Increased risk of urinary tract cancer in ESRD patients associated with usage of Chinese herbal products suspected of containing aristolochic acid.

Shuo-Meng Wang,Ming-Nan Lai,Ya-Yin Chen,Alan Wei,Pau-Chung Chen,Yeong-Shiau Pu,Jung-Der Wang,Francisco X Real

doi:10.1371/journal.pone.0105218

Abstract

IntroductionBoth end-stage renal disease (ESRD) and urothelial cancer (UC) are associated with the consumption of Chinese herbal products containing aristolochic acid (AA) by the general population. The objective of this study was to determine the risk of UC associated with AA-related Chinese herbal products among ESRD patients.MethodsWe conducted a cohort study using the National Health Insurance reimbursement database to enroll all ESRD patients in Taiwan from 1998–2002. Cox regression models were constructed and hazard ratios and confidence intervals were estimated after controlling for potential confounders, including age, sex, residence in region with endemic black foot disease, urinary tract infection, and use of non-steroidal anti-inflammatory drugs and acetaminophen.ResultsA total of 38,995 ESRD patients were included in the final analysis, and 320 patients developed UC after ESRD. Having been prescribed Mu Tong that was adulterated with Guan Mu Tong (Aristolochia manshuriensis) before 2004, or an estimated consumption of more than 1–100 mg of aristolochic acid, were both associated with an increased risk of UC in the multivariable analyses. Analgesic consumption of more than 150 pills was also associated with an increased risk of UC, although there was little correlation between the two risk factors.ConclusionConsumption of aristolochic acid-related Chinese herbal products was associated with an increased risk of developing UC in ESRD patients. Regular follow-up screening for UC in ESRD patients who have consumed Chinese herbal products is thus necessary.

Highlights

Both end-stage renal disease (ESRD) and urothelial cancer (UC) are associated with the consumption of Chinese herbal products containing aristolochic acid (AA) by the general population
A report published by the International Agency in Research on Cancer (IARC) [23] stated that the risk factors associated with UC include analgesics, herbal usage, heavy metals and tobacco smoking
After control of potential confounding by other risk factors, we found that the adjusted hazard ratios (aHR) for development of UTC increased for ESRD patients prescribed Mu Tong, and that the various estimated consumptions of AA were each associated with an increased risk of UTC in the multivariable analyses (Mu Tong: at 1–30 g, aHR = 1.8, 95% confidence interval (CI) = 1.3 to 2.6, and each 30 g increase, aHR = 1.3, 95% CI = 1.2 to 1.5; AA: at 1–100 mg, aHR = 2.1, 95% CI = 1.6 to 2.6, and each 100 mg increase, aHR = 1.6, 95% CI = 1.4 to 1.8)

Summary

Introduction

Both end-stage renal disease (ESRD) and urothelial cancer (UC) are associated with the consumption of Chinese herbal products containing aristolochic acid (AA) by the general population. The objective of this study was to determine the risk of UC associated with AA-related Chinese herbal products among ESRD patients. Prior studies observed increased risks of developing UC and ESRD in the general population in association with the consumption of Chinese herbal products [7][8], and patients with ESRD have a higher incidence of malignancies than the general population [9,10,11,12]. A report published by the International Agency in Research on Cancer (IARC) [23] stated that the risk factors associated with UC include analgesics (phenacetin), herbal usage (aristolochic acid), heavy metals (arsenic) and tobacco smoking

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