Elevated glucose in kidney organoids induces tissue-intrinsic inflammation driving epithelial detachment

We demonstrate that human kidney organoids treated with elevated glucose exhibit a phenotype of epithelial detachment driven by tissue-intrinsic upregulation of proinflammatory cytokines, which can be targeted therapeutically. High glucose induces morphological deterioration of organoids featuring podocyte and tubular cell detachment without cytotoxicity.

Cytokine addition sensitizes organoids to intermediate concentrations of elevated glucose. Transcriptomic analysis reveals that high glucose levels affect cytokine, inflammation, signaling, and cell adhesion pathways, resembling changes in human diabetic kidneys. Inhibitors of cytokines and signaling pathways rescue the high glucose phenotype, which is independent of osmotic effects.