Herbal Nephropathy and Balkan Endemic Nephropathy: The Pathogenic Role of Aristolochic Acid

Main Article Content

Koulouridis Ioannis, MD Msc Koulouridis Efstathios, MD, PhD Maha Qari, BDS, MS, DSc

Abstract

Aristolochic acid nephropathy is a worldwide iatrogenic disease affecting individuals consuming herbal remedies derived from Aristolochia and Asarum species. The disease is characterized by prominent renal atrophy and extensive interstitial fibrosis. A considerable proportion of patients, about 30-45 % develop also transitional cell carcinoma mainly of the upper urinary tract. A special attention to the disease was paid in early 90’s because of an epidemic of rapidly progressive interstitial nephropathy affecting young women consuming slimming pills, containing Chinese herbs, supplied from the same clinic in Brussels, Belgium. Detailed investigation of slimming pills showed that they inadvertently contained Aristolochic acid considered as the causative factor of the disease. Soon thereafter it was showed that another devastating chronic interstitial nephropathy accompanied also with increased incidence of upper urothelial cancer, known as Balkan Endemic Nephropathy, is the result of chronic intoxication of affected individuals with low doses of Aristolochic acid derived from the soil contamination from the plant Aristolochia clematitis. Although Aristolochic acid has already characterized as class I carcinogen for humans, Aristolochia species continues to be used as herbal remedies especially in Asia countries and China as well as in westernized communities. It is noteworthy that although Aristolochia species are used as herbal remedies since antiquity there are no references for nephrotoxicity and carcinogenicity until the Belgium epidemic. In this review article we attempt to elucidate the historical evolution of our knowledge upon the etiology of Aristolochic acid nephropathy as well as the underlying mechanisms of Aristolochic acid cytotoxicity.

Keywords: Herbal nephropathy, Balkan Endemic Nephropathy, Aristolochic acid toxicity

Article Details

How to Cite
IOANNIS, Koulouridis; EFSTATHIOS, Koulouridis; QARI, Maha. Herbal Nephropathy and Balkan Endemic Nephropathy: The Pathogenic Role of Aristolochic Acid. Medical Research Archives, [S.l.], v. 12, n. 6, june 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5565>. Date accessed: 21 dec. 2024. doi: https://doi.org/10.18103/mra.v12i6.5565.
Section
Research Articles

References

1. Sewell RDE, Rafician-Kopaci M. The history and ups and downs of herbal medicines usage. J Herb Med Pharmacol. 2014; 3(1): 1-3.
2. Petrovska BB. Historical review of medicinal plants’ usage. Pharmacogn Rev. 2012; 6(11): 1-5.
3. Grollman AP, Marcus DM. Global hazards of herbal remedies: lessons from Aristolochia. EMBO rep 2016; 17(5): 619-625.
4. Chen T. Genotoxicity of Aristolochic Acid: A Review. JFDA 2007; 15 (4): 387-399.
5. Jamshidi-Kia F, Lorigooini Z, Amini-Khoel H. Medicinal plants: Past history and future perspective. J Herb Med Pharmacol. 2018; 7(1): 1-7.
6. Raghavendra HL, Yogesh HS, Gopalakrishna B, Chandrashekhar VM, Sathish Kumar BP, Vadlapudi K. An overview of herbal medicine. Int J Ph Sci. 2009; 1(1): 1-20.
7. Rivera JO, Loya AM, Caballos R. Use of Herbal Medicines and Implications for Conventional Drug Therapy Medical Sciences. Altern Integ Med. 2013; 2:6 (doi.org/10.4172/2327-5162.1000130).
8. WHO monographs on selected medicinal plants. VOLUME 1. World Health Organization. Geneva. 1999.
9. Directive 2004/24/EC of the European parliament and of council of 31 March
2004.
10. Vanherweghem JL, Depierreux M, Tielemans C et al. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet 1993 Feb 13; 341 (8842): 387-91.
11. Cosyns JP, Jadoul M, Squifflet JP, De Plaen JF, Ferluca D, van Yperssele de Strihu C. Chinese herbs nephropathy: A clue to Balkan endemic nephropathy? Kidney Int 1994; 45: 1680-1688.
12. Jadot I, Decleves A-E, Nortier J, Caron N. An Integrated View of Aristolochic acid Nephropathy: Update of the Literature. Int J Mol Sci. 2017; 18, 297: 1-24.
13. Meyer MM, Chen T-P, Bennett WM. Chinese herb nephropathy. Bayl Univ Med Cent Proc. 2000; 13 (4): 334-337.
14. Nortier JL, Martinez M-C M, Schmeiser HH et al. Urothelial Carcinoma Associated with the Use of a Chinese Herb (Aristolochia fangchi). N Engl J Med. 2000; 342: 1686-1692.
15. Zhou Q, Jiang L, Su T, Liu G, Yang L. Overview of Aristolochic acid nephropathy: an update. Kidney Res Clin Pract. 2023; 42(5): 579-590.
16. Dimitrov PS, Simeonov VA, Stein AD. Balkan endemic nephropathy in Vratza, Bulgaria, 1964-1987: An epidemiologic analysis of population-based disease registers. Eur J Epidemiol. 2001; 17(9): 847-853.
17. Bamias G, Boletis J. Balkan Nephropathy: Evolution of Our Knowledge. AJKD 2008; 52(3): 606-616.
18. Velickovic LJ, Dolicanin Z, Stefanovic V. Endemic Nephropathy And Upper Urothelial Carcinoma- New Insights In Molecular Biology. Contributions. Sec. Med. Sci. 2014.
19. Crosby LM, Tatu CA, Pavlovic N, Oren WH. The continuing medical mystery of Balkan Endemic Nephropathy. J Rare Disorders 2015; 3(2): 22-37.
20. De Broe ME. Chinese herbs nephropathy and Balkan endemic nephropathy: toward a single entity, Aristolochic acid nephropathy. Kidney Int. 2012; 81: 513-515.
21. Ivic M. [Etiology of endemic nephropathy]. Lijec Vjesn. 1969; 91(12): 1273-1281 [Article in Croatian].
22. Grollman AP. Aristolochic Acid Nephropathy: Harbinger of a Global Iatrogenic disease. Environ Mol Mutagen. 2013; 54: 1-7.
23. Pohl J. Ueber das Aristolochin, einen giftigen Bestandtheil der Aristolochia-Arten. Archiv f. experiment. Pathol. U. Pharmakol 1981; 29: 282-302. [Article in German].
24. Vanhaelen M, Vanhaelen-Fastre R, But P, Vanherweghem JL. Identification of Aristolochic acid in Chinese herbs. Lancet 1994; 343(8890): 174.
25. Schmeiser HH, Bieter CA, Wiessler M, van Ypersele de Strihou C, Cosyns JP. Detection of DNA Adducts Formed by Aristolochic Acid in Renal Tissue from Patients with Chinese Herbs Nephropathy. Cancer Res. 1996; 56: 2025-2028.
26. Grollman AP, Shibutani S, Moriya M et al. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. PNAS 2007; 104 (29): 12123-12134.
27. Brzic´ Ι, Brener Μ, Carni Α et al. Different Ecological Niches of Poisonous Aristolochia clematitis in Central and Marginal Distribution Range - Another Contribution to a Better Understanding of Balkan Endemic Nephropathy. Plants 2023; 12, 3022.
28. Chan C-K, Liu Y, Pavlovic NM, Chan W. Aristolochic Acids: Newly Identified Exposure Pathways of this Class of Environmental and Food-Borne Contaminants and its Potential Link to Chronic Kidney Diseases. Toxics 2019; 7 (1): 14.
29. Chan C-K, Liu Y, Pavlovic NM, Chan W. Etiology of Balkan Endemic Nephropathy: An Update on Aristolochic Acids Exposure Mechanisms. Chem Res Toxicol. 2018; 31: 1109-1110.
30. Nardi E. The genus Aristolochia L. (Aristolochiacea) in Greece. Webbia 1991; 45(1): 31-69.
31. Scarborough J. Ancient Medicinal Use of Aristolochia: Birthwort’s Tradition and Toxicity. Pharmacy in History 2011; 53: 3-21.
32. Han J, Xian Z, Zhang Y, Liu J, Liang A: Systematic Overview of Aristolochic Acids: Nephrotoxicity, Carcinonenicity, and Underlying Mechanisms. Front. Pharmacol. 2019; 10: 648.
33. Su T, Zhang LX, Li XM, Zuo L, Zhang PH, Wang HY. Regular use of nephrotoxic medications is an independent risk factor for chronic kidney disease-results from a Chinese population study. Nephrol Dial Transplant 2011; 26: 1916-1923.
34. Stiborova M, Arit VM, Schmeiser HH. DNA Adducts Formed by Aristolochic Acid Are Unique Biomarkers of Exposure and Explain the Initiation Phase of Upper Urothelial Cancer. Int. J. Mol. Sci. 2017; 18: 2144.
35. Martinek V, Barta F, Hodek P et al: Comparison of the oxidation of carcinogenic Aristolochic acid I and II by microsomal cytochromes P450 in vitro: experimental and theoretical approaches. Monatsh Chem. 2017; 148: 1971-1981.
36. Chang S-Y, Weber EJ, Sidorenko VS et al. Human liver-kidney model elucidates the mechanism of Aristolochic acid nephrotoxicity. JCI Insight 2017; 2(22): e95978.
37. Anger EE, Yu F, Li J. (2020): Aristolochic Acid-Induced Nephrotoxicity: Molecular Mechanisms and Potential Protective Approaches. Int J Mol Sci. 21: 1157; doi:10.3390/ijms21031157.
38. Zhou Q, Jiang L, Su T, Liu G, Yang L. Overview of Aristolochic acid nephropathy: an update. Kidney Res Clin Pract. 2023; 42(5): 579-590.
39. Khan MA, Kassianos AJ, Hoy WE, Alam AK, Healy HG, Gobe GC. Promoting Plant based Therapies for Chronic Kidney Disease. J Evid Based Integr Med 2022; 27: 1-16.