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Original Investigation Pathogenesis and Treatment of Kidney Disease| Volume 54, ISSUE 4, P602-609, October 01, 2009

Forced Euvolemic Diuresis With Mannitol and Furosemide for Prevention of Contrast-Induced Nephropathy in Patients With CKD Undergoing Coronary Angiography: A Randomized Controlled Trial

      Background

      Contrast-induced nephropathy is common in patients with coronary angiography. Mechanistically, forced euvolemic diuresis with mannitol and furosemide ought to prevent contrast-induced nephropathy. Our objectives are to: (1) undertake a randomized trial testing this hypothesis, and (2) conduct a meta-analysis of our findings with 2 earlier studies.

      Study Design

      (1) Randomized allocation-concealed controlled trial with blinded ascertainment of outcomes, and (2) random-effects meta-analysis of 3 trials.

      Setting & Participants

      Single-center study of consenting adults with serum creatinine level greater than 1.7 mg/dL undergoing coronary angiography; patients unable to tolerate fluid challenge or receiving dialysis were excluded. Two previous trials had randomly assigned 159 patients.

      Intervention

      Forced euvolemic diuresis with saline, mannitol, and furosemide compared with saline hydration controls. All patients were pretreated with at least 500 mL of half-normal saline before angiography; during and 8 hours after, urine output was replaced milliliter per milliliter with half-normal saline.

      Outcomes & Measurements

      The primary outcome was contrast-induced nephropathy within 48 hours of the procedure, defined as a 0.5-mg/dL absolute or 25% relative increase in creatinine level.

      Results

      Overall, 92 patients were allocated to intervention (n = 46) or control (n = 46). Mean age was 64 ± 14 (SD) years, 23% were women, 37% had diabetes, 47% used oral furosemide, mean creatinine level was 2.8 ± 1.6 mg/dL, and most patients (72%) underwent diagnostic catheterization. Patients had a net positive fluid balance (389 ± 958 mL for intervention versus 655 ± 982 mL for controls; P = 0.2). Contrast-induced nephropathy occurred in 23 (50%) intervention patients versus 13 (28%) controls (relative risk, 1.77; 95% confidence interval, 1.03 to 3.05; P = 0.03; adjusted odds ratio, 3.73; P = 0.03). Within 48 hours, creatinine level had increased by 0.8 ± 1.1 mg/dL with intervention versus 0.2 ± 0.6 mg/dL for controls (P = 0.002). Overall, 11 (12%) patients died or required dialysis, with no difference according to allocation status (P = 0.5). Random-effects meta-analysis of published data (3 trials; 251 patients) suggests furosemide-based interventions lead to significant harm compared with hydration: pooled relative risk, 2.15; 95% confidence interval, 1.37 to 3.37; I2 = 0%.

      Limitations

      Small single-center study that cannot determine whether harms were related to furosemide, mannitol, or a combination.

      Conclusions

      Forced euvolemic diuresis led to a significantly increased risk of contrast-induced nephropathy. This strategy should be abandoned, and our results suggest that oral furosemide therapy perhaps should be held before angiography.

      Index Words

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      References

        • McCullough P.A.
        • Wolyn R.
        • Rocher L.L.
        • Levin R.N.
        • O'Neill W.W.
        Acute renal failure after coronary intervention: Incidence, risk factors, and relationship to mortality.
        Am J Med. 1997; 103: 368-375
        • Parfrey P.S.
        • Griffiths S.M.
        • Barret B.J.
        • et al.
        Contrast material induced renal failure in patients with diabetes mellitus, renal insufficiency, or both: A prospective controlled study.
        N Engl J Med. 1989; 320: 143-149
        • Manske C.
        • Sprafka J.
        • Strong J.
        • Wang Y.
        Contrast nephropathy in azotemic diabetic patients undergoing coronary angiography.
        Am J Med. 1990; 89: 615-620
        • Kelly A.M.
        • Dwamena B.
        • Cronin P.
        • Bernstein S.J.
        • Carlos R.C.
        Meta-analysis: Effectiveness of drugs for preventing contrast induced nephropathy.
        Ann Intern Med. 2008; 148: 284-294
        • Taylor A.J.
        • Hotchkiss D.
        • Morse R.W.
        • McCabe J.
        PREPARED: Preparation for Angiography in Renal Dysfunction.
        Chest. 1998; 114: 1570-1574
        • Mueller C.
        • Buerkele G.
        • Buettner H.J.
        • et al.
        Prevention of contrast media associated nephropathy: Randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty.
        Arch Intern Med. 2002; 162: 329-336
        • Spargias K.
        • Alexopoulos E.
        • Kyrzopoulos S.
        • et al.
        Ascorbic acid prevents contrast mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention.
        Circulation. 2004; 110: 2837-2842
      1. Prevention of radiographic contrast agent induced reductions in renal function by acetylcysteine.
        N Engl J Med. 2000; 343: 180-184
        • Brar S.S.
        • Shen A.
        • Jorgensen M.B.
        • et al.
        Sodium bicarbonate vs sodium chloride for the prevention of contrast medium induced nephropathy in patients undergoing coronary angiography: A randomized trial.
        JAMA. 2008; 300: 1038-1046
        • CONTRAST Investigators
        Fenoldopam mesylate for the prevention of contrast induced nephropathy: A randomized controlled trial.
        JAMA. 2003; 290: 2284-2291
        • Solomon R.
        • Werner C.
        • Mann D.
        • Delia J.
        • Silva P.
        Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents.
        N Engl J Med. 1994; 331: 1416-1420
        • Dussol B.
        • Morange S.
        • Loundoun A.
        • Auquier P.
        • Berland Y.
        A randomized trial of saline hydration to prevent contrast nephropathy in chronic renal failure patients.
        Nephrol Dial Transplant. 2006; 21: 2120-2126
        • Stevens M.A.
        • McCullough P.A.
        • Tobin K.J.
        • et al.
        A prospective randomized trial of prevention measure in patients at high risk of contrast nephropathy.
        J Am Coll Cardiol. 1999; 33: 403-411
        • Brezis M.
        • Epstein F.H.
        A closer look at radiocontrast induced nephropathy.
        N Engl J Med. 1989; 320: 179-181
        • Shilliday I.
        • Allison M.E.
        Diuretics in acute renal failure.
        Ren Fail. 1994; 16: 3-17
        • Majumdar S.R.
        • Kjellstrand C.M.
        Why do we use diuretics in acute renal failure?.
        Semin Dial. 1996; 9: 454-459
        • Weisberg L.S.
        • Kurnik P.B.
        • Kurnik B.R.C.
        Risk of contrast nephropathy in patients with and without diabetes mellitus.
        Kidney Int. 1994; 45: 259-265
        • Lassnigg A.
        • Donner E.
        • Grubhofer G.
        • Presterl E.
        • Druml W.
        • Hiesmayr M.
        Lack of renoprotective effects of dopamine and furosemide during cardiac surgery.
        J Am Soc Nephrol. 2000; 11: 97-104
        • Bassler D.
        • Montori V.M.
        • Briel M.
        • Glasziou P.
        • Guyatt G.
        Early stopping of randomized clinical trials for overt efficacy is problematic.
        J Clin Epidemiol. 2008; 61: 241-246
        • Hewitt C.
        • Mitchell N.
        • Torgerson D.
        Heed the data when results are not significant.
        BMJ. 2008; 336: 23-25
        • Ho K.M.
        • Sheridan D.J.
        Meta-analysis of frusemide to prevent or treat acute renal failure.
        BMJ. 2006; 333: 420-426
        • Barrett B.J.
        • Parfrey P.S.
        Preventing nephropathy induced by contrast medium.
        N Engl J Med. 2006; 354: 379-386

      Linked Article

      • Contrast-Induced Nephropathy: We Need All the Data to Discern the Truth
        American Journal of Kidney DiseasesVol. 54Issue 4
        • Preview
          Contrast-induced nephropathy (CIN) usually is defined as an acute deterioration in kidney function after intravascular injection of iodinated contrast media. The entity has engendered a vast amount of research interest during the past 30 years, partly because it appeared to be a major cause of acute kidney injury in general1 and partly because as a form of acute kidney injury with a predictable time of injury, it is open to application of timely preventive measures. Most cases of CIN are characterized by transient and minor changes in markers of kidney function, such as serum creatinine level.
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