title: Detection and management of nephrotoxicity during drug development.
abstract: BACKGROUND
  The kidneys are vulnerable to injury due to their high filtration capacity and high metabolic activity, and most drugs, especially hydrophilic drugs and their metabolites, are eliminated largely by kidneys in urine, thus increasing the risk of drug-induced nephrotoxicity (DIN). DIN accounts for 18 - 27% of community- and hospital-acquired episodes of acute kidney injury (AKI) and is a serious concern during development of novel therapeutic drugs.
  
  
  METHODS
  This review provides an overview of definitions, classification, risk factors, complications, and outcomes of DIN. In addition, it gives a practical source of information when dealing with nephrotoxicity issues during drug development and provides guidance on renal safety risk evaluation for clinical studies. Lastly, current research focus in the search for novel biomarkers of DIN is also provided.
  
  
  CONCLUSIONS
  To enable early detection of DIN and to ensure patients' safety through appropriate risk minimization and mitigation strategies, future research should focus on identification and validation of novel predictive biomarkers of kidney injury and development of DIN-specific classification and staging system. This could help in reducing the current high rate of attrition during drug development, and reduce marketing and post-marketing withdrawals of nephrotoxic drugs.
authors.affiliation: Hoffmann-La Roche Inc., Nutley, New Jersey, USA. mahmoud_loghman_adham@baxter.com
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Loghman-Adham
authors.forename: Chek Ing
authors.initials: CI
authors.lastname: Kiu Weber
authors.forename: Cornelia
authors.initials: C
authors.lastname: Ciorciaro
authors.forename: Jessica
authors.initials: J
authors.lastname: Mann
authors.forename: Matthias
authors.initials: M
authors.lastname: Meier
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D002908:Chronic Disease; D055808:Drug Discovery; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000175:diagnosis; D012307:Risk Factors; D012308:Risk Management