ArticleProceedings of the National Academy of Sciences of the United States of America2025
SLC39A8-mediated zinc dyshomeostasis potentiates kidney disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- Manganese: biology, physiology and role in disease.Cell discovery · 2026Review
- Zinc Signaling in Acute Kidney Injury.Cells · 2026Review
- Zincology: Decoding Homeostasis to Unveil Disease Mechanisms.Research (Washington, D.C.) · 2026Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors.
Funding
Abstract
While numerous genetic risk loci are linked to kidney disease, a unifying therapeutic target for diverse renal pathologies remains elusive. Here, through large-cohort polymorphic locus screening, we identify the SLC39A8 A391T variant (rs13107325) as a shared modifier of multiple kidney diseases. Functional characterization using Slc39a8 A391T knock-in mice and kidney-specific Slc39a8 knockout mice reveals that loss of SLC39A8 function reduces renal zinc accumulation, thereby mitigating susceptibility to kidney injury and disease progression. Mechanistically, we demonstrate that perturbed zinc homeostasis drives renal damage, and limiting zinc levels-whether via impaired SLC39A8 activity or direct chelation-activates the zinc-AKT-FOXO1-G6PC axis to confer protection. Critically, zinc chelation with EDTA recapitulates this benefit, significantly preventing and ameliorating experimental acute and chronic kidney disease. These findings establish renal zinc homeostasis as a key therapeutic node, with SLC39A8 and zinc-modulating strategies representing promising avenues for treating a broad range of kidney diseases.
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