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Am J Kidney Dis ; 33(6): 1011-7, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10352187


Rapidly progressive renal fibrosis after a slimming regimen including Chinese herbs containing aristolochic acid (AA) has been identified as Chinese-herb nephropathy (CHN). We reported urothelial atypia in three patients with CHN, with the subsequent development in one patient of overt transitional cell carcinoma (TCC). Therefore, it was decided to remove the native kidneys, as well as the ureters, in all patients with CHN. Nineteen kidneys and ureters removed during and/or after renal transplantation from 10 patients were studied to assess critically urothelial lesions and to characterize the cellular expression of p53, a tumor-suppressor gene overexpressed in several types of malignancies. Multifocal high-grade flat TCC in situ (carcinoma in situ; CiS) was observed, mainly in the upper urinary tract, in four patients, a prevalence of 40%. In one of those patients, a superficially invasive flat TCC of the right upper ureter, as well as two additional foci of noninvasive papillary TCC, were found in the right pelvis and left lower ureter, respectively. This patient also presented recurrent noninvasive papillary TCC of the bladder. Furthermore, in all cases, multifocal, overall moderate atypia was found in the medullary collecting ducts, pelvis, and ureter. All CiS and papillary TCC, as well as urothelial atypia, overexpressed p53. These results show that the intake of Chinese herbs containing AA has a dramatic carcinogenic effect. Carcinogenesis is associated with the overexpression of p53, which suggests a role for a p53 gene mutation. The relationship of this mutation with the reported presence of AA DNA adducts in the kidney remains to be explored.

Ácidos Aristolóquicos , Carcinógenos , Carcinoma in Situ/inducido químicamente , Carcinoma de Células Transicionales/inducido químicamente , Medicamentos Herbarios Chinos/efectos adversos , Enfermedades Renales/inducido químicamente , Neoplasias Renales/inducido químicamente , Fenantrenos/efectos adversos , Adulto , Femenino , Humanos , Riñón/patología , Enfermedades Renales/genética , Enfermedades Renales/patología , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/análisis , Uréter/patología , Neoplasias Ureterales/inducido químicamente
Kidney Int ; 45(6): 1680-8, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7933816


Rapidly progressive interstitial renal fibrosis has recently been reported in young women who have been on a slimming regimen including Chinese herbs. We examined four nephroureterectomies performed in three patients prior to or at the time of transplantation to determine the nature and topography of the kidney and urinary tract lesions in Chinese herbs nephropathy (CHN). Extensive, hypocellular, interstitial sclerosis, tubular atrophy and global sclerosis of glomeruli decreasing from the outer to the inner cortex, including the columns of Bertin, were observed in the four kidney specimens, together with severe fibromucoid to fibrous intimal thickening, mainly of interlobular arteries, normal or collapsed residual glomeruli, and mild to moderate atypia and atypical hyperplasia of the urothelium. In addition, bilateral pelvi-ureteric sclerosis was observed in one case. With the exception of the latter, these lesions are very similar to those described in Balkan endemic nephropathy (BEN). The clinical presentation of the patients was also similar to that observed in BEN: normal blood pressure, aseptic leukocyturia, low grade low molecular weight proteinuria, early and severe anemia. In conclusion, on morphological and clinical grounds, CHN appears similar to BEN. A common etiologic agent, aristolochic acid, is suspected. The known carcinogenic potential of this compound, taken together with our finding of multiple foci of cellular atypia of the urothelium suggest that CHN patients should undergo a regular follow-up for urothelial malignancy.

Nefropatía de los Balcanes/inducido químicamente , Medicamentos Herbarios Chinos/efectos adversos , Fallo Renal Crónico/inducido químicamente , Adulto , Nefropatía de los Balcanes/patología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Fibrosis , Humanos , Riñón/patología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Túbulos Renales/patología , Obesidad/tratamiento farmacológico