Contrast Induced NephropathyContrast Induced NephropathyCardiac InterventionCardiac InterventionDepartment of CardiologyDe...
Cardiorenal RiskCardiorenal RiskCardiacCardiacDiseaseDiseaseRenalRenalDiseaseDiseaseAcute Renal FailureAcute Renal Failure...
ControversialControversial• Thousands of literature and papers.• Hundreds of meta-analysis of the published papers.DENIAL ...
Topics for Consideration….Topics for Consideration….1. Basic understanding of renal function testsand their fallacies2. De...
Renal Function TestsRenal Function Tests1. Serum Creatinine• Calibration and Estimation• Many variables – Age, Race, Sex ....
How to Assess Renal Function?How to Assess Renal Function?Abbreviated Modification of Diet in Renal Diseaseequations (MDRD...
Definition of CINDefinition of CINCIN ↑ in Serum Creatinineconcentration0.5 mg/dL (44 mol/L) or25% above baseline within48...
• Non-oliguricNon-oliguric• ↓↓ renal function post-contrast in the absencerenal function post-contrast in the absenceof ot...
INCIDENCE OF CININCIDENCE OF CIN ::Marked variation in the reported incidence of CIN0 to >50%Causative Factors for the wid...
Predictors of All-Cause MortalityPredictors of All-Cause Mortalityto 7 Years BARI Trial + Registryto 7 Years BARI Trial + ...
Risk Factors for CINRisk Factors for CINPatient-related Risk FactorsPatient-related Risk Factors• Renal insufficiencyRenal...
RiskRiskScoreScoreRiskRiskof CINof CINRisk ofRisk ofDialysisDialysis≤≤ 55 7.5%7.5% 0.04%0.04%6 to 106 to 10 14.0%14.0% 0.1...
Prognostic significance of the proposed risk score for CIN extended toprediction of 1-year mortality. (Red bars = developm...
Proposed PathogenesisProposed PathogenesisFollowing exposure to contrast :• Renal GFR ↓ due to ↓ renal vasoconstriction.• ...
Pathogenesis…Pathogenesis…• ↑ Adenosine• ↑ Endothelin• ↑ Free radicals• ↓ NO• ↓ ProstaglandinInduced Vasodilatation
Physicochemical Properties of ContrastPhysicochemical Properties of ContrastAgentsAgentsTable 1. Properties of Commonly Us...
Renal Failure in Patients Undergoing CoronaryRenal Failure in Patients Undergoing CoronaryProcedures using Iso-osmolar or ...
• FluidsFluids• PharmacologicalPharmacological• Extra-corporealExtra-corporealStrategies to Reduce CMINStrategies to Reduc...
• 0.45% Saline0.45% Saline• ↑↑ Free water excretion & thus dilute CM in tubuleFree water excretion & thus dilute CM in tub...
• IV infusion vs Oral hydrationIV infusion vs Oral hydration• IV infusion vs IV bolusIV infusion vs IV bolusFluidsFluids
• Adenosine AntagonistsAdenosine Antagonists• StatinsStatins• Ascorbic AcidAscorbic Acid• Prostaglandin E1Prostaglandin E1...
• Anti-OxidantsAnti-Oxidants• Ascorbic AcidAscorbic Acid• StatinsStatins• N-AcetylcysteineN-Acetylcysteine• VasodilatorsVa...
Optimal Hydration RegimenOptimal Hydration RegimenMueller et alMueller et al Arch Intern MedArch Intern Med 200220021937 P...
Optimal HydrationOptimal Hydration0.9% NS vs 0.45% NS0.9% NS vs 0.45% NSP=.35P=.350123CN Mortality VascularIncidence,%0.9%...
Prevention of CIN withPrevention of CIN withSodium BicarbonateSodium BicarbonateMerten GJ et al.Merten GJ et al. JAMAJAMA,...
Prevention of CIN with SodiumPrevention of CIN with SodiumBicarbonate: ResultsBicarbonate: ResultsEndpointsEndpointsSodium...
REMEDIAL TrialREMEDIAL TrialSaline + NACSaline + NACN=118N=118Bicarbonate + NACBicarbonate + NACN=117N=117Saline+AA+NACSal...
REMEDIAL Trial: ResultsREMEDIAL Trial: ResultsSaline + NACBicarbonate +NACSaline +Ascorbic Acid+ NACP ValueN=111 N=108 N=1...
MEENAMEENADesignDesign• DESIGN: Prospective,randomized, parallel-group,single-center clinical evaluationof two hydration s...
MEENAMEENAp = 0.97p = 0.97p = 0.82p = 0.82
Sodium BicarbonateSodium BicarbonateStudyStudy NN(Saline, Bicarb)(Saline, Bicarb)ProcedureProcedure BaselineBaselineFuncti...
N-ACETYLCYSTEINE (NAC)N-ACETYLCYSTEINE (NAC)
CIN: Effect of n-AcetylcysteineCIN: Effect of n-Acetylcysteine• Prospective, randomizedProspective, randomized• 83 high ri...
Zagler et al. Am Heart J 2006;151:140-145.Relative Risk for Developing CIN after NACRelative Risk for Developing CIN after...
Meta-analysis: High vs.Meta-analysis: High vs.Low Osm Contrast MediaLow Osm Contrast Media• 39 Trials - 5146 patients39 Tr...
The NEPHRIC StudyThe NEPHRIC StudyNephrotoxicity in High-risk PatientsNephrotoxicity in High-risk Patientsa Double Blind R...
NEPHRICNEPHRIC Study: ProtocolStudy: Protocol• Randomized, double blind, prospective, multicenterRandomized, double blind,...
Primary Endpoint –Primary Endpoint –Peak Increase in Scr from Baseline to Day 3Peak Increase in Scr from Baseline to Day 3...
RECOVER Trial – Renal Toxicity Evaluation and ComparisonRECOVER Trial – Renal Toxicity Evaluation and ComparisonBetween Vi...
RECOVER Trial – Incidence of CINRECOVER Trial – Incidence of CINJo et al. JACC 2006; 48:924-3017.0%7.9%0.0%10.0%20.0%CINio...
24.2%16.2%0%10%20%30%Ioxaglate IodixanolICONICON TTrialrialPatientsPatients wwithith cchronichronic rrenalenal iinsufficie...
Rehospitalization with Renal Failure as aRehospitalization with Renal Failure as aPrimary DiagnosisPrimary DiagnosisLiss e...
Start of Dialysis after CoronaryStart of Dialysis after CoronaryAngiography or PCIAngiography or PCILiss et al. Kidney Int...
1-year Follow-up1-year Follow-upLiss et al. Kidney International 2006* Groups differ intime period !CMCM N of ptsN of ptsi...
CARECAREDesignDesign• DESIGN: Prospective,randomized, double-blind,parallel-group, multi-centerclinical evaluation ipamido...
CARECAREp = 0.39p = 0.39 p = 0.44p = 0.44 p = 0.15p = 0.15
CARECAREp = 0.11p = 0.11 p = 0.37p = 0.37 p = 0.20p = 0.20Diabetic SubgroupDiabetic Subgroup
Figure. Strategy for Management of Patients With Risk Factors for Contrast-InducedNephropathy *See Box for listing of risk...
Conclusions (1)Conclusions (1)• CRI is one of the most important independentCRI is one of the most important independentpr...
Conclusions (2)Conclusions (2)• Hydration pre-PCI (12 hours recommended)Hydration pre-PCI (12 hours recommended)• Avoid ne...
Take home message ?Take home message ?Perhaps testing Serum creatinine and GFR should become a regular practice to know th...
Contrast Induced Nephropathy
Contrast Induced Nephropathy
Contrast Induced Nephropathy
Upcoming SlideShare
Loading in...5
×

Contrast Induced Nephropathy

2,578

Published on

Published in: Health & Medicine
0 Comments
11 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
2,578
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
0
Comments
0
Likes
11
Embeds 0
No embeds

No notes for slide
  • There is a strong bidirectional association between cardiac diseases and renal insufficiency.
  • In multiple clinical trials and analyses, and you see just one of them, CKD represented the most significant independent predictor of long-term mortality.
  • Risk factors for CIN maybe divided into patient-related and procedure-related. Patient-related factors include Renal insufficiency Diabetes mellitus with renal insufficiency Age Volume depletion Hypotension Low cardiac output Class IV CHF Other nephrotoxins Renal transplant Hypoalbuminemia (<35 g/l) And procedure-related factors include Multiple contrast media injection within 72 hrs Intra-arterial injection site High volume of contrast media High osmolality of contrast media
  • Recently, CIN risk score was developed and validated based on the analysis of large prospectively created database. You may see that risk of CIN may be as high as 57% and risk of dialysis maybe as high as 12% in pts with multiple risk factors.
  • We also found a strong relationship between 1-year mortality and risk score of CIN.
  • A prospective randomized trial utilizing the oxygen radical scavenger, acetylcysteine, explored the role of oxidative injury in contrast induced nephropathy. Patients undergoing a contrast CT scan were randomized to usual care or pretreatment with 600 mg bid of acetylcysteine starting 24 hours before the contrast exposure and continuing for 24 hours after the exposure. A marked decrease in the incidence of contrast induced nephropathy (CIN) was noted. Although the study is very exciting, a number of limitations are worth noting. First, the low dose of contrast and the route of administration (intravenous) make it difficult to extrapolate the positive results to patients receiving 2-3 times as much contrast intraarterially. Second, the marked reduction in the incidence of CIN was associated with an actual decrease in serum creatinine in many patient, a finding difficult to explain based on the presumed mechanism of action of acetylcysteine. Finally, a number of other experiments involving animal models of renal injury have failed to produce such dramatic results using other free oxygen radical scavengers. This may simply mean that animal models don’t mimic human pathophysiology accurately. In any case, until additional studies in other clinical situations confirm the dramatic results found here, it should not be assumed that acetylcysteine is a magic bullet.
  • Solomon A meta-analysis of 39 clinical trials involving more than 5000 patients found that there were no significant benefits of low osmolar media compared to high osmolar media in low risk patients. However, in high risk patients (for example, those with baseline renal insufficiency), low osmolar media reduced the risk of contrast-induced nephropathy by 39%. Based upon the expected incidence of contrast-induced nephropathy, only a small number of high risk patients would need to be treated to prevent a single case of contrast-induced nephropathy. Since contrast-induced nephropathy is associated with significant morbidity, a cost-benefit analysis favors the use of low osmolar media in high risk patients.
  • This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading , let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)
  • This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading , let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)
  • Contrast Induced Nephropathy

    1. 1. Contrast Induced NephropathyContrast Induced NephropathyCardiac InterventionCardiac InterventionDepartment of CardiologyDepartment of CardiologyApollo Hospitals, HydergudaApollo Hospitals, HydergudaHyderabadHyderabadDr. R. Vishwanath MRCP(UK)
    2. 2. Cardiorenal RiskCardiorenal RiskCardiacCardiacDiseaseDiseaseRenalRenalDiseaseDiseaseAcute Renal FailureAcute Renal Failureand Deathand Deathin the Cardiac Patientin the Cardiac PatientMyocardial Infarction,Myocardial Infarction,Heart Failure,Heart Failure,Arrhythmias,Arrhythmias,and Cardiac Death inand Cardiac Death inthe Renal Patientthe Renal Patient
    3. 3. ControversialControversial• Thousands of literature and papers.• Hundreds of meta-analysis of the published papers.DENIAL RESPONSE !!!Experience Vs Evidence based practiceMany contradictory results
    4. 4. Topics for Consideration….Topics for Consideration….1. Basic understanding of renal function testsand their fallacies2. 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 Agents8. Preventive strategies.9. Management of CIN.10.Long term prognostic outcomes.
    5. 5. Renal Function TestsRenal Function Tests1. Serum Creatinine• Calibration and Estimation• Many variables – Age, Race, Sex .…A normal Serum Creatinine is not indicative ofa normal renal function.GFR
    6. 6. How to Assess Renal Function?How to Assess Renal Function?Abbreviated Modification of Diet in Renal Diseaseequations (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 femaleCockcroft-Gault equation:Serum Creatinine mg/dL] x 72
    7. 7. Definition of CINDefinition of CINCIN ↑ in Serum Creatinineconcentration0.5 mg/dL (44 mol/L) or25% above baseline within48 hours after contrastadministration
    8. 8. • Non-oliguricNon-oliguric• ↓↓ renal function post-contrast in the absencerenal function post-contrast in the absenceof 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 renaldysfunction is unclear.dysfunction is unclear.DefinitionDefinition
    9. 9. INCIDENCE OF CININCIDENCE OF CIN ::Marked variation in the reported incidence of CIN0 to >50%Causative Factors for the wide variation of CIN:Consensus on what is Renal dysfunction .Variability of risk factorsVarious types of contrast and variable procedures.Radiologic procedure.
    10. 10. Predictors of All-Cause MortalityPredictors of All-Cause Mortalityto 7 Years BARI Trial + Registryto 7 Years BARI Trial + RegistrySzczech L. et al.,Szczech L. et al., CirculationCirculation 2002; 105:2253-8.2002; 105:2253-8.
    11. 11. Risk Factors for CINRisk Factors for CINPatient-related Risk FactorsPatient-related Risk Factors• Renal insufficiencyRenal insufficiency• Diabetes mellitus withDiabetes mellitus withrenal 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 mediainjection 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 contrastmediamedia
    12. 12. RiskRiskScoreScoreRiskRiskof CINof CINRisk ofRisk ofDialysisDialysis≤≤ 55 7.5%7.5% 0.04%0.04%6 to 106 to 10 14.0%14.0% 0.12%0.12%11 to11 to161626.1%26.1% 1.09%1.09%≥≥ 1616 57.3%57.3% 12.6%12.6%Mehran et al. JACC 2004;44:1393-1399.HypotensionIABPCHFAge >75 yearsAnemiaDiabetesContrast media volumeRisk Factors555433Integer Score1 for each 100 cc3Scheme to Define CIN Risk ScoreScheme to Define CIN Risk ScoreSerum creatinine > 1.5mg/dl 4eGFR <60ml/min/1.73 m22 for 40 – 604 for 20 – 406 for < 20eGFR < 60ml/min/1.73 m2=186 x (SCr)-1.154x (Age)-0.203X (0.742 if female) x (1.210if African American)CalculateOR
    13. 13. Prognostic significance of the proposed risk score for CIN extended toprediction of 1-year mortality. (Red bars = development dataset; blue bars =validation dataset.)CIN Risk Score & 1-year MortalityCIN Risk Score & 1-year Mortality31.2 33.315.55.51.9 2.05.713.505101520253035Low Moderate High Very High1-yearmortalityRisk Groups:Risk Score: ≤5 6 to 10 11 to 15 ≥16Mehran et al. JACC 2004;44:1393-1399.
    14. 14. Proposed PathogenesisProposed PathogenesisFollowing exposure to contrast :• Renal GFR ↓ due to ↓ renal vasoconstriction.• Resultant Ischemia in the deeper portion of the outermedulla.• High Oxygen requirement and remote from the Vasarecta from which it’s blood supply is derived.Exact Mechanisms of CIN – Not fully knownPresent Proposed Etiology:Direct toxic affects of renal tubular cells, causingvacuolization, altered mitochondrial functionand apoptosis
    15. 15. Pathogenesis…Pathogenesis…• ↑ Adenosine• ↑ Endothelin• ↑ Free radicals• ↓ NO• ↓ ProstaglandinInduced Vasodilatation
    16. 16. Physicochemical Properties of ContrastPhysicochemical Properties of ContrastAgentsAgentsTable 1. Properties of Commonly Used Radiocontrast Media.
    17. 17. Renal Failure in Patients Undergoing CoronaryRenal Failure in Patients Undergoing CoronaryProcedures using Iso-osmolar or Low-osmolarProcedures using Iso-osmolar or Low-osmolarContrast MediaContrast MediaLiss et al. Kidney International 2006ContrastContrastmedia (CM)media (CM) CM propertiesCM properties NN Time periodTime periodIodixanolIodixanol iso-osmolar, nonionic,iso-osmolar, nonionic, 45 48545 485 2000-20032000-2003IoxaglateIoxaglate low-osmolar, nonionic,low-osmolar, nonionic, 12 44012 440 2000-20032000-2003• Swedish Coronary Angiography and Angioplasty Registry• Swedish Hospital Discharge Registry
    18. 18. • FluidsFluids• PharmacologicalPharmacological• Extra-corporealExtra-corporealStrategies to Reduce CMINStrategies to Reduce CMIN
    19. 19. • 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 reninangiotensin system.angiotensin system.• NaHCO3- (isotonic)NaHCO3- (isotonic)• Protection against free radical injuryProtection against free radical injuryFluidsFluids
    20. 20. • IV infusion vs Oral hydrationIV infusion vs Oral hydration• IV infusion vs IV bolusIV infusion vs IV bolusFluidsFluids
    21. 21. • 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 ReceptorAntagonistsAntagonistsDrugsDrugs
    22. 22. • 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 / MannitolDrugsDrugs
    23. 23. Optimal Hydration RegimenOptimal Hydration RegimenMueller et alMueller et al Arch Intern MedArch Intern Med 200220021937 Patients Screened317 Ineligible orNo Consent685 for Primary End PointAnalysis698 for Primary End PointAnalysis1620 Randomized809 Received 0.9% Saline124 Excluded From PrimaryEnd Point AnalysisRepeat Catheterization (n=78)Incomplete Data (n=46)811 Received 0.45%Sodium Chloride113 Excluded From PrimaryEnd Point AnalysisRepeat Catheterization (n=59)Incomplete Data (n=53)Bypass Grafting (n=1)
    24. 24. Optimal HydrationOptimal Hydration0.9% NS vs 0.45% NS0.9% NS vs 0.45% NSP=.35P=.350123CN Mortality VascularIncidence,%0.9% Saline0.45% Sodium ChlorideP=.93P=.93P=.04P=.04Mueller et alMueller et al Arch Intern MedArch Intern Med 20022002
    25. 25. Prevention of CIN withPrevention of CIN withSodium BicarbonateSodium BicarbonateMerten GJ et al.Merten GJ et al. JAMAJAMA, 2004;291:2328-2334, 2004;291:2328-2334Patients With Baseline Serum Creatinine >1.8 mg/dlPatients With Baseline Serum Creatinine >1.8 mg/dlwho Underwent Contrast Exposure (Iopamidol in All)who Underwent Contrast Exposure (Iopamidol in All)N=137N=137Sodium ChlorideSodium ChlorideHydration (154 mEq/L ofHydration (154 mEq/L ofSodium Chloride)Sodium Chloride)N=68N=68Sodium BicarbonateSodium BicarbonateHydration (154 mEq/L ofHydration (154 mEq/L ofSodium Bicarbonate)Sodium Bicarbonate)N=69N=69Primary endpoint: increase in serum creatinine ≥25%Primary endpoint: increase in serum creatinine ≥25%within 2 days post-exposurewithin 2 days post-exposure
    26. 26. Prevention of CIN with SodiumPrevention of CIN with SodiumBicarbonate: ResultsBicarbonate: ResultsEndpointsEndpointsSodiumSodiumChlorideChlorideN=59N=59SodiumSodiumBicarbonateBicarbonateN=60N=60PPvaluevalueIncidence of CIN (%)Incidence of CIN (%) 13.6%13.6% 1.7%1.7% 0.020.02Incidence of CINIncidence of CIN(↑SCr 0.5 mg/dL)(↑SCr 0.5 mg/dL)11.9%11.9% 1.7%1.7% 0.030.03Merten GJ et al.Merten GJ et al. JAMA,JAMA, 2004;291:2328-23342004;291:2328-2334
    27. 27. REMEDIAL TrialREMEDIAL TrialSaline + NACSaline + NACN=118N=118Bicarbonate + NACBicarbonate + NACN=117N=117Saline+AA+NACSaline+AA+NACN=116N=1167 excluded7 excludedPts with eGFR<40Pts with eGFR<40N=393N=393Randomized N=351Randomized N=351Excluded N=42Excluded N=42NAC =NAC = NN-acetylcysteine, AA = ascorbic acid-acetylcysteine, AA = ascorbic acid9 excluded9 excluded9 excluded9 excluded107 included107 includedinto analysisinto analysis108 included108 includedinto analysisinto analysis111 included111 includedinto analysisinto analysisBriguorio C. et al,Briguorio C. et al, CirculationCirculation 20072007
    28. 28. REMEDIAL Trial: ResultsREMEDIAL Trial: ResultsSaline + NACBicarbonate +NACSaline +Ascorbic Acid+ NACP ValueN=111 N=108 N=107Serum creatinineincrease by ≥25%11 (9.9%) 2 (1.9%)* 10 (10.3%) 0.010Serum creatinineincrease by ≥0.5 mg/dL12 (10.8%) 1 (0.9%)† 12 (11.2%) 0.026eGFR 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 groupBriguorio C. et al,Briguorio C. et al, CirculationCirculation 20072007
    29. 29. MEENAMEENADesignDesign• DESIGN: Prospective,randomized, parallel-group,single-center clinical evaluationof two hydration strategies forpatients undergoing coronaryangiography• OBJECTIVE: To compare theincidence of CIN betweenperiprocedural hydration withsodium bicarbonate vs. sodiumchloride (0.9%, normal saline)• PRIMARY ENDPOINT:Decrease in estimated GFR by ≥25% within 4 days of coronaryangiography353 patients enrolled between January 2006and January 2007353 patients enrolled between January 2006and January 2007236 patientsassigned to sodiumchloride236 patientsassigned to sodiumchloride178 patientsassigned to sodiumbicarbonate178 patientsassigned to sodiumbicarbonate156 evaluablepatient156 evaluablepatientBrar, S et. al., i2/ACC 2007147 evaluablepatient147 evaluablepatient22excluded22excluded28excluded28excludedHydration ProtocolHydration Protocol•3 mL/kg for 1 hr before the procedure•1.5 mL/kg during and for 4hrs post-procedureHydration ProtocolHydration Protocol•3 mL/kg for 1 hr before the procedure•1.5 mL/kg during and for 4hrs post-procedure
    30. 30. MEENAMEENAp = 0.97p = 0.97p = 0.82p = 0.82
    31. 31. Sodium BicarbonateSodium BicarbonateStudyStudy NN(Saline, Bicarb)(Saline, Bicarb)ProcedureProcedure BaselineBaselineFunctionFunction(mL/min/(mL/min/1.73m2)1.73m2)Fluid protocolFluid protocol CIN rateCIN rate(%)(%)ppRANDOMIZEDRANDOMIZEDBrarBrar 353353(175, 178)(175, 178)CardiacCardiac 48484848SalineSalineBicarbonateBicarbonate13.613.613.513.50.970.97BriguoriBriguori 219219(108, 111)(108, 111)CardiacCardiacPeripheralPeripheral32323535SalineSalineBicarbonateBicarbonate9.99.91.91.90.020.02MertenMerten 119119(59, 60)(59, 60)CardiacCardiacPeripheralPeripheral45454141SalineSalineBicarbonateBicarbonate13.713.71.71.70.020.02Masuda*Masuda* 5959(29, 30)(29, 30)EmergencyEmergencycardiaccardiac39394040SalineSalineBicarbonateBicarbonate3535770.010.01NON-RANDOMIZEDNON-RANDOMIZEDCARECARE 414414(246, 168)(246, 168)CardiacCardiac 50505050BicarbonateBicarbonate(-NAC)(-NAC)BicarbonateBicarbonate(+NAC)(+NAC)10.610.611.911.9NSNS
    32. 32. N-ACETYLCYSTEINE (NAC)N-ACETYLCYSTEINE (NAC)
    33. 33. 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 (75ml 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: creatinineincrease of 0.5 mg/dlincrease of 0.5 mg/dl• Hydration with 0.45% @ 1Hydration with 0.45% @ 1ml/kg/h x 24 hml/kg/h x 24 h21%2%0%5%10%15%20%25%Control (42) AC (41)CIM(%)TepelTepel NEJMNEJM 20002000p= 0.01p= 0.01
    34. 34. Zagler et al. Am Heart J 2006;151:140-145.Relative Risk for Developing CIN after NACRelative Risk for Developing CIN after NACRisk Ratio (Random)Risk Ratio (Random)95% Cl95% Cl0.10.1 11 1010Favors treatmentFavors treatment Favors controlFavors control0.20.2 0.50.5 22 55RR (Random)RR (Random)95% Cl95% ClControlControln/Nn/NNACNACn/Nn/NStudy orStudy orsubsturysubsturyReview:Review: Acetylcysteine and CINAcetylcysteine and CINComparison:Comparison: 01 NAC on CIN01 NAC on CINOutcome:Outcome: 01 CIN01 CINTotal 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)
    35. 35. 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 CRIpatientspatients• For CRI, NNT=8 (treat 8 toFor CRI, NNT=8 (treat 8 toprevent 1 CIN case)prevent 1 CIN case)• Low osmolal groupLow osmolal groupincluded Ioxaglateincluded Ioxaglate(Hexabrix); Iodixanol(Hexabrix); Iodixanol(Visipaque) not studied(Visipaque) not studiedBarrett and CarlisleBarrett and Carlisle J Am Soc NephrolJ Am Soc Nephrol 92;92;1.00.610.00.20.40.60.81.01.2High Osm Low OsmRelativeRiskofCIN
    36. 36. The NEPHRIC StudyThe NEPHRIC StudyNephrotoxicity in High-risk PatientsNephrotoxicity in High-risk Patientsa Double Blind Randomized Multicentrea Double Blind Randomized MulticentreStudy of Iso-osmolar and Low-osmolarStudy of Iso-osmolar and Low-osmolarNon-ionic Contrast MediaNon-ionic Contrast Media
    37. 37. 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 creatinineconcentration @ 3 days after angiographyconcentration @ 3 days after angiographyPatients with diabetes and serum creatinine 1.5-3.5 mg/dl whoPatients with diabetes and serum creatinine 1.5-3.5 mg/dl whounderwent coronary or aortofemoral angiographyunderwent coronary or aortofemoral angiographyIso-osmolar, non-ionicIso-osmolar, non-ionicIodixanol [Visipaque]Iodixanol [Visipaque]N=64N=64Mean Contrast Volume = 163 mlMean Contrast Volume = 163 mlPTCA – 17%PTCA – 17%Low-osmolar, non-ionicLow-osmolar, non-ionicIohexol [Omnipaque]Iohexol [Omnipaque]N=65N=65Mean Contrast Volume =Mean Contrast Volume = 162 ml162 mlPTCA – 25%PTCA – 25%Aspelin P et al,Aspelin P et al, NEJMNEJM, 2003; 348: 491-499, 2003; 348: 491-499
    38. 38. 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=0.002IodixanolIodixanol(Visipaque)IohexolIohexol(Omnipaque)n=62n=62 n=64n=64MeanMean 11.2 ±19.711.2 ±19.7 41.5 ± 68.641.5 ± 68.6MinimumMinimum - 19.0- 19.0 - 21.0- 21.0MaxMax 74.074.0 331.0331.0
    39. 39. RECOVER Trial – Renal Toxicity Evaluation and ComparisonRECOVER Trial – Renal Toxicity Evaluation and ComparisonBetween Visipaque and Hexabrix in Patients With RenalBetween Visipaque and Hexabrix in Patients With RenalInsufficiency Undergoing Coronary AngiographyInsufficiency Undergoing Coronary AngiographyJo et al. JACC 2006; 48:924-30Prospective, randomized trialProspective, randomized trial300 patientswith CrCl ≤ 60 ml/min149 pts. (135 pts. includedin primary analysis)ioxaglate151 pts. (140 pts. includedin primary analysis)iodixanolPrimary endpoint – Incidence of CINIncrease in SCr ≥ 25% or ≥ 0.5 mg/dl
    40. 40. RECOVER Trial – Incidence of CINRECOVER Trial – Incidence of CINJo et al. JACC 2006; 48:924-3017.0%7.9%0.0%10.0%20.0%CINioxaglateiodixanolP=0.021P=0.021N=300
    41. 41. 24.2%16.2%0%10%20%30%Ioxaglate IodixanolICONICON TTrialrialPatientsPatients wwithith cchronichronic rrenalenal iinsufficiencynsufficiencyuundergondergoinging PCIPCI wwith atith at lleast 150cc ofeast 150cc of ccontrastontrast vvolumeolumePatientsPatients wwithith cchronichronic rrenalenal iinsufficiencynsufficiencyuundergondergoinging PCIPCI wwith atith at lleast 150cc ofeast 150cc of ccontrastontrast vvolumeolumeIoxaglateIoxaglateN=74N=74IoxaglateIoxaglateN=74N=74IodixanolIodixanolN=71N=71IodixanolIodixanolN=71N=71NN=130=130P=0.26P=0.26Incidence of CINMehran R. et al, Transcatheter Cardiovascular Therapeutics.2006.
    42. 42. Rehospitalization with Renal Failure as aRehospitalization with Renal Failure as aPrimary DiagnosisPrimary DiagnosisLiss et al. Kidney International 20060.02% 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 3monthsIoxaglateIodixanol P<0.001P<0.001P<0.001P<0.001P=0.022P=0.022
    43. 43. Start of Dialysis after CoronaryStart of Dialysis after CoronaryAngiography or PCIAngiography or PCILiss et al. Kidney International 20060.00%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 monthsIoxaglateIodixanolP=0.098P=0.098P=0.010P=0.010P=0.009P=0.009
    44. 44. 1-year Follow-up1-year Follow-upLiss et al. Kidney International 2006* Groups differ intime period !CMCM N of ptsN of ptsiodixanoliodixanol 54 61654 616ioxaglateioxaglate 24 47924 479** iohexoliohexol 6 8546 854Renal failureRenal failureIodixanolIohexolIoxaglatefTime (years)%65432100 1 2 3 4 5 6 7 8 9 10 11 12
    45. 45. CARECAREDesignDesign• DESIGN: Prospective,randomized, double-blind,parallel-group, multi-centerclinical evaluation ipamidol-370and iodixanol-320• OBJECTIVE: To compare theincidence of CIN betweeniopamidol-370 and iodixanol-320• PRIMARY ENDPOINT:Increase in SCr ≥  0.5 mg/dL frombaseline to 45 to 120 hours afteradministration482 patients enrolled between July 2005 andJune 2006 in 25 clinical site in NorthAmerica482 patients enrolled between July 2005 andJune 2006 in 25 clinical site in NorthAmerica14 patients withdrewconsent14 patients withdrewconsent468 assigned to a treatment arm468 assigned to a treatment arm236 patientsassigned toIodixanol-320236 patientsassigned toIodixanol-320230 patientsassigned toIopamidol-370230 patientsassigned toIopamidol-370204 evaluablepatient204 evaluablepatientSolomon, RJ et. al., Circulation 115, 3189 (2007)210 evaluablepatient210 evaluablepatient26excluded26excluded26excluded26excluded
    46. 46. CARECAREp = 0.39p = 0.39 p = 0.44p = 0.44 p = 0.15p = 0.15
    47. 47. CARECAREp = 0.11p = 0.11 p = 0.37p = 0.37 p = 0.20p = 0.20Diabetic SubgroupDiabetic Subgroup
    48. 48. Figure. Strategy for Management of Patients With Risk Factors for Contrast-InducedNephropathy *See Box for listing of risk factors for contrast-induced nephropathy.Pannu, N. et al. JAMA 2006;295:2765-2779
    49. 49. Conclusions (1)Conclusions (1)• CRI is one of the most important independentCRI is one of the most important independentpredictors of poor outcome post PCIpredictors of poor outcome post PCI• CIN remains a frequent source of acute renalCIN remains a frequent source of acute renalfailure and is associated with increased morbidityfailure and is associated with increased morbidityand 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 ascareful post procedure management should becareful post procedure management should beroutine in all patientsroutine in all patients
    50. 50. 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 definitivedatadata• 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 requiresfurther investigationfurther investigation• Role of Cooling Therapy is being examined: COOL CIN StudyRole of Cooling Therapy is being examined: COOL CIN Study
    51. 51. 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.

    ×