Hiroki Hayashi1,2, Waichi Sato3,4, Tomoki Kosugi3, Kunihiro Nishimura5, Daisuke Sugiyama6, Naoko Asano3, Shinya Ikematsu7, Kimihiro Komori8, Kimitoshi Nishiwaki9, Kenji Kadomatsu10, Seiichi Matsuo3, Shoichi Maruyama3, Yukio Yuzawa4. 1. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan. hhayashi@fujita-hu.ac.jp. 2. Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakuho, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. hhayashi@fujita-hu.ac.jp. 3. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 4. Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakuho, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. 5. Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center, Osaka, Japan. 6. Department of Preventive Medicine and Public Health, Keio University, Tokyo, Japan. 7. Department of Bioresources Engineering, Okinawa National College of Technology, Okinawa, Japan. 8. Department of Vascular Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. 9. Department of Anesthesiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 10. Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Abstract
BACKGROUND: The mortality and morbidity associated with acute kidney injury (AKI) remains high, despite advances in interventions. A multifunctional heparin-binding growth factor, midkine (MK), is involved in the pathogenesis of ischemic kidney injury. However, the clinical relevance of MK has not yet been elucidated. The present study investigated whether urinary MK can serve as a novel biomarker of AKI. METHODS: We initially compared the predictive value of MK with other urinary biomarkers, including N-acetyl-β-D-glucosaminidase (NAG), interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL), for the detection and differential diagnosis of established AKI (549 patients). Subsequently, the reliability of MK for the early detection of AKI was prospectively evaluated in 40 patients undergoing elective abdominal aortic aneurysm surgery. Urine samples were obtained at baseline, the period of aortic cross-clamping and declamping, the end of the surgery, and on post-operative day 1. RESULTS: The areas under the receiver operating characteristic curves for the diagnosis of AKI in various kidney diseases were 0.88, 0.70, 0.72, and 0.84 for MK, NAG, IL-18, and NGAL, respectively. When the optimal cutoff value of urinary MK was set at 11.5 pg/mL, the sensitivity and specificity were 0.87 and 0.85, respectively. In the second study, urinary MK peaked at the period of aortic declamping, about 1 h after cross-clamping in patients with AKI. Interestingly, the rise of MK in AKI patients was very precipitous compared with other biomarker candidates. CONCLUSION: Urinary MK was prominent in its ability to detect AKI and may allow the start of preemptive medication.
BACKGROUND: The mortality and morbidity associated with acute kidney injury (AKI) remains high, despite advances in interventions. A multifunctional heparin-binding growth factor, midkine (MK), is involved in the pathogenesis of ischemic kidney injury. However, the clinical relevance of MK has not yet been elucidated. The present study investigated whether urinary MK can serve as a novel biomarker of AKI. METHODS: We initially compared the predictive value of MK with other urinary biomarkers, including N-acetyl-β-D-glucosaminidase (NAG), interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL), for the detection and differential diagnosis of established AKI (549 patients). Subsequently, the reliability of MK for the early detection of AKI was prospectively evaluated in 40 patients undergoing elective abdominal aortic aneurysm surgery. Urine samples were obtained at baseline, the period of aortic cross-clamping and declamping, the end of the surgery, and on post-operative day 1. RESULTS: The areas under the receiver operating characteristic curves for the diagnosis of AKI in various kidney diseases were 0.88, 0.70, 0.72, and 0.84 for MK, NAG, IL-18, and NGAL, respectively. When the optimal cutoff value of urinary MK was set at 11.5 pg/mL, the sensitivity and specificity were 0.87 and 0.85, respectively. In the second study, urinary MK peaked at the period of aortic declamping, about 1 h after cross-clamping in patients with AKI. Interestingly, the rise of MK in AKI patients was very precipitous compared with other biomarker candidates. CONCLUSION: Urinary MK was prominent in its ability to detect AKI and may allow the start of preemptive medication.
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