# Kidney organoids as a novel platform to evaluate heat‐stress‐induced acute kidney injury pathogenesis

## TL;DR

This study uses kidney organoids to investigate how heat stress causes acute kidney injury and identifies early biomarkers that could help in developing treatments.

## Contribution

The novel contribution is the use of human kidney organoids to model heat-stress-induced AKI and identify early biomarkers like TIMP-2*IGFBP7.

## Key findings

- Exposure to 41°C caused decreased viability, cytoskeleton damage, and collagen deposition in kidney organoids.
- TIMP-2*IGFBP7 appeared earlier than KIM-1 and NGAL, suggesting its potential as an early AKI biomarker.
- Heat stress suppressed oxidative phosphorylation and ATP metabolism while increasing histone expression.

## 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 their roles in heat‐induced AKI. The data support that kidney organoids serve as a valuable model for investigating heat‐induced AKI, providing insights into early injury biomarkers that are valuable for the development of treatments.