Translational challenges in in vitro nephrotoxicity models

European Society of Toxicology In Vitro > Projects / Activities > ASCCT / ESTIV webinars > Translational challenges in in vitro nephrotoxicity models

Tue, Oct 22, 2019 4:00 PM – 5:00 PM CEST

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Presenter: Roos Masereeuw, PhD, Div. Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands

ABSTRACT: Adverse effects caused by exposure to foreign compounds, including drugs, often involve the kidney. In fact, 14 to 26% of the acute kidney injury events reported can be related to drug-induced kidney injury. Although acute damage to the kidney may be reversible, depending on severity, 30% of the patients develop structural renal dysfunction leading to chronic kidney disease eventually progressing into end-stage kidney disease. Early prediction of adverse effects such as drug interactions and renal toxicity is therefore imperative for clinical practice and for the development of new and safe drugs. Current in vitro assays do not accurately allow such prediction, predominantly due to inadequate preservation of the organs’ microenvironment. The kidney epithelium is highly polarized, and the maintenance of this polarity is critical for optimal functioning and responsiveness to environmental signals influencing cell proliferation, migration and differentiation. This presentation will provide an overview of advances in 3D cultures of human renal cells and organoids in microfluidics, and in particular kidney tubules, thereby improving physiological performance of the tissue. These microphysiological systems have great potential for drug screenings and provide novel alternative strategies for the prediction of renal drug disposition and safety assessment in a human-specific context. However, knowledge gaps in quantitative translation of renal drug disposition from microphysiological systems still exist and will be discussed.