Chinese herbs nephropathy : pathology and etiology
(2000)
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- Authors
- Supervisors
- Rahier, Jacques
- Abstract
- Chinese herbs nephropathy (CHN) is a rapidly progressive interstitial nephropathy reported in young women who had followed a particular slimming regimen (Vanharwaghem et al., Lancet, 1993). It is characterized by early, severe anemia, mild tubular proteinuria, and normal arterial blood pressure (Kabanda et al., Kidney Int, 1995 ; Reginster et al., Nephrol Dial Transplant, 1997). The analysis of end-stage kidneys and upper urinary tract specimens removed at the time of renal transplantation (TP) in three patients with CHN allowed us to integrate the findings of renal interstitial fibrosis reported in early biopsies (Vanherweghem et al., Lancet, 1993) into a pathognomonic morphologic picture: an extensive, markedly a- or hypo-cellular interstitial fibrosis associated with tubular atrophy and global sclerosis of glomeruli with a decreasing cortico-medullar gradient (Cosyns et al., Kidney Int, 1994). We were puzzled by the presence of extensive urothelial atypia in the upper urinary tract of these patients warranting a careful follow-up to detect urinary tract malignancies. True bladder malignancies were subsequently identified (Cosyns et al, Lancet, 1994) and led our team to perform bilateral nephro-ureterectomies in all patient with CHN at the time of TP or shortly thereafter. We demonstrated a 40% prevalence of in situ urothelial carcinoma in 19 specimens removed from 10 such patients (Cosyns et al., Am J Kidney Dis, 1999), a finding subsequently confirmed by others (Nortier et la., New Engl J Med, 2000). <BR> Aristolochic acid (AA), a nephrotoxic and carcinogenic substance extracted from the Aristolochia species was identified in some herbs used to prepare the slimming pills (Van Haelen et al., Lancet, 1994) and suspected to be the cause of CHN. With the help of the Heidelberg group, we demonstrated the presence of pre-mutagenic AA-DNA adducts in the kidney tissue of CHN patients. We thus concluded that AA had indeed been ingested (Schmeiser at el., Cancer Res, 1996; Bieler et al., Carcinogenesis, 1997) and provided a pathophysiologic clue as to the CHN-associated malignancy. Our finding of immunohistochemical overexpression of p53, a tumor suppressive gene, in the neoplastic cells, further suggests that p53 is mutated in these cancers (Cosyns et al., Am J Kidney Dis, 1999). Moreover, induction of several salient pathologic and biologic features of CHN together with the development of urinary tract tumours in rabbits chronically administred AA as a single drug contained in the slimming pills (Cosyns et al, submitted). In contrast, the absence of renal interstitial fibrosis in rats after chronic AA exposure highlights species related diffenreces in the susceptibility to the toxicity of AA (Cosyns et al., Arch Toxicol, 1998). <BR> Finally, the similarities between CHN patients and those suffering from the Balkan endemic nephropathy (BEN) suggest that both conditions represent a single entity due ti AA (Cosyns et al., Kidney Int, 1994).
- Affiliations
Citations
Cosyns, J.-P. (2000). Chinese herbs nephropathy : pathology and etiology. https://hdl.handle.net/2078.5/111061