Kidney organoids as a novel platform to evaluate heat-stress-induced acute kidney injury pathogenesis.

ABSTRACT: Acute kidney injury (AKI) is a serious condition with significant global impact. To explore mechanisms and biomarkers of heat-stress-induced AKI, we used human kidney organoids derived from induced pluripotent stem cells via suspension culture. Organoids were exposed to 37, 39, and 41°C. At 41°C, we found the viability decreased over time, with cytoskeleton damage, impaired tubule absorption, apoptosis, and collagen deposition. Under extreme heat (41°C), elevated AKI markers KIM-1 and NGAL, along with cell cycle arrest markers TIMP-2*IGFBP7 were detected. Notably, TIMP-2*IGFBP7 appeared at 12 h post-exposure, preceding NGAL and KIM-1. Nascent and steady-state RNA analyses revealed suppressed oxidative phosphorylation and ATP metabolism, along with elevated histone expression, implicating t

SUBMITTER: Su Q 

PROVIDER: S-EPMC12821206 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature