![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](https://image.slidesharecdn.com/actualpresentationofcin-130607095025-phpapp01/85/Contrast-Induced-Nephropathy-6-320.jpg)
![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](https://image.slidesharecdn.com/actualpresentationofcin-130607095025-phpapp01/85/Contrast-Induced-Nephropathy-39-320.jpg)
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Contrast Induced Nephropathy
- 1. Contrast Induced NephropathyContrastInduced 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 AcuteRenal 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 ofliterature and papers. • Hundreds of meta-analysis of the published papers. DENIAL RESPONSE !!! Experience Vs Evidence based practice Many contradictory results
- 4. Topics for Consideration….Topicsfor 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 TestsRenalFunction 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 AssessRenal 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 CINDefinitionof 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 CININCIDENCEOF 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-CauseMortalityPredictors 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 forCINRisk 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 RiskofRisk 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 ofthe 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 Followingexposure 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 ofContrastPhysicochemical Properties of Contrast AgentsAgents Table 1. Properties of Commonly Used Radiocontrast Media.
- 18. Renal Failure inPatients 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 infusionvs Oral hydrationIV infusion vs Oral hydration • IV infusion vs IV bolusIV infusion vs IV bolus FluidsFluids
- 22. • Adenosine AntagonistsAdenosineAntagonists • 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 • AscorbicAcidAscorbic 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 RegimenOptimalHydration 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 CINwithPrevention 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 CINwith 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: ResultsREMEDIALTrial: 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 StudyStudyNN (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.
- 35. CIN: Effect ofn-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 StudyTheNEPHRIC 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 –PrimaryEndpoint – 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 PatientsPatientswwithith 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 RenalFailure 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 Dialysisafter 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 Lisset 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 forManagement 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.
Editor's Notes
- #3 There is a strong bidirectional association between cardiac diseases and renal insufficiency.
- #11 In multiple clinical trials and analyses, and you see just one of them, CKD represented the most significant independent predictor of long-term mortality.
- #12 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
- #13 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.
- #14 We also found a strong relationship between 1-year mortality and risk score of CIN.
- #36 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.
- #39 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.
- #53 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)
- #54 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)