title: Monitoring kidney safety in drug development: emerging technologies and their implications.
abstract: Drug-induced kidney injury is a serious and not uncommon adverse event which needs to be considered during drug development. The current standards used to monitor kidney function, such as blood urea nitrogen and serum creatinine, are late indicators of kidney injury and thus do not allow for timely intervention before loss of function. Improving the diagnosis and monitoring of kidney damage goes hand-in-hand with the identification of new biomarkers and the development of technologies that enable their sensitive and specific measurements. In order to move beyond restriction to internal company decisions, every entity that demonstrates the qualities of a biomarker must gain acceptance by health authorities if it is to be used for regulatory decision making in preclinical studies and clinical trials. This review focuses on the most promising achievements of new technologies applied to monitoring drug-induced nephrotoxicity (eg, gene expression, imaging, in vitro screening, protein assays) and on the use and implications of peripheral biomarkers such as the urinary protein biomarkers glutathione S-transferase-alpha, N-acetyl-beta-d-glucosaminidase, total protein, cystatin C, beta2-microglobulin, KIM-1, lipocalin-2 and serum cystatin C. Finally, the associated regulatory processes for use in clinics are also discussed.
authors.affiliation: Novartis Pharma AG, Klybeckstrasse 141, CH-4057 Basel, Switzerland. frank.dieterle@novartis.com
authors.forename: Frank
authors.initials: F
authors.lastname: Dieterle
authors.forename: Estelle
authors.initials: E
authors.lastname: Marrer
authors.forename: Eiko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Olivier
authors.initials: O
authors.lastname: Grenet
authors.forename: Andre
authors.initials: A
authors.lastname: Cordier
authors.forename: Jacky
authors.initials: J
authors.lastname: Vonderscher
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D023281:Genomics; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D007880:Legislation, Drug; D012079:Renal Circulation / Q000502:physiology; D012449:Safety; D014463:Ultrasonography