Rapidly progressive fibrosing interstitial nephritis associated with Chinese herbal drugs

doi:10.1016/S0272-6386(00)70343-X

American Journal of Kidney Diseases

Volume 35, Issue 2, February 2000, Pages 313-318

https://doi.org/10.1016/S0272-6386(00)70343-X Get rights and content

Abstract

Rapidly progressive fibrosing interstitial nephritis after a slimming regimen containing aristolochic acid has been identified as Chinese herbs nephropathy (CHNP). From 1995 to 1998, we observed 12 Chinese people from different areas of Taiwan who underwent renal biopsy for unexplained renal failure. Medical history gave no clue to the causes of impaired renal function except for the ingestion of traditional Chinese herbs. Although these patients ingested herbal drugs from various sources for different purposes, their renal biopsy samples showed amazingly similar histological findings, with extensive hypocellular interstitial fibrosis and atrophy and loss of tubules in all cases. Glomeruli were apparently intact. They also had similar clinical features, such as normal or mildly elevated blood pressure, early and severe anemia, low-grade proteinuria, glycosuria, and insignificant urinary sediments. Renal function deteriorated rapidly in most patients despite discontinuation of the herbal medicines. Seven patients underwent dialysis, and the remainder experienced slowly progressive renal failure. Bladder carcinoma was found in one patient. Morphologically and clinically, the nephropathy in our patients was similar to CHNP, reported in Belgium. Because of the complexity and unknown types of herbs used in different clinical situations, unidentified phytotoxins other than aristolochic acid might be responsible for this unique disease entity. We conclude that the relation of this nephropathy to the consumption of Chinese herbs is striking. Using uncontrolled herbal remedies carries a high risk for developing interstitial renal fibrosis and urothelial malignancy.

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Patients and methods

From January 1995 to July 1998, 12 Chinese patients who underwent renal biopsy for unexplained renal failure and were proven pathologically to have fibrosing interstitial nephritis are the basis of this report. They came from different areas in Taiwan. The common feature was a definite recent history of herbal medicine use for different durations. They had not previously taken other medications or undergone contrast medium studies. All patients had taken Chinese herbal regimens as plant

Discussion

CHNP, first reported in Belgium, is characterized by rapidly progressive fibrosing interstitial nephritis.¹ It is related to slimming regimens that include Chinese herbs. The renal lesion is remarkable for its extensive fibrotic process and rapidity of evolution.⁵ The aristolochic acid included in these Chinese herb preparations was suspected to induce nephrotoxicity.⁴ Despite discontinuation of the drugs, renal disease progresses rapidly to end-stage in most cases.⁶

Chinese herbal medicine has

References (19)

JL Vanherweghem et al.
Rapidly progressive interstitial renal fibrosis in young women: Association with slimming regimen including Chinese herbs
Lancet
(1993)
M Vanhaelen et al.
Identification of aristolochic acid in Chinese herbs
Lancet
(1994)
ME De Broe
On a nephrotoxic and carcinogenic slimming regimen
Am J Kidney Dis
(1999)
JP Cosyns et al.
Chinese herbs nephropathy: A clue to Balkan endemic nephropathy?
Kidney Int
(1994)
JL Vanherweghem et al.
Effects of steroids on the progression of renal failure in chronic interstitial renal fibrosis: A pilot study in Chinese herbs nephropathy
Am J Kidney Dis
(1996)
JP Cosyns et al.
Urothelial lesions in Chinese herb nephropathy
Am J Kidney Dis
(1999)
C Van Ypersele de Strihou et al.
The tragic paradigm of Chinese herbs nephropathy
Nephrol Dial Transplant
(1995)
JL Vanherweghem
Misuse of herbal remedies: The case of an outbreak of terminal renal failure in Belgium (Chinese herbs nephropathy)
J Altern Complement Med
(1998)
M Depierreux et al.
Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese herbs
Am J Kidney Dis
(1994)

There are more references available in the full text version of this article.

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Citation Excerpt :
AAs have been used worldwide (including in China, France, Belgium, Germany, USA, UK, Canada and Australia) for centuries [2–4]. AA I and AA II (with a difference of only one methoxy group, Fig. 1) are the main active compounds of AAs, which present in several herbal plants of the Aristolochiaceae and Asarum family [5]. Unfortunately, because of the DNA adducts formation, AA I and AA II were classified as carcinogenic to human and have been proven to be nephrotoxic [6–8].
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: Address reprint requests to Chwei-Shiun Yang, MD, 280 Jen-Ai Rd, Section 4, Division of Nephrology, Cathay General Hospital, Taipei, Taiwan. E-mail: [email protected]

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Case ReportsRapidly progressive fibrosing interstitial nephritis associated with Chinese herbal drugs

Abstract

Section snippets

Patients and methods

Discussion

Lancet

Lancet

Am J Kidney Dis

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

The tragic paradigm of Chinese herbs nephropathy

Nephrol Dial Transplant

Misuse of herbal remedies: The case of an outbreak of terminal renal failure in Belgium (Chinese herbs nephropathy)

J Altern Complement Med

Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese herbs

Am J Kidney Dis

Case Reports
Rapidly progressive fibrosing interstitial nephritis associated with Chinese herbal drugs