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

Haruka Shinke, Satohiro Masuda, Yousuke Togashi, Yasuaki Ikemi, Aiko Ozawa, Tomoko Sato, Young Hak Kim, Michiaki Mishima, Takaharu Ichimura, Joseph V. Bonventre, Kazuo Matsubara

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)989-996
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume76
Issue number5
DOIs
Publication statusPublished - Nov 1 2015
Externally publishedYes

Keywords

  • Acute kidney injury
  • Biomarker
  • Cisplatin
  • Lung cancer

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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