title: Profiling of Kidney Injury Biomarkers in Patients Receiving Cisplatin: Time-dependent Changes in the Absence of Clinical Nephrotoxicity.
abstract: The success of cisplatin-containing regimens to treat solid tumors is limited, in part, by nephrotoxicity. In rodents, several urinary proteins have emerged that are sensitive indicators of cisplatin-induced kidney injury. We sought to characterize time-dependent changes in the urinary concentrations of 12 proteins, including kidney injury molecule-1 (KIM-1), calbindin, beta 2-microglobulin (β2M), and trefoil factor 3 (TFF3) after cisplatin therapy. Urine was collected at baseline, 3 days (range, 2-5 days), and 10 days (range, 9-11 days) from 57 patients with solid tumors receiving outpatient cisplatin therapy (≥25 mg/m2). Serum creatinine was largely unchanged after cisplatin infusion. However, compared with baseline values, several novel biomarkers were significantly increased in the urine, including β2M, which was threefold higher by day 3 (P < 0.0001). Urinary KIM-1 and TFF3 were elevated twofold by day 10 (P = 0.002 and P = 0.002, respectively), whereas calbindin levels were increased eightfold (P < 0.0001). We report novel time-dependent changes in the urinary excretion of noninvasive markers of subclinical kidney injury after cisplatin treatment.
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Road, Piscataway, NJ, 08854, USA.
authors.forename: Blessy
authors.initials: B
authors.lastname: George
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Road, Piscataway, NJ, 08854, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 80045, USA.
authors.forename: Nickie
authors.initials: N
authors.lastname: Mercke
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 80045, USA.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Gomez
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 80045, USA.|Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: O'Bryant
authors.affiliation: Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Bowles
authors.affiliation: UNC Kidney Center and Division of Nephrology and Hypertension, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Yichun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: UNC Kidney Center and Division of Nephrology and Hypertension, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hogan
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 80045, USA.|Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Joy
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Road, Piscataway, NJ, 08854, USA.|Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA 8.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Aleksunes
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000378:metabolism* / Q000652:urine*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine*; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D003404:Creatinine; D002945:Cisplatin