Current Problems in Diagnostic Radiology 44 (2015) 501–504

Current Problems in Diagnostic Radiology

journal homepage: www.cpdrjournal.com

Contrast-Induced Nephropathy: Identifying the Risks, Choosing the Right

Agent, and Reviewing Effective Prevention and Management Methods☆, ☆☆
Refky Nicola, MS, DOa, Khalid W. Shaqdan, MDb, Khalid Aran, MDb, Mohammad Mansouri, MDb,
Ajay Singh, MDb, Hani H. Abujudeh, MD, MBAb,n
a
Division of Emergency Imaging, University of Rochester Medical Center, Rochester, NY
b
Division of Emergency Imaging, Massachusetts General Hospital, Boston, MA

With the rise in the use of intravenous iodinated contrast media for both computed tomography scan and angiographic studies, there is a greater
likelihood of complications. One of the most well-known adverse effects is contrast-induced media nephropathy, which is also called contrast-induced
acute kidney injury. This is third most common cause of hospital acquired acute renal failure. It is associated with an increase in morbidity, mortality, and
greater financial burden on healthcare system. Because of these factors, it is important for the radiologist to not only recognize risk factors, as well as the
signs and symptoms, but also to know how to manage patients appropriately.
& 2015 Mosby, Inc. All rights reserved.

Introduction baseline within 14 days. Yet, some patients progress quickly to

The administration of intravenous iodinated contrast media has
been of great value to the practice of radiology, but it is not
without risks. One of the major risks is contrast-induced nephr-
opathy (CIN). CIN has been associated with an increase in morbid-
ity, mortality, as well as prolonged hospital course. It is believed to
account for nearly 10% of hospital acquired acute renal failure.1-3 In
addition, CIN is responsible for one in 6 patients, who are in the
intensive care units because of decreased renal function, and on
hemodialysis after intravenous (IV) contrast administration.4 This
article will discuss the risk factors, recommend prophylactic
measures, and discuss the management of such adverse event. In
addition, this article will discuss some of the recent and more
controversial topics regarding contrast-induced nephropathy.
acute renal failure, which may require hemodialysis.5,6
The definition of acute renal failure is defined as the increase in
creatinine level of more than 0.3 mg/dL within 48 hours, an
increase of more than 50% of the baseline creatinine level within
7 days, or oliguria lasting for more than 6 hours.7 The grave
concern with acute renal failure is that it is also associated with a
mortality of 40%-90%.8
Incidence
In patients without history of renal disease, the risk of CIN is
less than 1%.9 It was previously believed that patients without any
history of pre-existing renal insufficiency have 12%-27% of CIN, and
if there was history of diabetic nephropathy, the incidence
increases to 50%.10

Definition of CIN
CIN is defined as an absolute (4 0.5 mg/dL) or relative (25%)
increase in serum creatinine (SCr) within 48-72 hours after
iodinated contrast medium administration in the absence of any
other explanation for the rise in SCr.2 SCr will usually peak at 2-3
days following contrast media use and then returns slowly to
☆
Presented as Education Exhibit, 100th RSNA meeting, Chicago, IL.
☆☆
Disclosures: H.H.A. is supported by a research grant from Bracco Group. He is a
consultant for the RGG Healthcare and also a consulting author for the Oxford
University Press.
n
Reprint requests: Hani H. Abujudeh, MD, MBA, Division of Emergency Imaging,
Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114-2696.
E-mail addresses: habujudeh@partners.org, rnicola04@yahoo.com
(H.H. Abujudeh).
Recent Controversies Regarding CIN
However, a recent study of over 50,000 patients undergoing
over 150,000 scans by McDonald et al,11 which was published in
Radiology in 2013, demonstrated that the risk of CIN with intra-
venous contrast has been overestimated if not exaggerated when
adjusted for presumed risk factors when comparing patients who
received IV contrast vs those who did not receive contrast. In
another study by McDonald et al,12 who performed a meta-
analysis and systemic review of over 1400 studies, found that
the relative risk of acute kidney injury is similar between contrast
medium group and control group regardless of IV contrast
medium type criteria for acute kidney injury, or history of diabetes
mellitus or renal insufficiency. In even more interesting study by

http://dx.doi.org/10.1067/j.cpradiol.2015.04.002
0363-0188/& 2015 Mosby, Inc. All rights reserved.
502 R. Nicola et al. / Current Problems in Diagnostic Radiology 44 (2015) 501–504
the McDonald et al demonstrated that intravenous contrast is not
associated with an increase risk of acute kidney injury, dialysis, or
even death even in patients with pre-existing comorbidities.
This has also been supported by Newhouse et al,13 who
demonstrated that the fluctuation of SCr in hospitalized patients
is irrespective of contrast administration and that the role of
contrast material in nephropathy is overemphasized, further
bolster these studies. Cramer et al14 and Heller et al15 have also
previously demonstrated these findings as well. Nevertheless,
several other publications and consensus panels have suggested
a direct correlation between contrast media and nephropathy.
Risk Factors
The single most important predictor of CIN risk is chronic
kidney disease (CKD). Patients with CKD have an increased risk by
more than 20 times that of a normal individual to develop CIN.16
Also, patients with a glomerular filtration rate (GFR) o30 mL/min
at the time of contrast administration are also at the highest risk.17
In addition, pre-existing condition of renal insufficiency (SCr level
4 1.5 mg/dL), diabetes mellitus, sepsis, hypotension, dehydration,
cardiovascular disease, use of diuretics, advanced age (4 70 years),
organ transplant, myeloma, hypertension, and hyeruricemia are
also strong risk factors. These risks can be further stratified
according to the Kidney Disease Outcomes Quality Initiative
(KDOQI) classification based on GFR. In 1990, Manske et al18
showed that patients with history of azotemia and diabetes
mellitus are associated with a 50% risk of developing CIN.
The risk of CIN has been associated with composition of the
contrast agent such as non-ionic or ionic, and monomer or dimers.
This is used to describe the ratio of iodine atoms to dissolved
particles. The lower the ratio, the more concentrated the contrast
agent and higher in osmolality, but demonstrates good contrast
opacification with the least toxic effect. However, the lower the
osmolality of the contrast agent, the fewer the incidence of
anaphylaxis and cardiovascular reactions occur.19
In a study of 1196 patients, patients receiving low-osmolar
contrast media such as iohexol were 3.3 times less likely to have
CIN than those who received high-osmolar contrast media such as
diatrizoate in patients with history renal insufficiency.16
Owing to the cumulative effects of multiple risk factors, an
assessment tool is needed to estimate the possible level of damage,
which may occur with multiple risk factors.
In a study of 8000 patients who underwent a percutaneous
coronary intervention over a period of 6 years, Mehran et al were
able to create a risk stratification score or a contrast media–
induced nephropathy score sheet based upon certain risk factors.
The risk factors which were included were hypotension, intra-
aortic balloon pump, congestive heart failure, CKD, age 4 75 years
old, anemia, and volume of contrast. With these factors, a risk
score can be obtained.
Patients with a score less than 5 have a 7.5% risk of CIN and
0.04% risk of dialysis, whereas patients with a score greater
than 16 have a 57.3% risk of CIN and 12.6% risk of dialysis
(Tables 1 and 2).20
Pathogenesis
Although the mechanism of CIN is not completely understood,
it is hypothesized that the constriction of the vessels within the
renal medulla leading to a reduction in oxygen delivery resulting
in a direct toxic effect upon the tubular cells in the kidneys.
Subsequently, the reduction in the perfusion in the kidney causes
the activation of the tubule-glomerular feedback response and the
release of endogenous vasoactive mediators such as endothelin
and adenosine. This is followed by a reduction in the production of
vasodilators such as nitric oxide and prostacyclin in the kidneys
which causes CIN.
Other proposed theories include reperfusion damage, increased
blood viscosity, direct cellular toxicity, and hormone release (eg,
angiotensin II or vasopressin)leading to more vasoconstriction and
further compromise renal function.17,21
Guidelines for the Prevention of CIN
Patients with a GFR 4 60 mL/min have normal or near normal
renal function and have very low risk of CIN and require no
prophylaxis or follow-up.6
With a GFR o45-59 mL/min, there is a low risk of CIN in
patients without risk factors. No specific prophylaxis or follow-up
is required. For patients with receive intra-arterial contrast media
preventative measures are recommended.
If the GFR is o45 mL/min, patients are at moderate risk for CIN
and preventative measures are recommended. IV hydration is
recommended for patients who receive intra-arterial contrast.
For IV administration, either oral or IV hydration can be used.6
Strategies for Prevention
Fluid Hydration
Intravenous therapy is the most reliable means to monitor and
administer fluids. Fluid administration is the most important
means of prevention. With regards to the type of fluid, isotonic
sodium chloride is more protective than hypotonic saline and
more effective volume expander.22
The protective effects of intravenous fluids work in 2 ways
against CIN by primarily volume expansion of the intravascular
space, thus decreasing the vasoconstrictive effects of contrast
in the medulla by blocking vasopressin. This is also important in
reducing the concentration and viscosity of contrast.23 There is
also a theoretical concern for prolonged tubular exposure to
iondinated contrast mediaum owing to low tubular flow rates.24
According to the Canadian Association of Radiologist consensus
guidelines for prevention of CIN update, which were published in
2014.6
1. For inpatients, 0.9% saline solution at 1 mL/kg/h for 12 hours
before the procedure and 12 hours after the procedure.25
2. For outpatients, isotonic saline or sodium bicarbonate solution
at 3 mL/kg/h, a minimum of 1 hour before the procedure and
6 hours after the procedure is a reasonable abbreviated
alternative.26,27
Nephrotoxic Medications
Medications such as nonsteriodal anti-inflammatory drugs,
aminoglycosides, and diuretics should be withheld for at least
24-48 hours before and after the exposure to contrast medium to
minimize the likelihood of CIN.28
Intravenous Bicarbonate
The effectiveness of intravenous has demonstrated mixed
results and its popularity have subsided. Many studies have
refuted the use of sodium bicarbonate and have compared its
effectiveness with saline in the prevention of CIN.29 Some studies
have even suggested that sodium chloride is superior to sodium
 R. Nicola et al. / Current Problems in Diagnostic Radiology 44 (2015) 501–504 503

Table 1 hours after angioplasty, and finally the third group was given a
Points based, risk scores, risk of CIN, and risk of dialysis double dose of NAC, 1200 mg IV bolus and 1200 mg orally twice
daily for 48 hours after PA. The results showed higher NAC doses
Risk factors Points were more beneficial.32 However, in a recent meta-analysis in 2013
by Sun Z et al33 demonstrated that NAC is not a substitute for
Chronic CHF 5
Systolic BP o80 mm Hg 5 hydration and the benefits of IV NAC are uncertain.
Intra-aortic balloon pump 5 Theophylline has also shown mixed results. Initially, Stacul et
Age 4 75 y 4 al34 demonstrated that theophylline has significant benefit by
Anemia (Hct o 36 women, o39 men) 3 blocking the adenosine receptors which helps reduce the inci-
Diabetes mellitus 3
Serum creatinine 4 1.5 mg/dL 4
dence of CIN. However, a meta-analysis of other studies showed no
Or Est GFR 40-59 mL/min 2 reduction of dialysis or mortality with theophylline.35
Or Est GFR 20-39 mL/min 4 Over the past few years, much debate has been centered over
Or Est GFR o 20 mL/min 6 the effect of angiotensin converting enzyme inhibitors (ACE-I) or
Contrast media volume (per 100 mL) of contrast used 1
angiotensin receptor blockers (ARB). In a study of 412 patients in
Risk score Risk of CIN (%) Risk of dialysis (%) which 65% of patients were taking ACE-I and 33 patients were
taking ARB, patients who were treated for renal artery angioplasty
o5 7.5 0.04 and stent before contrast exposure develop significantly more
6-10 14 0.12 often CIN within 72 hours after contrast media application. This
11-16 26.1 1.09
4 16 57.3 12.6
suggests that ACE-I or ARB may be independent risk predictors.36
The notion of hemofiltration or prophylactic dialysis is not
BP, blood pressure; CHF, congestive heart failure; Est, estimated; Hct, hematocrit. recommended for CIN, as there is no concrete evidence and
prophylactic dialysis is associated with increased CIN.
bicarbonate in the prevention of CIN.30 In the most recent article
by Zhang et al31 in British Medical Journal suggests that sodium New Research
bicarbonate can be effective in preventing CIN in patients with
pre-existing renal insufficiency but it does not have any effect on Renal guard system is known as a fluid management device
the likelihood of dialysis or patient mortality, thus it will not that guides fluid replacement and may minimize the risk of
improve the clinical prognosis in patients with CIN. volume depletion in the setting of a forced diuresis. The volume
infusion and urine output per hour is significantly greater than
with conventional hydration regiments. However, a high volume
N-Acetylcysteine forced diuresis raises concerns about electrolyte abnormalities
Much discussion has been made generated regarding the such as hypokalemia, which can result in arrhythmia in certain
preventative effects of N-acetylcysteine( NAC) on CIN. Tepel et patient populations. Therefore, additional studies are necessary
al19 first described NAC with regards to its efficacy in preventing before renal guard system can be implemented clinically.37
CIN. Since then, many trials also have raised doubts about the
efficacy of intravenous NAC and its effect on CIN. There has been
more than 30 meta-analysis and 40 clinical trials performed yet Special Considerations
the results are inconclusive. Nevertheless, NAC is still the standard
of care and routinely administered because of its low cost and lack Metformin
of major adverse effects.32 Study by Marenzi et al concluded that
IV and oral NAC may prevent CIN and improve hospital outcome. Metformin is for patients with noninsulin-dependent diabetes
The study involved 354 patients who were undergoing primary mellitus whose hyperglycemia is not controlled by diet or sulfo-
angioplasty (PA). Patients were randomized to one of 3 groups. The nylurea therapy alone. The mechanism of action is by decreasing
first group was a placebo. The remaining 2 groups were NAC, hepatic glucose production, thus enhancing the peripheral glucose
600 mg IV bolus before PA and 600 mg orally twice daily for the 48 uptake in order to increase the sensitivity of peripheral tissues to

Table 2
eGFR assigned risks, recommendations, and follow up

GFR (mL/min) Risk Recommendations Follow-up

4 60 Very low risk Hold metformfor 48-h pre/post procedure No follow-up required
Encourage oral fluids until 2-h preprocedure

30-59 Moderate risk Consider a noncontrast study Follow-up SCr in 48-72 h

Discontinue nephrotoxic meds, hold 24-48 h, metformin 48 h
IV isotonic (NaCl/NaHCO3)
1.0-1.5 mL/kg/h, 3-12 h pre and 6-24 h post
Limit contrast volume
o30 mL, diagnostic
o100 mL, diagnostic þ intervention
Consider LOCM or IOCM
Consider: NAC 1200 mg orally twice daily pre and postprocedure

o30 High risk Consider noncontrast CT SCr before discharge and/or 24-72 h
Hospital admission
Consider nephrology consult
Consider hemofiltration pre and postprocedure
Strategies as indicated for eGFR30-59

CT, computed tomography; eGRF, estimated GRF; IOCM, iso-osmolar contrast media; LOCM, low-osmolar contrast media.
504 R. Nicola et al. / Current Problems in Diagnostic Radiology 44 (2015) 501–504
insulin. Metformin is typically excreted in the kidneys by glomer-
ular filtration and excretion. The most significant side effect is the
potential of metformin associated lactic acidosis in certain
patients. This occurs at a rate of 0 to 0.084 cases per 100 patient
years, but the mortality rate is 50%.38
Frequently, lactic acidosis occurs because of other existing
comorbidities such as cardiovascular or renal disease. Pre-
existing medical conditions, which decrease metformin excretion
or increase blood lactate levels, are important risk factors. In
addition, any risk factors, which affect the metabolism of lactate
acid or increase production of lactic acid, are contraindicated to
the use of metformin.
Therefore, patients undergoing an IV contrast study, who are
great risk for CIN and who are taking metformin, have a higher
propensity to develop lactic acidosis. As a result, before the
procedure appropriate hydration and limiting the amount of
contrast can less the risk of CIN.39
Therefore, it is advised that metformin should be discontinued
approximately 48 hours before the any contrast study. The ideal
recommendation is that patients with estimated GFR o 45 mL/
min should stop their metformin at the time of contrast injection
and should not be restarted for at least 48 hours and can only
restart it if their renal function remains stable ( o25% increase
compared with baseline creatinine.40
Dialysis Patients
Dialysis patients do not need fluid hydration before contrast
administration. In addition, the coordination of contrast admin-
istration and timing of hemodialysis is not necessary. However,
renal protective measures should be considered for patients with
residual kidney function.
Conclusion
The use of contrast adds great value for both computed
tomography and angiographic studies. However, it is not with
inherent risk factors. One of the most concerning risk factors is
CIN. Therefore, it is important for the practicing radiologist to
become familiar with the predisposing risks, the preventive
measures, and recommendations for patients with special circum-
stances. With this information, patients will have better outcomes
and have less of a likelihood of developing acute renal failure.
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