title: Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges.
abstract: Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well as their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules.
authors.affiliation: Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810, United States. Electronic address: Rounak.nassirpour@pfizer.com.
authors.forename: Rounak
authors.initials: R
authors.lastname: Nassirpour
authors.affiliation: Drug Safety, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, United States.
authors.forename: Shashi K
authors.initials: SK
authors.lastname: Ramaiah
authors.affiliation: Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810, United States.
authors.forename: Laurence O
authors.initials: LO
authors.lastname: Whiteley
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D035683:MicroRNAs / Q000378:metabolism*; D009399:Nephrons / Q000378:metabolism*; D018675:Toxicity Tests
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Acute kidney injury; Biomarkers; Drug induced nephrotoxicity; MicroRNAs