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Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery

  • Nephrology - Original Paper
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Abstract

Purpose

Serum uric acid (SUA) is a novel risk factor for acute kidney injury (AKI), which adversely affects renal blood flow autoregulation, glomerular filtration rate (GFR), and promotes inflammation and angiogenesis. This pilot study investigated the effect of lowering SUA therapy on AKI, by using traditional and non-traditional markers.

Materials and methods

In this prospective, double-blind, placebo-controlled, randomized pilot trial, 26 hyperuricemic patients undergoing cardiac surgery were randomized to receive rasburicase or placebo in the preoperative period.

Results

Subjects receiving rasburicase showed no difference in serum creatinine compared with the control group receiving placebo. Despite no difference in primary endpoint, the rasburicase group had less evidence of renal structural injury as reflected by urine neutrophil-associated lipocalin (uNGAL) concentrations, especially in subjects with higher SUA levels, more severe renal dysfunction (baseline GFR ≤ 45 mL/min/1.73 m2) or heart failure (left ventricular ejection fraction ≤45 %).

Conclusions

In this study, rasburicase showed no benefit on postoperative serum creatinine in hyperuricemic subjects undergoing cardiac surgery. However, the observation that markers of structural renal injury such as uNGAL tended to be lower in rasburicase-treated subjects suggests potential different effects of uricase treatment on hemodynamic alterations in renal function versus structural mechanisms of kidney injury.

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Acknowledgments

The investigators acknowledge the active support of DSMB members Abraham Hartzema, PharmD, MSPH, PhD, Meenakshi Devidas, PhD, Edward A. Ross, M.D. and Daniel F. Pauly, M.D., PhD. Many thanks to Matthew Pfeiffer, ARNP, Michael Stagliano, ARNP, Michelle Armstrong, RN, Debbie Kahler, PharmD, Susan Beltz, PharmD, Rajesh Mohandas, M.D., Robert Roberge, RN, Jean Dubois, RN and Mike Flanagan, RN, for assistance with the study. We thank Dr. Michael Bennett, Dr. Prasad Devarajan and Dr. Charles Edelstein for the measurement of the biomarkers. The investigators also thank Nicholas J. Sarlis, MD, PhD, Senior Medical Director, sanofi-aventis US for his support. Study was performed under an investigator-requested grant from sanofi-aventis US.

Conflict of interest

The authors do not have any other conflicts of interest.

Author information

Authors and Affiliations

  1. Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, FL, USA

    A. Ahsan Ejaz, Bhagwan Dass, Vijaykumar Lingegowda, Noel I. Ejaz & Richard J. Johnson

  2. Division of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Michiko Shimada

  3. Division of Thoracic and Cardiovascular Surgery, University of Florida, Gainesville, FL, USA

    Thomas M. Beaver

  4. Division of Inflammation Biology and Surgical Sciences, University of Florida, Gainesville, FL, USA

    Amer S. Abouhamze

  5. Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, CO, USA

    Richard J. Johnson

Authors
  1. A. Ahsan Ejaz
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  2. Bhagwan Dass
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  3. Vijaykumar Lingegowda
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  4. Michiko Shimada
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  5. Thomas M. Beaver
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  6. Noel I. Ejaz
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  7. Amer S. Abouhamze
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  8. Richard J. Johnson
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Corresponding author

Correspondence to A. Ahsan Ejaz.

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Ejaz, A.A., Dass, B., Lingegowda, V. et al. Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery. Int Urol Nephrol 45, 449–458 (2013). https://doi.org/10.1007/s11255-012-0192-2

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  • DOI: https://doi.org/10.1007/s11255-012-0192-2

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