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Contrast medium-induced nephropathy (CIN) is a well-known complication of coronary angiographic procedures, especially in patients treated with primary angioplasty. To prevent CIN, we examined using a local application of N-acetylcysteine (NAC) for the prevention of CIN during primary angioplasty. We hypothesized that a local application of NAC into the renal arteries would provide the benefit of a higher local concentration, lower first-pass metabolism, and faster efficacy. To evaluate the effects of NAC by the intrarenal route, we performed a prospective, randomized clinical study in patients with acute myocardial infarction treated with primary angioplasty.Participants were 312 patients with ST-segment elevation myocardial infarction undergoing primary angiography. Eligible patients were randomly assigned to receive intravenous NAC, intrarenal NAC, or placebo.Overall, CIN occurred in 74 (23.7%) of the 312 patients. The rate of CIN was 25% in the intravenous NAC group, 22.9% in the intrarenal NAC group, and 23.2% in the placebo group, with no significant effect seen for either treatment (P=0.64). We did find a significant correlation between CIN and ejection fraction (P=0.05) and baseline renal function (P=0.01).Both intrarenal and intravenous applications of NAC failed to show any benefit over placebo in the prevention of CIN. This result shows that NAC application does not have any prophylactic effect, dose dependent or otherwise, on CIN, as previously reported. Our results suggest that more attention should be paid to optimize hemodynamic variables for the prevention of CIN.