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

https://doi.org/10.1053/j.ajkd.2009.03.024Get rights and content

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.

Section snippets

Setting and Participants

Between May 1996 and October 2000, all consecutive patients referred for cardiac angiography at the University of Alberta Hospital (Edmonton, Alberta, Canada) were screened for eligibility. Inclusion criteria were age 21 years or older and established CKD, defined as serum creatinine level greater than 1.7 mg/dL in the week before the procedure and on the morning of the procedure before any study interventions occurred. All patients were clinically stable and undergoing elective procedures;

Results

During 4 years of active recruitment, 92 patients were enrolled in the study. Mean patient age was 64 ± 14 years, 23% were women, 37% had diabetes, 77% had hypertension, and 47% used oral furosemide. Mean serum creatinine level at baseline was 2.8 ± 1.6 mg/dL, and average estimated glomerular filtration rate was 27 ± 11 mL/min/1.73 m2. Most (72%) patients underwent only diagnostic coronary angiography. There were no clinically important or statistically significant differences between

Discussion

Forced euvolemic diuresis with saline, mannitol, and furosemide has a sound pathophysiological mechanistic basis,11, 12, 13, 14, 15, 16 and we hypothesized that it ought to be useful for preventing contrast-induced renal injury in high-risk patients undergoing coronary angiography. We tested this hypothesis in a randomized controlled trial, successfully achieved forced euvolemic diuresis, and found that our intervention strategy almost doubled rates of contrast-induced nephropathy. The

Acknowledgements

We thank Dr Ross Tsuyuki (Director), Paula Priest, Ruth Dupuit, and the staff at EPICORE Center (Edmonton, AB, Canada) for ensuring that the study was undertaken as carefully and rigorously as possible.

Support: This study was supported by peer-reviewed grants from the Alberta Heritage Foundation for Medical Research (AHFMR) and the University of Alberta Hospital Foundation. Dr Majumdar receives salary support from AHFMR (Health Scholar).

Financial Disclosure: None.

References (22)

  • Prevention of radiographic contrast agent induced reductions in renal function by acetylcysteine

    N Engl J Med

    (2000)
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    Originally published online as doi: 10.1053/j.ajkd.2009.03.024 on June 18, 2009.

    Trial registration: www.ClinicalTrials.gov; study number: NCT00175227.

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