Narrative review of proximal tubular epithelial cell in-vitro co-culture models

Abstract Kidney diseases are among the leading causes of death globally. With the increasing rates of acute kidney injury (AKI) requiring hospitalisation, a better understanding of pathophysiological mechanisms is needed to treat the patients more efficiently. Nephrotoxicity is one of the most common causes of AKI, mainly due to the high availability of over-the-counter drugs and natural supplements, which may interact with prescribed drugs at the level of pharmacokinetics, among other factors. The latter can lead to clinically relevant complications (including AKI), which is even more pronounced given the increasingly ageing population in the Western world and the associated increase in polypharmacy. Drug testing starts at the preclinical level, where a reliable model is needed to predict human response to a tested drug with sufficient accuracy. Recently, in-vitro kidney models of different complexities have been created to study various aspects of kidney diseases. Because the proximal tubule plays a vital role in several mechanisms, many models include proximal tubular epithelial cells (PTECs). Monocultures of PTECs do not represent in-vivo tissue accurately enough. Therefore, more complex models with more cell types are being built. To our knowledge, this is the first review focusing on co-culture models and cell types used alongside PTECs for studying the nephrotoxicity of drugs and other mechanisms of AKI and chronic kidney disease.