title: Monitoring treatment of acute kidney injury with damage biomarkers.
abstract: BACKGROUND
  Damage biomarkers may identify mechanisms and sites of acute kidney injury (AKI). However, the utility of novel AKI biomarkers differs by context, and their utility for monitoring treatment of AKI is unknown. We hypothesized that selected AKI biomarkers would facilitate monitoring of mechanism-specific treatment. We examined this using a panel of biomarkers to monitor cisplatin-induced AKI treatment with alpha-lipoic acid (α-LA) that has previously been demonstrated to ameliorate cisplatin induced AKI.
  
  
  METHODS
  AKI was induced in male Sprague Dawley rats using cisplatin (6mg/kg) in the presence or absence of a single dose of α-LA (100mg/kg). A panel of 12 urinary kidney damage biomarkers (CystatinC, NGAL albumin, alpha-1-acid glycoprotein, clusterin, KIM-1, osteopontin, total protein, cytochrome C, epidermal growth factor, interleukin-18 and malondialdehyde was examined as well as histological injury, serum creatinine and cystatin C, and clinical parameters.
  
  
  RESULTS
  Cisplatin treatment modified all parameters, except interleukin-18 and malondialdehyde, with each parameter demonstrating a different temporal profile. α-LA treatment attenuated renal tubular injury scores (P <0.05), decreased peak serum creatinine (p=0.004) and cystatin C (p=0.04), and urinary damage biomarkers of proximal tubular injury (CystatinC, NGAL, albumin, and alpha-1-acid glycoprotein). Other urinary biomarkers were not modified. Neither α-LA alone, nor the cisplatin vehicle (DMSO) modified biomarker profiles.
  
  
  CONCLUSIONS
  α-LA treatment ameliorated cisplatin-induced AKI. Protection was demonstrated by reduced structural damage, improved glomerular filtration and reduced excretion of urinary biomarkers of proximal tubular damage. Effective treatment of AKI can be monitored by site and perhaps by mechanism-specific kidney damage biomarkers.
authors.affiliation: Prince Of Wales Clinical School, University of New South Wales, Randwick, NSW, Australia; Northern Clinical School, University of Melbourne, Epping, Victoria, Australia. Electronic address: timothy.pianta@nh.org.au.
authors.forename: T J
authors.initials: TJ
authors.lastname: Pianta
authors.affiliation: Prince Of Wales Clinical School, University of New South Wales, Randwick, NSW, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Succar
authors.affiliation: Anatomical Pathology, Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Davidson
authors.affiliation: Clinical Pharmacology, University of Sydney, NSW, Australia.
authors.forename: N A
authors.initials: NA
authors.lastname: Buckley
authors.affiliation: Prince Of Wales Clinical School, University of New South Wales, Randwick, NSW, Australia.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Endre
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002945:Cisplatin; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011237:Predictive Value of Tests; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology*; D013997:Time Factors; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D008063:Thioctic Acid; D002945:Cisplatin
keywords: Acute kidney injury; Acute tubular injury; Alpha-lipoic acid; Biomarkers; Cisplatin