Renal insufficiency following contrast media administration trial (REMEDIAL) - A randomized comparison of 3 preventive strategies

Background - Volume supplementation by saline infusion combined with N-acetylcysteine (NAC) represents an effective strategy to prevent contrast agent - induced nephrotoxicity (CIN). Preliminary data support the concept that sodium bicarbonate and ascorbic acid also may be effective in preventing CIN. Methods and Results - Three hundred twenty-six consecutive patients with chronic kidney disease, referred to our institutions for coronary and/or peripheral procedures, were randomly assigned to prophylactic administration of 0.9% saline infusion plus NAC (n = 111), sodium bicarbonate infusion plus NAC (n = 108), and 0.9% saline plus ascorbic acid plus NAC (n = 107). All enrolled patients had serum creatinine >= 2.0 mg/dL and/or estimated glomerular filtration rate < 40 mL center dot min(-1) center dot 1.73 m(-2). Contrast nephropathy risk score was calculated in each patient. In all cases, iodixanol (an iso-osmolar, nonionic contrast agent) was administered. The primary end point was an increase of >= 25% in the creatinine concentration 48 hours after the procedure (CIN). The amount of contrast media administered (179 +/- 102, 169 +/- 92, and 169 +/- 94 mL, respectively; P = 0.69) and risk scores (9.1 +/- 3.4, 9.5 +/- 3.6, and 9.3 +/- 3.6; P = 0.21) were similar in the 3 groups. CIN occurred in 11 of 111 patients (9.9%) in the saline plus NAC group, in 2 of 108 (1.9%) in the bicarbonate plus NAC group (P = 0.019 by Fisher exact test versus saline plus NAC group), and in 11 of 107 (10.3%) in the saline plus ascorbic acid plus NAC group (P = 1.00 versus saline plus NAC group). Conclusions - The strategy of volume supplementation by sodium bicarbonate plus NAC seems to be superior to the combination of normal saline with NAC alone or with the addition of ascorbic acid in preventing CIN in patients at medium to high risk.