Preprint links macrophage oxysterol 25-hydroxycholesterol to heightened statin-related kidney injury in cell, mouse and organoid models
- Examines whether 25-hydroxycholesterol, an oxysterol released by activated macrophages, makes kidney cells more vulnerable to statin toxicity.
- Atorvastatin and fluvastatin killed proximal tubular cells when paired with 25-HC, and statin-treated mice developed kidney injury after a small inflammatory challenge.
- Reduced protein prenylation disturbed autophagosome-lysosome function; mevalonate or macrophage depletion lessened injury, and kidney organoids showed higher KIM-1.
💡 Points
A statin plus an inflammatory oxysterol is a plausible toxic pairing: blocking the mevalonate pathway curbs prenylation, and mevalonate rescue fits an on-target mechanism. Still, in vitro and mouse statin exposures often exceed free plasma levels, so dose relevance is unproven, and this preprint is not peer reviewed. Human association data linking 25-HC, inflammation and kidney outcomes are needed to bridge the translational gap.
Macrophage-Derived 25-Hydroxycholesterol Drives Statin-Associated Acute Kidney Injury ↗