1) Contrast induced nephropathy (CIN) is a serious complication of cardiac procedures and can lead to acute renal failure, increased mortality, and long term renal dysfunction. 2) Many risk factors increase a patient's likelihood of developing CIN, including pre-existing renal insufficiency, diabetes, older age, hypotension, and the volume and osmolality of contrast agent used. 3) Preventive strategies aim to reduce renal ischemia and oxidative stress through hydration with intravenous fluids like sodium bicarbonate or sodium chloride, as well as pharmacological interventions including N-acetylcysteine. Larger clinical trials are still needed to determine the most effective prevention protocols.

1. Contrast Induced NephropathyContrast Induced Nephropathy
Cardiac InterventionCardiac Intervention
Department of CardiologyDepartment of Cardiology
Apollo Hospitals, HydergudaApollo Hospitals, Hyderguda
HyderabadHyderabad
Dr. R. Vishwanath MRCP(UK)

2. Cardiorenal RiskCardiorenal Risk
CardiacCardiac
DiseaseDisease
RenalRenal
DiseaseDisease
Acute Renal FailureAcute Renal Failure
and Deathand Death
in the Cardiac Patientin the Cardiac Patient
Myocardial Infarction,Myocardial Infarction,
Heart Failure,Heart Failure,
Arrhythmias,Arrhythmias,
and Cardiac Death inand Cardiac Death in
the Renal Patientthe Renal Patient

3. ControversialControversial
• Thousands of literature and papers.
• Hundreds of meta-analysis of the published papers.
DENIAL RESPONSE !!!
Experience Vs Evidence based practice
Many contradictory results

4. Topics for Consideration….Topics for Consideration….
1. Basic understanding of renal function tests
and their fallacies
2. Definition of CIN in vogue.
3. Incidence of CIN.
4. Predictors for the development of CIN.
5. Recognition of high risk patients.
6. Proposed Pathogenesis of CIN.
7. Radio Contrast Agents
8. Preventive strategies.
9. Management of CIN.
10.Long term prognostic outcomes.

5. Renal Function TestsRenal Function Tests
1. Serum Creatinine
• Calibration and Estimation
• Many variables – Age, Race, Sex .…
A normal Serum Creatinine is not indicative of
a normal renal function.
GFR

6. How to Assess Renal Function?How to Assess Renal Function?
Abbreviated Modification of Diet in Renal Disease
equations (MDRD) equation:
eGFR, ml/min/1.73 m2
= 186 x (Serum Creatinine [mg/dL]) -1.154 x
(Age-0.203x (0.742 if female) x (1.210 if African American)
(140- age) x Body Weight [kg]*
Creatinine Clearance, ml/min =
* Multiple by 0.8 in female
Cockcroft-Gault equation:
Serum Creatinine mg/dL] x 72

7. Definition of CINDefinition of CIN
CIN ↑ in Serum Creatinine
concentration
0.5 mg/dL (44 mol/L) or
25% above baseline within
48 hours after contrast
administration

8. • Non-oliguricNon-oliguric
• ↓↓ renal function post-contrast in the absencerenal function post-contrast in the absence
of other causes.of other causes.
• Recovery usually occurs within 5 to 14 days.Recovery usually occurs within 5 to 14 days.
However the long term outcome on renalHowever the long term outcome on renal
dysfunction is unclear.dysfunction is unclear.
DefinitionDefinition

9. INCIDENCE OF CININCIDENCE OF CIN ::
Marked variation in the reported incidence of CIN
0 to >50%
Causative Factors for the wide variation of CIN:
Consensus on what is Renal dysfunction .
Variability of risk factors
Various types of contrast and variable procedures.
Radiologic procedure.

10. Predictors of All-Cause MortalityPredictors of All-Cause Mortality
to 7 Years BARI Trial + Registryto 7 Years BARI Trial + Registry
Szczech L. et al.,Szczech L. et al., CirculationCirculation 2002; 105:2253-8.2002; 105:2253-8.

11. Risk Factors for CINRisk Factors for CIN
Patient-related Risk FactorsPatient-related Risk Factors
• Renal insufficiencyRenal insufficiency
• Diabetes mellitus withDiabetes mellitus with
renal insufficiencyrenal insufficiency
• AgeAge
• Volume depletionVolume depletion
• HypotensionHypotension
• Low cardiac outputLow cardiac output
• Class IV CHFClass IV CHF
• Other nephrotoxinsOther nephrotoxins
• Renal transplantRenal transplant
• Hypoalbuminemia (<35 g/l)Hypoalbuminemia (<35 g/l)
Procedure-related Risk FactorsProcedure-related Risk Factors
• Multiple contrast mediaMultiple contrast media
injection within 72 hrsinjection within 72 hrs
• Intra-arterial injection siteIntra-arterial injection site
• High volume of contrast mediaHigh volume of contrast media
• High osmolality of contrastHigh osmolality of contrast
mediamedia

12. RiskRisk
ScoreScore
RiskRisk
of CINof CIN
Risk ofRisk of
DialysisDialysis
≤≤ 55 7.5%7.5% 0.04%0.04%
6 to 106 to 10 14.0%14.0% 0.12%0.12%
11 to11 to
1616
26.1%26.1% 1.09%1.09%
≥≥ 1616 57.3%57.3% 12.6%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
Scheme to Define CIN Risk ScoreScheme to Define CIN 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

13. Prognostic significance of the proposed risk score for CIN extended to
prediction of 1-year mortality. (Red bars = development dataset; blue bars =
validation dataset.)
CIN Risk Score & 1-year MortalityCIN Risk Score & 1-year Mortality
31.2 33.3
15.5
5.5
1.9 2.0
5.7
13.5
0
5
10
15
20
25
30
35
Low Moderate High Very High
1-yearmortality
Risk Groups:
Risk Score: ≤5 6 to 10 11 to 15 ≥16
Mehran et al. JACC 2004;44:1393-1399.

14. Proposed PathogenesisProposed Pathogenesis
Following exposure to contrast :
• Renal GFR ↓ due to ↓ renal vasoconstriction.
• Resultant Ischemia in the deeper portion of the outer
medulla.
• High Oxygen requirement and remote from the Vasa
recta from which it’s blood supply is derived.
Exact Mechanisms of CIN – Not fully known
Present Proposed Etiology:
Direct toxic affects of renal tubular cells, causing
vacuolization, altered mitochondrial function
and apoptosis

15. Pathogenesis…Pathogenesis…
• ↑ Adenosine
• ↑ Endothelin
• ↑ Free radicals
• ↓ NO
• ↓ Prostaglandin
Induced Vasodilatation

17. Physicochemical Properties of ContrastPhysicochemical Properties of Contrast
AgentsAgents
Table 1. Properties of Commonly Used Radiocontrast Media.

18. Renal Failure in Patients Undergoing CoronaryRenal Failure in Patients Undergoing Coronary
Procedures using Iso-osmolar or Low-osmolarProcedures using Iso-osmolar or Low-osmolar
Contrast MediaContrast Media
Liss et al. Kidney International 2006
ContrastContrast
media (CM)media (CM) CM propertiesCM properties NN Time periodTime period
IodixanolIodixanol iso-osmolar, nonionic,iso-osmolar, nonionic, 45 48545 485 2000-20032000-2003
IoxaglateIoxaglate low-osmolar, nonionic,low-osmolar, nonionic, 12 44012 440 2000-20032000-2003
• Swedish Coronary Angiography and Angioplasty Registry
• Swedish Hospital Discharge Registry

19. • FluidsFluids
• PharmacologicalPharmacological
• Extra-corporealExtra-corporeal
Strategies to Reduce CMINStrategies to Reduce CMIN

20. • 0.45% Saline0.45% Saline
• ↑↑ Free water excretion & thus dilute CM in tubuleFree water excretion & thus dilute CM in tubule
• 0.9% Saline0.9% Saline
• ↑↑ Na+ at the DCT, thus ↓ stimulation of reninNa+ at the DCT, thus ↓ stimulation of renin
angiotensin system.angiotensin system.
• NaHCO3- (isotonic)NaHCO3- (isotonic)
• Protection against free radical injuryProtection against free radical injury
FluidsFluids

21. • IV infusion vs Oral hydrationIV infusion vs Oral hydration
• IV infusion vs IV bolusIV infusion vs IV bolus
FluidsFluids

22. • Adenosine AntagonistsAdenosine Antagonists
• StatinsStatins
• Ascorbic AcidAscorbic Acid
• Prostaglandin E1Prostaglandin E1
• N-Acetyl CysteineN-Acetyl Cysteine
• Dopamine & FenoldopamDopamine & Fenoldopam
• Calcium Channel BlockersCalcium Channel Blockers
• Atrial Natriuretic PeptideAtrial Natriuretic Peptide
• L-ArginineL-Arginine
• FrusemideFrusemide
• MannitolMannitol
• Endothelin ReceptorEndothelin Receptor
AntagonistsAntagonists
DrugsDrugs

23. • Anti-OxidantsAnti-Oxidants
• Ascorbic AcidAscorbic Acid
• StatinsStatins
• N-AcetylcysteineN-Acetylcysteine
• VasodilatorsVasodilators
• Theophylline / AminophylinneTheophylline / Aminophylinne
• Prostaglandin E1Prostaglandin E1
• Dopamine / FenoldopamDopamine / Fenoldopam
• Calcium Channel BlockersCalcium Channel Blockers
• Endothelin Receptor AntagonistsEndothelin Receptor Antagonists
• Nitric Oxide EnhancersNitric Oxide Enhancers
• StatinsStatins
• L-ArginineL-Arginine
• DiureticsDiuretics
• Frusemide / MannitolFrusemide / Mannitol
DrugsDrugs

25. Optimal Hydration RegimenOptimal Hydration Regimen
Mueller et alMueller et al Arch Intern MedArch Intern Med 20022002
1937 Patients Screened
317 Ineligible or
No Consent
685 for Primary End Point
Analysis
698 for Primary End Point
Analysis
1620 Randomized
809 Received 0.9% Saline
124 Excluded From Primary
End Point Analysis
Repeat Catheterization (n=78)
Incomplete Data (n=46)
811 Received 0.45%
Sodium Chloride
113 Excluded From Primary
End Point Analysis
Repeat Catheterization (n=59)
Incomplete Data (n=53)
Bypass Grafting (n=1)

26. Optimal HydrationOptimal Hydration
0.9% NS vs 0.45% NS0.9% NS vs 0.45% NS
P=.35P=.35
0
1
2
3
CN Mortality Vascular
Incidence,%
0.9% Saline
0.45% Sodium Chloride
P=.93P=.93
P=.04P=.04
Mueller et alMueller et al Arch Intern MedArch Intern Med 20022002

27. Prevention of CIN withPrevention of CIN with
Sodium BicarbonateSodium Bicarbonate
Merten GJ et al.Merten GJ et al. JAMAJAMA, 2004;291:2328-2334, 2004;291:2328-2334
Patients With Baseline Serum Creatinine >1.8 mg/dlPatients With Baseline Serum Creatinine >1.8 mg/dl
who Underwent Contrast Exposure (Iopamidol in All)who Underwent Contrast Exposure (Iopamidol in All)
N=137N=137
Sodium ChlorideSodium Chloride
Hydration (154 mEq/L ofHydration (154 mEq/L of
Sodium Chloride)Sodium Chloride)
N=68N=68
Sodium BicarbonateSodium Bicarbonate
Hydration (154 mEq/L ofHydration (154 mEq/L of
Sodium Bicarbonate)Sodium Bicarbonate)
N=69N=69
Primary endpoint: increase in serum creatinine ≥25%Primary endpoint: increase in serum creatinine ≥25%
within 2 days post-exposurewithin 2 days post-exposure

28. Prevention of CIN with SodiumPrevention of CIN with Sodium
Bicarbonate: ResultsBicarbonate: Results
EndpointsEndpoints
SodiumSodium
ChlorideChloride
N=59N=59
SodiumSodium
BicarbonateBicarbonate
N=60N=60
PP
valuevalue
Incidence of CIN (%)Incidence of CIN (%) 13.6%13.6% 1.7%1.7% 0.020.02
Incidence of CINIncidence of CIN
(↑SCr 0.5 mg/dL)(↑SCr 0.5 mg/dL)
11.9%11.9% 1.7%1.7% 0.030.03
Merten GJ et al.Merten GJ et al. JAMA,JAMA, 2004;291:2328-23342004;291:2328-2334

29. REMEDIAL TrialREMEDIAL Trial
Saline + NACSaline + NAC
N=118N=118
Bicarbonate + NACBicarbonate + NAC
N=117N=117
Saline+AA+NACSaline+AA+NAC
N=116N=116
7 excluded7 excluded
Pts with eGFR<40Pts with eGFR<40
N=393N=393
Randomized N=351Randomized N=351
Excluded N=42Excluded N=42
NAC =NAC = NN-acetylcysteine, AA = ascorbic acid-acetylcysteine, AA = ascorbic acid
9 excluded9 excluded9 excluded9 excluded
107 included107 included
into analysisinto analysis
108 included108 included
into analysisinto analysis
111 included111 included
into analysisinto analysis
Briguorio C. et al,Briguorio C. et al, CirculationCirculation 20072007

30. REMEDIAL Trial: ResultsREMEDIAL Trial: Results
Saline + NAC
Bicarbonate +
NAC
Saline +
Ascorbic Acid
+ NAC
P Value
N=111 N=108 N=107
Serum creatinine
increase by ≥25%
11 (9.9%) 2 (1.9%)* 10 (10.3%) 0.010
Serum creatinine
increase by ≥0.5 mg/dL
12 (10.8%) 1 (0.9%)† 12 (11.2%) 0.026
eGFR decrease by
≥25%
10 (9.2%) 1 (0.9%)† 10 (10.3%) 0.018
*P=0.019P=0.019, †P<0.01P<0.01 vs. saline + NAC group
Briguorio C. et al,Briguorio C. et al, CirculationCirculation 20072007

31. MEENAMEENA
DesignDesign
• DESIGN: Prospective,
randomized, parallel-group,
single-center clinical evaluation
of two hydration strategies for
patients undergoing coronary
angiography
• OBJECTIVE: To compare the
incidence of CIN between
periprocedural hydration with
sodium bicarbonate vs. sodium
chloride (0.9%, normal saline)
• PRIMARY ENDPOINT:
Decrease in estimated GFR by ≥
25% within 4 days of coronary
angiography
353 patients enrolled between January 2006
and January 2007
353 patients enrolled between January 2006
and January 2007
236 patients
assigned to sodium
chloride
236 patients
assigned to sodium
chloride
178 patients
assigned to sodium
bicarbonate
178 patients
assigned to sodium
bicarbonate
156 evaluable
patient
156 evaluable
patient
Brar, S et. al., i2/ACC 2007
147 evaluable
patient
147 evaluable
patient
22
excluded
22
excluded
28
excluded
28
excluded
Hydration ProtocolHydration Protocol
•3 mL/kg for 1 hr before the procedure
•1.5 mL/kg during and for 4hrs post-
procedure
Hydration ProtocolHydration Protocol
•3 mL/kg for 1 hr before the procedure
•1.5 mL/kg during and for 4hrs post-
procedure

32. MEENAMEENA
p = 0.97p = 0.97
p = 0.82p = 0.82

33. Sodium BicarbonateSodium Bicarbonate
StudyStudy NN
(Saline, Bicarb)(Saline, Bicarb)
ProcedureProcedure BaselineBaseline
FunctionFunction
(mL/min/(mL/min/1.73m2)1.73m2)
Fluid protocolFluid protocol CIN rateCIN rate
(%)(%)
pp
RANDOMIZEDRANDOMIZED
BrarBrar 353353
(175, 178)(175, 178)
CardiacCardiac 4848
4848
SalineSaline
BicarbonateBicarbonate
13.613.6
13.513.5
0.970.97
BriguoriBriguori 219219
(108, 111)(108, 111)
CardiacCardiac
PeripheralPeripheral
3232
3535
SalineSaline
BicarbonateBicarbonate
9.99.9
1.91.9
0.020.02
MertenMerten 119119
(59, 60)(59, 60)
CardiacCardiac
PeripheralPeripheral
4545
4141
SalineSaline
BicarbonateBicarbonate
13.713.7
1.71.7
0.020.02
Masuda*Masuda* 5959
(29, 30)(29, 30)
EmergencyEmergency
cardiaccardiac
3939
4040
SalineSaline
BicarbonateBicarbonate
3535
77
0.010.01
NON-RANDOMIZEDNON-RANDOMIZED
CARECARE 414414
(246, 168)(246, 168)
CardiacCardiac 5050
5050
BicarbonateBicarbonate
(-NAC)(-NAC)
BicarbonateBicarbonate
(+NAC)(+NAC)
10.610.6
11.911.9
NSNS

34. N-ACETYLCYSTEINE (NAC)N-ACETYLCYSTEINE (NAC)

35. CIN: Effect of n-AcetylcysteineCIN: Effect of n-Acetylcysteine
• Prospective, randomizedProspective, randomized
• 83 high risk patients83 high risk patients
 CrCl < 50 ml/minCrCl < 50 ml/min
 Diabetes 33%Diabetes 33%
• IV CONTRAST for CT (75IV CONTRAST for CT (75
ml of Low Osmolar CM)ml of Low Osmolar CM)
• n-AC 600 bid x 2 days pre-n-AC 600 bid x 2 days pre-
• CIN definition: creatinineCIN definition: creatinine
increase of 0.5 mg/dlincrease of 0.5 mg/dl
• Hydration with 0.45% @ 1Hydration with 0.45% @ 1
ml/kg/h x 24 hml/kg/h x 24 h
21%
2%
0%
5%
10%
15%
20%
25%
Control (42) AC (41)
CIM(%)
TepelTepel NEJMNEJM 20002000
p= 0.01p= 0.01

36. Zagler et al. Am Heart J 2006;151:140-145.
Relative Risk for Developing CIN after NACRelative Risk for Developing CIN after NAC
Risk Ratio (Random)Risk Ratio (Random)
95% Cl95% Cl
0.10.1 11 1010
Favors treatmentFavors treatment Favors controlFavors control
0.20.2 0.50.5 22 55
RR (Random)RR (Random)
95% Cl95% Cl
ControlControl
n/Nn/N
NACNAC
n/Nn/N
Study orStudy or
substurysubstury
Review:Review: Acetylcysteine and CINAcetylcysteine and CIN
Comparison:Comparison: 01 NAC on CIN01 NAC on CIN
Outcome:Outcome: 01 CIN01 CIN
Total events:Total events: 124 (NAC), 162 (Control)124 (NAC), 162 (Control)
Test for heterogenety:Test for heterogenety: Ch=27.54 (P0.005), 1Ch=27.54 (P0.005), 122
=56.4%=56.4%
Test for overall effect:Test for overall effect: Z=1.88 (Z=1.88 (P=0.05P=0.05))
Allaqaband et al 8/45 6/40 1.19 (0.45, 3.12)
Briguori et al 6/92 10/91 0.59 (0.23, 1.57)
Diaz-Sandoval et al 2/25 13/29 0.18 (0.04, 0.72)
Durham et al 10/38 9/41 1.20 (0.55, 2.63)
Goldenberg et al 4/41 3/39 1.27 (0.30, 5.31)
Gomes et al 8/78 8/78 1.00 (0.40, 2.53)
Kay et al 4/102 12/98 0.32 (0.11, 0.96)
Nguyen-Ho et al 9/95 19/85 0.42 (0.20, 0.89)
Oldemeyer 4/49 3/47 1.28 (0.30, 5.41)
Pate et al 57/238 50/239 1.14 (0.82, 1.60)
RAPIDO 2/41 8/39 0.24 (0.05, 1.05)
Shyu 2/60 15/61 0.14 (0.03, 0.57)
Fung et al 8/46 6/45 1.30 (0.49, 3.46)
Total: (95% Cl)Total: (95% Cl) 950950 932932 0.68 (0.46, 1.02)0.68 (0.46, 1.02)

37. Meta-analysis: High vs.Meta-analysis: High vs.
Low Osm Contrast MediaLow Osm Contrast Media
• 39 Trials - 5146 patients39 Trials - 5146 patients
• CIN > 0.5 mg/dlCIN > 0.5 mg/dl
• CIN in 7% of all patientsCIN in 7% of all patients
• CIN in 30% of CRICIN in 30% of CRI
patientspatients
• For CRI, NNT=8 (treat 8 toFor CRI, NNT=8 (treat 8 to
prevent 1 CIN case)prevent 1 CIN case)
• Low osmolal groupLow osmolal group
included Ioxaglateincluded Ioxaglate
(Hexabrix); Iodixanol(Hexabrix); Iodixanol
(Visipaque) not studied(Visipaque) not studied
Barrett and CarlisleBarrett and Carlisle J Am Soc NephrolJ Am Soc Nephrol 92;92;
1.0
0.61
0.0
0.2
0.4
0.6
0.8
1.0
1.2
High Osm Low Osm
RelativeRiskofCIN

38. The NEPHRIC StudyThe NEPHRIC Study
Nephrotoxicity in High-risk PatientsNephrotoxicity in High-risk Patients
a Double Blind Randomized Multicentrea Double Blind Randomized Multicentre
Study of Iso-osmolar and Low-osmolarStudy of Iso-osmolar and Low-osmolar
Non-ionic Contrast MediaNon-ionic Contrast Media

39. NEPHRICNEPHRIC Study: ProtocolStudy: Protocol
• Randomized, double blind, prospective, multicenterRandomized, double blind, prospective, multicenter
• Primary endpoint: peak increase in serum creatininePrimary endpoint: peak increase in serum creatinine
concentration @ 3 days after angiographyconcentration @ 3 days after angiography
Patients with diabetes and serum creatinine 1.5-3.5 mg/dl whoPatients with diabetes and serum creatinine 1.5-3.5 mg/dl who
underwent coronary or aortofemoral angiographyunderwent coronary or aortofemoral angiography
Iso-osmolar, non-ionicIso-osmolar, non-ionic
Iodixanol [Visipaque]Iodixanol [Visipaque]
N=64N=64
Mean Contrast Volume = 163 mlMean Contrast Volume = 163 ml
PTCA – 17%PTCA – 17%
Low-osmolar, non-ionicLow-osmolar, non-ionic
Iohexol [Omnipaque]Iohexol [Omnipaque]
N=65N=65
Mean Contrast Volume =Mean Contrast Volume = 162 ml162 ml
PTCA – 25%PTCA – 25%
Aspelin P et al,Aspelin P et al, NEJMNEJM, 2003; 348: 491-499, 2003; 348: 491-499

40. Primary Endpoint –Primary Endpoint –
Peak Increase in Scr from Baseline to Day 3Peak Increase in Scr from Baseline to Day 3
(µmol/l)(µmol/l) p=0.002p=0.002
IodixanolIodixanol
(Visipaque)
IohexolIohexol
(Omnipaque)
n=62n=62 n=64n=64
MeanMean 11.2 ±19.711.2 ±19.7 41.5 ± 68.641.5 ± 68.6
MinimumMinimum - 19.0- 19.0 - 21.0- 21.0
MaxMax 74.074.0 331.0331.0

41. RECOVER Trial – Renal Toxicity Evaluation and ComparisonRECOVER Trial – Renal Toxicity Evaluation and Comparison
Between Visipaque and Hexabrix in Patients With RenalBetween Visipaque and Hexabrix in Patients With Renal
Insufficiency Undergoing Coronary AngiographyInsufficiency Undergoing Coronary Angiography
Jo et al. JACC 2006; 48:924-30
Prospective, randomized trialProspective, randomized trial
300 patients
with CrCl ≤ 60 ml/min
149 pts. (135 pts. included
in primary analysis)
ioxaglate
151 pts. (140 pts. included
in primary analysis)
iodixanol
Primary endpoint – Incidence of CIN
Increase in SCr ≥ 25% or ≥ 0.5 mg/dl

42. RECOVER Trial – Incidence of CINRECOVER Trial – Incidence of CIN
Jo et al. JACC 2006; 48:924-30
17.0%
7.9%
0.0%
10.0%
20.0%
CIN
ioxaglate
iodixanol
P=0.021P=0.021
N=300

43. 24.2%
16.2%
0%
10%
20%
30%
Ioxaglate Iodixanol
ICONICON TTrialrial
PatientsPatients wwithith cchronichronic rrenalenal iinsufficiencynsufficiency
uundergondergoinging PCIPCI wwith atith at lleast 150cc ofeast 150cc of ccontrastontrast vvolumeolume
PatientsPatients wwithith cchronichronic rrenalenal iinsufficiencynsufficiency
uundergondergoinging PCIPCI wwith atith at lleast 150cc ofeast 150cc of ccontrastontrast vvolumeolume
IoxaglateIoxaglate
N=74N=74
IoxaglateIoxaglate
N=74N=74
IodixanolIodixanol
N=71N=71
IodixanolIodixanol
N=71N=71
NN=130=130
P=0.26P=0.26
Incidence of CIN
Mehran R. et al, Transcatheter Cardiovascular Therapeutics.
2006.

44. Rehospitalization with Renal Failure as aRehospitalization with Renal Failure as a
Primary DiagnosisPrimary Diagnosis
Liss et al. Kidney International 2006
0.02% 0.03%
0.10%
0.07%
0.20%
0.30%
0.00%
0.10%
0.20%
0.30%
0.40%
Within 1 week Within 1 month Within 3
months
Ioxaglate
Iodixanol P<0.001P<0.001
P<0.001P<0.001
P=0.022P=0.022

45. Start of Dialysis after CoronaryStart of Dialysis after Coronary
Angiography or PCIAngiography or PCI
Liss et al. Kidney International 2006
0.00%
0.02%
0.10%
0.02%
0.10%
0.20%
0.00%
0.05%
0.10%
0.15%
0.20%
0.25%
Within 1 week Within 1 month Within 3 months
Ioxaglate
Iodixanol
P=0.098P=0.098
P=0.010P=0.010
P=0.009P=0.009

46. 1-year Follow-up1-year Follow-up
Liss et al. Kidney International 2006
* Groups differ in
time period !
CMCM N of ptsN of pts
iodixanoliodixanol 54 61654 616
ioxaglateioxaglate 24 47924 479
** iohexoliohexol 6 8546 854
Renal failureRenal failure
Iodixanol
Iohexol
Ioxaglate
f
Time (years)
%
6
5
4
3
2
1
0
0 1 2 3 4 5 6 7 8 9 10 11 12

47. CARECARE
DesignDesign
• DESIGN: Prospective,
randomized, double-blind,
parallel-group, multi-center
clinical evaluation ipamidol-370
and iodixanol-320
• OBJECTIVE: To compare the
incidence of CIN between
iopamidol-370 and iodixanol-320
• PRIMARY ENDPOINT:
Increase in SCr ≥ 0.5 mg/dL from
baseline to 45 to 120 hours after
administration
482 patients enrolled between July 2005 and
June 2006 in 25 clinical site in North
America
482 patients enrolled between July 2005 and
June 2006 in 25 clinical site in North
America
14 patients withdrew
consent
14 patients withdrew
consent
468 assigned to a treatment arm468 assigned to a treatment arm
236 patients
assigned to
Iodixanol-320
236 patients
assigned to
Iodixanol-320
230 patients
assigned to
Iopamidol-370
230 patients
assigned to
Iopamidol-370
204 evaluable
patient
204 evaluable
patient
Solomon, RJ et. al., Circulation 115, 3189 (2007)
210 evaluable
patient
210 evaluable
patient
26
excluded
26
excluded
26
excluded
26
excluded

48. CARECARE
p = 0.39p = 0.39 p = 0.44p = 0.44 p = 0.15p = 0.15

49. CARECARE
p = 0.11p = 0.11 p = 0.37p = 0.37 p = 0.20p = 0.20
Diabetic SubgroupDiabetic Subgroup

50. Figure. Strategy for Management of Patients With Risk Factors for Contrast-Induced
Nephropathy *See Box for listing of risk factors for contrast-induced nephropathy.
Pannu, N. et al. JAMA 2006;295:2765-2779

51. Conclusions (1)Conclusions (1)
• CRI is one of the most important independentCRI is one of the most important independent
predictors of poor outcome post PCIpredictors of poor outcome post PCI
• CIN remains a frequent source of acute renalCIN remains a frequent source of acute renal
failure and is associated with increased morbidityfailure and is associated with increased morbidity
and mortality, and higher resource utilizationand mortality, and higher resource utilization
• Several factors predispose patients to CINSeveral factors predispose patients to CIN
• Preventive measures pre procedure, as well asPreventive measures pre procedure, as well as
careful post procedure management should becareful post procedure management should be
routine in all patientsroutine in all patients

52. Conclusions (2)Conclusions (2)
• Hydration pre-PCI (12 hours recommended)Hydration pre-PCI (12 hours recommended)
• Avoid nephrotoxic drugs (NSAIDS, antibiotics, metformin etc)Avoid nephrotoxic drugs (NSAIDS, antibiotics, metformin etc)
• Role of n-acetylcysteine is disputableRole of n-acetylcysteine is disputable
• No Role for IV FenoldopamNo Role for IV Fenoldopam
• Sodium bicarbonate may be useful, but need more definitiveSodium bicarbonate may be useful, but need more definitive
datadata
• Limit contrast agent volumeLimit contrast agent volume
• Low-osmolar agents are better than high-osmolarLow-osmolar agents are better than high-osmolar
 Within non-ionic contrast, the data are contradictoryWithin non-ionic contrast, the data are contradictory
 Allow time before repeat procedures / staged procedures.Allow time before repeat procedures / staged procedures.
• Role of local drug delivery for prevention of CIN requiresRole of local drug delivery for prevention of CIN requires
further investigationfurther investigation
• Role of Cooling Therapy is being examined: COOL CIN StudyRole of Cooling Therapy is being examined: COOL CIN Study

53. Take home message ?Take home message ?
Perhaps testing Serum creatinine and GFR
should become a regular practice to know the
true incidence at our centre.