Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute kidney injury. The risk of developing CIN is highest in patients with preexisting chronic kidney disease, diabetes, or those receiving a high volume of contrast agent. Nonionic, low-osmolar contrast agents have been shown to reduce the risk of CIN compared to ionic, high-osmolar agents. Preventive strategies focus on minimizing contrast volume, adequate hydration, and avoiding nephrotoxic medications.

1. Contrast Induced
Nephropathy (CIN )
Dr. Sahar Gamal El-DinDr. Sahar Gamal El-Din
National Heart InstituteNational Heart Institute

2. Introduction
Definition
Prevalence
Pathophysiology
Risk factors
Risk scoring and stratifications
Diagnosis
Preventive strategies
Summary and recommendations

3. Introduction
Iodinated contrast medium was first
used in 1954.
Association of contrast use with renal
impairment was first made with use of
iodopyracet, a di-iodinated pyridine
derivative ≥ 50yrs ago.
The use of intravascular iodinated
contrast agents has continued to increase
over recent years. It is recognised that
there are potential risks associated with
the IV administration of iodinated
contrast agents. Am J Med 1997;103:368 75.‑

4. Definition
CIN is defined as an elevation of serum
creatinine (Scr) of more than 25% or ≥0.5
mg/dl (44 μmol/l) from baseline within 48 h
after excluding other factors that may cause
nephropathy, such as nephrotoxins,
hypotension, urinary obstruction, or
atheromatous emboli.
Kidney inter., Suppl. 2012; 2: 1–138.

5. Prevalence & Impact
 CIN is one of the major causes ofCIN is one of the major causes of
hospital acquired acute kidney injury (AKI)‑hospital acquired acute kidney injury (AKI)‑
and represents about 12% of the cases. It is theand represents about 12% of the cases. It is the
third most common cause after renalthird most common cause after renal
hypoperfusion (42%) and postoperative renalhypoperfusion (42%) and postoperative renal
injury (18%).injury (18%).
 The reported incidence of CIN afterThe reported incidence of CIN after
ercutaneous coronary intervention (PCI) variesercutaneous coronary intervention (PCI) varies
between 0 and 24%, depending on thebetween 0 and 24%, depending on the
prevalence of associated risk factors, with theprevalence of associated risk factors, with the
higher incidence being reported afterhigher incidence being reported after
emergency PCI.emergency PCI.
A systematic review. Am J Med 2012;125:66 78.‑

6.  The incidence of CIN is low in patients with
normal renal function (0-5%).However, several
prospective controlled trials reported an
incidence of 12-27% in patients with
preexisting renal impairment.Furthermore, in
one study, an incidence as high as 50% was
reported in patients with diabetic nephropathy
undergoing coronary angiography inspite of
the use of low osmolar CM‑ (LOCM) and
adequate hydration.
 Notably, up to 15% of them required dialysis.
 Development of CIN is associated with a
longer hospital stay, an increased morbidity
and mortality, in addition to a higher cost.
Am J Kidney Dis 2007;50:712 20‑

7.  Elevation of post PCI Scr may have‑Elevation of post PCI Scr may have‑
prognostic significance regardless ofprognostic significance regardless of
initial kidney function. In fact, even ainitial kidney function. In fact, even a
slight elevation in Scr (25-35 μmol/l) isslight elevation in Scr (25-35 μmol/l) is
associated with an increase in 30 day‑associated with an increase in 30 day‑
mortality. Furthermore, post PCI Scr‑mortality. Furthermore, post PCI Scr‑
elevation has been reported to beelevation has been reported to be
associated with a higher 1 year mortality‑associated with a higher 1 year mortality‑
than periprocedural myonecrosis.than periprocedural myonecrosis.
Am J Cardiol 2004;94:786 9‑ .

8. Pathophysiology
 Although the definite mechanism of CINAlthough the definite mechanism of CIN
is not well understood, several‑is not well understood, several‑
mechanisms have been proposed.mechanisms have been proposed.

10. •Vasoconstriction:
 CIN is primarily an ischemic form of AKI
caused by the vasoconstrictive properties of
contrast media.
 Animal studies show a biphasic response after
contrast injection. There is an initial renal
vasodilation followed by intense and
prolonged (3 hrs) vasoconstriction.
 There is a selective decrease in the medullary
blood flow and oxygen saturation due to an
imbalance between vasodilators and
vasoconstrictors
Catheter Cardiovasc Interv 2008;71:62 72‑ .

11.  The principal vasoconstrictors are Adenosine and
Endothelin.
 Contrast media seem to reduce renal blood flow
directly through afferent arteriole vasoconstriction
via activation of adenosine receptor A1.
 In concert, contrast agents also disrupt the
vasodilatory systems like NO and prostaglandins
bringing about an intense vasocontriction and
reduced medullary blood supply.

13. •Oxidative stress:
 The intense vasoconstriction and loss of
autoregulatory capacity can contribute to
additional renal injury through the release of
reactive oxygen species (eg, superoxide [OH].).
 Damage is due to overwhelming of the anti-
oxidant factors by the excess generation of
ROS.
 Underlying diseases like CKD and Diabetes
already have high ROS and thus predisposes
for CIN.
 Benefit of anti-oxidants gives an indirect clue.

14. •Direct tubular toxicity:
 Marked osmotic diuresis is observed following
contrast administration.
 “osmotic nephrosis”
 The most common histopathologic features of
this disorder include intense focal or diffuse
vacuolization of the proximal tubules or overt
tubular necrosis.

16. Stages of CIN
stage Description eGFR
1 Kidney damage
(protein in the urine)
and normal GFR
More than 90
2 Kidney damage and
mild decrease in GFR
60-89
3 Moderate decrease in
GFR
30-59
4 Severe decrease in
GFR
15-29
5 Kidney failure
(dialysis or kidney
transplant needed)
Less than 15

17. Risk factors
 Multiple risk factors may contribute to the
development of CIN; these factors are divided
into two groups; patient .and procedure related.‑ ‑
1. Patient related:‑
 Preexisting renal insufficiency (estimated
glomerular filtration rate (eGFR) <60 ml/min)
and diabetes mellitus are the most important
patient related risk factors.‑
 Others, include age >75 years, uncontrolled
hypertension, hypotension requiring inotropes,
congestive heart failure (CHF),hyperuicemia
anemia, hypoalbuminemia, and liver cirrhosis.

18. Risk factors
2. Procedure related :‑ include high contrast
volume, osmolality or viscosity, and
repeated exposures to CM within 72 h.
 Mode of administration (IA>IV)
 PCI for acute MI.
 Use of intra aortic balloon pump (IABP).‑
 Other factors that may increase the risk
of CIN include the concomitant use of
diuretics or nephrotoxic drugs (NSAIDs
and aminoglycosides). Adv Med Sci 2009;54:221 4.‑

19. Risk scoring and stratifications
Several risk stratification scoring systems
have been developed to assess the risk of
developing CIN.
One of the main goals of these scoring
systems is to help clinicians and patients
weigh the risk of the exposure versus its
benefit.
Mehran risk score is most popular one.

20. Risk models
McCullough et al. Am J Cardiol 2006

21. Risk
Score
Risk
of CIN
Risk of
Dialysis
≤ 5 7.5% 0.04%
6 to 10 14.0% 0.12%
11 to 16 26.1% 1.09%
≥ 16 57.3% 12.6%
Mehran et al. JACC 2004;44:1393-1399.
Hypotension
IABP
CHF
Age >75 years
Anemia
Diabetes
Contrast media volume
Risk Factors
5
5
5
4
3
3
Integer Score
1 for each 100 cc3
CIN Mehran Risk Score
Serum creatinine > 1.5mg/dl 4
eGFR <60ml/min/1.73 m2
2 for 40 – 60
4 for 20 – 40
6 for < 20
eGFR < 60ml/min/1.73 m2
=
186 x (SCr)-1.154
x (Age)-0.203
X (0.742 if female) x (1.210
if African American)
Calculate
OR

22. Diagnosis
 Elevation of Scr of more than 25% above
baseline and within 48 h post CM
administration is the key diagnostic criteria
after excluding other causes.
 Additional laboratory findings such as acidosis
and/or hyperkalemia may be present.
 In regards to urine output; patient may be
oliguric, anuric, or have normal urine output.
 Findings on urine examination are usually
nonspecific. Nat Clin Pract Cardiovasc Med 2005;2:80 1.‑

23. Preventive strategies
 Several pharmacological and nonpharmacological
approaches have been evaluated for the
prevention of CIN.
 The prevention strategies are most important in
patients at high risk for CIN, such as those with
AKI or preexisting chronic kidney disease (CKD).
 It is well established that minimizing the volume
of CM, preventing volume depletion and avoiding
activation of renal vasoconstriction are the most
effective measures to prevent CIN. In addition, the
concomitant use of diuretics or nephrotoxins (e.g.
(NSAIDs), cytotoxic drugs, and aminoglycosides)
should be avoided. Swiss Med Wkly 2012;142:w13608.

24. Nonpharmacological approach
Contrast medium related factors :
CM is a diagnostic iodinated material used to
enhance the visibility of blood vessels. It is
mainly excreted through the kidneys with
less than 1% eliminated via extrarenal routes
in patients with normal kidney function.
The half life of CM is about 2 h with 75%‑
excreted within 4 h and 98% within 24 h.
Circ Cardiovasc Interv 2010;3:346 50.‑

25.  Type of contrast agent — A decreased
incidence of contrast nephropathy appears to
be associated with nonionic agents which, is
defined as either low osmolal (500 to 850
mosmol/kg) or iso-osmolal (approximately 290
mosmol/kg). Most studies have evaluated the
relative effectiveness of nonionic low osmolal
agents versus ionic hyperosmolal agents.
 The ionic low-osmolal agent ioxaglate also
appears to be associated with a lower risk of
contrast nephropathy compared to ionic
hyperosmolal agents . However, there are few
direct comparisons between the various agents.
Am J Med 2012;125:66 78‑

26.  Nonionic low osmolal agents LOCMLOCM— As noted,
low osmolal agents are less hyperosmolal than
conventional agents (600 to 850 mosmol/kg versus
1500 to 1800 mosmol/kg) but still hyperosmolal to
plasma.
 Although the optimal renoprotective role of
nonionic low osmolal contrast agents may vary
with the clinical setting, such agents are now
administered for the majority of radiologic
procedures using intravascular contrast media, as a
result of cost reductions, increased patient
tolerability, decreased hypersensitivity reactions,
and, in patients at risk, a lower incidence of
contrast nephropathy.

27.  There appears to be little or no advantage in
the prevention of contrast nephropathy when
compared to ionic hyperosmolal agents in
patients with normal renal function a group
that is at low risk.
 In studies of patients with moderate renal
insufficiency (serum creatinine concentration
between 1.4 and 2.4 mg/dL [123 to 211 µmol/L]),
some nonionic, low osmolality agents
compared to hyperosmolal agents have been
associated with a reduced incidence of a mild
to moderate decline in renal function .

28. The best data come from a randomized
trial of almost 1200 patients undergoing
coronary angiography, which compared
the low osmolal nonionic agent iohexol
with the high osmolal agent diatrizoate .
A benefit from iohexol was seen in
patients with renal insufficiency alone or
with diabetes mellitus.
Am J Kidney Dis 2004; 44:12.

29. Among patients with a baseline serum
creatinine above 1.4 mg/dL (123 µmol/L),
a rise in the serum creatinine of at least
1.0 mg/dL (88 µmol/L) was seen less often
after the use of iohexol (7.2 versus 15.8
percent with an ionic agent).
The benefit was greater in diabetic
patients (11.8 versus 27 percent)
Circulation. 2007;115:3189-3196

30. Nonionic iso-osmolal agents IOCM :
 Iodixanol, the only currently available iso-
osmolal nonionic contrast agent
(approximately 290 mosmol/kg), may be
associated with a lower risk of nephropathy
than some low osmolal agents, particularly
iohexol, among diabetic patients with
chronic kidney disease (CKD) and a reduced
glomerular filtration rate who are given
intraarterial contrast, mostly for coronary
angiography.

31. A meta-analysis of 16 randomized trials also
suggested that iodixanol was associated with
a reduction in risk among patients with
chronic kidney disease who received
contrast when compared to iohexol (relative
risk 0.19, 95% CI 0.07-0.56) but not when
compared to other nonionic low osmolal
contrast agents (relative risk 0.79, 95% CI
0.56-1.12) .

32. Meta-analysis of IOCM v. LOCMMeta-analysis of IOCM v. LOCM
Favors IOCM Favors LOCM
Heinrich et al. Radiology 2009;250:68-86

33. In summary, the data support a benefit of
iso-osmolal iodixanol compared to low
osmolal iohexol among patients who have
diabetes and chronic kidney disease, but
not a benefit for iodixanol compared to
other nonionic low osmolal agents.
Thus, the positive findings in the initial
trial may represent an adverse effect of
iohexol rather than a beneficial effect of
nonionic iso-osmolal agents.

34. Meta-analysis of IOCM v. LOCM
3.5%
15.5%
2.4%
5.1%
0.6%
1.9% 1% 1.6%
0
2
4
6
8
10
12
14
16
+CKD/+DM +CKD/-DM -CKD/+DM -CKD/-DM
NS
NS NS
P=0.003
%pts
IOCM LOCM
McCullough et al. JACC 2006;48:692-9

35.  It has been initially thought gadolinium based‑
CM would be safer than iodinated CM in
patients with preexisting CKD or those at high
risk for CIN.
 Nevertheless, case reports and small studies
reported evidence of nephrotoxicity using
gadolinium based CM, especially when used‑
in high doses in patients with preexisting CKD
or those at high risk for CIN.
 A long half life of gadolinium based CM and‑ ‑
its lower clearance due to a small volume of
distribution , and its excretion through
glomerular filtration may contribute to the
nephrotoxic effect
Eur Radiol 2002;12:2600 5.‑

36. More importantly, gadolinium based CM‑
have been associated with the development
of nephrogenic systemic fibrosis in patients
with significant decrease in GFR. Therefore,
its use is contraindicated in patients with
GFR less than 30 ml/min/1.73 m2 and it
should be used with caution in patients with
GFR between 30 and 60 ml/min/1.73 m2.
Gadolinium based CM might be a‑
reasonable option in patients with severe
allergy to iodine or iodine CM.
Catheter Cardiovasc Interv 2011;78:747 54.‑

37. After considering all the published data,
the ACC/AHA guidelines on percutaneous
coronary intervention were revised to
suggest the use of either an iso-osmolal
contrast agent or a low molecular weight
contrast agent other than iohexol or the
ionic low osmolal agent, ioxaglate .

38. Contrast agents
Class Agents Osmolality
(msom)
Osmolality
(compared
to plasma)
High-
osmolar
Ionic
monomers
Iothalamate (conray)
Diatrizoate
(hypaque)
Metrizoate
1400-2000 5-8
Low-
osmolar
Non-ionic
monomers
Iohexol (omnipaque)
Ioversol (optiray)
Iopamidol
Iopromide
600-800 2-3
Ionic
dimer
Ioglaxate
Iso-
osmolar
Nonionic
dimer
Iodixanol(visipaque)
Iotrolan
300 1

39. Hemodialysis and hemofiltration
Intermittent hemodialysis or peritoneal
dialysis has been shown to efficiently
remove CM from the circulation; several
studies have been carried out to evaluate the
effectiveness of prophylaxis dialysis strategy.
A study by Lee et al., showed a protective
effect, all other clinical trials did not find any
benefit of immediate hemodialysis after
exposure to CM in patients with preexisting
CKD undergoing angiography.
Int J Artif Organs 2008;31:515 24.‑

40.  Hemofiltration is another preventive strategy
that have been studied for CIN prevention in
patients at high risk.
 Marenzi et al., found that periprocedural
hemofiltration for 24 h after CM exposure was
an effective strategy for the prevention of CIN
in patients with preexisting CKD leading to a
decrease in the in hospital mortality and a‑
better long term outcomes.‑
 However, these modalities are not yet
supported with sufficient evidence.
Additionally, these modalities require
intensive care unit (ICU) admission and may
not be practical in most settings.Am J Med 2006;119:155 62.‑

41. Pharmacological approach

42. •Hydration:
 The benefit of hydration in prevention was
detected by retrospective analysis, and trials
on benefit of hydration is limited by absence
of controls.
 However, it remains the most efficient
method of prevention of CIN.
 IV crystslloids are given at 1-1.5ml/kg/hr,
beginning 12 hrs before the procedure and
continuing up to 6-24 hrs after it.

43.  The mechanisms by which IV hydration
decreases the risk of CIN are:
 IV half-normal (0.5 N) saline may cause an
increase in free water excretion, leading to
dilution of the contrast agents within the
tubule lumen.
 0.9% saline was found better probably due to
increased delivery of sodium to the distal
nephron, leading to reduced activation of the
RAS via the macula densa.
 Intravenous volume expansion would also
minimize reductions in the renal production of
Clin J Am Soc Nephrol 2008;3:273 80.‑

44.  Mueller et al compared hydration with 0.45%
and 0.9% NaCl in 1620 patients who were
undergoing cardiac catheterization. The
incidence of CIN was 2% and 0.7% respectively
(p=0.04). The benefit was more in those with
diabetes.
Arch. Intern. Med. 162, 329–336 (2002).
 Two small studies suggest that sustained fluid
administration within 12 h before and within
12 h after administration of contrast medium is
superior to bolus administration at the time of
contrast administration
Clin. Nephrol. 62, 1–7 (2004).
J. Invasive Cardiol. 15, 699–702 (2003).

45. Optimal Hydration
0.9% NS vs 0.45% NS
P=.35
0
1
2
3
CN Mortality Vascular
Incidence,%
0.9% Saline
0.45% Sodium Chloride
P=.93
P=.04
Mueller et al Arch Intern Med 2002

46.  In an emergency situation full preprocedure
volume expansion is not possible, and there is a
lack of published evidence to guide clinicians
about appropriate alternatives.
 The CIN Consensus Working Panel agreed that
in emergency situations, where the potential
benefit from an urgent investigation outweighs
the risks of waiting, the procedure can be
undertaken without knowledge of renal
function, which precludes risk stratification
according to renal function.

47.  Oral hydration — Given that an increasing number
of individuals receive contrast as outpatients, three
small trials have evaluated the effectiveness of oral
hydration or salt loading in preventing contrast
nephropathy.
 The one trial that included only unrestricted oral
fluids (ie, no salt) found a much higher rate of acute
renal failure after contrast than those given isotonic
saline.
 In this trial, 53 patients were randomly assigned to
either unrestricted oral fluids or to normal saline at 1
mL/kg per hour for 24 hours beginning 12 hours prior
to the scheduled catheterization . Acute renal failure
was significantly more common with oral hydration
(35 versus 4 percent).
Nephron Clin Pract 2003; 93:C29.

48.  The two trials that included salt loading as part
of the protocol showed no difference in
outcome compared to intravenous saline:
 In one trial, 36 patients with serum creatinine
≥1.4 mg/dL (≥124 micromol/L) who required
cardiac catheterization were randomly assigned
to an outpatient oral hydration followed by six
hours of intravenous one-half isotonic saline
for six hours before the procedure or an
inpatient hydration regimen .
 There was no difference in the maximal
change in creatinine between the two groups.

49.  The second trial compared salt loading with
tablets (1 g/10 kg per day in two or three doses
for two days before contrast) and saline
hydration (15 mL/kg for six hours prior to
contrast) in 153 patients with CKD (mean
serum creatinine 2.2 mg/dL [200 micromol/L]) .
 There was no difference in the proportion of
patients with an increase in serum creatinine of
≥0.5 mg/dL (44 micromol/L) between the two
groups.
 Thus, the safety and efficacy of oral hydration
or salt loading for the prevention of contrast
nephropathy remains uncertain.
Nephrol Dial Transplant 2006; 21:2120.

50. •Sodium bicarbonate
 The beneficial role of sodium bicarbonate was
first studied by Merten et al. (RCT of 119
patients). Significant reduction in CIN with
NaHCO3 as compared to NaCl infusion.
JAMA 291, 2328–2334 (2004)
.
 NaHCO3 is given at a dose of 3ml/kg/hr infusion
for 1 hr before procedure of a 154mEq/L
NaHCO3 solution which is continued post
procedure at 1mL/kg/hr for 6 hours.

51.  The role of bicarbonate is unclear and
controversial. It might be related to an increase
in tubular fluid pH level and prevent the
formation of free radicals.
 But bicarbonate is a pro-oxidant specially in
the presence of ROS.
 In vitro studies also showed that although
NAC and ascorbic acid prevented contrast
induced apoptosis of tubular cells, bicarbonate
failed to do so. Clin J Am Soc Nephrol 2008;3:10 8.‑

52. 1. This metanalysis highlights that the perceived benefit of
sodium bicarbonate is largely driven by small,
underpowered RCTs
2. Among the large randomized trials there was no evidence
of benefit for hydration with NaHCO3 compared with NaCl
for the prevention of CI-AKI.
Clin J Am Soc Nephrol 4: 1584–1592, 2009
Trials those who included patients with CKD2-4 as
well as normal renal function.

53. 1. Although the summary of the published data favours
bicarbonate but this is due the effect of the smaller,
poorer quality trials .
2. In summary this metanalaysis concluded that the benefit
of bicarb may be over-estimated and the routine clinical
use recommendation maybe still premature

55. • This meta-analysis demonstrated a higher incidence of CIN than
recently reported, with important variation among different
Cohorts
• There was a protective effect of sodium bicarbonate on the risk
of CIN, especially in patients who underwent coronary procedures
and those with CKD, without effect on need for RRT or mortality.
• Due to the borderline statistical significance, the relative low
quality of the individual studies, heterogeneity and publication
bias, only a limited recommendation can be made in favour of the
use of sodium bicarbonate.

56. •N Acetylcysteine (‑ NAC ) :
 Due to the role of ROS in the pathogenesis of CIN it
was postulated that NAC, an antioxidant may be
helpful in preventing the development of CIN.
 NAC induces glutathione synthesis. It also plays a role
in counteracting vasoconstriction by ↑NO
 First benefit was reported by Tepel et al in 2000 in a
trial published in NEJM. (NAC+hydration was
compared with hydration with 0.45% NaCl alone).
 Some other trial published after that showed
ambiguous results.
The ambiguity of these initial results could have been due to
many factors. The main reasons could have been:
1.The dose of NAC was low.
2.The ROS generation lasts much longer than anticipated.
3.It is the peak levels of NAC during the procedure that is more
important.

57. This MA failed to provide conclusive proof of benefit in
favor of NAC

58. N Engl J Med 2006;354:2773-82.
 354 consecutive patients undergoing PCI were
randomized to one of three groups:
1. 116 patients were assigned to a standard dose
of NAC (a 600-mg intravenous bolus before
primary angioplasty and 600 mg orally twice
daily for the 48 hours after angioplasty),
2. 119 patients to a double dose of NAC(a 1200-
mg intravenous bolus and 1200 mg orally twice
daily for the 48 hours after intervention),
3. 119 patients to placebo.

59.  The serum creatinine concentration increased
25 % or more from baseline after primary
angioplasty in 39 of the control patients (33%),
17 of the patients receiving standard-dose N-
acetylcysteine (15 %), and 10 patients receiving
highdose N-acetylcysteine (8%, P<0.001).
 NAC has a dose dependent reduction in the
risk of developing CIN with a p<0.001 for this
dose-trend.
 Similar findings were also confirmed by 2
earlier trials
the RAPPID study. J Am Coll Cardiol 2003;41:2114-8.
Eur Heart J 2004;25: 206-11.

60. •Current status of NAC
-ACT Trial (Circulation. 2011;124:1250-1259)
 RCT on 2308 patients undergoing an
intravascular angiographic procedure with at
least 1 risk factor for CIN randomized to NAC
1200 mg or placebo.
 The incidence of CIN(primary end point) was
12.7% in the NAC group and 12.7% in the control
group (relative risk, 1.00; 95% CI 0.81 to 1.25;
P=0.97).

61.  A combined end point of mortality or need for
dialysis at 30 days was also similar in both
groups.
 Consistent effects were observed in all subgroups
analyzed, including those with renal impairment.
Conclusions—NAC does not reduce the risk of CIN
or other clinically relevant outcomes in at-risk
patients undergoing coronary and peripheral
vascular angiography.
Blood Coagul Fibrinolysis 2006;17:29 34‑ .

62. Ascorbic acid :
 Ascorbic acid is an antioxidant which has been
studied in the prevention of CIN.
 One randomized controlled trial (n = 231)
found that ascorbic acid reduced the incidence
of CIN in patients undergoing coronary
angiography in comparison with placebo.
 However, another randomized double blind‑
trial (n = 143) failed to show benefit of ascorbic
acid in the prevention of CIN in patients with
renal dysfunction.

63.  A recently published randomized controlled
trial (n = 212) compared a high dose of NAC to
a high dose of ascorbic acid in patients with
renal dysfunction (CrCl < 60 ml/min)
undergoing coronary angiography.
 The study found that the incidence of CIN was
higher in patients receiving ascorbic acid than
those who received NAC; however, the
difference was not statistically significant.
 Therefore, the use of ascorbic acid is not
recommendedin the prevention of CIN.
Clin Nephrol 2007;68:279 86.‑

64. •Adenosine receptor antagonists
 Adenosine induced vasoconstriction has been
shown to be an important pathogenetic
mechanism in the development of CIN.
 When given before contrast media, oral or IV
administered theophylline, a nonselective
adenosine-receptor antagonist, have been
shown to reduce the incidence of CIN in many
studies.
 Trials have used theophylline in doses of 5
mg/kg iv, 2.88 mg/kg orally, and 165 mg iv.

65. There was a trend towards reduction in CIN use with
theophylline use, and this reduction is comparable with that of
NAC.
The main issue of theophylline use in patients with renal
insufficiency is its safety profile
Role of highly selective A1 receptor antagonists should be
evaluated

66. A recent study showed theophylline plus
bicarbonate prophylaxis significantly
reduced the incidence of CI AKI‑
compared to bicarbonate alone.
 However, many recent clinical trials,
meta analyses, and systemic review did‑
not support the beneficial effect of
theophylline in prevention of CIN.

67. Since the results of studies using
theophylline were inconsistent and the
relevant clinical benefit is doubtful,
current recommendation does not support
its use in the prevention of CIN.
In addition, there is the possibility of
gastrointestinal, neurological and
cardiovascular side effects with
theophylline.
Kidney Dis Transpl 2010;21:276 83.‑

68.  HMG CO A reductase inhibitors (statins)
 Because of their antioxidative &
anti inflammatory properties they may reduce‑
the risk of CIN!
 Some studies suggested that the chronic use of
statin has a protective effect against CIN, with a
reduction in the incidence of dialysis and long
term mortality.
 In a recent systematic review and meta analysis;‑
chronic statin treatment (≥7 days) reduced the
risk of CIN (P < 0.05), whereas a short term‑
high dose therapy did not.‑
Am Heart J 2008;155:499.e1 8.‑

69.  Nevertheless, other studies have reported a
null effect for statin use and an even higher
incidence of CIN in the statin group.
 The role of statin use in preventing CIN is
inconclusive, and this could be attributed in
part to the variability of statin dosing and
length of use.
 A large controlled randomized trial is needed
to assure the beneficial effect of statins in
preventing CIN.
Am J Cardiol 2011;108:1 7.‑

70. Calcium channel blockers
 The data available for the use of CCBs is limited.
 CCBs are known to have an attenuating affect
both the magnitude and duration of renal
vasoconstriction after CM exposure, suggesting
its potential benefit in reducing CIN.
 In fact one trial showed a beneficial effect of
starting CCBs shortly prior to PCI in reducing
CIN. However, this benefit was not observed in
other trials.
Int J Cardiol 2013;167:1396 9.‑

71. Allopurinol
 Allopurinol is a xanthine oxidase inhibitor
which may limit the fall in the GFR after CM
exposure by limiting oxygen free radical‑
formation, inhibiting adenine nucleotide
degradation and by decreasing the
vasodilatation response to intrarenal adenosine
in the renal vasculature.
 In one study, allopurinol (4 mg/kg) was given
orally starting 24 h before CM exposure and
showed a protective effect against CIN.

72. A recent trial (n = 159) randomized patients
undergoing coronary procedures (Scr > 1.1
mg/dl) to allopurinol (300 mg orally) with
hydration or hydration alone.
This trial found allopurinol may protect
against CIN in high risk patients receiving‑
CM.
The beneficial effect of allopurinol in the
prevention of CIN needs further studies.
Int J Cardiol 2013;167:1396 9.‑

73. Fenoldopam
 Fenoldopam mesylate is a selective
dopamine 1 receptor agonist known to produce‑
both systemic and renal arteriolar
vasodilatation.
 It has been shown to reduce the incidence of
CIN in high risk patients undergoing PCI in
one study; however, a large randomized
controlled trial (n = 52,315) failed to show any
protective effect against CIN.
JAMA 2003;290:2284 91.‑

74. Dopamine
 Dopamine (in a renal dose 0.5-2.5 μg/kg/min)
has a dilatory effect on the renal vasculature
and has an ability to increase renal blood flow
&GFR with a potential benefit in the
prevention of CIN.
 Positive trials were small, non randomized,‑
inadequately powered, and with questionable
end points of clinical significance.‑
 On the other hand, negative trial, were large,
randomized, controlled, and with adequate
statistical power;therefore, the use of
dopamine in prevention of CIN is no longer
recommended
Am J Cardiol 1999;83:260 3.‑

75. Prostaglandin E1 (alprostadil)
Prostaglandin E1 is a well known‑
vasodilator that improves renal blood flow.
It has shown some benefit in small clinical
studies.
Nevertheless, the risk of CIN increased with
higher infusion rate, likely due to
prostaglandin (PG) induced hypotension.‑
Further large trials are required to prove the
protective effect and address the safety
concerns. Am J Ther 2001;8:155 62.‑

76. Avoidance of nephrotoxic drugs
 The common potential nephrotoxic drugs
include angiotensin converting enzymes
inhibitors (ACEIs), angiotensin receptor
antagonists, aminoglycosides, amphotericin B,
diuretics, NSAIDs/cyclooxygenase (COX) 2‑
inhibitors, and antiviral drugs like acyclovir
and foscarnet.
 The concomitant use of these drugs with CM
administration should be avoided when
possible in order to reduce the risk of CIN.

77. Metformin is mainly eliminated via the
kidneys (90%). As a result, metformin will
accumulate in the event of AKI.
It is recommended that metformin should
be held 24-48 h before CM exposure to
avoid the risk of lactic acidosis and
restarted when clinically appropriate (e.g.
no development of CIN or when renal
function returns to baseline).
Am J Cardiol 2006;98(suppl):59 77K.‑

78. •Summary and recommendations
 CIN is a common cause of acute renal
functional impairment and accounts for
significant morbidity and mortality.
 Patients with CKD, DM, congestive HF,
elderly, hypotension, and anaemia are at
particular risk.
 Optimal therapy to prevent contrast-induced
acute renal failure remains uncertain.
 Patients with near-normal renal function are at
little risk and few precautions are necessary
other than avoidance of volume depletion.

79.  Recommend preventive measures for patients at
increased risk of contrast nephropathy, which is
defined a serum creatinine ≥1.5 mg/dL (132
micromol/L) or an estimated glomerular filtration
rate <60 ml/1.73 m2, particularly in those with
diabetes.
 We recommend NOT using high osmolal agents
(1400 to 1800 mosmol/kg) (Grade 1A).
 We recommend the use of iodixanol or nonionic
low osmolal agents such as iopamidol or ioversol
rather than iohexol (Grade 1B).

80.  Use lower doses of contrast and avoid repetitive,
closely spaced studies (eg, <48 hours apart).
 Avoid volume depletion and nonsteroidal
antiinflammatory drugs.
 If there are no contraindications to volume
expansion, we recommend isotonic intravenous
fluids prior to and continued for several hours after
contrast administration (Grade 1B).
 The optimal type of fluid and timing of
administration are not well established. We suggest
isotonic bicarbonate rather than isotonic saline
(Grade 2B).

81.  Despite conflicting data, we suggest
that acetylcysteine be administered the day
before and the day of the procedure, based
upon its potential for benefit and low toxicity
and cost (Grade 2B).
 Based upon the lack of convincing evidence of
benefit and the potential risk of anaphylactoid
reactions, we suggest not using intravenous
acetylcysteine for the prevention of contrast
nephropathy (Grade 2B).

82. Among patients with stage 3 and 4 CKD, we
recommend NOT performing prophylactic
hemofiltration or hemodialysis after contrast
exposure (Grade 1B).
Among patients with stage 5 CKD, we
suggest prophylactic hemodialysis after
contrast exposure if there is already a
functioning hemodialysis access (Grade 2C).

83. Guidelines for the Prevention of Contrast Induced Nephropathy: Intravenous ContrastGuidelines for the Prevention of Contrast Induced Nephropathy: Intravenous Contrast
SparrowSparrow
Andrew B. MacKersie, M.D.Andrew B. MacKersie, M.D.
February 19, 2013February 19, 2013
1 of 21 of 2
General Guidelines for all patients with GFR <= 40 mL/min:
•Consider alternative imaging studies not requiring iodinated contrast medium (CM).
•Contrast volume is minimized per standard protocols.
•Avoid repeat contrast studies within 24 hours. Follow-up GFR prior to repeat contrast injection.
***Following guidelines assume stable GFR. Patients with acute renal insufficiency are at high risk for CIN.***
GFR < 30 mL/min
High risk for CIN
•Consider alternative study
•IV 0.9% Saline Hydration
•Follow-up GFR in 48 hours
•Physician Approval Only
GFR 30-40mL/min
Low to Moderate risk for CIN
•Inpatient - IV 0.9% Saline
•Outpatient-
• IV 0.9% Saline or
• Oral hydration
GFR > 40 mL/min
Very Low risk for CIN
•Proceed with examination.
Peri-Procedural Fluid Administration Protocols
Intravenous:
Inpatients: IV 0.9% saline at 100 ml/hr 6 to 12 hours before and continuing 4 to 12 hours after CM.
Outpatients: IV 0.9% saline at 100 ml/hr 6 hours prior to CM. Liberal oral fluids immediately following CM.
Oral hydration: Liberal fluids the day before and up to 2 hours before CM and immediately following CM.
***Salty foods the day before the examination to encourage volume expansion.***

84. Guidelines for the Prevention of Contrast Induced Nephropathy: Intravenous ContrastGuidelines for the Prevention of Contrast Induced Nephropathy: Intravenous Contrast
SparrowSparrow
Andrew B. MacKersie, M.D.Andrew B. MacKersie, M.D.
February 19, 2013February 19, 2013
2 of 22 of 2
Indications for GFR determination prior to IV Iodinated Contrast Media:
• Kidney problems
• Kidney disease
• Renal insufficiency/failure
• Kidney surgery or kidney transplant
• Kidney injury
• Diabetes (treated with insulin or other medication)
• Certain diseases: (e.g. multiple myeloma or systemic lupus erythematosa)
• Potentially Nephrotoxic Medications, e.g.:
• chronic or high-dose NSAID therapy
• aminoglycoside antibiotics
• Cardiovascular disease:
• History of congestive heart failure and hypertension requiring medication
• Peripheral vascular disease – all CTA runoff examinations
• 70 years of age or older
• Inpatients and emergency department patients
• Note: GFR results are required within 30 days for outpatients