Cliniques Universitaires St Luc, Renal Department, Brussels, Belgium Email: vanypersele{at}nefr.ucl.ac.be
Sir,
Muniz Martinez et al. [1] report, in 71 patients with Chinese herbs nephropathy (CHN), an interesting relationship between the total amount of ingested Stephania tetrandra/Aristolochia fangchi herbs and the progression rate of renal failure. Five years ago we reached a similar conclusion in an analysis of 15 patients: we demonstrated a striking relationship between the duration of Chinese herbs ingestion and creatinine doubling time [2].
In both approaches, the amount of ingested S. tetrandra (often replaced by A. fangchi) or the duration of Chinese herbs ingestion are used as surrogate markers of A. fangchi and, hence, of aristolochic acid (AA) intake. Unfortunately these premises suffer from the fact that the actual aristolochic acid content, measured in 1994 by Vanhaelen et al. [3] in 12 batches of Chinese herb powder utilized in Belgium in the preparation of the slimming pills, proved highly variable from none to 1.56 mg/g (mean (SD) 0.65 (0.56) mg/g) [3]. The actual AA intake of the CHN patients remains, therefore, imprecise. Nevertheless, the concurrence of both approaches is very suggestive of an AA dose effect on the progression of the renal disease.
Muniz-Martinez et al. [1] also claim that steroid therapy given to 15 of 44 patients, who eventually reached end-stage renal failure, slowed the progression of renal failure but had no effect in the seven out of 27 patients who did not yet suffer from end-stage renal failure. It would be of interest to have further details on the duration and intensity of steroid therapy, the serum creatinine level at the onset of treatment and the reasons for allocating patients to this therapeutic modality. In the absence of this information, it is difficult to conclude to a beneficial effect of steroid treatment.
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Department of Nephrology, Hôpital Erasme, Brussels, Belgium Email: jnortier{at}ulb.ac.be
Sir,
We acknowledged that van Ypersele de Strihou's team has previously suggested a correlation between the severity of the renal disease and the duration of exposure to Chinese herbs in their cohort of CHN patients [1]. However, we did not consider their observation as definite evidence, for the following reasons:
(i) Their observation was based on a small number of patients (n=11). This increases the probability of hazards due to variations, as underlined by themselves, in the aristolochic acid (AA) content from one batch of Chinese herbs to another and thus, probably, effective AA exposure from one patient to another. This kind of bias could be reduced by increasing the number of the patients, as we did.
(ii) In the absence of quantitative determination of S. tetrandra intake, they used the duration of Chinese herb ingestion to reflect exposure to A. fangchi. This, obviously, is only a crude approximation. First, we have noticed from repeated anamnestic inquiries and extensive examination of the prescriptions in our 71 CHN patients that random quantitative changes have been made in the composition of the prescribed herbal components (from 0 to 300 mg of S. tetrandra). Secondly, several patients had sometimes interrupted their medications for several months. Taking into account the cumulative total ingested dose delivered by the pharmacists as we did, is a more reliable way to quantify risk exposure.
(iii) To evaluate the progression rate of renal failure, they used the time needed to double serum creatinine. The validity of this method in evaluating the slope may be criticized, considering that, in our experience, blood sample collections were particularly erratic with time in CHN patients. The use of the time course of the inverse of blood creatinine levelas we didseemed to us more relevant.
Finally, addressing the question related to the beneficial effect of steroids in slowing down the progression of CHN requires more details and is of a sufficiently high degree of interest to be discussed in a separate letter, which will be especially devoted to this issue [2].
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