Contrast Induced Nephropathy: Predictors, Prevention, and Management

1. Contrast Induced Nephropathy: Predictors, Prevention, and Management

2. Disclosures:Research Grant to CRF: Tyco, GuerbertConsultant/ Advisory Board:FlowMedica How to prevent CIN?How to prevent CIN?

3. Cardiorenal Risk There is a strong bidirectional association between cardiac diseases and renal insufficiency. There is a strong bidirectional association between cardiac diseases and renal insufficiency.

4. How to Assess Renal Function?

5. Predictors of All-Cause Mortality to 7 Years BARI Trial + Registry In multiple clinical trials and analyses, and you see just one of them, CKD represented the most significant independent predictor of long-term mortality.In multiple clinical trials and analyses, and you see just one of them, CKD represented the most significant independent predictor of long-term mortality.

6. Risk Factors for CIN Patient-related Risk Factors Renal insufficiency Diabetes mellitus withrenal insufficiency Age Volume depletion Hypotension Low cardiac output Class IV CHF Other nephrotoxins Renal transplant Hypoalbuminemia (<35 g/l) Procedure-related Risk Factors Multiple contrast media injection within 72 hrs Intra-arterial injection site High volume of contrast media High osmolality of contrast media Risk factors for CIN maybe divided into patient-related and procedure-related. Patient-related factors includeRenal insufficiency Diabetes mellitus withrenal 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 Risk factors for CIN maybe divided into patient-related and procedure-related. Patient-related factors includeRenal insufficiency Diabetes mellitus withrenal 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

7. Scheme to Define CIN Risk Score 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.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.

8. CIN Risk Score & 1-year Mortality We also found a strong relationship between 1-year mortality and risk score of CIN.We also found a strong relationship between 1-year mortality and risk score of CIN.

9. Preventive Trials How to prevent CIN?How to prevent CIN?

10. Hydration

11. Optimal Hydration Regimen

12. Optimal Hydration0.9% NS vs 0.45% NS

13. Prevention of CIN with Sodium Bicarbonate

14. Prevention of CIN with Sodium Bicarbonate: Results

15. REMEDIAL Trial

16. REMEDIAL Trial: Results

17. MEENA

18. MEENA

19. Sodium Bicarbonate

20. N-ACETYLCYSTEINE (NAC)

21. CIN: Effect of n-Acetylcysteine Prospective, randomized 83 high risk patients CrCl < 50 ml/min Diabetes 33% IV CONTRAST for CT (75 ml of Low Osmolar CM) n-AC 600 bid x 2 days pre- CIN definition: creatinine increase of 0.5 mg/dl Hydration with 0.45% @ 1 ml/kg/h x 24 h 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. 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.

22. N- acetylcysteine (NAC) and Contrast-induced Nephropathy: a Meta-analysis of 13 Randomized Placebo Controlled Trials

23. Relative Risk for Developing CIN after NAC

24. Meta-analysis: High vs.Low Osm Contrast Media 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.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.

25. The NEPHRIC Study Nephrotoxicity in High-risk Patientsa Double Blind Randomized Multicentre Study of Iso-osmolar and Low-osmolar Non-ionic Contrast Media

26. NEPHRIC Study: Protocol Randomized, double blind, prospective, multicenter Primary endpoint: peak increase in serum creatinine concentration @ 3 days after angiography

27. Primary Endpoint �Peak Increase in Scr from Baseline to Day 3

28. RECOVER Trial � Renal Toxicity Evaluation and Comparison Between Visipaque and Hexabrix in Patients With Renal Insufficiency Undergoing Coronary Angiography

29. RECOVER Trial � Incidence of CIN

30. ICON Trial

31. Renal Failure in Patients Undergoing Coronary Procedures using Iso-osmolar or Low-osmolar Contrast Media

32. Rehospitalization with Renal Failure as a Primary Diagnosis

33. Start of Dialysis after Coronary Angiography or PCI

34. 1-year Follow-up

35. CARE

36. CARE

37. CARE

38. Conclusions (1) CRI is one of the most important independent predictors of poor outcome post PCI CIN remains a frequent source of acute renal failure and is associated with increased morbidity and mortality, and higher resource utilization Several factors predispose patients to CIN Preventive measures pre procedure, as well as careful post procedure management should be routine in all 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)

39. Conclusions (2) Hydration pre-PCI (12 hours recommended) D/C nephrotoxic drugs (NSAIDS, antibiotics, etc) Role of n-acetylcysteine is disputable No Role for IV Fenoldopam Sodium bicarbonate may be useful, but need more definitive data Limit contrast agent volume Low-osmolar agents are better than high-osmolar Within non-ionic contrast, the data are contradictory Role of local drug delivery for prevention of CIN requires further investigation Role of Cooling Therapy is being examined: COOL CIN Study 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)