Aristolochic Acid Toxicity and Associated Nephropathies
Summary
Aristolochic acids are a group of plant‐derived nitrophenanthrene carboxylic acids known to cause severe renal injury and urothelial carcinoma. Historically implicated in traditional herbal remedies and environmental contamination, these compounds provoke a distinct form of interstitial nephritis characterised by progressive tubular atrophy, interstitial fibrosis and a high risk of upper tract urothelial malignancies. Two main clinical entities arise from chronic exposure: aristolochic acid nephropathy, often observed in individuals self‐medicating with herbal products, and Balkan endemic nephropathy, restricted to populations consuming AA‐contaminated grain. Pathogenesis involves enzymatic activation of AA, formation of DNA adducts, persistent mutational stress and dysregulation of vasoactive mediators, culminating in irreversible renal scarring. Despite widespread bans, ongoing global use of AA‐containing plants and under‐recognition of exposure perpetuate the disease burden. Emerging insights into molecular mechanisms and biomarker development are vital for improved diagnosis, risk assessment and therapeutic innovation.
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Aristolochic Acid Toxicity and Associated Nephropathies publication trend
The graph below shows the total number of articles in aristolochic acid toxicity and associated nephropathies across all publications each year (not limited to Nature Index journals).
Technical terms
Aristolochic acids (AAs): Nitrophenanthrene carboxylic acids derived from Aristolochia plants, nephrotoxic and carcinogenic.
Aristolochic acid nephropathy (AAN): Progressive interstitial nephritis caused by AA exposure, marked by tubular atrophy and fibrosis.
Balkan endemic nephropathy (BEN): Geographically restricted chronic renal disease linked to dietary contamination with AAs.
DNA adduct: Covalent attachment of a chemical to DNA bases, serving as a biomarker of exposure and mutagenesis.
Organic anion transporters (OATs): Renal membrane proteins mediating uptake of organic anions, including AAs, into tubular cells.
Mutational signature: Distinctive pattern of base substitutions in the genome, reflecting specific carcinogenic processes.
References
- An Integrated View of Aristolochic Acid Nephropathy: Update of the Literature. International Journal of Molecular Sciences (2017).
- Systematic Overview of Aristolochic Acids: Nephrotoxicity, Carcinogenicity, and Underlying Mechanisms. Frontiers in Pharmacology (2019).
- Balkan endemic nephropathy: an update on its aetiology. Archives of Toxicology (2016).
- DNA Adducts Formed by Aristolochic Acid Are Unique Biomarkers of Exposure and Explain the Initiation Phase of Upper Urothelial Cancer. International Journal of Molecular Sciences (2017).
- Chinese Herbs Containing Aristolochic Acid Associated with Renal Failure and Urothelial Carcinoma: A Review from Epidemiologic Observations to Causal Inference. BioMed Research International (2014).
- Aristolochic Acid-Induced Nephrotoxicity: Molecular Mechanisms and Potential Protective Approaches. International Journal of Molecular Sciences (2020).
- Probenecid prevents acute tubular necrosis in a mouse model of aristolochic acid nephropathy. Kidney International (2012).
- Aristolochic acid mutational signature defines the low-risk subtype in upper tract urothelial carcinoma. Theranostics (2020).
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