Contrast-Induced Nephropathy: Evidenced Based Prevention

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1 Contrast-Induced Nephropathy: Evidenced Based Prevention Michael J Cowley, MD, FSCAI Nothing to disclose

2 Contrast-Induced Nephropathy (CIN) Definitions New onset or worsening of renal function after contrast administration without other identifiable causes: of serum creatinine by >25% from baseline or absolute of >0.5 mg/dl ( 44.2 mol/l) Time course predictable: Onset hrs after exposure Peak Cr at 3-5 days Return to baseline in 1-2 wks (~ 10 days)

3 Contrast-Induced Nephropathy Incidence of CIN depends on Definition used % Incidence N=1826 consecutive pts undergoing PCI Cr Rise >25% 14.5 Cr Rise >50% Doubling Cr Rise > 1 mg/dl Post Cr >5 or dialysis Definition of Renal Outcome McCullough P: Am J Med 1997;103:368-75

4 Kidney Disease Outcome Quality Initiative Classification of Renal Function Stage I Stage II Stage III Stage IV Stage V CKD Risk Factors/Damage with Preserved GFR Mild Kidney Dysfunction Moderate Kidney Dysfunction Severe Kidney Dysfunction Kidney Failure ESRD Estimated GFR Am J Kid Disease, Feb 2002, Supplement

5 Contrast-Induced Nephropathy* In-hospital Mortality % 40 p < No ARF ARF Dialysis *CIN= Cr > 0.5 mg/dl McCullough et al: Am J Med 1997; 103:

7 CIN and Follow-Up Outcome 84% 61%

8 Contrast Nephropathy (CIN) Risk Score Risk Factors Integer Score Hypotension 5 IABP 5 CHF Age >75 years 5 4 Risk Score Risk of CIN Risk of Dialysis Anemia % 0.04% Diabetes Contrast Volume 3 1 for each 100 cc 3 Calculate % 0.12% Serum Cr > 1.5mg/dl 4 OR egfr <60ml/min/1.73 m 2 2 for for for < % 1.09% % 12.6% egfr < 60ml/min/1.73 m 2 = 186 x (SCr) x (Age) X (0.742 if female) x (1.210 if African American) Mehran R et al J Am Coll Cardiol 2004; 44:

9 Risk Score for Contrast-Induced Nephropathy % Incidence of CIN CIN Dialysis Risk Score Low Moderate High Very High < >16 Mehran R et al: J Am Coll Cardiol 2004; 44:

10 Risk Score for Contrast-Induced Nephropathy 50 1 Year Mortality % Risk Score Low Moderate High Very High < >16 Mehran R et al J Am Coll Cardiol 2004; 44:

11 Mechanisms for Contrast-Induced Nephropathy Contrast agents cause renal vasodilation then vasoconstriction High osmolality causes greater vasoconstriction Vasoconstriction causes hypoxia in renal medulla Hypoxia causes of oxidative free radical production CIN mediated by formation of oxidative free radicals

Medullary Hypoxia Following Contrast Administration 34 HCO 3 ~24 ph~7.25 28 HCO 3 ~12 O 2 50 mmhg HCO 3 ~7 ph~6.0 O 2 10-20 mmhg PaO 2 (mmhg) 22 Factors Contributing to CIN 1.

12 Medullary Hypoxia Following Contrast Administration 34 HCO 3 ~24 ph~ HCO 3 ~12 O 2 50 mmhg HCO 3 ~7 ph~6.0 O mmhg PaO 2 (mmhg) 22 Factors Contributing to CIN 1. Contrast-induced vasoconstriction 2. Medullary hypoxia (po 2 ~10-20 mmhg) 3. Low medullary ph (~6.0), increasing: free radical ( OH) formation superoxide (O 2- ) formation HCO 3 ~0 ph~5.5 HCO 3 ~24-30 ph~7.4 Liss P et al Kidney Int 1998; 53: Ringers Iopromide Ioxaglate Iotrolan Minutes

13 Prevention of Contrast Nephropathy Avoid nephrotoxic drugs Minimize contrast volume Use low or iso-osmolar contrast agent Hydration (target Urine output >150 ml/hr for 6 hrs post procedure

14 Prevention of Contrast Nephropathy Avoid nephrotoxic drugs Minimize contrast volume Use low or iso-osmolar contrast agent Hydration (target Urine output >150 ml/hr for 6 hrs post procedure Possibly beneficial: N-acetylcysteine NaHCO3 Adenosine antagonists (aminophylline, theophylline) Hemofiltration and dialysis

15 Prevention of Contrast Nephropathy Definitely Avoid NSAIDS (both COX-1 and COX-2 inhibitors) Diuretics Aminoglycosides Cyclosporin Amphotericin B Nephrotoxic Drugs Unclear Risk ACEI/ARB

16 Catheterization and Cardiovascular Interventions 2009; 74:

17 Schweiger M, et al: Cathet Cardiovasc Interventions 2007; 69:

18 Risk Factors for CIN Impaired renal function (egfr<60*) Advanced age Diabetes Hemodynamic instability Anemia Volume depletion Nephrotoxic medications Large contrast media volume exposure * ml/min/1.73m 2

19 Strategies for Prevention of CIN Generally Accepted Measures Volume repletion Use low osmolarity contrast media Minimize contrast volume Hold concomitant nephrotoxic drugs Klein L: CCI 2009

20 Contrast Volume and CIN Predictors of Safe Contrast Volume 1) Contrast volume to Creat clearance ratio (V/CrCl)* - Ratio > 3.7 is good predictor of CIN 2) Max Contrast dose (MCD)** = 5 x wt [kg] / serum Cr 3) CV/CCC*** (Calculated Cr Cl)<2-3 - Calculate target contrast dose using these formulae - Try not to exceed the calculated maximal contrast dose * Laskey WK et al: J Am Coll Cardiol 2007;50: ** Marenzi G et al Ann Intern Med 2009; 150: *** Gurm H: JACC 2011; 58:

22 Contrast Volume to CrCl Ratio Cr >0.5 mg/dl after PCI was considered abnormal CrCl (Cockcroft-Gault method): CrCl (ml/min) = Age (yrs) x wt (kg)/72 x scr (mg/dl) { 0.85 for females} Laskey W: Cathet Cardiovasc Interv 2007;69:

23 Contrast Volume vs CIN V / CrCl < 3.7 GFR Max Contrast Volume Laskey WK et al: J Am Coll Cardiol 2007;50:

24 Gurm H: JACC 2011; 58:

25 Safe Contrast Volume for PCI 8 Incidence of CIN % < CV/CCC >3 Gurm H: JACC 2011; 58:

26 Safe Contrast Volume for PCI Incidence of CIN Gurm H: JACC 2011; 58:

27 Safe Contrast Volume for PCI Incidence of CIN CIN + Dialysis % % < >3 0.0 < >3 CV/CCC Gurm H: JACC 2011; 58:

28 Contrast Volume and CIN 561 pts with STEMI having primary PCI Mean Cr 1.09±0.27 mg/dl (egfr<60 in 30.5%) CIN incidence (25% ): 20.5% CIN incidence (0.5 mg/dl ): 12.5% Contrast Ratio = actual contrast dose/maxcd * (MCD (ml) = 5 x wt [kg] / serum Cr (mg/dl) CIN Hosp Mortality 21.4% (vs 0.9%, p<0.001) Max CD exceeded in 130 pts (23%) Mortality (for CR>1): 13% vs 2.8% (p<0.001) Marenzi G et al Ann Intern Med 2009; 150:

29 Contrast Volume and CIN Ultra-Low Contrast Volume in CKD pts 185 pts with Stage 3-5 CKD having Cor angio All had egfr <60 ml/min All received pre-hydration and n-acetylcysteine All received iso-somolar contrast Median contrast volume = 27 ml (IQR: ml) CIN: Cr > 0.5 mg/dl Biplane angio in 114 (62%) CV = ml (vs with monoplane) Kane GC et al: J Am Coll Cardiol 2008; 51: 89-90

30 Contrast Volume and CIN High Risk (Stage 3-5) CKD pts undergoing cardiac catheterization 40 Overall Incidence of CIN = 15.1% % 30 p= ml ml ml Quartiles of Contrast Volume ml Kane GC et al: J Am Coll Cardiol 2008; 51: 89-90

31 Therapies for Prevention of CIN

32 N-Acetylcysteine for Contrast Nephropathy: Meta-Analysis of 26 Randomized Trials CIN Risk Reduction 38% (P<0.0001) Kelly, AM et al Ann Intern Med 2008;148:

33 NaHCO3 vs Saline to Prevent Contrast ATN Meta-Analysis of 12 Randomized Trials (RCT) CIN Risk Reduction 61% (p=0.008) p=0.008 Navaneethan SD et al Am J Kidney Dis 2009; 53:

35 % 10 Statins and CIN Risk N=29,409 pts with PCI; CIN = Cr > 0.5 mg/dl p< Statin No Statin p= CIN Dialysis Mean contrast volume = 220 ml Khanal S et al J Am Coll Cardiol 2004; 45(5): 420A

37 ARMYDA - CIN Effect of High Dose Atorvastatin on CIN* CIN egfr Atorva Placebo *CIN: Cr >0.5 mg or 25% from baseline Patti G: AJC 2011; 108: 1-7

38 2011 ACCF/AHA/SCAI PCI Guideline Risk Reduction for Contrast-induced AKI Recommendation COR LE Risk assessment for contrast-induced AKI I C Adequate preparatory hydration I B Minimization of contrast volume in CKD pts I B Administration of N-acetyl-L-cysteine for the prevention of contrast-induced AKI III: No Benefit A GNL 2011

39 Contrast Nephropathy CIN is an important cause of morbidity occurs in ~ 15% of pts; causes ESRD in 1% GFR <60 ml/min is threshold for risk of CIN CIN can be minimized by: Identifying patients at risk Use of generally accepted Interventions: Hydration Summary Use of low contrast volumes Avoidance of nephrotoxic medications NaHCO3 & n-acetylcysteine may also have benefit

SAFETY IN THE CATH LAB How to Minimise Contrast Toxicity

SAFETY IN THE CATH LAB How to Minimise Contrast Toxicity Dr. Vijay Kunadian MBBS, MD, MRCP Senior Lecturer and Consultant Interventional Cardiologist Institute of Cellular Medicine, Faculty of Medical