title: Kidney-on-a-Chip Technology for Drug-Induced Nephrotoxicity Screening.
abstract: Improved model systems to predict drug efficacy, interactions, and drug-induced kidney injury (DIKI) are crucially needed in drug development. Organ-on-a-chip technology is a suitable in vitro system because it reproduces the 3D microenvironment. A kidney-on-a-chip can mimic the structural, mechanical, transport, absorptive, and physiological properties of the human kidney. In this review we address the application of state-of-the-art microfluidic culturing techniques, with a focus on culturing kidney proximal tubules, that are promising for the detection of biomarkers that predict drug interactions and DIKI. We also discuss high-throughput screening and the challenges for in vitro to in vivo extrapolation (IVIVE) that will need to be overcome for successful implementation.
authors.affiliation: Department of Pharmacology and Toxicology, Radboudumc, PO Box 9101, Nijmegen, HB 6500 The Netherlands. Electronic address: martijn.wilmer@radboudumc.nl.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Wilmer
authors.affiliation: MIMETAS BV, JH Oortweg 19, Leiden, CH, 2333 The Netherlands.
authors.forename: Chee Ping
authors.initials: CP
authors.lastname: Ng
authors.affiliation: MIMETAS BV, JH Oortweg 19, Leiden, CH, 2333 The Netherlands.
authors.forename: Henriëtte L
authors.initials: HL
authors.lastname: Lanz
authors.affiliation: MIMETAS BV, JH Oortweg 19, Leiden, CH, 2333 The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Vulto
authors.affiliation: University of Applied Sciences Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, 4132 Muttenz, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Suter-Dick
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, Utrecht, CG 3584 The Netherlands.
authors.forename: Rosalinde
authors.initials: R
authors.lastname: Masereeuw
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D008954:Models, Biological; D009924:Organ Culture Techniques / Q000379:methods*
keywords: drug screening; high-throughput screening; kidney; microfluidics; nephrotoxicity; organ-on-a-chip