title: Cisplatin nephrotoxicity is not detected by urinary cell-cycle arrest biomarkers in lung cancer patients.
abstract: OBJECTIVE
  Cisplatin is a chemotherapeutic agent with potential nephrotoxicity. Delayed increase in serum creatinine after cisplatin administration shows that serum creatinine may not be a sufficient marker for early detection of nephrotoxicity. Urinary insulin-like growth factor binding protein-7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) which are cell-cycle arrest biomarkers have been proposed recently for early detection of acute kidney injury (AKI). Herein, we evaluated urinary TIMP-2/IGFBP7 levels before and after cisplatin administration to patients with lung cancer and their role was examined in the early diagnosis of AKI.
  
  
  METHODS
  Patients with glomerular filtration rate above 60 mL/min who had cisplatin treatment were enrolled. Urinary TIMP-2/IGFBP7 and serum creatinine levels were measured before and at 24th hour after cisplatin administration. Serum creatinine level was also measured at 48th hour after treatment.
  
  
  RESULTS
  Cisplatin-associated AKI was detected in 13 patients (28%) among the 45 patients enrolled. There was no difference between creatinine, IGFBP7 and (IGFBP7 × TIMP-2)/1000 levels before and after treatment; urinary TIMP-2 level at 24th hour was significantly higher than the level before the treatment (p = 0.02). (IGFBP7 × TIMP-2)/1000 values were not different between patients with or without AKI. The area under the curve of (IGFBP7 × TIMP-2)/1000 at 24th hour of the treatment was 0.46 (CI 0.26-0.67).
  
  
  CONCLUSIONS
  Although urinary IGFBP7 and TIMP-2 levels are used as biomarkers for early detection of AKI for patients in intensive care units and after surgery, they seem not to be useful for early detection of AKI due to cisplatin.
authors.affiliation: Department of Internal Medicine, Okmeydani Training and Research Hospital, Istanbul, Turkey. zktprk@gmail.com.
authors.forename: Zeki
authors.initials: Z
authors.lastname: Toprak
authors.affiliation: Department of Nephrology, Okmeydani Training and Research Hospital, Istanbul, Turkey.
authors.forename: Egemen
authors.initials: E
authors.lastname: Cebeci
authors.affiliation: Department of Internal Medicine, Okmeydani Training and Research Hospital, Istanbul, Turkey.
authors.forename: Serife Aysen
authors.initials: SA
authors.lastname: Helvaci
authors.affiliation: Department of Internal Medicine, Okmeydani Training and Research Hospital, Istanbul, Turkey.
authors.forename: Ilkim Deniz
authors.initials: ID
authors.lastname: Toprak
authors.affiliation: Department of Internal Medicine, Okmeydani Training and Research Hospital, Istanbul, Turkey.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Kutlu
authors.affiliation: Department of Medical Oncology, Okmeydani Training and Research Hospital, Istanbul, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Sakin
authors.affiliation: Department of Internal Medicine, Okmeydani Training and Research Hospital, Istanbul, Turkey.
authors.forename: Tufan
authors.initials: T
authors.lastname: Tukek
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000175:diagnosis / Q000652:urine*; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000652:urine; D059447:Cell Cycle Checkpoints; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; C560823:TIMP2 protein, human; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2; D003404:Creatinine; D002945:Cisplatin
keywords: Acute renal injury; Cell cycle; Cisplatin; Insulin-like growth factors; Nephrotoxicity; Tissue inhibitor of metalloproteinases