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Urinary kidney injury molecule-1 and monocyte chemotactic protein-1 are noninvasive biomarkers of cisplatin-induced nephrotoxicity in lung cancer patients

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Abstract

Purpose

Acute kidney injury (AKI) is a common and serious adverse effect of cisplatin-based chemotherapy. However, traditional markers of kidney function, such as serum creatinine, are suboptimal, because they are not sensitive measures of proximal tubular injury. We aimed to determine whether the new urinary biomarkers such as kidney injury molecule-1 (KIM-1), monocyte chemotactic protein-1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL) could detect cisplatin-induced AKI in lung cancer patients in comparison with the conventional urinary proteins such as N-acetyl-β-d-glucosaminidase (NAG) and β2-microglobulin.

Methods

We measured KIM-1, MCP-1, NGAL, NAG, and β2-microglobulin concentrations in urine samples from 11 lung cancer patients, which were collected the day before cisplatin administration and on days 3, 7, and 14. Subsequently, we evaluated these biomarkers by comparing their concentrations in 30 AKI positive (+) and 12 AKI negative (−) samples and performing receiver operating characteristic (ROC) curve analyses.

Results

The urinary levels normalized with urine creatinine of KIM-1 and MCP-1, but not NGAL, NAG, and β2-microglobulin in AKI (+) samples were significantly higher than those in AKI (−) samples. In addition, ROC curve analyses revealed that KIM-1 and MCP-1, but not NGAL, could detect AKI with high accuracy (area under the curve [AUC] = 0.858, 0.850, and 0.608, respectively). The combination of KIM-1 and MCP-1 outperformed either biomarker alone (AUC = 0.871).

Conclusions

Urinary KIM-1 and MCP-1, either alone or in combination, may represent biomarkers of cisplatin-induced AKI in lung cancer patients.

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Abbreviations

AKI:

Acute kidney injury

KIM-1:

Kidney injury molecule-1

MCP-1:

Monocyte chemotactic protein-1

NGAL:

Neutrophil gelatinase-associated lipocalin

AUC-ROC:

Area under the receiver operating characteristic curve

Scr:

Serum creatinine

BUN:

Blood urea nitrogen

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Science, Culture, Sports, and Technology of Japan (MEXT); a Grant-in-Aid for Research on Biological Markers for New Drug Development and Health and Labour Sciences Research Grants from the Ministry of Health, Labour, and Welfare of Japan (08062855); and a funding program for Next Generation World-Leading Researchers (LS073 to SM) from the Council for Science and Technology Policy of the Japan Society for the Promotion of Science.

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Author notes

  1. Satohiro Masuda

    Present address: Department of Pharmacy, Kyushu University Hospital, Higashi-ku, Fukuoka, 812-8582, Japan

Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan

    Haruka Shinke, Satohiro Masuda, Aiko Ozawa, Tomoko Sato & Kazuo Matsubara

  2. Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan

    Satohiro Masuda, Yasuaki Ikemi & Kazuo Matsubara

  3. Department of Respiratory Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan

    Yousuke Togashi, Young Hak Kim & Michiaki Mishima

  4. Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Harvard Institutes of Medicine, Room 576, 4 Blackfan Circle, Boston, MA, 02115, USA

    Takaharu Ichimura & Joseph V. Bonventre

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  1. Haruka Shinke
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Correspondence to Satohiro Masuda.

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Shinke, H., Masuda, S., Togashi, Y. et al. Urinary kidney injury molecule-1 and monocyte chemotactic protein-1 are noninvasive biomarkers of cisplatin-induced nephrotoxicity in lung cancer patients. Cancer Chemother Pharmacol 76, 989–996 (2015). https://doi.org/10.1007/s00280-015-2880-y

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  • DOI: https://doi.org/10.1007/s00280-015-2880-y

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