Aristolochic acid as a causative factor in a case of Chinese herbal nephropathy.

Sir, Chinese herbal nephropathy (CHN) is a newly described type of interstitial nephritis with a characteristic histological pattern. It was initially described in a series of Belgian patients who were inadvertently given a contaminated herbal preparation as part of a slimming regimen w1x. The toxic agent was putatively identified as 'aristolochic acid' (AA), the active principle from species of Aristolochia now known to be a mixture of nitrophenanthrene derivatives such as aristolochic acid I and aristolochic acid II w1x. The likelihood that AA was the causative agent of CHN was strengthened by the finding of AA-DNA adducts in the kidneys and urothelial tracts of patients affected by this condition w2x. In those 524 Nephrol Dial Transplant (2002) 17: 524 cases, the inclusion of AA resulted from the substitution of Aristolochia species for Stephania tetrandra in the slimming pills. Despite these findings, doubt has been cast on the pathogenic role of AA, in part because of the concomitant administration of other prescription medication w3x. We have recently reported two cases of CHN in the United Kingdom that were caused by AA and that led to a permanent ban of AA by the Medicines Control Agency w4x. Similar bans are now in force in Canada, Australia and other European Union countries. Here we report the case of a 59-year-old man who developed renal failure (urea 26.8 mmolul (normal range: 2.8–7.6 mmolul), creatinine 660 mmolul (normal range: 80–133 mmolul)) and pancytopenia 9 ul)) following a 5-year period of ingesting a Chinese herbal preparation to treat hepatitis B. Renal biopsy revealed a histological pattern of cortical interstitial fibrosis with relative glomerular preservation, which is characteristic of this form of nephropathy. Analysis of the herbal preparation by liquid chromatography and mass spectrography revealed the presence of aristolochic acids I and II, which are nitrophenanthrene derivatives that have been causally associated with the development of Chinese herbal nephropathy (Figure 1). Autoimmune serology was normal or negative, as was protein electrophoresis. Ultrasound examination of the kidneys excluded obstruction. Due to his worsening pancytopenia, he underwent a bone marrow aspirate, which showed a hypocellular marrow with increased macrophage activity with no primary haematological abnormality. A bone marrow trephine showed normal cellularity with all three haemopoietic cell lineages present although there was a slight decrease in megakaryocytes. We concluded that the most likely diagnosis was AA nephropathy and, possibly, associated bone marrow suppression. The case presented here further implicates …