Risks of Kidney Failure Associated With Consumption of Herbal Products Containing Mu Tong or Fangchi: A Population-Based Case-Control Study

Lai, Min-Nan; Lai, Jung‐Nien; Chen, Pau‐Chung; Hsieh, Shu Ching; Hu, Fang; Wang, Jung‐Der

doi:10.1053/j.ajkd.2009.10.055

Cited by 84 publications

(102 citation statements)

References 21 publications

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“…dA-AL-I adducts also are present in 60% of patients with RCC; however, in this control group, A:T to T:A approximately one-third of the population of Taiwan has been exposed to Chinese medicinal herbs containing, or likely to contain, AA (13)(14)(15), and that a linear dose-response relationship exists between consumption of herbal remedies containing AA and the risk of developing urinary tract cancer. These epidemiologic studies likely underestimate AA exposure because they consider only Aristolochia-based prescriptions written by physicians over a period of 7 y, and Aristolochia herbs have long been available in Taiwan from alternative sources.…”

Section: Discussionmentioning

confidence: 69%

“…Using this approach, more than half of the 23 million residents of Taiwan were estimated to have used Chinese herbal remedies between 1997 and 2003, with more than one-third of the entire population using herbs containing, or likely to contain, AA (14). Additionally, these population-based studies documented a linear dose-response relationship between exposure to AA-containing herbs and the risk of developing urinary tract cancers (13) or end-stage renal failure (15). Importantly, among the 15-54 age subgroup, more than 60% of all Chinese herb prescriptions were written for women.…”

Section: Discussionmentioning

confidence: 99%

“…The high level of exposure to AA in Taiwan has been documented by a systematic analysis of prescriptions filled by a 200,000 person random sample of the entire insured population of Taiwan between 1997 and 2003, revealing that approximately one-third of these individuals consumed herbs containing, or likely to contain, AA (14). Moreover, consumption of AA is associated, in a dosedependent manner, with an increased risk of developing end-stage renal disease or urothelial carcinoma (13,15). Importantly, 43% of these carcinomas were located in the upper urinary tract (13).…”

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confidence: 99%

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Aristolochic acid-associated urothelial cancer in Taiwan

Chen

Dickman

Moriya³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

357

391

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Aristolochic acid, a potent human carcinogen produced by Aristolochia plants, is associated with urothelial carcinoma of the upper urinary tract (UUC). Following metabolic activation, aristolochic acid reacts with DNA to form aristolactam (AL)-DNA adducts. These lesions concentrate in the renal cortex, where they serve as a sensitive and specific biomarker of exposure, and are found also in the urothelium, where they give rise to a unique mutational signature in the TP53 tumor-suppressor gene. Using AL-DNA adducts and TP53 mutation spectra as biomarkers, we conducted a molecular epidemiologic study of UUC in Taiwan, where the incidence of UUC is the highest reported anywhere in the world and where Aristolochia herbal remedies have been used extensively for many years. Our study involves 151 UUC patients, with 25 patients with renal cell carcinomas serving as a control group. The TP53 mutational signature in patients with UUC, dominated by otherwise rare A:T to T:A transversions, is identical to that observed in UUC associated with Balkan endemic nephropathy, an environmental disease. Prominent TP53 mutational hotspots include the adenine bases of 5′ AG (acceptor) splice sites located almost exclusively on the nontranscribed strand. A:T to T:A mutations also were detected at activating positions in the FGFR3 and HRAS oncogenes. AL-DNA adducts were present in the renal cortex of 83% of patients with A:T to T:A mutations in TP53, FGFR3, or HRAS. We conclude that exposure to aristolochic acid contributes significantly to the incidence of UUC in Taiwan, a finding with significant implications for global public health.upper urinary tract carcinoma | traditional Chinese medicine | transitional cell carcinoma | DNA damage | herbal medicine

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Aristolochic acid-associated urothelial cancer in Taiwan

Chen

Dickman

Moriya³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

357

391

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“…In their analysis of those supplements they found alkaloid-like material in the capsules taken by the patients but not in the samples of the Chinese powders provided by the import company casting serious doubt on the actual components of these supplements. Lai et al in a study done in Taiwan highlighted the risk of kidney failure due to aristolochic acid consumption in herbal products containing Mu Tong or Fangchi [13] . Yang et al reported rapidly progressive fibrosing interstitial nephritis with Chinese herbal drugs [14] .…”

Section: Discussionmentioning

confidence: 99%

A case report of chronic interstitial nephritis associated with Chinese herbal supplement Zi Xiu Tang Bee Pollen

Joshi

Obi²

2014

CRIM

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We report a case of renal failure associated with ingestion of Chinese herbal weight loss supplement called Zi Xiu Tang Bee Pollen. A 33 year old African American female who had been ingesting Zi Xiu Tang Bee Pollen for about one year in duration. The patient presented to our facility with renal failure requiring dialysis for one month from unknown etiology. The patient had a normal creatinine level a few months prior to starting dialysis. The patient had no additional medical history. Her urine studies were positive for sterile pyuria, suggestive of interstitial nephritis. She subsequently underwent a kidney biopsy which showed severe chronic interstitial nephritis due to Zi Xiu Tang Bee Pollen. The Chinese herbal supplement was discontinued, but patient remained dialysis dependent. Our literature search showed one other reported case of bee pollen associated with acute interstitial nephritis that required short term hemodialysis with renal recovery after discontinuation of supplement. This unique case highlights the growing health risks posed by nonprescription diet supplements and they can potentially add to the increasing burden of kidney disease.

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“…Taiwan has the highest incidence of AAN in the world. 12, 13 Lai et al 12 conducted a population-based case-control study and found that consumption of AA-containing herbal products is associated with an increased risk of urinary tract cancer in a dose-dependent manner. In 2004, Xu et al 14 from our hospital reported that the wide use of Chinese herbal medicine ''Gan Lu Xiao Du Wan'' (containing Mu Tong mainly), which contains substantial amounts of AA, leads to high incidence of AAN in Wenzhou China.…”

Section: Introductionmentioning

confidence: 99%

Analysis of potential risk factors for cancer incidence in patients with aristolochic acid nephropathy from Wenzhou, China

et al. 2014

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Background: The purpose of this study was to investigate the cancer incidence in patients with end-stage aristolochic acid nephropathy (AAN). Methods: A total of 102 patients with end-stage AAN treated in our hospital between 2004 and 2013 were included in this study. The correlation of cancer incidence with age, gender, dosage of aristolochic acid (AA), the type of renal replacement therapies, and the polymorphisms of quinone oxidoreductase 1 (NQO1) C609T and cytochrome P450 1A1 (CYP1A1) A4889G was examined. Results: The cancer incidence rate in our patients was 41.2% (42 in 102) including 39 cases of urinary cancer. The mortality rate in the patients with cancer was significantly higher than that in the patients without cancer (31%, 13/42 vs. 11.7%, 7/60, p50.05). Thirteen patients developed cancer before entering end-stage renal disease (ESRD). Cancer incidence was significantly associated with the dosage of AA consumption (p ¼ 0.091). Hemodialysis, peritoneal dialysis and renal transplant did not affect the cancer incidence in our patients differently, but appeared to be associated with cancer at particular locations of urinary system. The patients undergoing hemodialysis seemed to more likely have bladder cancer (72.72%), while the patients receiving peritoneal dialysis appeared to develop cancer predominantly in the upper urinary tract (66.67%). Conclusions: The cancer initiation in our patients seems significantly correlate with the dosage of AA consumption. Different renal replacement therapies appear to be associated with cancer at particular locations of urinary system in our patients.

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Risks of Kidney Failure Associated With Consumption of Herbal Products Containing Mu Tong or Fangchi: A Population-Based Case-Control Study

Cited by 84 publications

References 21 publications

Aristolochic acid-associated urothelial cancer in Taiwan

Aristolochic acid-associated urothelial cancer in Taiwan

A case report of chronic interstitial nephritis associated with Chinese herbal supplement Zi Xiu Tang Bee Pollen

Analysis of potential risk factors for cancer incidence in patients with aristolochic acid nephropathy from Wenzhou, China

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