Preventing Contrast-Induced Nephropathy in Patients Undergoing Primary PCI

Contrast-induced nephropathy (CIN) continues to be one of the most common major adverse side effect of cardiac catheterization, and is associated with short- and long-term morbidity and mortality.^1,2 This is particularly true in the population presenting with acute ST-elevation myocardial infarction (STEMI). A recent study evaluating the epidemiology of CIN in over 8000 patients undergoing PCI found that CIN occurred in 12% of STEMI, which was significantly higher compared with patients undergoing non-emergent catheterization (9.2% in unstable angina and NSTEMI patients and 4.5% undergoing elective PCI). Even in patients with baseline GFR >60, the incidence of CIN in the STEMI population was 9.2%.³ Such a high incidence of this complication invokes the need to define measures to decrease the occurrence of CIN in patients presenting with STEMI.

The study by Kanei et al in the current issue of the Journal sought to evaluate one factor that may play a part: contrast media choice.⁴ The authors performed a retrospective analysis of CIN incidence in 212 acute STEMI patients who received either iso-osmolar contrast or low-osmolar contrast during emergent cardiac catheterization (primary PCI or rescue PCI for failed thrombolysis). Because it was a retrospective study, the choices of contrast type and hydration protocol were determined by each individual operator. Of note, patients with higher CIN risk scores (age >75 years, congestive heart failure, diabetes mellitus, use of intra-aortic balloon pump, hypotension, contrast volume, and baseline renal function) were more likely to receive iso-osmolar contrast. There was no statistically significant difference in incidence of CIN or major adverse cardiac events (MACE), including death, myocardial infarction, and target vessel revascularization, between the iso-osmolar and low-osmolar groups. This study suggests that choice of contrast media is unlikely to influence the occurrence of CIN provided either iso-osmolar or low-osmolar contrast media is used.

The impact of specific contrast media on the occurrence of CIN has been extensively evaluated in the past, although most of the studies to date have been underpowered. While hyperosmolar contrast is associated with worse outcomes compared with low-osmolar contrast, the relative benefit of iso-osmolar contrast over low-osmolar contrast remains debatable. One small, randomized, controlled trial of 129 diabetic patients with chronic kidney disease undergoing coronary or aortofemoral angiography did show a significant reduction in CIN in patients receiving iso-osmolar contrast compared to low-osmolar contrast (3% vs 26%, P=.002).⁵ A subsequent meta-analysis pooling 16 trials and over 2000 subjects, however, revealed no significant difference in the rate of CIN in patients who received iodixanol (iso-osmolar) compared to those who received low-osmolar contrast. This finding extended to a subgroup analysis of diabetic patients (914 patients in seven studies).⁶ A large observational study from our group corroborated these results.⁷

If the choice between iso-osmolar and low-osmolar contrast does not significantly change the risk of CIN, then what other measures can be utilized to reduce renal complications in patients undergoing primary PCI for STEMI? The emergent nature of the procedure precludes the use of adequate hydration, the only proven effective prophylactic therapy. Other therapies such as N-acetylcysteine have not demonstrated any benefit in this setting.⁸ One important strategy remains minimization of contrast volume. Studies by McCullough,⁹ Freeman,¹⁰ and Mehran¹¹ have shown that total contrast volume is an independent predictor of CIN. A recent study from our group found that the risk of CIN and nephropathy requiring dialysis trended toward significance when contrast volume exceeded twice the calculated creatinine clearance (CCC) and was significantly elevated when the volume exceeded thrice the CCC.¹² Using this algorithm is relatively easy in patients with normal baseline renal function, but may be more challenging when a patient has stage 3 or 4 chronic kidney disease. In such situations, it is critical that the operator be cognizant of the patient’s calculated creatinine clearance and limit contrast use by employing strategies such as the use of biplane angiography, limiting unnecessary contrast puffs, avoiding left ventriculography, and employing “dry cine” and IVUS to guide stent sizing and placement.

Among patients undergoing primary PCI, no other evidence-based measures have yet been shown to decrease the risk of CIN. Postprocedure hydration (particularly in the setting of low left ventricular end diastole pressure) with isotonic crystalloid (saline or bicarbonate solution) and avoidance of potentially nephrotoxic medications (NSAIDs, aminoglycosides, calcineurin inhibitors, high-dose loop diuretics) and repeat dye loads are reasonable measures and merit consideration.

References

1. Marenzi G, Lauri G, Assanelli E, et al. Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction. J Am Coll Cardiol. 2004;44(9):1780-1785.
2. Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002;105(19):2259-2264.
3. Chong E, Poh KK, Liang S, et al. Comparison of risks and clinical predictors of contrast-induced nephropathy in patients undergoing emergency versus nonemergency percutaneous coronary interventions. J Interv Cardiol. 2010;23(5):451-459.
4. Kanei Y, Ayabe K, Ratcliffe J, et al. The impact of iso-osmolar contrast use in emergent percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Invasive Cardiol. 2011;23(11):448-450.
5. Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med. 2003;348(6):491-499.
6. Reed M, Meier P, Tamhane UU, Welch KB, Moscucci M, Gurm HS. The relative renal safety of iodixanol compared with low-osmolar contrast media: a meta-analysis of randomized controlled trials. JACC Cardiovasc Interv. 2009;2(7):645-654.
7. Reed MC, Moscucci M, Smith DE, et al. The relative renal safety of iodixanol and low-osmolar contrast media in patients undergoing percutaneous coronary intervention. Insights from Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2). J Invasive Cardiol. 2010;22(10):467-472.
8. Thiele H, Hildebrand L, Schirdewahn C, et al. Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate Percutaneous Coronary Intervention Acute Myocardial Infarction N-ACC) trial. J Am Coll Cardiol. 2010;55(20):2201-2209.
9. McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med. 1997;103(5):368-375.
10. Freeman RV, O’Donnell M, Share D, et al. Nephropathy requiring dialysis after percutaneous coronary intervention and the critical role of an adjusted contrast dose. Am J Cardiol. 2002;90(10):1068-1073.
11. Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol. 2004;44(7):1393-1399.
12. Gurm HS, Dixon SR, Smith DE, et al. Renal function-based contrast dosing to define safe limits of radiographic contrast media in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol. 2011;58(9):907-914.

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From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical Center, Ann Arbor, Michigan.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Address for correspondence: Hitinder S. Gurm, MD, Division of Cardiovascular Medicine, University of Michigan Cardiovascular Center, 2A394, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5853. Email: hgurm@med.umich.edu