonazotemic patients, however,
with or without DM, there was no reduction in
nephrotoxicity with iohexol compared with dia-
trizoate—not surprising because patients with
normal renal function are not at risk for CIN.57
A meta-analysis at approximately the same
time also concluded that LOCM are less nephro-
toxic than HOCM in patients with preexisting
CKD.35 Based on these studies, it was recom-
Fig. 3. Chemical structure of IOCM: iodixanol (Visipa-
que). IOCM have an iodine-to-molecule ratio of 6:1. mended that LOCM be used in patients at high
(From Solomon R. Contrast media: are there differ- risk for CIN-CKD with or without DM.49 Shortly
ences in nephrotoxicity among contrast media? Bio- after these observations, the costs of LOCM
Med research international. 2014;2014:934947; with became comparable to HOCM and LOCM
permission.) became the standard CM used in patients who

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 282
Table 1
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Summary of contrast media and their chemical properties

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Number of

Lohani & Rudnick

Iodine Atoms
Chemical per Molecule Osmolality, Viscosity, 37 C Monomer
Generic Name Brand Name Type Property in Solution mOsm/kg H2O (cP [mPa$s]) or Dimer
Iothalamate Conray-30 HOCM Ionic 6 600 4 Monomer
Conray-43 1000
Conray 1400
Diatrizoate Gastrografin HOCM Ionic 6 1940 10.5 Monomer
meglumine/ MD-Gastroview 2000
sodium MD-76 1551
Ioxaglate Hexabrix LOCM Ionic 3 w600 7.5 Dimer
Iodipamide Cholografin LOCM Ionic 3 664 Dimer
Iopamidol Isovue-200 LOCM Nonionic 3 413 4.7 Monomer
Isovue-250 524
Isovue-300 616
Isovue-370 796
Iopromide Ultravist-150 LOCM Nonionic 3 328 4.9 Monomer
Ultravist-240 483
Ultravist-300 610
Ultravist-370 774
Ioversol Optiray-240 LOCM Nonionic 3 502 5.5 Monomer
Optiray-300 651
Optiray-320 702
Optiray-350 792
Ioxilan Oxilan-300 LOCM Nonionic 3 610 5.1 Monomer
Oxilan-350 721
Iohexol Omnipaque-140 LOCM Nonionic 3 322 6.3 Monomer
Omnipaque-180 408
Omnipaque-240 520
Omnipaque-300 672
Omnipaque-350 844
Iodixanol Visipaque-270 IOCM Nonionic 1.5 290 6.3 Dimer
Visiipaque-320 290 11.8
American College of Radiology Manual on CM, Version 10.3. 2018.
Abbreviations: HOCM, high osmolar Contrast Media; IOCM, iso osmolar contrast Media; LOCM, low osmolar contrast Media.
From ACR Manual on Contrast Media. 11th ed. ACR. ACR Committee on Drugs and Contrast, USA, 2020; with permission.
 Contrast Media 283

required intravascular CM due to their lower clinical difference. No difference in comparative

adverse event profile, regardless of risk of CIN. CIN risk was noted based on route of administra-
The incidence of CIN with LOCM is low in the tion (intra-arterial pooled RR 0.80; 95% [CI: 0.64-
general population (<2%).58 During coronary 1.01]; P 5 .059]; intravenous 0.84; 95% [CI: 0.42-
angiography, CKD patients, especially if they 1.71]; P 5 .64]).66 No differences were found in
also have DM, are at increased risk; incidence CIN risk among types of LOCM 1 one LOCM
rates range from 12% to 50%.51,52,59–65 was not superior to another in the systematic re-
view and in a small RCT.66,89–93
ISO-OSMOLAR CONTRAST MEDIA AND Iodixanol has not been shown be superior to
CONTRAST-INDUCED NEPHROPATHY— LOCM for cardiovascular events, as demon-
CLINICAL STUDIES strated in a meta-analysis of RCTs comparing
iodixanol and LOCM that included cardiac
As discussed previously, iodixanol (Visipaque) is events (cardiac death, coronary artery bypass
the only IOCM available in the United graft, myocardial infarction, repeat percuta-
States.59,66 Based on studies that demonstrated neous coronary intervention [PCI], stroke, throm-
that LOCM were less nephrotoxic than HOCM in boembolic event, angina pectoris, arrhythmia,
high-risk patients, studies were conducted with dyspnea, and ventricular extrasystoles).82 In a
the hope of demonstrating that IOCM would more recent metanalysis of 8 prospective RCTs
be less nephrotoxic than LOCM. Table 2 sum- studying iodixanol and LOCM iopromide only
marizes many of the larger studies of CIN (3532 patients), there was no significant differ-
comparing LOCM with IOCM. ence in the CIN incidence between iodixanol
Similar to the studies in Table 2, several other and iopromide (odds ratio [OR] 0.50; 95% CI:
studies have failed to demonstrate a reduced 0.19-1.35; P 5 0 .17).83 Iodixanol was associ-
CIN risk with IOCM compared with ated, however, with a statistically significant
LOCM.58,67–72 Given the large number of trials reduction in cardiovascular adverse events
that have evaluated CIN risk between LOCM compared with iopromide (OR 0.47; 95% [CI:
and IOCM, several systematic reviews and 0.30-0.73; P 5 0 .0009]) but only 104 cardiovas-
meta-analyses comparing the nephrotoxicity of cular events were recorded from both groups,
iodixanol to LOCM have been published.66,73–85 limiting the clinical implications of this finding.83
A meta-analysis by Heinrich and colleagues75 us- In a meta-analysis of 12 prospective trials (952
ing data pooled from 25 trials (3270 patients) patients) by Han and colleagues84 only in DM
found no difference in the CIN rate between patients, there was no statistically significant
iodixanol and LOCM. When comparing studies reduction of incident CIN associated with iodix-
using a specific LOCM, CIN risk was greater for anol compared with LOCM iohexol (RR 0.72;
iohexol than for iodixanol with intraarterial 95% [CI: 0.49-1.04; P 5 .08]). In another recent
administration and renal insufficiency (relative meta-analysis by Zhao, 15 prospective RCTs,
risk [RR] 0.38; 95% CI: 0.21-0.68), whereas there including 2190 DM patients with or without
was no difference between iodixanol and the CKD receiving iodixanol or an LOCM, were eval-
other (noniohexol) LOCM (RR 0.95; 95% CI: uated. Again, there was no significant difference
0.50-1.78).75 It is possible that iohexol carries in CIN between the IOCM and LOCM groups
an increased CIN risk compared with noniohexol (OR 1.66; 95% [CI: 0.97-2.94; P 5 .06]). Similar
LOCM, because studies have shown a decreased findings were noted when only DM with CKD
AKI risk with iodixanol compared with iohexol were included. When CIN was defined only by
versus when compared with noniohexol an increase of serum creatinine (SCr) greater
LOCM.59,76,86–88 than or equal to 0.5 mg/dL, however, less neph-
Eng and colleagues66 reviewed 25 random- rotoxicity was noted with IOCM compared with
ized controlled trials (RCTs) for iodixanol with LOCM (OR 2.77; 95% [CI: 1.09-7.05; P 5 .03]).
LOCM (5053 patients); 18 studies with intra- Only 82 total patients, however, developed
arterial and 7 with intravenous CM use (Fig. 4). CIN from both groups making the clinical signif-
In this meta-analysis, a slight reduction in CIN icance of this observation unclear.85
risk was noted with iodixanol compared with a
diverse group of LOCM that just reached statis- ISO-OSMOLAR CONTRAST MEDIA AND
tical significance (pooled RR 0.80; 95% [CI: 0.65- CONTRAST-INDUCED NEPHROPATHY—
0.99]; P 5 .045). The point estimate of this EXPERIMENTAL STUDIES
reduction, however, did not exceed a minimally
important RR difference of 0.25; hence, the A proposed hypothesis for less nephrotoxicity
lower did not exceed a minimally important with IOCM is less osmolar diuresis with these

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Lohani & Rudnick

Table 2
Summary of studies on contrast-induced nephropathy incidence between the iso-osmolar contrast media iodixanol versus low-osmolar contrast media
Mean Definition of
Low-Osmolar Chronic Serum Contrast- Indication Contrast-Induced
Author, Contrast Kidney Diabetes Creatinine Induced for Contrast Nephropathy
Year Media Disease (N) Mellitus (%) (mg/dL) Nephropathy Media Rate (%) Comments
Chalmers & Iohexol 102 3 IOCM: 3.05 Scr [ >10% RA, PA IOCM: 15 Very sensitive
Jackson,110 LOCM: 3.34 LOCM: 31 definition CIN—
1999 (P<.005) loss of specificity
Aspelin Iohexol 129 100 IOCM: 1.49 Scr 0.5 mg/dL CA, PA IOCM: 3 Greatest Y CIN with
et al,86 LOCM: 1.60 LOCM: 26 IOCM of all
2003 (P 5 .002) studies—
magnitude not
duplicated in
subsequent
studies
McCullough Iohexol 735 21 CKD SCr [ 0.5 mg/dL CA, PA CKD Limitations:
et al,73 Iopamidol IOCM: 1.43 IOCM: 1.4 inclusion
2006 Iopromide LOCM:1.50 LOCM: 3.5 nonpublished
Ioxaglate (P 5 .001) data and
CKD and DM: grouping of
IOCM: 3.5 multiple LOCM
LOCM: 15.5
(P 5 .003)
Solomon Iopamidol 482 40 IOCM: 1.44 SCr  0.5 mg/dL CA CKD Major adverse
et al,88  0.41 IOCM: 6.7 events > for
2007 LOCM: 1.46  0.36 LOCM: 4.4 IOCM
(P 5 .39)
CKD and DM:
IOCM: 13
LOCM: 5.1
(P 5 .11)
Ioversol 337 52 Scr [ 0.5 mg/dL IOCM: 22
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Rudnick IOCM: 1.99 LOCM: 24 Premature

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et al,59 LOCM: 1.92 CA  PCI (P 5 .78) termination trial

2008 due to [CIN in
NAC patients /
underpowered

Laskey Iopamidol 526 100 IOCM: 1.63 SCr [ 0.5 mg/dL CA IOCM: 11 No difference in CIN
et al,87 LOCM:1.6 LOCM: 10 between IOCM
2009 (P 5 .7) and LOCM
Abbreviations: CA, coronary angiography; CKD, chronic kidney disease; CIN, contrast induced nephropathy; DM, diabetes mellitus; IOCM, iso osmolar contrast Media; LOCM, low
osmolar contrast Media; N, number of patients; PA, peripheral and aortic angiography; RA, renal angiography; SCr, serum creatinine.

Contrast Media
285
286 Lohani & Rudnick

Fig. 4. Graphic summary of meta-analysis of RCTs comparing iodixanol and LOCM with CIN as the primary
outcome. The solid vertical line represents the null hypothesis (RR 5 1), and the dashed vertical line represents
the pooled estimate from the meta-analysis. Studies are shown in reverse chronologic order, grouped by route
of administration. CI, confidence interval; LOCM, low osmolar contrast Media; RR, relative risk. (From Weisberg
LS, Kurnik PB, Kurnik BR. Risk of radiocontrast nephropathy in patients with and without diabetes mellitus. Kidney
international. 1994;45(1):259-265; with permission.)

agents compared with LOCM. Osmolar diuresis In 1 study, iodixanol significantly decreased
increases distal sodium delivery, which in turn in- outer medullary vasa rectae vasoconstriction
creases oxygen requirement required in the along with decreasing NO bioavailability.98 In
reabsorption of sodium in the thick ascending another study, iodixanol caused significantly
limb of the loop of Henle producing hypoxia as greater increase in urine viscosity than LOCM
well as volume depletion along with activation iopromide and depressed GFR, whereas iopro-
of vasoregulatory hormones. These regulatory mide did not affect the GFR. Saline attenuated
mechanisms are significantly impaired in pa- these effects of iodixanol, possibly explaining
tients with DM and CKD, explaining the the protective effects of volume expansion in
increased nephrotoxicity of these sub- CIN.99 Blood oxygenation level–dependent
groups.32,86,94 Despite these advantages of (BOLD) imaging and diffusion-weighted imaging
lower osmolality, animal studies comparing are magnetic resonance imaging techniques to
IOCM with LOCM have not for the most part assess renal oxygenation. In a study using
demonstrated a lower rate of renal abnormal- BOLD techniques, iodixanol compared with
ities with the IOCM, possibly because of the iopromide caused increased hypoxia in the outer
adverse effects of increased viscosity.24,34,95,96 medullary area.100 Other studies using BOLD
Experimental studies in rats suggest that the techniques have demonstrated similar adverse
high viscosity of dimeric CM might be a risk fac- effects on medullary blood flow and oxygen
tor by causing red cells sludging in the vasa recta levels with iodixanol.101–103
of the renal tubules and other small renal vessels Not all experimental studies, however,
contributing to outer medullary ischemia.97 demonstrate increased nephrotoxicity of

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 Contrast Media 287

iodixanol compared with LOCM. In a partially observations demonstrating reduced nephro-

nephrectomized animal model, iohexol toxicity of iodixanol compared with iohexol.
compared with iodixanol induced a significantly Even though experimental studies have
greater reduction in renal function, severe renal been divided, with some literature support-
tissue damage, intrarenal hypoxia, and ing73,106 and some not supporting68,69,107,108
apoptotic tubular cells.104 Cheng and col- the hypothesis of reduced nephrotoxicity with
leagues105 demonstrated that iohexol induced iodixanol compared with LOCM, overwhelming
more severe nephrotoxicity than iodixanol evidence with many clinical studies and system-
in vivo due to apoptosis, destruction of antioxi- atic reviews has failed to show that iodixanol is
dative defense, activation of NLRP3 inflamma- less nephrotoxic than LOCM. Hence, currently
some, mitochondrial damage, and mitophagy. the choice of IOCM versus LOCM in practice de-
These results are consistent with clinical pends on cost and institution preference.83 The

Table 3
Summary of society guidelines about type of contrast media
Society Guideline Comments
Acute Kidney Injury Recommends using either IOCM Does not favor IOCM vs LOCM
Work Group, 2012111 or LOCM, rather than HOCM in
patients at increased risk of CI-
AKI. (1B)
Use the lowest possible CM dose
in patients at risk for CI-AKI (not
graded)
American College of PCI focused update 2007 guideline on IOCM use in
Cardiology/American 2009: In CKD patients not on high-risk patients, now deleted
Heart Association chronic dialysis undergoing Current guidelines recommend
angiography, either an IOCM focusing on hydration and
(level of evidence A) or a minimizing contrast volume;
LOCM other than ioxaglate or does not favor IOCM vs LOCM
iohexol is indicated (level of
evidence B)112
2011: insufficient strength and
consistency of relationships
between IOCM or LOCM and
CIN to enable guideline
statement on selection among
IOCM and LOCM113
European Society of No evidence that IOCM are Recommends using the lowest
Urogenital Radiology, associated with a significantly dose of either LOCM or IOCM
2011114 lower PC-AKI than LOCM. Avoid
HOCM.
ACR, 201828 LOCM—less nephrotoxic than Does not favor IOCM vs LOCM
HOCM in patients with renal
insufficiency
CIN in LOCM not significantly
different in patients with normal
renal function
Studies failed to establish a clear
advantage of iodixanol over
LOCM regarding PC-AKI or CIN.
UpToDate115 Use iodixanol or LOCM- iopamidol
or ioversol vs iohexol in patients
at CIN risk. Avoid HOCM.
Abbreviations: ACR, American college of radiology; CIN, contrast induced nephropathy; CKD, chronic kidney disease,
CM, contrast media; HOCM, high osmolar contrast media; IOCM, iso osmolar contrast media; LOCM, low osmolar
contrast media; PC-AKI, post contrast acute kidney injury.

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288 Lohani & Rudnick

cost of iodixanol in many centers is significantly 5. Frank O, Alwens W. Kreislaufstudien am rontgen-

higher than the cost of LOCM. schirm. Munch Med Wochenschr 1910;57:950.
6. Berberich J, Hirsch S. Die röntgenographische
Darstellung der Arterien und Venen am lebenden
SOCIETY GUIDELINES
Menschen. J Mol Med 1923;2(49):2226–8.
Based on the cumulative experimental and clin- 7. Cameron DF. Aqueous solutions of potassium
ical data comparing the nephrotoxicity between and sodium iodids as opaque mediums in roent-
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