CLINICAL STUDIES
A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy
Results of the P.R.I.N.C.E. study
Melissa A. Stevens, MDa,
Peter A. McCullough, MD, MPHa*,1,
Kenneth J. Tobin, DOa,
John P. Speck, MDa,
Douglas C. Westveer, MD, FACCa,
Debra A. Guido-Allen, BSNa,
Gerald C. Timmis, MD, FACCa and
William W. O’Neill, MD, FACCa
a William Beaumont Hospital, Royal Oak, Michigan, USA
* Henry Ford Health System, Detroit, Michigan, USA
Manuscript received August 3, 1998;
revised manuscript received September 2, 1998,
accepted October 22, 1998.
Reprint requests and correspondence: Dr. Peter A. McCullough, Henry Ford Health System, One Ford Place, Suite 3C, Detroit, Michigan 48202
Objectives
This study was done to test the hypothesis that a forced diuresis with maintenance of intravascular volume after contrast exposure would reduce the rate of contrast-induced renal injury.
Background
We have previously shown a graded relationship with the degree of postprocedure renal failure and the probability of in-hospital death in patients undergoing percutaneous coronary intervention. Earlier studies of singular prevention strategies (atrial natriuretic factor, loop diuretics, dopamine, mannitol) have shown no clear benefit across a spectrum of patients at risk.
Methods
A prospective, randomized, controlled, single-blind trial was conducted where 98 participants were randomized to forced diuresis with intravenous crystalloid, furosemide, mannitol (if pulmonary capillary wedge pressure <20 mm Hg), and low-dose dopamine (n = 43) versus intravenous crystalloid and matching placebos (n = 55).
Results
The groups were similar with respect to baseline serum creatinine (2.44 ± 0.80 and 2.55 ± 0.91 mg/dl), age, weight, diabetic status, left ventricular function, degree of prehydration, contrast volume and ionicity, and extent of peripheral vascular disease. The forced diuresis resulted in higher urine flow rate (163.26 ± 54.47 vs. 122.57 ± 54.27 ml/h) over the 24 h after contrast exposure (p = 0.001). Two participants in the experimental arm versus five in the control arm required dialysis, with all seven cases having measured flow rates <145 ml/h in the 24 h after the procedure. The mean individual change in serum creatinine at 48 h, the primary end point, was 0.48 ± 0.86 versus 0.51 ± 0.87, in the experimental and control arms, respectively, p = 0.87. There were no differences in the rates of renal failure across six definitions of renal failure by intent-to-treat analysis. However, in all participants combined, the rise in serum creatinine was related to the degree of induced diuresis after controlling for baseline renal function, r = –0.36, p = 0.005. The rates of renal failure in those with urine flow rates greater than 150 ml/h in the postprocedure period were significantly lower, 8/37 (21.6%) versus 28/61 (45.9%), p = 0.03.
Conclusions
Forced diuresis with intravenous crystalloid, furosemide, and mannitol if hemodynamics permit, beginning at the start of angiography provides a modest benefit against contrast-induced nephropathy provided a high urine flow rate can be achieved.
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