Tier 3 — preclinical

The metabolite alpha-ketoglutarate inhibits vascular calcification partially through modulation of the TET2/NLRP3 inflammasome signaling pathway

Fu M, Lan Z, Ye Y, Gong Y, Liang Q, Li M, Feng L, Chen A, Dong Q, Li Y, Wang S, Liu X, Zhang X, Ou JS, Lu L, Yan J

Kidney International 2025 108(2):233-252

Bibliography

PubMed: PMID 40383231
DOI: 10.1016/j.kint.2025.04.016
Funding: Academic cardiovascular and renal research funding is reported in the full article.
Competing interests: No retail Ca-AKG finished-product trial was conducted.

Design	Rodent CKD calcification study with rat/human vascular smooth-muscle cells and arterial-ring experiments.
Model	CKD rats and mice, rodent and human VSMCs, arterial rings.
Sample	Multiple in-vivo, ex-vivo and cell cohorts.
Intervention	AKG exposure with genetic/pharmacologic manipulation of TET2 and NLRP3 signaling.
Duration	Study-specific calcification protocols.
Endpoints	Vascular calcification; Mineral deposition; TET2 expression; NLRP3 inflammasome; IL-1β; Aortic calcification

This 2025 Kidney International paper connects AKG to vascular-calcification biology through epigenetic and inflammatory signaling.

AKG reduced calcification in cell, arterial-ring and CKD rodent models; TET2 and NLRP3 signaling contributed to the effect.

Human vascular cells and tissue were studied ex vivo, but this is not a human oral Ca-AKG supplementation trial.

AKG reduced calcification in rat and human vascular smooth-muscle-cell models.
Aortic calcification was reduced in CKD rodents.
TET2 upregulation and suppression of NLRP3/caspase-1/IL-1β signaling contributed mechanistically.

Editorial review

Last verified 20 September 2026