Contrast agents and Contrast Induced Nephropathy

Contrast induced Nephropathy

1. C ontrast agents Sonali Inamdar

2. Classification of contrast agents

3. Contrast agents – function Employ iodine on a tri-iodinated benzene ring Radio- opacification achieved : function of iodine concentration

4. M aximum allowable contrast dose MACD = five times body weight (kg)/serum Cr (mg/ dL )

5. Definition CIN

6. CIN – introduction T ransient rise in serum creatinine levels : > 15% CI-AKI :   13% in nondiabetics and 20% with DM undergoing PCI 28% with ACS Single most important risk : preexisting CKD. Even mild AKI : longer hospital stays and greater inpatient costs, worse short- and long-term mortality

7. Predictors of all cause mortality to 7 years BARI trial + registry

8. Modified from James MT, Ghali WA, Knudtson ML, et al: Associations between acute kidney injury and cardiovascular and renal outcomes after coronary angiography. Circulation 123:409, 2011 .

9. PATHOGENESIS A cute tubular necrosis (ATN ) Mechanism : not well understood Renal vasoconstriction resulting in medullary hypoxia - mediated by alterations in nitric oxide, endothelin , and/or  adenosine ATN is a direct result of the cytotoxic effects of the contrast agents Relatively rapid recovery of renal function . (few days versus 1-3 weeks)

10. Risk factors for CIN

11. Classification of contrast agents

12. Ionic versus nonionic Low osmolality contrast media

13. Ionic agents : interact with thrombin at anion binding site, resulting in steric hinderance of ability of thrombin to thrombin to activate platelet thrombin receptor

14. Iodixanol ( Iso-osmolar ) versus low – osmolar   I odixanol  : reduction in risk with CKD versus   iohexol (relative risk [RR] 0.19, 95% CI 0.07-0.56) (NEPHRIC study) No risk reduction when compared with other nonionic low- osmolal contrast agents (RR 0.79, 95% CI 0.56-1.12)

15. ICON trial NO difference upto 30 day follow up

16. American College of Cardiology/American Heart Association (ACC/AHA)guidelines on percutaneous coronary intervention (PCI) Use of either an iso-osmolal contrast agent or a low-molecular-weight contrast agent other than iohexol or the ionic low- osmolal agent, ioxaglate

17. CIN prevention trials

18. Hydration   Isotonic or one-half isotonic saline Isotonic or one-half isotonic saline at a rate of 1  mL /kg/hour, started the morning of the procedure and continued until 8 AM the next morning Baseline creatinine same (0.9 mg/ dL   ) 450 , 350, and 1200 mL of fluid prior to, during, and after the procedure, respectively. C ontrast-induced nephropathy overall incidence : 1.4 percent L ower in patients given isotonic saline (0.7 versus 2 percent). Benefit with isotonic saline : pronounced in diabetic patients (0 versus 5.5 percent) and those given >250 mL of contrast (0 versus 3 percent).

19. Isotonic or one-half isotonic saline N o difference with significant renal dysfunction (serum creatinine >1.6 mg/ dL ) L imitation - patients with underlying renal dysfunction - at increased risk for contrast nephropathy.

20. N- Acetyl Acetylcysteine   T hiol compound with antioxidant and vasodilatory properties P ossible mechanism of benefit : minimizing both vasoconstriction and oxygen-free radical generation H eterogeneity and conflicting results in trials The joint ACC/AHA guidelines do not recommend acetylcysteine

21. Relative risk of CIN with NAC

22. Dosing The most commonly studied dose is 600 mg orally twice daily Studies : comparing 600 and 1200 mg twice daily suggested slightly better outcomes with the higher dose P referred dose : 1200 mg administered orally twice daily on the day before and the day of the procedure to patients at risk for contrast nephropathy.

23. CONTRAST trial – Fenoldopam (dopamine agonist)

24. Intravenous bicarbonate   Alkalinization : protects against free radical injury Sodium bicarbonate versus IV saline trials : Conflicting results H eterogeneity in studies Metanalysis : either equivalent or better outcomes with sodium bicarbonate.

25. Trimetazidine   A cellular anti-ischemic agent   Preserves the intracellular concentration of ATP and inhibits the extracellular leakage of potassium during cellular ischaemia Provided added protection to isotonic saline from contrast-mediated nephropathy in an initial, small, randomized prospective study

26. Withholding ACE inhibitors and/or ARBs    Some studies : patients on ACE-I or ARB : at higher risk for CIN Not clear whether holding or withdrawing : provides any benefit. Study : 220 patients who were on ACE-I or ARBs and had an eGFR of 15 to 60  mL /min/1.73 m 2  were randomly assigned prior to angiography to either an ACE inhibitor/ARB discontinuation group, in which the ACE inhibitor or ARB was held 24 hours prior to procedure, or to a control group in which these agents were continued There was no significant difference in the incidence of contrast nephropathy between patients who had the ACE inhibitor and/or ARB withdrawn and those who did not.

27. The issue of whether to withhold ACE inhibitors and ARBs prior to contrast procedure is not resolved ACE/ARB may protect against contrast-induced nephropathy by blocking renin-angio II vasoconstriction.

28. Mehran score

29. Adapted from McCullough PA. Contrast-induced acute kidney injury.  J Am Coll Cardiol   2008;51:1419–1428.) Limit contrast volume : < 30 ml for diagnostic <100 ml for intervention

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