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

• Published in: Cancer chemotherapy and pharmacology Vol. 76; no. 5; pp. 989 - 996
• Main Authors: Shinke, Haruka, Masuda, Satohiro, Togashi, Yousuke, Ikemi, Yasuaki, Ozawa, Aiko, Sato, Tomoko, Kim, Young Hak, Mishima, Michiaki, Ichimura, Takaharu, Bonventre, Joseph V., Matsubara, Kazuo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2015; Springer Nature B.V
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - urine; Acute-Phase Proteins - urine; Adenocarcinoma - drug therapy; Adenocarcinoma - urine; Aged; Antineoplastic Agents, Alkylating - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Area Under Curve; beta 2-Microglobulin - urine; Biomarkers - urine; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - urine; Carcinoma, Small Cell - drug therapy; Carcinoma, Small Cell - urine; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - urine; Chemokine CCL2 - urine; Cisplatin - administration & dosage; Cisplatin - adverse effects; Creatinine - urine; Etoposide - administration & dosage; Female; Hepatitis A Virus Cellular Receptor 1; Humans; Lipocalin-2; Lipocalins - urine; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - urine; Male; Medicine; Medicine & Public Health; Membrane Glycoproteins - urine; Middle Aged; Neoplasm Proteins - urine; Oncology; Original Article; Pharmacology/Toxicology; Proto-Oncogene Proteins - urine; Receptors, Virus; ROC Curve; Vinblastine - administration & dosage; Vinblastine - analogs & derivatives; Vinorelbine; Biomarker; Acute kidney injury; Lung cancer; Cisplatin
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-015-2880-y

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.