The document discusses the history and chemical properties of radiographic contrast agents, focusing on iodinated contrast agents, their mechanisms of action, and the risks associated with their use, particularly contrast-induced nephropathy (CIN). It outlines the differences between high, low, and iso-osmolar contrast media, detailing their physiological effects and adverse reactions. The document also addresses alternative agents like gadolinium and carbon dioxide, highlighting their application in imaging and safety concerns related to renal function.

1. Radiographic Contrast Agents And
Contrast-induced Nephropathy
Dr. Yogesh Shilimkar
1

2. HISTORY AND CHEMICAL PROPERTIES OF
CONTRAST MEDIA
• In 1896, Wilhelm Roentgen invented radiographs.
• Shortly thereafter, Hashek and Lindenthal used calcium and mercury
compounds to perform the first angiography in an amputated hand.
• Initial investigators realized that elements with high atomic numbers would
enhance tissue on x-ray images.
• Bismuth, lead, barium salts, and other elements initially were evaluated as
CM but all were abandoned due to toxicity.
2

3. • A solution of sodium iodide was first used by Cameron in 1918.
• In the early 1920s, Osborne and colleagues noted that urine of
syphilis patients treated with iodine compounds was radiopaque.
• Uroselectan and diodrast, iodinated derivatives of iodopyridine (a 5-
carbon ring molecule), were the earliest contrast media used
worldwide.
• In 1951, Wallingord and Swick introduced a 6-carbon benzene ring as
the iodine carrier leading to the development of acetrizoate (Urokon),
the first true iodinated benzoic acid derivative.
3

4. Iodinated Contrast Agents
4

5. • All contrast agents have a basic structure of a benzene ring, which is
composed of 6 joined carbon atoms, each of which has an attached
hydrogen atom.
• Contrast media consist of triiodinated benzene rings, whereby 3
hydrogen atoms are replaced with attached iodine atoms.
• Monomers contain 1 triiodinated benzene ring, and dimers contain 2
triiodinated benzene rings.
5

6. • Attachment at the first carbon atom differentiates ionic from
nonionic contrast agents, with sodium or meglumine,
attached in ionic agents and an amide group attached in
nonionic agents.
• The iodine molecule is attached at carbon atoms 2, 4, and 6.
• Iodine has a tight bond to the carbon atoms, which augments
attenuation by increasing the linear coefficient of radiation.
• Side chains containing OH groups are attached at carbon
atoms 1, 3, and 5 and functions to raise solubility and
decrease protein binding.
6

7. • Iodinated contrast agents are hydrophilic and quickly distribute
throughout the extravascular space, do not cross lipid membranes
and, therefore, remain extracellular.
• The circulatory half-life - 1 to 2 hours, with primarily renal excretion
via glomerular filtration.
• Ionic, high-osmolar contrast agents have calcium-chelating properties
as they are preserved in EDTA, which contributes to their
hemodynamic and electrophysiologic side effects such as
bradyarrhythmias and ventricular fibrillation.
• Therefore, calcium was added to contrast formulations to reduce these
adverse effects.
7

8. Iodine
• Atomic number - 53 , Atomic weight - 127
• Radioopacity depends on:
• iodine concentration of the solution, so dependent on number of
iodine atoms in each molecule of the contrast medium.
• Iodine particle ratio:
• the ratio of number of iodine atoms per molecule to the number
of osmotically active particles per molecule of solute in solution
8

9. Why Iodine?
• The iodine atom, with its relatively high atomic weight, attenuates x-rays.
• Iodine’s K shell binding energy of 33.2 keV is ideal for x-ray photon
absorption.
• Covalent bonding of 3 iodine atoms to a benzene ring at the 2, 4, and 6
position allows iodine to be delivered intravascularly, free of the side
effects of free iodine, and also increases the effective molecular
concentration of iodine, improving the ability to attenuate x-rays.
• An iodine concentration of 320 to 370 mg/mL is optimal for angiographic
studies.
9

10. High Osmolar contrast media
• Also known as Ratio- 1.5 ionic compounds/Conventional
contrast media
• These early CM are ionic, containing a sodium or meglumine
atom that dissociate in aqueous solution from a benzene ring
molecule carrying 3 iodine atoms.
• Because these ionic CM require 2 osmotically active particles
to deliver 3 iodine atoms, this resulted in extremely high
osmolality of approximately 2000 mOsm/L; thus, these CM
have been termed, HOCM.
• Their utility is limited because of cardiotoxicity related to
calcium binding and repolarization charges.
10

11. • These agents have
• sodium concentration roughly equal to blood,
• pH titrated between 6.0 and 7.0, and
• a low concentration (0.1 to 0.2 mg/mL) of calcium
disodium EDTA.
• Higher or lower sodium concentrations may
contribute to ventricular arrhythmias during coronary
injection, and calcium binding by sodium citrate may
cause greater myocardial depression.
11

12. • Examples of high osmolar contrast media:
• Renografin (Bracco),
• Hypaque (Nycomed), and
• Angiovist (Berlex) ,
• These are mixtures of the meglumine and sodium salts of
diatrizoic acid.
• Functionally similar agents are based on
• iothalamic acid (Conray) or
• metrizoic acid (lsopaque).
12

13. Low Osmolar contrast media
• High osmolality of high osmolar CM was reduced by substituting the
ionized carboxyl radical in the benzene ring with a nonionized amide
(CONH2) radical, reducing the osmolality of the CM molecule by 50%.
• Subsequently the ratio-3 lower-osmolality contrast materials (LOCM)
were introduced.
• These include:
• Ionic dimers
• Nonionic monomers
13

14. Ionic dimers
• Ioxaglate (Hexabrix)
• Mixture of sodium and meglumine salts
• Two benzene rings (each with 3 iodine atoms) are linked by a bridge to
form a large compound, carries only one carboxyl group, so known as
monoacid dimers
• Iodine particle ratio is= 6:2 or 3:1
• Molecular weight is= 1269
• Osmolality ~ 580 mOsmol/kg H2O
14

15. Nonionic monomers
• Carboxyl group (-COOH) at C-1 is replaced by non ionising radical &
CONH2
• Iodine particle ratio= 3:1
• Molecular weight= 600-800
• Osmolality ̴ 600 mOsmol/kg H2O
15

16. • These low-osmolality contrast agents are water-soluble in a
noncharged form, without an associated cation.
• Examples Nonionic monomers:
• iopamidol (Isovue),
• iohexol (Omnipaque),
• metrizamide (Amipaque),
• Ioversol (Optiray), and
• ioxilan ( Oxilan).
16

17. • LOCM resulted in significantly less pain and less
hypotension than high osmolar contrast media, with
no difference in radiographic properties.
• The LOCM agents resulted in
• less cardiac depression during angiography,
• Less blood volume increase,
• Less renal toxicity, and
• Less anaphylactic reactions.
17

18. Iso-osmolar contrast media
• In order to reduce osmolality further, a new contrast was developed by
attaching 2 nonionic benzene rings to produce a dimer, each containing 3
atoms of iodine, resulting in each osmotically active molecule having 6
iodine atoms.
• Due to the reduction in molecules needed to deliver the optimal iodine
concentration, the osmolality of this CM was reduced and is iso-osmolar
(290 mOsm/kg H2O) to plasma, termed, iso-osmolar CM (IOCM).
• High viscosity.
18

19. • The only IOCM approved by the FDA (approval 1996)
is iodixanol (Visipaque).
• Iodine particle ratio= 6:1
• Molecular weight= 1550-1626
• Osmolality = 290 mOsmol/kg H2O
19

20. High
Osmolar
Ionic
monomers
3 iodinated molecules with 2 osmotically active particles or ratio 1.5 (3:2)
agents
Low viscosity
Diatrizoate (Hypaque and Renografin); osmolality: 1500–1800 mosmol/kg
water
Low
Osmolar
Ionic
dimers
6 iodine molecules for 2 osmotically active particles; 6:2 agents, or ratio 3.0
Low viscosity
Ioxaglate (Hexabrix); osmolality: 580 mosmol/kg water
Non-ionic
monomers
3 iodine atoms with 1 osmotically active particle; 3:1 agents, or ratio 3.0
Intermediate viscosity
Iohexol (Omnipaque): 322–844 mosmol/kg water
Ioversol (Optiray): 502–792 mosmol/kg water
Iopadimol (Isovue): 524–794 mosmol/kg water
Ioxilan (Oxilan): 585–695 mosmol/kg water
Iso-osmolar Non-ionic
dimer
6 iodine atoms for 1 osmotically active particle; 6:1 agents, or ratio 6.0
High viscosity
Iodixanol (Visipaque); osmolality: 290 mosmol/kg water
20

21. PHYSIOLOGIC EFFECTS
• Hemodynamic effects include
• a mild and transient decrease in ventricular function and increase in ventricular filling
pressures, effects that are greater with high-osmolar than with low- or iso-osmolar
agents.
• Contrast administration also increases intravascular volume, again more
profoundly with high-osmolar than low- or iso-osmolar agents.
• These effects are important in patients with heart failure.
• Another hemodynamic effect of intra-arterial contrast administration is
transient arteriolar vasodilation, resulting in decreased vascular resistance,
increased blood flow, and potentially decreased systemic pressure.
21

22. • Electrophysiologic effects include
• transient changes on the surface electrocardiogram such as QRS
prolongation, axis shift, ST-segment depression, PR prolongation,
and QT prolongation.
• Bradyarrhythmias - often transient, generally respond to coughing
or to IV atropine.
• These arrhythmias are more common following injection of
the right coronary artery and may reflect a vagal response as
well as a direct effect on the sinoatrial node.
22

23. • Contrast also lowers the myocardial ventricular fibrillation
threshold.
• The bradycardia and ventricular fibrillation potential are
exacerbated by concomitant ischemia.
• All of these electrophysiologic effects are more common
with the high-osmolar agents than the low- or iso-osmolar
agents.
23

24. COAGULATION ISSUES
• Both ionic and non-ionic agents have anticoagulant and antiplatelet effects,
these being pronounced with ionic agents.
• With the introduction of non-ionic contrast media, there was a concern for
potential thrombus formation in angiographic catheters.
• In initial EPIC trial, GUSTO IIB trial & RESTORE trial, there was less
refractory ischemia & fewer ischemic events with ionic agents as compared
to nonionic agents.
• However, later COURT trial, VIP trial and VICC trial demonstrated no
significant difference between ionic or nonionic agents regarding
thrombotic complications of either type of agent.
24

25. ADVERSE REACTIONS
25

26. Immediate (within 1 hour)
Mechanism Symptoms Signs Treatment
Physiologic Warmth, local
pain/burning,
nausea
Transient ECG changes
(ST-T wave
abnormalities)
Transient, self-limited;
antiemetic, analgesic;
switch to low- or
isoosmolar, nonionic agent
Vasovagal Nausea,
weakness, near-
syncope
Hypotension
bradycardia,
diaphoresis, cool skin
IV fluid, atropine,
antiemetic
Hypersensitivity
type 1
Pruritus,
dyspnea,
dysphagia,
cough,
weakness, near-
syncope
Urticarial rash,
angioedema, stridor,
wheezing, hypotension
(with widened pulse
pressure), tachycardia
Epinephrine (100 μg IV,
repeat as needed),
phenylephrine,
antihistamines, IV fluids,
airway support, inhaled β-
and α- adrenergic agents
26

27. Delayed (1 hour-10 days)
Mechanism Symptoms Signs Treatment
Hypersensitivity
(type 4)
Skin erythema,
pruritus, pain
Maculopapular rash Transient, self-
limited (days);
antipruritics;
topical/oral
corticosteroids.
Contrast
nephropathy
Hyperthyroidism Heat intolerance,
palpitations,
anxiety,
tremors
Tachycardia, tremor,
low TSH, elevated
T3, T4
β-Blockers
Hypothyroidism Fatigue, cold
intolerance, dry skin
Bradycardia, high
TSH, low T3, T4
Levothyroxine
27

28. Gadolinium
• Gadolinium is a rare earth metal that has paramagnetic properties.
• These properties allow movement of the metal ions within a
magnetic field.
• In its salt form, gadolinium is very toxic.
• However, through a process of chelation by which large molecules
create a complex surrounding gadolinium ions, less toxic gadolinium
compounds have been developed and are currently used for imaging.
28

29. • It is used in radiographic imaging in patients with severe iodine
allergy.
• In the recommended concentration of 0.4 mmol/kg body weight, only
small doses can be injected in the coronary circulation, and image
quality is inferior to iodinated contrast, but is still diagnostic.
• The viscosity of the agent can cause cardiac arrhythmias, in particular
ventricular fibrillation.
• This adverse effect is enhanced by catheter dampening of the
coronary artery.
29

30. • Gadolinium does not prevent contrast-induced nephropathy.
• It is well tolerated in patients with serum creatinine levels of <2.0 mg/dL
but can worsen renal function in patients with creatinine levels >2.0 mg/dL.
• In patients with renal insufficiency (estimated glomerular filtration rate <30
mL/min) and end-stage renal disease, the heavy metal accumulates in body
tissues, causing nephrogenic systemic fibrosis.
• Therefore , the current recommendation is to avoid the use of gadolinium
• in patients with advanced renal failure (GFR < 30 ml/min/1.73 m2) ,
• in patients on dialysis , and
• in patients with hepatorenal syndrome.
30

31. Carbon Dioxide
• Carbon dioxide, given via an injector, in the vasculature is absorbed over a
2-minute period by the blood, where it is converted into sodium
bicarbonate and excreted by the lungs as carbon dioxide.
• It produces radiologic contrast and does not cause an allergic reaction &
nephrotoxicity.
• The image quality is less than iodinated contrast and requires
enhancement by digital subtraction angiography.
• Carbon dioxide imaging is used in
• below-the-diaphragm visceral, renal, and lower extremity angiography,
• renal stent placement, and
• endovascular aortic repair for abdominal aortic aneurysms.
31

32. • Delivery of carbon dioxide is through special injectors and connecting
tubes, free of air contamination.
• Generally, 20 to 40 mL of carbon dioxide is injected through 3- to 4-Fr
catheters.
• It is not used in coronary or pulmonary angiography because it
produces a “vapor lock” that resolves over a 2-minute period of
absorption of the gas, and in the coronary circulation, this may cause
myocardial ischemia similar to coronary air embolism.
• In the pulmonary circulation, this vapor lock is similar to pulmonary
air embolism, resulting in hypotension.
32

33. Contrast induced nephropathy
33

34. INTRODUCTION
• Contrast-induced nephropathy (CIN):
• responsible for one third of all hospital-acquired acute kidney injury
• affects between 1% and 2% of the general population and
• up to 50% of high-risk subgroups following coronary angiography (CAG)
or percutaneous coronary intervention (PCI).
• Varying terminology to describe CIN has been used, e.g.,
• contrast-induced acute kidney injury [CI-AKI],
• contrast nephropathy,
• contrast-associated AKI.
Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk.
Kidney Int Suppl 2006: S11–15
34

35. DEFINITION AND DIAGNOSTIC CRITERIA OF CIN
• Most commonly, CI-AKI is defined as
• an absolute serum creatinine (sCr) increase of ≥0.5 mg/dL (44
μmol/L) or
• a ≥25% relative increase in sCr from baseline within 48 to 72 hours
of CM exposure.
• Kidney Disease Improving Global outcomes (KDIGO) working
group criteria:
• an increase in sCr ≥0.3 mg/dL (≥26.5 μmol/L) within 48 hours; or
• an increase in sCr ≥1.5 times the baseline value within 7 days; or
• a urine volume less than 0.5 mL/kg/h for 6 hours.
35

36. • Definition proposed by Harjai et al aims to classify CIN according to
three grades corresponding to three relative and absolute creatinine
rise cut-offs, including a group with only minor rise (<25% or 0.5
mg/dL), which also correlates with long-term adverse outcomes
36

37. MECHANISMS UNDERLYING CIN
• CI-AKI has three potential pathophysiologic
mechanisms:
(1) Direct toxicity of nephrons by iodinated contrast
material
(2) Microshowers of atheroemboli to the kidneys, and
(3) Intrarenal vasoconstriction induced by contrast material
or atheroemboli.
37

38. 38

39. RISK FACTORS
39

40. Procedure related risk factors
• The total volume of contrast (>350 mL or >4 mL/kg) and previous
contrast exposure within 72 h are directly related to the development
of CIN.
• Ratio of the volume of contrast media to creatinine clearance (V/CrCl)
greater than 3.7:1 correlates strongly with the risk of developing CIN
in patients with moderate CKD undergoing CA.
• Periprocedural haemodynamic instability requiring the use of
inotropic agents or intra-arterial balloon pump therapy is particularly
high-risk feature.
40

41. • In ACS patients who underwent invasive management, RA was associated
with a reduced risk of AKI compared with FA.
• It is hypothesized that a reduction of atheroemboli to the renal circulation may
have been one of the contributing factors that led to the reduction of AKI
associated with radial compared to femoral access
41

42. Assessment of risk
42

43. • A number of risk factors have been integrated into a well-known post-
procedure risk scoring system and validated in a large cohort study by
Mehran et al
43

44. 44

45. • A limitation of this scoring systems is that calculation is only
possible after contrast has been administered.
• However, it is clinically desirable to be able to predict the risk
of CIN before the patient is exposed to contrast allowing
appropriate precautionary measures to be taken.
• Such a pre-procedural CIN risk score has been proposed by
Maioli et al, following validation in a prospective cohort
study.
45

46. 46

47. Biomarkers for Risk Prediction and Early
Detection of Contrast-Induced Acute
Kidney Injury
47

48. Problems with SCr
• Relatively insensitive to the rapid GFR changes seen in AKI,
particularly in patients with normal baseline renal function.
• SCr levels are influenced by age, sex, muscle mass,
nutritional status, and hydration.
• Elevations in SCr typically take 2–3 days to reach the
current diagnostic threshold following an acute renal
insult, thus reducing its usefulness as a marker of AKI.
48

49. • Studies suggest that serum Cystatin C (sCyC) increases earlier (as early
as 8 hours after contrast application) and is less influenced by non-
renal factors compared to sCr.
49

50. • This study identified a
15% increase of sCyC as
the optimal cutoff to
predict CI-AKI.
50

51. • This study reported that
• a CyC increase <10% at 24 hours is a reliable marker for ruling out CI-AKI and
• a CyC increase ≥10% at 24 hours is an independent predictor of 1-year MAE.
• In both studies an increase of sCyC predicted major adverse events;
patients with a rise in both sCyC and sCr had the highest risk.
51

52. Neutrophil Gelatinase–Associated Lipocalin
• NGAL is a reliable marker for
the early detection of CI-AKI
and prediction of 1-year
major adverse events.
• Serum and urine NGAL levels
rise within 2 and 4 hours,
respectively, after contrast
administration.
• Urine NGAL less than 20 ng/mL
and serum NGAL less than 179
ng/mL at 6 hours were
identified as cutoffs to rule out
CI-AKI.
52

53. • Other biomarkers that have been investigated for the
early detection and risk assessment of CI-AKI include:
• serum liver fatty acid-binding protein (L-FABP),
• serum kidney injury marker 1 (KIM-1), and
• urine interleukin 18 (IL-18).
53

54. PROGNOSIS OF CONTRAST-INDUCED ACUTE
KIDNEY INJURY
• CIN is often regarded in clinical practice as a transient event.
• In up to 80% of cases, SCr levels normalise after
approximately 1–3 weeks.
• However, CIN is of clinical importance as a number of clinical
trials have revealed that it portends a multitude of short-
term and long-term adverse events.
54

55. • In the analysis of the NCDR database by Tsai et al.
• the rate of new required dialysis was 0.3%.
• The rate of new required dialysis was 4.3% in patients with CKD and
• 7.2% in patients with ST-segment elevation myocardial infarction (STEMI).
55

56. The incidence of death, bleeding, and MI stratified by the absence and
presence of AKI and the presence of dialysis in NCDR analysis
56

57. • Resolution of an AKI
episode within 48
hours is associated with
better outcomes than
longer durations of AKI.
• Patients with AKI
episodes persisting
beyond 7 days are
more likely to develop
CKD.
57

58. 58

59. PREVENTION STRATEGIES TO MINIMIZE
THE RISK OF CONTRAST-INDUCED ACUTE
KIDNEY INJURY
59

60. • For all patients referred for procedures using contrast, a CIN
risk assessment should be performed which includes
• baseline measurement of SCr and
• calculation of eGFR using a suitable formula, for example,
Modification of Diet in Renal Disease or Chronic Kidney Disease–
Epidemiology.
• If patients are identified as being at risk of CIN, particularly if
eGFR is <40 mL/min, clinical indications for the contrast
procedure should be reviewed and preventative measures
instigated.
60

61. Minimising contrast volume
• The maximal acceptable contrast dose (MACD) which is defined as
• “5 mL×body weight [kg])/baseline serum creatinine [mg/dL]”
• This value should not be exceeded.
• A single invasive approach should ideally be adopted, with CAG followed
by ad hoc PCI to reduce the risk of atheroembolic complications while
minimizing contrast volumes to <4 mL/kg or V/CrCl <3.7:1.
• A slight reduction in contrast volume was documented with the use of
an automated contrast injector system, although it did not impact the
occurrence of CI-AKI.
61

62. • The lower the eGFR, the less contrast material may cause CI-
AKI.
• In general, it is desirable to limit the contrast medium to less
than 30 mL for a diagnostic procedure and less than 100 mL
for an interventional procedure.
• If staged procedures are planned and CI-AKI has occurred
with the first procedure, it is advantageous to have more
than 10 days between the first and second contrast
exposures.
62

63. “Ultra-low contrast coronary angiography”
• It uses meticulous contrast sparing techniques such as
• Use small diameter catheters (i.e., 5–6 French) without side-holes
• Limit the volume of contrast injected from the catheter to 1–2 cm3 per injection
using a 3-cm3 syringe.
• During PCI, prior to exchange of devices such as balloon catheters, remove contrast
from the guide catheter by back bleeding contrast out of the ‘‘Y’’ connector.
• If available, display previous angiographic images alongside active fluoroscopy screen
as a reference to use as guidance during guide wire, balloon, stent and ultrasound
passage.
• Absolutely no contrast ‘‘puffing’’ during the procedure.
• Use IVUS liberally for pre-PCI assessment of the lesion, selection of therapeutic
modalities, and post-PCI result assessment
• These techniques can reduce contrast load during diagnostic and PCI
procedures to under 10 to 20 cc.
63

64. • Dedicated devices to reduce overall CV have been developed.
• The DyeVert PLUS system is a device that is connected between the
injection syringe and the manifold via a 4-way stopcock, allowing
diversion of excess contrast during manual injection.
• The fraction of CM that would not contribute to coronary
opacification, but rather would reflux into the aortic root, is diverted
into a reservoir chamber.
• In initial trial, there were no differences in the rates of CI-AKI.
64

65. • The next-generation DyeVert system was evaluated in a multicenter
single-arm pilot study, in which up to 40% of CV was saved (p <
0.0001).
• Future research is needed to assess whether this reduction in CV
translates into clinically meaningful benefit.
65

66. • The type of CM plays an important role in the development
of CI-AKI.
• Low-osmolar CM (LOCM) compared to high-osmolar CM
(HOCM) has decreased the risk of CI-AKI regardless of pre
existing CKD; therefore, LOCM is favored in current clinical
practice.
• A benefit of iso-osmolar CM (IOCM) over LOCM with regard
to CI-AKI is uncertain due to mixed results of available
studies on this topic.
66

67. • CONCLUSION:
• The incidence of CIN in patients with diabetes and chronic kidney
disease was not significantly different after CT using iopamidol 370
(796 mOsm/kg)or iodixanol 320- Visipaque (290mOsm/kg).
67

68. • Conclusion:
• The rate of contrast-induced nephropathy is not statistically different after the
intraarterial administration of iopamidol or iodixanol to high-risk patients,
with or without diabetes mellitus.
68

69. • The nephrotoxicity associated with iodixanol was not significantly different
from that observed with ioversol in CKD patients undergoing coronary
angiography, although in diabetic patients, mean peak percentage change
in baseline serum creatinine was significantly lower in the iodixanol group.
69

70. • Nephropathy induced by contrast medium may be less likely to
develop in high-risk patients when iodixanol (visipaque) is used rather
than a low-osmolar, nonionic contrast medium.
70

71. • The IOCM
iodixanol was
significantly
less
nephrotoxic
than
ioxaglate, an
ionic, dimeric
LOCM.
71

72. • Compilation of pooled odds ratios from head-to-head trials for IA, IV,
and mixed IA and IV metaanalyses of the incidence of CI-AKI
72

73. • Patients should be advised to stop all non-essential nephrotoxic
medications for 24h prior to and for 48 h following the contrast
procedure pending SCr measurement.
• It is also recommended that patients receiving intra-arterial contrast
with an eGFR of <60 mL/min/1.73 m2, or those receiving intravenous
contrast with an eGFR of <45 mL/min/1.73 m2, discontinue
metformin for 48 h prior to contrast exposure and restart once a 48 h
SCr measurement excludes CIN.
• This is to mitigate the risk of lactic acidosis due to reduced renal
clearance of metformin that may occur following a potential CIN
episode, rather than metformin nephrotoxicity per se.
73

74. Periprocedural Hydration
• The most effective prophylactic intervention prior to contrast exposure.
• Supplementing intravascular volume ensures renal blood flow is
maintained and acts to dilute contrast in both blood plasma and tubular
filtrate.
• In lower risk ambulant patients, the oral route may be appropriate if
adequate fluid intake is assured.
• However, in moderate/higher risk or in hospitalised patients intravenous
hydration with a crystalloid fluid is preferred over oral hydration as it
guarantees delivery of appropriate fluid volumes and has been
demonstrated as superior in clinical trials.
74

75. • The choice of which crystalloid to use is, however, less clear.
• When compared with isotonic (normal) saline (0.9%), intravenous sodium
bicarbonate (1.26%) may have additional ROS scavenging properties
mediated through urine alkalinisation and lacks chloride ions that are
thought to exacerbate renal vasoconstriction.
• In view of the current lack of evidence supporting the use of sodium
bicarbonate 1.26% and with some studies offering conflicting evidence, the
current ESC guidelines recommend pre-hydration with sodium chloride
0.9%.
• For elective day case patients and for those with CCF in whom large
volumes of intravenous fluid may provoke pulmonary oedema, it is also
reasonable to use an alternative protocol delivering a shorter duration and
volume of sodium chloride 0.9%.
75

76. • In AMACING (A Maastricht Contrast-Induced Nephropathy Guideline) randomized
trial, intravenous 0.9% sodium chloride was directly compared with no
prophylaxis in 660 patients with an estimated GFR of 30–59mL/min/1.73m2
undergoing an elective procedure requiring iodinated contrast material.
• Within 2 - 6 days after contrast exposure, no prophylaxis was non-inferior to
intravenous hydration for the prevention of CIN and cost-saving.
• However, the validity of this finding is diminished by substantial underenrollment,
low rates of intraarterial procedures (48%) and interventional procedures (16%),
and moderate chronic kidney disease in a majority of patients.
• Given the known impact of low effective circulating volumes on the risk of CIN,
there is still consensus that adequate hydration is needed to prevent CIN.
76

77. IVF Infusion Rate to Prevent CIN
• IVF = 1 ml/kg/hr (max 100 ml/hr), 12 hours pre and upto 24 hours
post procedure
• CHF (NYHA > 2) or LVEF ≤ 35% = 0.5 ml/kg/hr (Max 50 ml/hr)
• Emergent procedure? (Suggested regimen)
Fluid bolus of 3ml/kg prior to procedure. Hydration during
procedure and 12 hrs after if possible
77

78. What is Optimal hydration?
Ask POSEIDON
78

79. • The optimum rate and volume of intravenous fluid delivery a
significant challenge:
• underhydration increases CIN risk, whereas
• overhydration may precipitate acute pulmonary oedema in
vulnerable patients with severe CKD and CCF.
• Two hydration optimisation strategies have been trialled in
CIN:
• LV end diastolic pressure (LVEDP) guided volume expansion and
• high urine output matched fluid replacement (RENALGUARD).
79

80. Prevention of Contrast Renal Injury with Different
Hydration Strategies (POSEIDON) study
• In this study, fluid administration to prevent CI-AKI was guided by the LVEDP.
• Total of 396 patients with an eGFR of 60 mL/min/1.73 m2 and one additional
risk factor.
• Randomized to
• either a standard hydration protocol (1.5 mL/kg/h) or
• the LVEDP-guided strategy with isotonic saline:
• 5 mL/kg/h for left ventricular end-diastolic pressure lower than 13 mm Hg,
• 3 mL/kg/h for pressure of 13–18 mm Hg, and
• 1·5 mL/kg/h for pressure higher than 18 mm Hg.
• The overall rate of CI-AKI was significantly lower in the LVEDP-guided
hydration group compared to the control (6.7% vs. 16.3%; relative risk 0.41;
95% CI 0.22 to 0.79; P = .005).
80

81. RenalGuard system
• The concept of the RenalGuard system is
based on measuring urine output by a
Foley catheter and simultaneously
infusing an equivalent volume of isotonic
saline.
• After a 250 mL bolus of saline at 90
minutes prior to contrast application, a
continuous infusion of IV furosemide 0.25
to 0.5 mg/kg is started.
• The system automatically adjusts the rate
of the continuous IV saline infusion to
maintain a urine output rate greater than
300 mL/h throughout the procedure and
for 4 hours thereafter.
81

82. • In REMEDIAL II trial, a strategy of controlled forced diuresis using the
RenalGuard system was investigated.
• The study demonstrated superiority of the RENALGUARD system plus oral
NAC in preventing CIN (11%, 16/146) against a control group receiving
sodium bicarbonate plus oral NAC (20.5%, 30/146) (p value – 0.025, OR
0.47; 95% CI 0.24 to 0.92).
82

83. 83

84. N-Acetyl Cysteine and Sodium Bicarbonate
• N-acetyl cysteine (NAC) is assumed to limit CI-AKI by acting as a
scavenger of ROS and promoting vasodilatory effects in the renal
medulla.
• It has been widely investigated for the prevention of CI-AKI with
mixed results.
• Earlier trials with small sample sizes suggested a potential benefit of
NAC, whereas larger studies failed to show a significant reduction in
CI-AKI.
84

85. • Acetylcysteine does not reduce the risk of contrast-induced acute
kidney injury or other clinically relevant outcomes in at-risk patients
undergoing coronary and peripheral vascular angiography.
85

86. • Similarly, isotonic sodium bicarbonate (NaHCO3) was
hypothesized to prevent CI-AKI due to inhibition of
free-radical formation by alkalinizing the renal tubular
fluid.
• Although smaller studies suggested a benefit of
NaHCO3 administration for CI-AKI prevention, these
findings were not confirmed in larger studies.
86

87. • Among patients at high risk for renal complications who were
undergoing angiography, there was no benefit of intravenous sodium
bicarbonate over intravenous sodium chloride or of oral
acetylcysteine over placebo for the prevention of death, need for
dialysis, or persistent decline in kidney function at 90 days or for the
prevention of contrast-associated acute kidney injury.
87

88. • As such the ESC guidelines recommend that NAC is not to be
used alone, although it may be used in addition to standard
intravenous hydration regimes.
• KDIGO guidelines recommend using oral NAC together with
IV isotonic crystalloids, in patients with increased risk of CI-
AKI.
• Routine use of NAC for CI-AKI prevention is class III in the
ACC/AHA guidelines.
88

89. Statins
• More recently high-dose statin therapy (eg, rosuvastatin 40/20 mg,
atorvastatin 80 mg or simvastatin 80 mg) has shown efficacy in
preventing CIN in statin-naïve patients in several clinical studies and
as such is regarded as reasonable preventative therapy in the current
ESC guidelines.
• Initial PROMISS trial investigated short-term pretreatment with high-
dose simvastatin in patients with baseline renal insufficiency
undergoing coronary angiography and did not show a benefit of this
strategy with regard to deterioration of renal function.
89

90. • PRATO-ACS trial showed that high-dose rosuvastatin (40 mg
loading and 20 mg/day maintenance) compared to no statin
significantly reduced CI-AKI and 30-day rates of
cardiovascular and renal events (death, dialysis, MI, stroke,
or persistent renal damage) in statin-naïve patients
undergoing PCI.
• TRACK-D study was the largest trial investigating the role of
statins in CI-AKI prevention.
• A significant reduction of CI-AKI was reported for the statin group
compared to the control (2.3% vs. 3.9%; P = .01).
90

91. Impact of oxygen therapy for prevention of CIN
91

92. • Conclusion:
• Oxygenation, a simple, nonpharmacological strategy, may be beneficial when
using contrast media in patients with impaired renal function from
noninvasive angiography to emergency catheterization.
92

93. • Conclusion:
• Oxygen therapy has no effect on the occurrence of CIN.
93

94. 94

95. 95

96. • Hemofiltration: The benefit of hemofiltration in the high risk groups, needs
to be studied further.
• Hemodialysis: Patients on hemodialysis need not be volume loaded before
contrast administration and dialysis after the procedure is useful only if
patient has evidence of volume overload.
• Repeat contrast exposure: No studies have been conducted for the ideal
timing for a repeat contrast exposure, but since in majority of CIN patients
renal function is restored in 3 weeks, this time period is usually advised.
• Other pharmacological agents such as dopamine, fenoldopam have shown
no benefit in the prevention of CIN, forced diuresis with mannitol or
furesomide may even be harmful.
96

97. Approach
97

98. 98

99. Management
• Decline in renal function:
• The most common manifestation of CIN is asymptomatic transient decline in renal
function, which usually normalizes within 10-14 days.
• Serial creatinine:
• Patients at high risk should especially be followed up with serial creatinine
measurements daily for 5 days.
• Electrolyte and fluid balance:
• If oliguric renal failure occurs, the management should be similar to as that for acute
renal failure due to other causes, including judicious acid-base, electrolyte and fluid
balance.
• Dialysis:
• Temporary dialysis may be required in severe cases, with a minority of patients
requiring permanent dialysis
99

100. European Society of Cardiology CIN prevention guidelines, 2018
Recommendation Detail Class Level
Patients undergoing coronary angiography or MSCT
It is recommended that all patients
are assessed for the risk of contrast
induced
nephropathy.
I C
Adequate hydration is recommended. I C
100

101. Recommendation Detail Class Level
Patients with moderate or severe CKD (National Kidney Foundation stages 3b and 4)
Use of low-osmolar or iso-osmolar
contrast media is recommended.
I A
It is recommended that the volume of
contrast media be minimized.
Total contrast volume/GFR <3.7 I B
In statin-naive patients, pre-treatment
with high dose statins should be
considered.
Rosuvastatin 40/20 mg or atorvastatin
80 mg.
IIa A
Pre- and post-hydration with isotonic
saline should be considered if the
expected contrast volume is >100 mL
1 mL/kg/h 12 h before and continued
for 24 h after the procedure (0.5
mL/kg/h if LVEF ≤ 35% or NYHA > 2).
IIa C
As an alternative to the pre- and post-
hydration regimen, tailored hydration
regimens may be considered.
IIb B
101

102. Recommendation Detail Class Level
Patients with severe CKD (National Kidney Foundation stage 4)
Prophylactic haemofiltration
6 h before complex PCI may
be Considered
Fluid replacement rate
1000 mL/h without
negative loss and saline
hydration continued for
24 h after the procedure.
IIb B
Haemodialysis is not
recommended as a
preventive measure.
III B
102

103. Have a Heart,
Be kind to Kidneys
103