Human and Experimental Features of Aristolochic Acid Nephropathy (aan; Formerly Chinese Herbs Nephropathy - Chn): Are They Relevant to Balkan Endemic Nephropathy (ben)?

Chinese herbs nephropathy, a rapidly progressive interstitial nephropathy, has been reported in young Belgian women given a slimming regimen including Chinese herbs. It is characterized by early, severe anemia, mild tubular proteinuria, and normal arterial blood pressure. Renal histology shows an extensive, remarkably aor hypocellular interstitial fibrosis associated with tubular atrophy and global sclerosis of glomeruli with a decreasing cortico-medullary gradient. A 40% to 46% prevalence of upper urothelial malignancy of the upper urinary tract has been reported. The nephrotoxic and carcinogenic aristolochic acids (AAs), extracted from the Aristolochia species, have been identified in herbs included in the slimming pills. The hypothesis that these alkaloids were the cause of CHN was substantiated by the identification of pre-mutagenic AA-DNA adducts in the kidney tissue of CHN patients. The causal role of AAs in CHN has eventually been demonstrated by the induction of the salient biologic and morphologic features of CHN in rabbits fed pure AAs without other components of the slimming regimen. Biological and morphological features of human and experimental AA-induced nephropathy are strikingly similar to those reported in BEN suggesting that AAs play also an etiological role in BEN, a hypothesis considered many years ago and yet to be fully explored. Confirmation of this hypothesis requires evidence that patients with an unequivocal diagnosis of BEN have ingested foods containing AAs and harbour AA-DNA adducts in their renal tissue.