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

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.