Kidney-on-a-Chip Technology for Drug-Induced Nephrotoxicity Screening

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.

TrendsMore physiologically relevant screening devices are needed for drug-induced nephrotoxicity screening because traditional 2D models are poor predictors of in vivo biomarkers.Researchers are increasingly investigating innovative cell types, 3D microfluidic platforms, and biomarker profiling, but biological and technological constraints that challenge their relevance for in vivo physiology and biomarker development will need to be overcome.To become standard in drug screening and biomarker discovery tools, advanced platforms need to be validated against established nephrotoxicity assays and extrapolated to in vivo results.