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. Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation

J Am Coll Cardiol. 1999 Feb;33(2):403-11. doi: 10.1016/s0735-1097(98)00574-9.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / therapeutic use
  • Contrast Media / adverse effects*
  • Coronary Angiography
  • Coronary Disease / diagnostic imaging
  • Creatinine / blood
  • Crystalloid Solutions
  • Diuresis
  • Diuretics / administration & dosage
  • Diuretics / therapeutic use*
  • Dopamine / administration & dosage
  • Dopamine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Furosemide / administration & dosage
  • Furosemide / therapeutic use
  • Humans
  • Isotonic Solutions
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced
  • Kidney Diseases / prevention & control*
  • Male
  • Mannitol / administration & dosage
  • Mannitol / therapeutic use
  • Plasma Substitutes / administration & dosage
  • Plasma Substitutes / therapeutic use
  • Prospective Studies
  • Pulmonary Wedge Pressure
  • Rehydration Solutions / administration & dosage
  • Rehydration Solutions / therapeutic use
  • Risk Factors
  • Single-Blind Method
  • Treatment Outcome


  • Cardiotonic Agents
  • Contrast Media
  • Crystalloid Solutions
  • Diuretics
  • Isotonic Solutions
  • Plasma Substitutes
  • Rehydration Solutions
  • Mannitol
  • Furosemide
  • Creatinine
  • Dopamine