02024nas a2200205   4500000000100000008004100001260001500042100002400057700002300081700002000104700002400124700002500148700002500173245009700198856003900295300001400334490000700348520144900355022001401804       2023                            d  c2023-06-191 aVivian V. T. Nguyen1 aVasiliki Gkouzioti1 aChristian Maass1 aMarianne C. Verhaar1 aRobin W. M. Vernooij1 aBas W. M. van Balkom00aA systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology  uhttps://doi.org/10.1242/dmm.050113  admm0501130 v163 aAs 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.  a1754-8403