Radiocontrast-induced nephropathy (RCIN) is a common cause of hospital-acquired
acute renal failure and is associated with a high mortality rate. RCIN is potentially preventable, because administration of the
radiocontrast agent is predictable, and a high-risk population has been identified. This multicenter, prospective, randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of intravenous
atrial natriuretic peptide (
anaritide,
ANP 4-28) to prevent RCIN. Patients with stable
chronic renal failure (serum
creatinine greater than 1.8 mg/dL or serum
creatinine between 1.5 and 1.8 mg/dL with estimated
creatinine clearance of < or = 65 mL/min) were assigned to receive either placebo or one of three doses of
anaritide (0.01 microg/kg/min, 0.05 microg/kg/min, or 0.1 microg/kg/min) for 30 minutes before and continuing for 30 minutes after radiocontrast administration. All patients were given intravenous 0.45% saline for 12 hours before the radiocontrast procedure and continuing for 12 hours after the last dose of radiocontrast. Both ionic and nonionic
radiocontrast agents were administered. RCIN was defined as either an absolute increase of serum
creatinine of > or = 0.5 mg/dL or a percent increase of > or = 25% over baseline. Of the 247 patients who completed the study, 50% had
diabetes mellitus. There were no statistical differences in baseline serum
creatinine, change in serum
creatinine, or the incidence of RCIN. The incidence of RCIN was placebo, 19%;
anaritide (0.01), 23%;
anaritide (0.05), 23%;
anaritide (0.1), 25%. Patients with
diabetes mellitus had a significantly greater incidence of RCIN: placebo, 26% versus 9%;
anaritide (0.01), 33% versus 13%;
anaritide (0.05), 26% versus 21%;
anaritide (0.1), 39% versus 8% (diabetic v nondiabetic, P < 0.002). There was no effect in the diabetic or nondiabetic groups by
anaritide on the incidence of RCIN. Comparison of the highest-risk group of patients, defined as patients with
diabetes mellitus and a baseline serum
creatinine > or = 1.8 mg/dL, with the lowest-risk group, defined as patients without
diabetes mellitus and a baseline serum
creatinine of 1.8 mg/dL or less, did not show a beneficial effect of
anaritide administration. In conclusion, administration of intravenous
anaritide before and during a radiocontrast study did not reduce the incidence of RCIN in patients with preexisting
chronic renal failure, with or without
diabetes mellitus.