title: Urinary kidney injury molecule-1 and monocyte chemotactic protein-1 are noninvasive biomarkers of cisplatin-induced nephrotoxicity in lung cancer patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Shinke
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan. satomsdb@pharm.med.kyushu-u.ac.jp.|Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan. satomsdb@pharm.med.kyushu-u.ac.jp.|Department of Pharmacy, Kyushu University Hospital, Higashi-ku, Fukuoka, 812-8582, Japan. satomsdb@pharm.med.kyushu-u.ac.jp.
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Department of Respiratory Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Togashi
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Ikemi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Ozawa
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Respiratory Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Young Hak
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Respiratory Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
authors.affiliation: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine, Room 576, 4 Blackfan Circle, Boston, MA, 02115, USA.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Ichimura
authors.affiliation: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine, Room 576, 4 Blackfan Circle, Boston, MA, 02115, USA.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.|Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsubara
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine; D000230:Adenocarcinoma / Q000188:drug therapy / Q000652:urine; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000652:urine; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000652:urine; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000652:urine; D018932:Chemokine CCL2 / Q000652:urine*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003404:Creatinine / Q000652:urine; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000652:urine*; D011518:Proto-Oncogene Proteins / Q000652:urine; D012372:ROC Curve; D011991:Receptors, Virus; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D000209:Acute-Phase Proteins; D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; C117339:NBAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D001613:beta 2-Microglobulin; D014747:Vinblastine; D005047:Etoposide; D003404:Creatinine; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Acute kidney injury; Biomarker; Cisplatin; Lung cancer