A kidney-on-chip model to treat chronic kidney disease

Chronic kidney disease (CKD) affects an average of one in every 10 adults, making it one of the most challenging public health issues in the world. The main cause of CKD is renal fibrosis — accumulation of the extracellular matrix on the kidney — which disrupts the organ’s normal function.

Accurate treatment of CKD is also hindered by inadequate preclinical models, so Yao et al. created a kidney-on-chip (KOC) model that could serve as a platform for anti-renal fibrosis research.

The chip is made of two parts: a flow perfusion chamber where the kidney organoid is generated, and a reservoir chamber to keep out bubbles that arise from the blood-like flow simulated by the KOC platform.

“After finalizing the blueprint, we fabricated the KOC using computer numerical control technology, with polysulfone — a novel biomedical material — as the main substrate,” said author Liyu Liu. “This material exhibits significant low drug adsorption characteristics, which can effectively enhance the accuracy and credibility of drug experiments conducted on the chip.”

The researchers were then able to induce renal fibrosis by stimulating the signal protein TGF-β1, which was shown by buildup of the extracellular matrix on the organoid. They also observed two types of cell transitions — epithelial to mesenchymal and fibroblast to myofibroblast — which are hallmarks of renal fibrosis.

The researchers were surprised to find that fluid shear stress from the microenvironment on the chip was able to regulate the fibrosis process, a mechanism that has been overlooked in traditional static models of renal fibrosis.

“Based on our established KOC model, we plan to systematically test several clinically promising anti-fibrotic drugs that target key mechanisms recapitulated in our system,” said author Yunying Shi. “We will use the KOC to evaluate these candidates based on their ability to prevent or reverse hallmark fibrotic phenotypes.”

Source: “A kidney organoid chip facilitating organoid development and in vitro renal fibrosis modeling,” by Xiyao Yao, Yamei Li, Yidan Gao, Lianjie Zhou, Yangjuan Bai, Bingqi Yang, Liang Feng, Lanlan Wang, Liyu Liu, and Yunying Shi, Biomicrofluidics (2026). The article can be accessed at https://doi.org/10.1063/5.0296663 .