Chronic kidney disease (CKD) typically appears alongside other comorbidities, highlighting an underlying complex pathophysiology that is thought to be vastly modulated by the bidirectional gut-kidney crosstalk. By combining advances in tissue engineering, biofabrication, microfluidics, and biosensors, microphysiological systems (MPSs) have emerged as promising approaches for emulating the in vitro interconnection of multiple organs, while addressing the limitations of animal models. Mimicking the (patho)physiological states of the gut-kidney axis in vitro requires an MPS that can simulate not only this direct bidirectional crosstalk but also the contributions of other physiological participants such as the liver and the immune system. We discuss recent developments in the field that could potentially lead to in vitro modeling of the gut-kidney axis in CKD.
Chronic Kidney Disease: A Metabolic Disorder with Disrupted Inter-Organ and Inter-Organismal SignalingChronic kidney disease (CKD) is the most widespread kidney disease and is characterized by the gradual loss of organ function over time, which impairs the ability to filter metabolic waste products from the blood (Box 1). The kidneys have many highly specialized functions, such as blood filtration and active secretion for the removal of metabolic waste, reabsorption of essential nutrients, maintenance of blood volume and electrolyte homeostasis, and metabolic and endocrine activity [1].
HighlightsGut microbiota-derived metabolites are key molecular mediators of the microbiota-host axis.The excretory capacity of the kidney is an essential part of human gut microbial symbiosis.Chronic kidney disease (CKD) is a metabolic disease in which gut microbiotaderived metabolites accumulate in the blood and adversely affect host physiological functions.Intestine-on-a-chip models have been developed that recapitulate the 3D epithelial barrier, the gut-microbiome interaction, and intercellular crosstalk with remote organs.Components of the immune system are pivotal in remote communication between the gut and kidney.The combination of engineered microphysiological systems with highthroughput multiomic analysis will provide novel insights into organ intercommunication in CKD.