Efficacy of urinary midkine as a biomarker in patients with acute kidney injury

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

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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.

Original languageEnglish
Pages (from-to)597-607
Number of pages11
JournalClinical and Experimental Nephrology
Volume21
Issue number4
DOIs
Publication statusPublished - 01-08-2017

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)

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    Hayashi, H., Sato, W., Kosugi, T., Nishimura, K., Sugiyama, D., Asano, N., Ikematsu, S., Komori, K., Nishiwaki, K., Kadomatsu, K., Matsuo, S., Maruyama, S., & Yuzawa, Y. (2017). Efficacy of urinary midkine as a biomarker in patients with acute kidney injury. Clinical and Experimental Nephrology, 21(4), 597-607. https://doi.org/10.1007/s10157-016-1318-0