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Efficacy of urinary midkine as a biomarker in patients with acute kidney injury
Authors:Hiroki Hayashi  Waichi Sato  Tomoki Kosugi  Kunihiro Nishimura  Daisuke Sugiyama  Naoko Asano  Shinya Ikematsu  Kimihiro Komori  Kimitoshi Nishiwaki  Kenji Kadomatsu  Seiichi Matsuo  Shoichi Maruyama  Yukio Yuzawa
Institution:1.Department of Nephrology,Nagoya University Graduate School of Medicine,Nagoya,Japan;2.Department of Nephrology,Fujita Health University School of Medicine,Toyoake,Japan;3.Department of Preventive Medicine and Epidemiology,National Cerebral and Cardiovascular Center,Osaka,Japan;4.Department of Preventive Medicine and Public Health,Keio University,Tokyo,Japan;5.Department of Bioresources Engineering,Okinawa National College of Technology,Okinawa,Japan;6.Department of Vascular Surgery,Nagoya University Graduate School of Medicine,Nagoya,Japan;7.Department of Anesthesiology,Nagoya University Graduate School of Medicine,Nagoya,Japan;8.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.
Keywords:
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