Article révisé par les pairs
Résumé : BACKGROUND: Renal failure after ingestion of Chinese herbs between 1990 and 1992 was related to the replacement of Stephania tetrandra by Aristolochia fangchi (ST-AF), containing nephrotoxic and carcinogenic aristolochic acids. However, the relationship between ST-AF and renal failure is still a matter of debate. We therefore tested the impact of the ST-AF ingested dose on the progression of renal function deterioration. METHODS: Analysis of medical charts and prescriptions between 1990 and 1992 was carried out to determine the presence of risk factors for kidney failure and the cumulative dose of pill components. Individual progression rate of renal impairment was studied by the time-course of the inverse of blood creatinine level (1/P(creat)). RESULTS: Patients were divided into an end-stage renal disease (ESRD) group (n=44) and a chronic renal failure (CRF) group (n=27) according to their P(creat) at the time of this study. The mean number of risk factors (+/-SD) was equally distributed within both groups (1.50+/-0.18 vs 1.59+/-0.17, P=0.74). Patients from the ESRD group ingested significantly higher cumulative doses of ST--AF (192+/-13.1 g vs 138+/- 16.3 g), Magnolia officinalis, (80.1+/-6.3 g vs 59.8+/-11.7 g), diethylpropion (14.7+/-1.4 g vs 10.0+/-1.4 g) and fenfluramine (14.1+/-1.6 g vs 8.7+/-1.3 g). In the ESRD group, some patients who had received steroids had a slower progression to ESRD than the others. In multiple regression analysis, ST-AF emerged as the only significant drug predicting the slope of the progression of renal failure. Moreover, hypothesizing a linear dose-response relationship, the risk of developing ESRD linearly increased with ST-AF doses. CONCLUSIONS: The relationship between the cumulative ST-AF dose and the renal failure progression rate confirms that regular ingestion of Aristolochia sp. extracts is causally involved in the onset of chronic interstitial nephropathy leading to ESRD.