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Nephropathy induced by aristolochic acid (AA) containing herbs

Marc E De Broe, MD, PhD
Section Editor
Gary C Curhan, MD, ScD
Deputy Editor
Alice M Sheridan, MD


In 1991, physicians in Belgium noted an increasing number of women who presented with acute, often near end-stage renal disease (ESRD) following exposure to aristolochic acid (AA) at a weight reduction clinic [1,2]. An initial survey of seven nephrology centers in Brussels identified 14 women under the age of 50 years who had presented with advanced renal failure due to biopsy-proven chronic tubulointerstitial nephritis over a three-year period; nine of these patients had been exposed to the same slimming regimen [1]. A total of more than 300 cases have been identified, a third of whom have already undergone renal transplantation.

The epidemiology is unknown, as is the risk for development of severe renal damage. However, the publication of case reports from several countries in Europe and Asia, particularly in China, indicate that the incidence of herbal medicine-induced nephrotoxicity is more common than previously thought [3-6].


The major lesion, which is located principally in the cortex, is extensive interstitial fibrosis with atrophy and loss of the tubules. Cellular infiltration of the interstitium is scarce. Thickening of the walls of the interlobular and afferent arterioles result from endothelial cell swelling. The glomeruli are relatively spared, and immune deposits are not observed. These findings suggest that the primary lesions may be centered in the vessel walls, thereby leading to ischemia and interstitial fibrosis.

An extremely high incidence of cellular atypia and urothelial (transitional cell) carcinoma of the renal pelvis, ureter, and bladder has been associated with AA nephropathy [7-9].


In 1969. it was first suggested that ingestion of flour contaminated with seeds from Aristolochia clematitis may be the cause of Balkan endemic nephropathy (BEN) when it was noted that seeds from these plants, which grew abundantly in local wheat fields, commingled with wheat grain during the harvesting process [10]. Support for AA as the major nephrotoxin is provided by more recent findings in animal models (rabbit, rat, and mice) of disease [11-15]. In one study, for example, rabbits were given intraperitoneal injections of AA (0.1 mg AA/kg five days a week for 17 to 21 months) [11]. Histologic examination of the kidneys and genitourinary tract revealed renal hypocellular interstitial fibrosis and atypical and malignant uroepithelial cells.


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Literature review current through: Sep 2016. | This topic last updated: Jul 7, 2016.
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