ArticleJCI insight2024
Aldehyde dehydrogenase 2 preserves kidney function by countering acrolein-induced metabolic and mitochondrial dysfunction.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism.Annals of medicine · 2026Review
- Chronic Kidney Disease in Children Within Five Years After Ifosfamide Chemotherapy for Childhood Cancer: A Dutch Pediatric Oncology Cohort Study.Cancer medicine · 2026Article
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- Effects of Flammable and Non-Flammable Nicotine Products on Kidney Health.Medical sciences (Basel, Switzerland) · 2026Review
- Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Rare variant optimized GWAS with functional validation identifies causal architecture of kidney function in East Asian population.Scientific reports · 2026Article
- Association of ALDH2 rs671 Polymorphism with chronic kidney disease incidence in a population-based Korean cohort.Scientific reports · 2026Article
- Reactive carbonyl species in health and chronic disease: from methylglyoxal to an integrative network of metabolic regulation.Cardiovascular diabetology · 2026Review
- Integrative Meta-Analysis and WGCNA Reveal Candidate Diagnostic Hub Genes in Clear Cell Carcinoma.International journal of cell biology · 2026Article
- The missing links in mitochondrial MR studies for CKD: tissue specificity and clinical relevance; a letter to the editor.International urology and nephrology · 2026Article
- Multi-omics and machine learning identify FN1 and ALDH2 as diagnostic biomarkers and therapeutic targets in early and late diabetic kidney disease.Renal failure · 2025Article
- Glycolysis to lactylation: Unraveling the metabolic and epigenetic landscape in tissue fibrosis (Review).Molecular medicine reports · 2025Review
- Acrolein exposure associated with kidney damage: a cross‑sectional study.Scientific reports · 2025Article
- Article
- Identification of ALDH2 as a novel target for the treatment of acute kidney injury in kidney transplantation based on WGCNA and machine learning algorithms and exploration of its potential mechanism of action using animal experiments.Frontiers in immunology · 2025Article
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8 authors.
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Abstract
The prevalence of chronic kidney disease (CKD) varies by race because of genetic and environmental factors. The Glu504Lys polymorphism in aldehyde dehydrogenase 2 (ALDH2), commonly observed among East Asian people, alters the enzyme's function in detoxifying alcohol-derived aldehydes, affecting kidney function. This study investigated the association between variations in ALDH2 levels within the kidney and the progression of kidney fibrosis. Our clinical data indicate that diminished ALDH2 levels are linked to worse CKD outcomes, with correlations between ALDH2 expression, estimated glomerular filtration rate, urinary levels of acrolein - an aldehyde metabolized by ALDH2 - and fibrosis severity. In mouse models of unilateral ureteral obstruction and folic acid nephropathy, reduced ALDH2 levels and elevated acrolein were observed in kidneys, especially in ALDH2 Glu504Lys-knockin mice. Mechanistically, acrolein modifies pyruvate kinase M2, leading to its nuclear translocation and coactivation of HIF-1α, shifting cellular metabolism to glycolysis, disrupting mitochondrial function, and contributing to tubular damage and the progression of kidney fibrosis. Enhancing ALDH2 expression through adeno-associated virus vectors reduced acrolein and mitigated fibrosis in both WT and Glu504Lys-knockin mice. These findings underscore the potential therapeutic significance of targeting the dynamic interaction between ALDH2 and acrolein in CKD.
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