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.
OBJECTIVE
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.
Stevens
M A
MA
William Beaumont Hospital, Royal Oak, Michigan, USA.
McCullough
P A
PA
Tobin
K J
KJ
Speck
J P
JP
Westveer
D C
DC
Guido-Allen
D A
DA
Timmis
G C
GC
O'Neill
W W
WW
D000368:Aged; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003287:Contrast Media / Q000009:adverse effects*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging; D003404:Creatinine / Q000097:blood; D000077324:Crystalloid Solutions; D004231:Diuresis; D004232:Diuretics / Q000008:administration & dosage / Q000627:therapeutic use*; D004298:Dopamine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005665:Furosemide / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007552:Isotonic Solutions; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000627:therapeutic use; D010952:Plasma Substitutes / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure; D015532:Rehydration Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors; D016037:Single-Blind Method; D016896:Treatment Outcome