@article{2101, author = {Vivian V. T. Nguyen and Vasiliki Gkouzioti and Christian Maass and Marianne C. Verhaar and Robin W. M. Vernooij and Bas W. M. van Balkom}, title = {A systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology}, abstract = {As kidney diseases affect ∼10% of the world population, understanding the underlying mechanisms and developing therapeutic interventions are of high importance. Although animal models have enhanced knowledge of disease mechanisms, human (patho-)physiology may not be adequately represented in animals. Developments in microfluidics and renal cell biology have enabled the development of dynamic models to study renal (patho-)physiology in vitro. Allowing inclusion of human cells and combining different organ models, such as kidney-on-a-chip (KoC) models, enable the refinement and reduction of animal experiments. We systematically reviewed the methodological quality, applicability and effectiveness of kidney-based (multi-)organ-on-a-chip models, and describe the state-of-the-art, strengths and limitations, and opportunities regarding basic research and implementation of these models. We conclude that KoC models have evolved to complex models capable of mimicking systemic (patho-)physiological processes. Commercial chips and human induced pluripotent stem cells and organoids are important for KoC models to study disease mechanisms and assess drug effects, even in a personalized manner. This contributes to the Reduction, Refinement and Replacement of animal models for kidney research. A lack of reporting of intra- and inter-laboratory reproducibility and translational capacity currently hampers implementation of these models.}, year = {2023}, journal = {Disease Models & Mechanisms}, volume = {16}, pages = {dmm050113}, month = {2023-06-19}, issn = {1754-8403}, url = {https://doi.org/10.1242/dmm.050113}, doi = {10.1242/dmm.050113}, }