Monitoring kidney safety in drug development: emerging technologies and their implications

Curr Opin Drug Discov Devel. 2008 Jan;11(1):60-71.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Drug Design
  • Drug Evaluation, Preclinical
  • Drug-Related Side Effects and Adverse Reactions*
  • Genomics
  • Humans
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / diagnosis*
  • Kidney Diseases / diagnostic imaging
  • Kidney Diseases / genetics
  • Legislation, Drug
  • Renal Circulation / physiology
  • Safety
  • Ultrasonography