Contrast induced-Acute Kidney Injury


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  • Rct have not founf thesehematoligical effects due to cocncomitant use of antiplatelet and anticoaugs
  • Osmoality dependent lead to release of adenosine
  • To compare similar degrees of injury regardless of the baseline serum level, the relative change in serum creatinine is a preferable metric (Table 2b). With a relative change definition, all patients lose the same percentage of renal function regardless of the level of renal function at baseline. There is still a bias, however, for a smaller absolute loss of GFR to satisfy the definition of CIN when there is a lower GFR at baseline. Finally, it follows from the above discussion that in patients with milder degrees of renal insufficiency (creatinine less than 2 mg/dl), the incidence of CIN will always be less when a 0.5 mg/dl absolute increase is used as a definition compared to a 25% increase in serum creatinine. A greater loss of GFR is necessary to satisfy the definition of CIN when the absolute change in serum creatinine is used (Table 2a vs b).Which definition, absolute or relative increase in serum creatinine, reflects outcomes the best? Gruberget al.1 correlated outcomes following contrast exposure in patients who underwent cardiac catheterization. A worse outcome (at 1 year) was found in those
  • Peterm Mc cullough
  • There is no question that ccin lead to increased mortalityThis is the data from aretropective study of more than 16k pts who received contrast for any radiological procedure Odds of dying was 5 times high if cinoccured
  • How about CIN after PCI Ina study by peter mccollough the risk of inhospital mortality wasignificanlty higher in pts who had arf after pci and it was higher if they needed dialysis comapred to very low risk with no CIN
  • Thirty-one patients required hemodialysis during hospitalization.Their in-hospital mortality was 22.6%. Fourpatients were discharged on chronic dialysis. The cumulativeone-year mortality was significantly higher in patientswith renal function deterioration (37.7% vs. 19.4%, p 50.001, Table 5 and Fig. 2)—35.4% for those who did notrequire dialysis and 45.2% for those who required dialysis.Of the 17 patients who required in-hospital dialysis andwho were alive at one year, 3 required chronic dialysis.When the one-year mortality was compared with regardto the percent increase in creatinine, there was a noticeabledifference in patients with a 25% increase or greater (Fig. 3).Myocardial infarction and revascularization events weresimilar in both groupsAcute deterioration in renal function is a recognized complication after coronary angiographyand intervention.OBJECTIVES The goal of this study was to determine the impact on acute and long-term mortality andmorbidity of contrast-induced deterioration in renal function after coronary intervention.METHODS We studied 439 consecutive patients who had a baseline serum creatinine $1.8 mg/dL(159.1 mmol/L) who were not on dialysis who underwent percutaneous coronary interventionin a tertiary referral center. All patients were hydrated before the procedure, and almost allreceived ioxaglatemeglumine; 161 (37%) patients had an increase in serum creatinine $25%within 48 h or required dialysis and 278 (63%) did not. In-hospital and out-of-hospitalclinical events (death, myocardial infarction, repeat revascularization) were assessed by sourcedocumentation.RESULTS Independent predictors of renal function deterioration were left ventricular ejection fraction(p 5 0.02) and contrast volume (p 5 0.01). In-hospital mortality was 14.9% for patients withfurther renal function deterioration versus 4.9% for patients with no creatinine increase (p 50.001); other complications were also more frequent. Thirty-one patients required hemodialysis;their in-hospital mortality was 22.6%. Four patients were discharged on chronicdialysis. The cumulative one-year mortality was 45.2% for those who required dialysis, 35.4%for those who did not require dialysis and 19.4% for patients with no creatinine increase (p 50.001). Independent predictors of one-year mortality were creatinine elevation (p 5 0.0001),age (p 5 0.03) and vein graft lesion location (p 5 0.08).CONCLUSIONS For patients with pre-existing renal insufficiency, renal function deterioration after coronaryintervention is a marker for poor outcomes. This is especially true for patients who requiredialysis. (J Am CollCardiol 2000;36:1542– 8) © 2000 by the American College ofCardiologyAcute deterioration in renal function is a recognized complicationafter coronary angiography, particularly for patientswith pre-existing chronic renal insufficiency (CRI)(1– 4). Previous studies have shown that 12 to 14% ofpatients who develop acute renal insufficiency during hospitalizationdo so after procedures involving radiographiccontrast (5,6). For patients with abnormal baseline renalfunction, the incidence of progressive deterioration can be ashigh as 42% (1,7). For hospitalized, critically ill patients,this carries a poor prognosis, especially if dialysis becomesnecessary (5–10).The expanding use of diagnostic and therapeutic percutaneousinterventions makes it important to understand thepotential risks
  • Based on risk score you see that there is linear and exponential increase in the incidenc of CINFrom 7.5 to 14 to 16 and 57
  • They also found that this score predicted need for inhospital dialysis and higher score were significantly associated with need for hd
  • Prognostic significance of the score and higher score had higher one yr mortality
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  • This is alist of ailed therapies thathave been tried and they should no longer be used infact some of these therapies can cause harmHypothesis discusss
  • Interestingly you see that pts with 0.9 hydration had less cin as compared to .45When you can hydrate the pt.
  • Trial terminated earlierHad not presecified the the P and P0.02Alpha errorNonetheless it was positive trial and a s you know law of nature is for every pos trail there is one negative trial
  • Study in pts not undergoing cath or pci
  • Barrettecarlisle radiology1993
  • To convert into a dichotomous variable they used mrcd ratioAsmrcd is a continous variable and can’t comape
  • 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
    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
    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