title: Efficacy of urinary midkine as a biomarker in patients with acute kidney injury.
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.
  
  
  CONCLUSIONS
  Urinary MK was prominent in its ability to detect AKI and may allow the start of preemptive medication.
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan. hhayashi@fujita-hu.ac.jp.|Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakuho, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. hhayashi@fujita-hu.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakuho, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Waichi
authors.initials: W
authors.lastname: Sato
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosugi
authors.affiliation: Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Preventive Medicine and Public Health, Keio University, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Asano
authors.affiliation: Department of Bioresources Engineering, Okinawa National College of Technology, Okinawa, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ikematsu
authors.affiliation: Department of Vascular Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Komori
authors.affiliation: Department of Anesthesiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Nishiwaki
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakuho, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yuzawa
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000209:etiology / Q000652:urine*; D000328:Adult; D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000601:surgery*; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D009414:Nerve Growth Factors / Q000652:urine*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D016482:Urinalysis; D014656:Vascular Surgical Procedures / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; C066254:MDK protein, human; D009414:Nerve Growth Factors; D000078792:Midkine
keywords: Acute kidney injury; Acute tubular necrosis; Biomarker; Midkine