Spheroids, organoids and kidneys-on-chips: how complex human cellular models have assisted in the study of kidney disease and renal ciliopathies

Kidney disease is one of the leading causes of morbidity worldwide, emphasizing the importance for physiologically accurate disease models. With most of the approved renal drugs failing to perform as well in human clinical trials as they did in animal testing, it is imperative that new and improved human-based models are developed to test these potential therapeutics. One option is to use patient derived cell lines, grown in both two-dimensional (2D) and three-dimensional (3D) structures, known as spheroids and organoids. Despite their contributions to the field, the lack of physiological accuracy, including the absence of fluid flow, and mechanistic effects in these 2D and 3D models means there is still room for improvement. Organ-on-a-chip (OOAC) technology offers itself as a potential candidate model to overcome these limitations. Over recent years OOAC technology has grown in popularity, with multiple organ systems, including lung, liver, and kidney described in the literature. In this review, traditional human cellular based models, including monolayer, spheroid and organoid models will be discussed. Human kidney-on-a-chip models will also be discussed, while exploring the advantages and potential limitations of this rapidly emerging field for the study of human kidney disease and drug testing.