Haruka Shinke1, Satohiro Masuda2,3,4, Yousuke Togashi5, Yasuaki Ikemi6, Aiko Ozawa1, Tomoko Sato1, Young Hak Kim5, Michiaki Mishima5, Takaharu Ichimura7, Joseph V Bonventre7, Kazuo Matsubara1,6. 1. Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan. 2. Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan. satomsdb@pharm.med.kyushu-u.ac.jp. 3. Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan. satomsdb@pharm.med.kyushu-u.ac.jp. 4. Department of Pharmacy, Kyushu University Hospital, Higashi-ku, Fukuoka, 812-8582, Japan. satomsdb@pharm.med.kyushu-u.ac.jp. 5. Department of Respiratory Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan. 6. Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan. 7. Renal Division, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine, Room 576, 4 Blackfan Circle, Boston, MA, 02115, USA.
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.
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 cancerpatients 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 cancerpatients, 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 cancerpatients.
Entities:
Keywords:
Acute kidney injury; Biomarker; Cisplatin; Lung cancer
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