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Mujeeb Sheikh
Kidney in CV disease Cardiorenal overlap CKD is important independent predictor of mortality  in patients with CAD (BERR...
Kidney in CV disease Acute Renal failure    Contrast induced nephropathy(CIN)    Postbypass ARF CIN is now the 3rd lea...
BASIC PRINCIPLES OF CONTRAST MEDIA
Contrast Media classification
Contrast media used in Cath Lab
Contrast Pharmacology Contrast sole function is to attenuate X-ray Radio-opacification achieved by given volume of  cont...
Side effects of contrast Allergic reaction      Non IgE mediated      Ionic>Nonionic,(0.27%, SCAI registry)     Ioxoglate...
Pathophysiology of CIN
Contrast Media Induce Medullary Hypoxia                           A temporary increase in renal transport work            ...
CI-AKI or CINDefinition: New onset acute kidney injury (absolute Cr rise 0.5 mg- 1  mg/dl or relative, 25%-50% from basel...
Epidemiological Issues Small numbers – not mega RCT Varying treatments used    Differing hydration regimens Varying de...
CIN definition in clinical trials
CIN-definition
McCullough PA, Am J Med 1997
Incidence Incidence ranges from 1%-35% Low risk population incidence is 1.5% Mayo retrospective series evaluated 7852 p...
RISK FACTORSNon modifiable   Modifiable CKD             Volume depletion DM              Volume of contrast Age(>75yr...
CIN and High risk groups Baseline Cr < 2.0 mg/dl, diabetic patients had higher  risk of ARF than nondiabetic pts   Cr < ...
Predictors of ARF requiring dialysisafter PCI                                             Mean contrast vol               ...
OUTCOMES OF CIN
CIN & Mortality Retrospective case control  study of 16,248 hospitalized  patients who received  contrast Cases with CIN...
CIN after PCI & MortalityDerivation-validationmethod in 1800 patiensIncidence of CIN 14% and  ARF requiring HD was7.7%M...
Clinical outcomes of CIN patientsrequiring HD after PCI                                     Long-term outcome   Gruberg L ...
Long term outcome of CIN Mayo retrospective series  evaluated 7852 pts. who had  undergone cath /PCI found  an incidence ...
Prognostic implications of CINfollowing PCI in pts with CKD 439 pts with baseline serum cr. > 1.8 All well hydrated, all...
CIN prognosis after PCI in CKDIn hospital outcome                    One year outcome          No Cr Rise   25% Cr        ...
CIN and long term mortality Gruberg et al, 2000
Predicting CIN Developmental data  set(n=8752) Validation data  set(n=2786) Multivariate logistic  regression to identi...
RISK SCORE
CIN risk score & HD
CIN and I yr Mortality
PREVENTING CONTRAST INDUCED        NEPHROPATHY
CIN Prevention(literature review)                                                   35                                    ...
Post intervention prevention ofCIN-AKI Failed agents for prevention/mitigation of contrast- induced nephropathy   Calciu...
What is optimal hydration?           Dal lake, Kashmir
Hydration RegimenHydration started at 8am on the day ofelective cath andcontinued for another12 hrs (1ml/kg) aftercath.Pts...
NS vs.0.45NS
Prevention of CIN with sodium bicarbonate                                          Baseline Cr >1.8mg/dl                  ...
Results (primary endpoint)                    Sodium        Sodium     P value                    bicarbonate   chloride  ...
MEENA study (N=400)
N-Acetylcysteine (NAC) Prospective RCT 83 high risk pts Cr Cl <50ml/min Diabetes 33% IV contrast CT (low  osmolal,75m...
NAC & PCI N=79 Mean Cr 2.3mg/dl                     *APART trial n=45 All received hydration               Mean Cr 1.6mg/d...
NAC & relative risk    META-ANALYSIS of 7 RCT Birke et al., Lancet 2003
Does type of contrast matter?                                  Patients with diabetes and CKD                             ...
ResultsCr (µmol),P=0.002
Renal failure in pts undergoing coronary procedures using Iso-Osmolar or Low Osmolar CM Swedish coronary angiography    a...
Rehospitilization with ARF as theprimary diagnosis
Long term Results                    * Groups differ in time period
“Adjusted” contrast dose Michigan Data Base- 16,592    PCI’s   Developmental, validation data    set   MRCD = 5cc X bod...
Adjusted contrast dose
Take home points Contrast-Induced Nephropathy is a common  complication in higher-risk patients Even with chemical resol...
Recommendations
 THANK YOU
Contrast induced-Acute Kidney Injury
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Contrast induced-Acute Kidney Injury

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Cardiology Grand rounds/UTMC

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Contrast induced-Acute Kidney Injury

  1. 1. Mujeeb Sheikh
  2. 2. Kidney in CV disease Cardiorenal overlap CKD is important independent predictor of mortality in patients with CAD (BERRY trial) Even in absence of CV risk factors, pts with renal insufficiency have elevated risk of CV disease Mild elevation in CR(>1.5mg/dl) are associated with development of CV events Microalbuminuria is independent risk factor for CV events, with RR higher than serum Cr ( 1.59 vs. 1.40) Hall Wo et al Am J Med Sci ,1999 Mann JF et al, Ann Intern Med 2001
  3. 3. Kidney in CV disease Acute Renal failure  Contrast induced nephropathy(CIN)  Postbypass ARF CIN is now the 3rd leading cause of in-hospital ARF* CIN in patients with PCI  Poor procedural success  Longer hospital stay and increased mortality * Nash et al , Am J kidney Dis ,2002;39:930
  4. 4. BASIC PRINCIPLES OF CONTRAST MEDIA
  5. 5. Contrast Media classification
  6. 6. Contrast media used in Cath Lab
  7. 7. Contrast Pharmacology Contrast sole function is to attenuate X-ray Radio-opacification achieved by given volume of contrast is function of iodine concentration Rough estimate : 125 ml contrast = 500ml of plasma volume expansion Excreted by kidney exclusively Anticoagulant and antiplatelet effect of CM has no clinical relevance
  8. 8. Side effects of contrast Allergic reaction Non IgE mediated Ionic>Nonionic,(0.27%, SCAI registry) Ioxoglate (Hexabrix) significantly higher allergic reaction as compared to Iopamidol (Isovue) * Cardiovascular Electrophysiological Heart blocks Arrhythmias Hemodynamic Vasodilatation (hypotension) Increased volume overload * Gertz et al, JACC,1992;19:899-906
  9. 9. Pathophysiology of CIN
  10. 10. Contrast Media Induce Medullary Hypoxia A temporary increase in renal transport work in the thick ascending limb of Henles loop ( in oxygen consumption) + Constriction of medullary capillaries ( in medullary oxygen delivery) LEAD TO MEDULLARY ANGINA Solomon, et al. Kidney Int 1998; 230-242
  11. 11. CI-AKI or CINDefinition: New onset acute kidney injury (absolute Cr rise 0.5 mg- 1 mg/dl or relative, 25%-50% from baseline) after contrast administration and in the absence of other etiologyTime course of CI-AKI: Occurs after 24-48 hrs of contrast Cr peaks in 3-5days and normalizes in 7-10 days(70%) In 30%, 3 weeks to return baseline or progress to CKD Predominantly non-oliguric AKI and with mild proteinuria
  12. 12. Epidemiological Issues Small numbers – not mega RCT Varying treatments used  Differing hydration regimens Varying definitions  Outcomes vary by definitions How much of CIN is due to contrast?  Atheroembolism, hemodynamics  Cause and effect???
  13. 13. CIN definition in clinical trials
  14. 14. CIN-definition
  15. 15. McCullough PA, Am J Med 1997
  16. 16. Incidence Incidence ranges from 1%-35% Low risk population incidence is 1.5% Mayo retrospective series evaluated 7852 pts. who had undergone cath /PCI found an incidence of 3.3% *  ARF defined as 0.5 mg/dl  Baseline Cr was predictor * Rihal CS et al, Circulation 2002
  17. 17. RISK FACTORSNon modifiable Modifiable CKD  Volume depletion DM  Volume of contrast Age(>75yr)  Multiple injection of contrast Class IV CHF within 72 hrs Renal tx  Intraarterial vs. intravenous ?  High osmolal contrast (Not used anymore)
  18. 18. CIN and High risk groups Baseline Cr < 2.0 mg/dl, diabetic patients had higher risk of ARF than nondiabetic pts  Cr < 1.1(risk 3.7 % vs 2.0%, p=0.05)  Cr 1.2-1.9(risk 4.5% vs 1.9%, p<0.001) Baseline Cr > 2.0 mg/dl, risk high regardless of diabetes status  Cr. 2.0-2.9 mg/dl, risk 22.4%  Cr > 3 mg/dl, risk 30.6%
  19. 19. Predictors of ARF requiring dialysisafter PCI Mean contrast vol 250cc,(Cath+ PCI) Mean age 65yrs Predictors of CIN Crcl >DM> contrast dose
  20. 20. OUTCOMES OF CIN
  21. 21. CIN & Mortality Retrospective case control study of 16,248 hospitalized patients who received contrast Cases with CIN(n=183) matched with controls(n=174)  Matched for baseline creatinine  APACHE score Levy EM,JAMA 1995
  22. 22. CIN after PCI & MortalityDerivation-validationmethod in 1800 patiensIncidence of CIN 14% and ARF requiring HD was7.7%Multivariate predictors:CrCl, diabetes and contrastdoseNo case of CIN in patientswith contrast dose of <100ml McCullough PA et al, Am J Med,1997
  23. 23. Clinical outcomes of CIN patientsrequiring HD after PCI Long-term outcome Gruberg L et al Cath Cardiovasc Interv, 2001
  24. 24. Long term outcome of CIN Mayo retrospective series evaluated 7852 pts. who had undergone cath /PCI found an incidence of 3.3%  ARF defined as 0.5 mg/dl  CIN was related to baseline serum Cr and diabetes Rihal CS et al Circ 2002
  25. 25. Prognostic implications of CINfollowing PCI in pts with CKD 439 pts with baseline serum cr. > 1.8 All well hydrated, all received non ionic dye 161 pts(37%) had increase in serum cr > 25% and 278(63%) did not
  26. 26. CIN prognosis after PCI in CKDIn hospital outcome One year outcome No Cr Rise 25% Cr No Cr Rise 25% Cr P<0.001 P<0.001 28.7%30% 50% P<0.001 40% 37.7% P=NS20% 15.9% P=NS 14.9% 30% 23.6% 21.4% 19.4% 20% 13.4%10% 12.4% 4.9% 10% 0% 0% Death Non-Q MI Death MI TLR Gruberg et al JACC, 2000
  27. 27. CIN and long term mortality Gruberg et al, 2000
  28. 28. Predicting CIN Developmental data set(n=8752) Validation data set(n=2786) Multivariate logistic regression to identify variables, p<0.0001 C statistics 0.67Mehran et al JACC,2000
  29. 29. RISK SCORE
  30. 30. CIN risk score & HD
  31. 31. CIN and I yr Mortality
  32. 32. PREVENTING CONTRAST INDUCED NEPHROPATHY
  33. 33. CIN Prevention(literature review) 35 randomized control trial 56 review articles& comments No FDA approved therapy for prevention or treatment
  34. 34. Post intervention prevention ofCIN-AKI Failed agents for prevention/mitigation of contrast- induced nephropathy  Calcium channel antagonists  adenosine antagonists  dopamine  Mannitol  Furosemide  Endothelin-receptor antagonists
  35. 35. What is optimal hydration? Dal lake, Kashmir
  36. 36. Hydration RegimenHydration started at 8am on the day ofelective cath andcontinued for another12 hrs (1ml/kg) aftercath.Pts encouraged todrink fluids Mueller et al Arch intern med ,2002
  37. 37. NS vs.0.45NS
  38. 38. Prevention of CIN with sodium bicarbonate Baseline Cr >1.8mg/dl Iopamidol contrast usedRegimen N=1373ml/kg bolus for 1hrbefore & 1ml/kg 6hr after Sodium chloride Sodium bicarbonate N=68 N=69 Primary Endpoint was increase in serum Cr >25% Merten et al, JAMA2004
  39. 39. Results (primary endpoint) Sodium Sodium P value bicarbonate chloride (N=60) (N=59) CIN % 1.7 % 13.6% 0.02 CIN (^ 0.5mg/dl) 1.7% 11.9% 0.03
  40. 40. MEENA study (N=400)
  41. 41. N-Acetylcysteine (NAC) Prospective RCT 83 high risk pts Cr Cl <50ml/min Diabetes 33% IV contrast CT (low osmolal,75ml) NAC 600mg BID X 2 days Hydration 0.45 saline at 1ml/kg Tepel, NEJM 2000
  42. 42. NAC & PCI N=79 Mean Cr 2.3mg/dl *APART trial n=45 All received hydration Mean Cr 1.6mg/dl NAC 600mg q12 x4 doses, before NAC IV before PCI and 3 doses BID PCI after PCI P=NSCaputo Am j kidney Dis, 2000 * Diaz-Sandoval et al Am J Cardiol 2002
  43. 43. NAC & relative risk META-ANALYSIS of 7 RCT Birke et al., Lancet 2003
  44. 44. Does type of contrast matter? Patients with diabetes and CKD (1.5-3.5 mg/dl) NEPHRIC STUDY Undergoing coronary angiography/Aortofemoral angiography Iso-Osmolol, Nonionic Low Osmolar, Nonionic Iodixanol N=64 Iohexinol N=65 Mean contrast vol. 163 ml Mean contrast vol.162 ml PCI Randomized control trial Primary endpoint was CIN Serum Cr at 72 hrs after Cath Aspelin ,NEJM 2003
  45. 45. ResultsCr (µmol),P=0.002
  46. 46. Renal failure in pts undergoing coronary procedures using Iso-Osmolar or Low Osmolar CM Swedish coronary angiography and angioplasty registry Swedish hospital discharge registry Only included diabetic and CKD pts Only pts receiving PCI Also patients receiving iohexol fr0m 1999-2003 Mean contrast volume: iodixanol: 138±89 ml vs. ioxaglate: 147±105 mlLiss et al., kidney International 2006
  47. 47. Rehospitilization with ARF as theprimary diagnosis
  48. 48. Long term Results * Groups differ in time period
  49. 49. “Adjusted” contrast dose Michigan Data Base- 16,592 PCI’s Developmental, validation data set MRCD = 5cc X body weight (kg)/serum cr. MRCD ratio= total contrast vol./MRCD NRD(0.44 %, 0.35%), mortality(39%, 26%) Unadjusted contrast dose not a univariate predictor AJC 2002; 90: 1068-1073
  50. 50. Adjusted contrast dose
  51. 51. Take home points Contrast-Induced Nephropathy is a common complication in higher-risk patients Even with chemical resolution of CIN and a return of serum creatinine towards baseline, the 1-year mortality remains over 25%, making prevention mandatory in higher-risk patients High-risk characteristics include renal insufficiency (Cr > 1.5 mg/dL) diabetes and contrast dose Pathophysiology of CIN seems to involve contrast- induced renal medullary ischemia
  52. 52. Recommendations
  53. 53.  THANK YOU

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