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Nephrotoxicity of Herbal Products

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Toxicology of Herbal Products

Abstract

The kidney is one of the major routes of excretion of drugs and metabolites, and given its high blood flow and metabolic activity, it is highly susceptible to injury by toxic drugs and herbs. In addition, high concentrations of toxic metabolites are in close contact with tubular cells due to urine concentration, especially during a state of fluid deprivation. The incidence of nephrotoxicity related to alternative medicines is not known. However, regarding the large number of individuals consuming herbs as alternative remedies and regarding the lack of control of over-the-counter products, clinicians should consider alternative medicine consumption in the differential diagnosis of unexplained kidney injury.

This chapter will describe the major forms of renal involvement associated with the use of traditional medicinal products, including acute kidney injury, tubular function defects, electrolyte disturbances, systemic hypertension, chronic kidney disease, renal papillary necrosis, lithiasis, and urothelial cancer. The most famous example of kidney injury caused by herbal products is aristolochic acid nephropathy, which was first reported in 1993; it eventually involved hundreds of cases of chronic kidney disease and urothelial cancer in Europe and Asia, and raised global public health concerns. In addition, the so-called “Balkan endemic nephropathy” is obviously due to wheat contamination with the seeds of Aristolochia clematitis naturally growing in the fields, leading to chronic kidney failure and urothelial cancers. In addition to aristolochic acids included in Aristolochia species, several nephrotoxic herbs have also been written up in case reports and article reviews and are described in terms of their specific nephrotoxic pathways.

Finally, besides these mechanistic aspects, we will review and compare various methods proposed to assess the renal toxicity of herbs and natural products, i.e., in silico, in vitro, and in vivo approaches. Further developments in “omics” investigation would be helpful for screening potential subjects at risk of developing kidney injuries.

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References

  • Adams M, Berset C, Kessler M et al (2009) Medicinal herbs for the treatment of rheumatic disorders – a survey of European herbals from the 16th and 17th century. J Ethnopharmacol 121:343–359

    Article  PubMed  Google Scholar 

  • Adelekun TA, Ekwere TR, Akinsola A (1999) The pattern of acute toxic nephropathy in Ife, Nigeria. West Afr J Med 18:60–63

    CAS  PubMed  Google Scholar 

  • Akyol AD, Yildirim Y, Toker E et al (2011) The use of complementary and alternative medicine among chronic renal failure patients. J Clin Nurs 20:1035–1043

    Article  PubMed  Google Scholar 

  • Ardalan MR, Khodaie L, Nasri H et al (2015) Herbs and hazards: risk of aristolochic acid nephropathy in Iran. Iran J Kidney Dis 9:14–17

    PubMed  Google Scholar 

  • Arlt VM, Stiborova M, Schmeiser HH (2002) Aristolochic acid as a probable human cancer hazard in herbal remedies: a review. Mutagenesis 17:265–277

    Article  CAS  PubMed  Google Scholar 

  • Aslam M, Davis SS, Healy MA (1979) Heavy metals in some Asian medicines and cosmetics. Public Health 93:274–284

    Article  CAS  PubMed  Google Scholar 

  • Balachandran P, Wei F, Lin RC et al (2005) Structure activity relationships of aristolochic acid analogues: toxicity in cultured renal epithelial cells. Kidney Int 67:1797–1805

    Article  CAS  PubMed  Google Scholar 

  • Barrett B, Kiefer D, Rabago D (1999) Assessing the risks and benefits of herbal medicine: an overview of scientific evidence. Altern Ther Health Med 5:40–49

    CAS  PubMed  Google Scholar 

  • Baudoux TE, Pozdzik AA, Arlt VM et al (2012) Probenecid prevents acute tubular necrosis in a mouse model of aristolochic acid nephropathy. Kidney Int 82:1105–1113

    Article  CAS  PubMed  Google Scholar 

  • Beger RD, Sun J, Schnackenberg LK (2010) Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity. Toxicol Appl Pharmacol 243:154–166

    Article  CAS  PubMed  Google Scholar 

  • Bertrand B (2009) L’herbier toxique. Codes secrets pour plantes utiles, Plume de carotte edn. Plume de carotte, Toulouse

    Google Scholar 

  • Boudonck KJ, Rose DJ, Karoly ED et al (2009) Metabolomics for early detection of drug-induced kidney injury: review of the current status. Bioanalysis 1:1645–1663

    Article  CAS  PubMed  Google Scholar 

  • Catania JM, Parrish AR, Gandolfi AJ (2001) Toxicity of a sevoflurane degradation product incubated with rat liver and renal cortical slices. Drug Chem Toxicol 24:347–357

    Article  CAS  PubMed  Google Scholar 

  • Chan W, Lee KC, Liu N et al (2008) Liquid chromatography/mass spectrometry for metabonomics investigation of the biochemical effects induced by aristolochic acid in rats: the use of information-dependent acquisition for biomarker identification. Rapid Commun Mass Spectrom 22:873–880

    Article  CAS  PubMed  Google Scholar 

  • Chawla LS, Kimmel PL (2012) Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int 82:516–524

    Article  PubMed  Google Scholar 

  • Chen M, Su M, Zhao L et al (2006) Metabonomic study of aristolochic acid-induced nephrotoxicity in rats. J Proteome Res 5:995–1002

    Article  CAS  PubMed  Google Scholar 

  • Chen CH, Dickman KG, Moriya M et al (2012) Aristolochic acid-associated urothelial cancer in Taiwan. Proceedings of the National Academy of Sciences of the United States of America

    Google Scholar 

  • Coghlan ML, Haile J, Houston J et al (2012) Deep sequencing of plant and animal DNA contained within traditional Chinese medicines reveals legality issues and health safety concerns. PLoS Genet 8:e1002657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colson CRD, De Broe ME (2005) Kidney injury from alternative medicines. Adv Chron Kid Dis 12:261–275

    Article  Google Scholar 

  • Committee on the Framework for Evaluating the Safety of the Dietary Supplements, National Research Council (2004) Dietary supplements: a framework for evaluating safety. Washington, DC

    Google Scholar 

  • Cosyns JP, Jadoul M, Squifflet JP et al (1994) Chinese herbs nephropathy: a clue to Balkan endemic nephropathy? Kidney Int 45:1680–1688

    Article  CAS  PubMed  Google Scholar 

  • Cosyns JP, Jadoul M, Squifflet JP et al (1999) Urothelial lesions in Chinese-herb nephropathy. Am J Kidney Dis 33:1011–1017

    Article  CAS  PubMed  Google Scholar 

  • Cosyns JP, Dehoux JP, Guiot Y et al (2001) Chronic aristolochic acid toxicity in rabbits: a model of Chinese herbs nephropathy? Kidney Int 59:2164–2173

    Article  CAS  PubMed  Google Scholar 

  • Couceiro M, Afreen F, Zobayed S et al (2006) Variation in concentrations of major bioactive compounds of St. John’s wort: effects of harvesting time, temperature and germplasm. Plant Sci 170:128–134

    Article  CAS  Google Scholar 

  • Dan H, Peng RX, Ao Y et al (2008) Segment-specific proximal tubule injury in tripterygium glycosides intoxicated rats. J Biochem Mol Toxicol 22:422–428

    Article  CAS  PubMed  Google Scholar 

  • De Broe ME (2012) Chinese herbs nephropathy and Balkan endemic nephropathy: toward a single entity, aristolochic acid nephropathy. Kidney Int 81:513–515

    Article  PubMed  CAS  Google Scholar 

  • De Broe ME, Porter George A (2008) Clinical nephrotoxins: renal injury from drugs and chemicals. Kluwer Academic Publishers, Dordrecht, The Netherlands

    Google Scholar 

  • De Smet PA (2007) Clinical risk management of herb-drug interactions. Br J Clin Pharmacol 63:258–267

    Article  PubMed  Google Scholar 

  • Debelle FD, Nortier JL, De Prez EG et al (2002) Aristolochic acids induce chronic renal failure with interstitial fibrosis in salt-depleted rats. J Am Soc Nephrol 13:431–436

    CAS  PubMed  Google Scholar 

  • Debelle FD, Vanherweghem JL, Nortier JL (2008) Aristolochic acid nephropathy: a worldwide problem. Kidney Int 74:158–169

    Article  CAS  PubMed  Google Scholar 

  • Depierreux M, Van Damme B, Vanden Houte K et al (1994) Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese herbs. Am J Kidney Dis 24:172–180

    Article  CAS  PubMed  Google Scholar 

  • Devarajan P (2008) Proteomics for the investigation of acute kidney injury. Contrib Nephrol 160:1–16

    Article  CAS  PubMed  Google Scholar 

  • Dickman KG, Sweet DH, Bonala R et al (2011) Physiological and molecular characterization of aristolochic acid transport by the kidney. J Pharmacol Exp Ther 338:588–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Djukanovic L, Radovic M, Bakovic J et al (2002) Epidemiology of end-stage renal disease and current status of hemodialysis in Yugoslavia. Int J Artif Organs 25:852–859

    CAS  PubMed  Google Scholar 

  • Dunn JP, Krige JE, Wood R et al (1991) Colonic complications after toxic tribal enemas. Br J Surg 78:545–548

    Article  CAS  PubMed  Google Scholar 

  • Ebbels TM, Keun HC, Beckonert OP et al (2007) Prediction and classification of drug toxicity using probabilistic modeling of temporal metabolic data: the consortium on metabonomic toxicology screening approach. J Proteome Res 6:4407–4422

    Article  CAS  PubMed  Google Scholar 

  • el Dirdiri NI, Barakat SE, Adam SE (1987) The combined toxicity of Aristolochia bracteata and Cadaba rotundifolia to goats. Vet Hum Toxicol 29:133–137

    PubMed  Google Scholar 

  • European Food Safety Authority (2009) Guidance on safety assessment of botanicals and botanical preparations intended for use as ingredients in food supplements. EFSA J 7:1249–1268

    Google Scholar 

  • Fadrowski JJ, Navas-Acien A, Tellez-Plaza M et al (2010) Blood lead level and kidney function in US adolescents: the third National Health and Nutrition Examination Survey. Arch Intern Med 170:75–82

    Article  CAS  PubMed  Google Scholar 

  • Ferraro PM, Costanzi S, Naticchia A et al (2010) Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999–2006. BMC Public Health 10:304

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gabardi S, Munz K, Ulbricht C (2007) A review of dietary supplement-induced renal dysfunction. Clin J Am Soc Nephrol 2:757–765

    Article  CAS  PubMed  Google Scholar 

  • Gandolfi AJ, Brendel K (1990) In vitro systems for nephrotoxicity studies. Toxicol In Vitro 4:337–345

    Article  CAS  PubMed  Google Scholar 

  • Garvey GJ, Hahn G, Lee RV et al (2001) Heavy metal hazards of Asian traditional remedies. Int J Environ Health Res 11:63–71

    Article  CAS  PubMed  Google Scholar 

  • Gibbs A (2005) Comparison of the specificity and sensitivity of traditional methods for assessment of nephrotoxicity in the rat with metabonomic and proteomic methodologies. J Appl Toxicol 25:277–295

    Article  CAS  PubMed  Google Scholar 

  • Gokmen MR, Cosyns JP, Arlt VM et al (2013) The epidemiology, diagnosis, and management of aristolochic acid nephropathy: a narrative review. Ann Intern Med 158:469–477

    Article  PubMed  Google Scholar 

  • Grollman AP (2013) Aristolochic acid nephropathy: harbinger of a global iatrogenic disease. Environ Mol Mutagen 54:1–7

    Article  CAS  PubMed  Google Scholar 

  • Grubbs V, Plantinga LC, Tuot DS et al (2013) Americans’ use of dietary supplements that are potentially harmful in CKD. Am J Kidney Dis 61:739–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guh JY, Chen HC, Tsai JF et al (2007) Herbal therapy is associated with the risk of CKD in adults not using analgesics in Taiwan. Am J Kidney Dis 49:626–633

    Article  PubMed  Google Scholar 

  • Harmon RC, Duffy SP, Terneus MV et al (2009) Characterization of a novel model for investigation of radiocontrast nephrotoxicity. Nephrol Dial Transplant 24:763–768

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto K, Higuchi M, Makino B et al (1999) Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants. J Ethnopharmacol 64:185–189

    Article  CAS  PubMed  Google Scholar 

  • He CC, Dai YQ, Hui RR et al (2011) NMR-based metabonomic approach on the toxicological effects of a Cimicifuga triterpenoid. J Appl Toxicol 32:88–97

    Google Scholar 

  • Heinrich M, Chan J, Wanke S et al (2009) Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2 – a global assessment based on bibliographic sources. J Ethnopharmacol 125:108–144

    Article  CAS  PubMed  Google Scholar 

  • Hess S, De Geest S, Halter K et al (2009) Prevalence and correlates of selected alternative and complementary medicine in adult renal transplant patients. Clin Transpl 23:56–62

    Article  Google Scholar 

  • Hsieh SC, Lin IH, Tseng WL et al (2008) Prescription profile of potentially aristolochic acid containing Chinese herbal products: an analysis of National Health Insurance data in Taiwan between 1997 and 2003. Chin Med 3:13

    Article  PubMed  PubMed Central  Google Scholar 

  • Ioset JR, Raoelison GE, Hostettmann K (2003) Detection of aristolochic acid in Chinese phytomedicines and dietary supplements used as slimming regimens. Food Chem Toxicol 41:29–36

    Article  CAS  PubMed  Google Scholar 

  • Isnard Bagnis C, Deray G, Baumelou A et al (2004) Herbs and the kidney. Am J Kidney Dis 44:1–11

    Article  PubMed  Google Scholar 

  • Ivic M (1969) Etiology of endemic nephropathy. Lijec Vjesn 91:1273–1281

    CAS  PubMed  Google Scholar 

  • Jelakovic B, Karanovic S, Vukovic-Lela I et al (2012) Aristolactam-DNA adducts are a biomarker of environmental exposure to aristolochic acid. Kidney Int 81:559–567

    Article  CAS  PubMed  Google Scholar 

  • Jordan SA, Cunningham DG, Marles RJ (2010) Assessment of herbal medicinal products: challenges, and opportunities to increase the knowledge base for safety assessment. Toxicol Appl Pharmacol 243:198–216

    Article  CAS  PubMed  Google Scholar 

  • Krumbiegel G, Hallensleben J, Mennicke WH et al (1987) Studies on the metabolism of aristolochic acids I and II. Xenobiotica 17:981–991

    Article  CAS  PubMed  Google Scholar 

  • Ladda MA, Goralski KB (2016) The effects of CKD on cytochrome P450-mediated drug metabolism. Adv Chronic Kidney Dis 23:67–75

    Article  PubMed  Google Scholar 

  • Lai MN, Lai JN, Chen PC et al (2009) Increased risks of chronic kidney disease associated with prescribed Chinese herbal products suspected to contain aristolochic acid. Nephrology (Carlton) 14:227–234

    Article  CAS  Google Scholar 

  • Laïs E (2003) Le grand livre des plantes magiques. Jardin de sorcières, Rustica edn. Rustica, Paris

    Google Scholar 

  • Lao YM, Jiang JG, Yan L (2009) Application of metabonomic analytical techniques in the modernization and toxicology research of traditional Chinese medicine. Br J Pharmacol 157:1128–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lemy A, Wissing KM, Rorive S et al (2008) Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: a case series with 15-year follow-up. Am J Kidney Dis 51:471–477

    Article  PubMed  Google Scholar 

  • Lin S, Chan W, Li J et al (2010) Liquid chromatography/mass spectrometry for investigating the biochemical effects induced by aristolochic acid in rats: the plasma metabolome. Rapid Commun Mass Spectrom 24:1312–1318

    Article  CAS  PubMed  Google Scholar 

  • Luyckx VA (2012) Nephrotoxicity of alternative medicine practice. Adv Chronic Kidney Dis 19:129–141

    Article  PubMed  Google Scholar 

  • Luyckx VA, Naicker S (2008) Acute kidney injury associated with the use of traditional medicines. Nat Clin Pract Nephrol 4:664–671

    Article  PubMed  Google Scholar 

  • Luyckx VA, Steenkamp V, Stewart MJ (2005) Acute renal failure associated with the use of traditional folk remedies in South Africa. Ren Fail 27:35–43

    Article  PubMed  Google Scholar 

  • Lv H, Liu L, Palacios G et al (2011) Metabolomic analysis characterizes tissue specific indomethacin-induced metabolic perturbations of rats. Analyst 136:2260–2269

    Article  CAS  PubMed  Google Scholar 

  • Ma C, Bi K, Su D et al (2010) Serum and kidney metabolic changes of rat nephrotoxicity induced by morning glory seed. Food Chem Toxicol 48:2988–2993

    Article  CAS  PubMed  Google Scholar 

  • Mai I, Stormer E, Bauer S et al (2003) Impact of St. John’s wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 18:819–822

    Article  CAS  PubMed  Google Scholar 

  • Marcus DM, Grollman AP (2002) Botanical medicines – the need for new regulations. N Engl J Med 347:2073–2076

    Article  PubMed  Google Scholar 

  • Martins AM, Toyama MH, Havt A et al (2002) Determination of Crotalus durissus cascavella venom components that induce renal toxicity in isolated rat kidneys. Toxicon 40:1165–1171

    Article  CAS  PubMed  Google Scholar 

  • Minigh JL, Valentovic MA (2003) Characterization of myoglobin toxicity in renal cortical slices from Fischer 344 rats. Toxicology 184:113–123

    Article  CAS  PubMed  Google Scholar 

  • Mosihuzzaman M, Choudhary I,M (2008) Protocols on safety, efficacy, standardization and documentation of herbal medicine. Pure Appl Chem 80:2195–2230

    Article  CAS  Google Scholar 

  • Navas-Acien A, Tellez-Plaza M, Guallar E et al (2009) Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis. Am J Epidemiol 170:1156–1164

    Article  PubMed  PubMed Central  Google Scholar 

  • Newmaster SG, Grguric M, Shanmughanandhan D et al (2013) DNA barcoding detects contamination and substitution in North American herbal products. BMC Med 11:222

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nortier JL, Martinez MC, Schmeiser HH et al (2000) Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med 342:1686–1692

    Article  CAS  PubMed  Google Scholar 

  • Nortier J, Pozdzik A, Roumeguere T et al (2015) Néphropathie aux acides aristolochiques (“néphropathie aux herbes chinoises”). Nephrol Ther 11:574–588

    Article  PubMed  Google Scholar 

  • Nowack R, Balle C, Birnkammer F et al (2009) Complementary and alternative medications consumed by renal patients in southern Germany. J Ren Nutr 19:211–219

    Article  PubMed  Google Scholar 

  • Nwoko CO, Mgbeahuruike L (2011) Heavy metal contamination of ready-to-use herbal remedies in South Eastern Nigeria. Pak J Nutr 10:959–964

    Article  CAS  Google Scholar 

  • Obi E, Akunyili DN, Ekpo B et al (2006) Heavy metal hazards of Nigerian herbal remedies. Sci Total Environ 369:35–41

    Article  CAS  PubMed  Google Scholar 

  • Olowu WA, Niang A, Osafo C et al (2016) Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review. Lancet Glob Health 4:e242–e250

    Article  PubMed  Google Scholar 

  • Pavlovi NM (2013) Balkan endemic nephropathy – current status and future perspectives. Clin Kidney J 6:257–265

    Article  Google Scholar 

  • Perazella MA (2009) Renal vulnerability to drug toxicity. Clin J Am Soc Nephrol 4:1275–1283

    Article  CAS  PubMed  Google Scholar 

  • Ponce D, Dias DB, Nascimento GR et al (2016) Long-term outcome of severe acute kidney injury survivors followed by nephrologists in a developing country. Nephrology (Carlton) 21:327–334

    Article  Google Scholar 

  • Pozdzik AA, Salmon IJ, Debelle FD et al (2008a) Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation. Kidney Int 73:595–607

    Article  CAS  PubMed  Google Scholar 

  • Pozdzik AA, Salmon IJ, Husson CP et al (2008b) Patterns of interstitial inflammation during the evolution of renal injury in experimental aristolochic acid nephropathy. Nephrol Dial Transplant 23:2480–2491

    Article  PubMed  Google Scholar 

  • Rouse RL, Zhang J, Stewart SR et al (2011) Comparative profile of commercially available urinary biomarkers in preclinical drug-induced kidney injury and recovery in rats. Kidney Int 79:1186–1197

    Article  CAS  PubMed  Google Scholar 

  • Sabath E, Robles-Osorio ML (2012) Renal health and the environment: heavy metal nephrotoxicity. Nefrologia 32:279–286

    PubMed  Google Scholar 

  • Saper RB, Kales SN, Paquin J et al (2004) Heavy metal content of Ayurvedic herbal medicine products. JAMA 292:2868–2873

    Article  CAS  PubMed  Google Scholar 

  • Schilter B, Andersson C, Anton R et al (2003) Guidance for the safety assessment of botanicals and botanical preparations for use in food and food supplements. Food Chem Toxicol 41:1625–1649

    Article  CAS  PubMed  Google Scholar 

  • Schmeiser HH, Nortier JL, Singh R et al (2014) Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid nephropathy. Int J Cancer 135:502–507

    Article  CAS  PubMed  Google Scholar 

  • Shanley PF, Brezis M, Spokes K et al (1986) Differential responsiveness of proximal tubule segments to metabolic inhibitors in the isolated perfused rat kidney. Am J Kidney Dis 7:76–83

    Article  CAS  PubMed  Google Scholar 

  • Sieber M, Wagner S, Rached E et al (2009) Metabonomic study of ochratoxin a toxicity in rats after repeated administration: phenotypic anchoring enhances the ability for biomarker discovery. Chem Res Toxicol 22:1221–1231

    Article  CAS  PubMed  Google Scholar 

  • Siew ED, Peterson JF, Eden SK et al (2012) Outpatient nephrology referral rates after acute kidney injury. J Am Soc Nephrol 23:305–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stanifer JW, Jing B, Tolan S et al (2014) The epidemiology of chronic kidney disease in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health 2:e174–e181

    Article  PubMed  Google Scholar 

  • Taber SS, Pasko DA (2008) The epidemiology of drug-induced disorders: the kidney. Expert Opin Drug Saf 7:679–690

    Article  CAS  PubMed  Google Scholar 

  • Taft DR (2004) The isolated perfused rat kidney model: a useful tool for drug discovery and development. Curr Drug Discov Technol 1:97–111

    Article  CAS  PubMed  Google Scholar 

  • Tatu CA, Orem WH, Finkelman RB et al (1998) The etiology of Balkan endemic nephropathy: still more questions than answers. Environ Health Perspect 106:689–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tyagi R, Rana P, Gupta M et al (2013) Differential biochemical response of rat kidney towards low and high doses of NiCl2 as revealed by NMR spectroscopy. J Appl Toxicol 33:134–141

    Article  PubMed  CAS  Google Scholar 

  • Vanhaelen M, Vanhaelen-Fastre R, But P et al (1994) Identification of aristolochic acid in Chinese herbs. Lancet 343:174

    Article  CAS  PubMed  Google Scholar 

  • Vanherweghem JL (1997) Aristolochia sp and chronic interstitial nephropathies in Indians. Lancet 349:1399

    Article  CAS  PubMed  Google Scholar 

  • Vanherweghem LJ (1998) Misuse of herbal remedies: the case of an outbreak of terminal renal failure in Belgium (Chinese herbs nephropathy). J Altern Complement Med 4:9–13

    Article  CAS  PubMed  Google Scholar 

  • Vanherweghem JL, Depierreux M, Tielemans C et al (1993) Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet 341:387–391

    Article  CAS  PubMed  Google Scholar 

  • Vanherweghem JL, Abramowicz D, Tielemans C et al (1996) 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 27:209–215

    Article  CAS  PubMed  Google Scholar 

  • Vickers AE, Fisher RL (2004) Organ slices for the evaluation of human drug toxicity. Chem Biol Interact 150:87–96

    Article  CAS  PubMed  Google Scholar 

  • Vickers AE, Rose K, Fisher R et al (2004) Kidney slices of human and rat to characterize cisplatin-induced injury on cellular pathways and morphology. Toxicol Pathol 32:577–590

    Article  CAS  PubMed  Google Scholar 

  • Wei L, Liao P, Wu H et al (2008) Toxicological effects of cinnabar in rats by NMR-based metabolic profiling of urine and serum. Toxicol Appl Pharmacol 227:417–429

    Article  CAS  PubMed  Google Scholar 

  • Wei L, Liao P, Wu H et al (2009) Metabolic profiling studies on the toxicological effects of realgar in rats by (1)H NMR spectroscopy. Toxicol Appl Pharmacol 234:314–325

    Article  CAS  PubMed  Google Scholar 

  • WHO traditional medicine strategy 2014–2023 (2013) www.who.int/medicines/publications/traditional/trm_strategy14_23/en/(last access December 14, 2016)

    Google Scholar 

  • Williamson EM, Chan K, Xu Q et al (2015) Evaluating the safety of herbal medicines: integrated toxicological approaches. Science 347:S47–S49

    Google Scholar 

  • Wojcikowski K, Wohlmuth H, Johnson DW et al (2009) An in vitro investigation of herbs traditionally used for kidney and urinary system disorders: potential therapeutic and toxic effects. Nephrology (Carlton) 14:70–79

    Article  Google Scholar 

  • World Health Organization (2004) WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems. See http://apps.who.int/medicinedocs/en/d/Js7148e/

    Google Scholar 

  • World Health Organization (2007) WHO guidelines for assessing quality of herbal medicines with reference to contaminants and residues. See http://apps.who.int/medicinedocs/fr/m/abstract/Js14878e/

    Google Scholar 

  • Wu KM, Farrelly JG, Upton R et al (2007) Complexities of the herbal nomenclature system in traditional Chinese medicine (TCM): lessons learned from the misuse of Aristolochia-related species and the importance of the pharmaceutical name during botanical drug product development. Phytomedicine 14:273–279

    Article  CAS  PubMed  Google Scholar 

  • Xia S, Liu H, Zhu H et al (2009) NMR-based metabonomic study on rat’s urinary metabolic response to dosage of triptolide. Chin J Chem 27:751–758

    Article  CAS  Google Scholar 

  • Yamani A, Bunel V, Antoine MH et al (2015) Substitution between Aristolochia and Bryonia genus in North-Eastern Morocco: toxicological implications. J Ethnopharmacol 166:250–260

    Article  PubMed  Google Scholar 

  • Yang MH, Chen KK, Yen CC et al (2002) Unusually high incidence of upper urinary tract urothelial carcinoma in Taiwan. Urology 59:681–687

    Article  PubMed  Google Scholar 

  • Yu CC, Lin JL, Lin-Tan DT (2004) Environmental exposure to lead and progression of chronic renal diseases: a four-year prospective longitudinal study. J Am Soc Nephrol 15:1016–1022

    Article  CAS  PubMed  Google Scholar 

  • Yu FY, Wu TS, Chen TW et al (2011) Aristolochic acid I induced oxidative DNA damage associated with glutathione depletion and ERK1/2 activation in human cells. Toxicol In Vitro 25:810–816

    Article  CAS  PubMed  Google Scholar 

  • Yuan SY, Yang CR, Cheng CL et al (2011) Comparative nephrotoxicity of aristolochic acid and tetrandrine in vitro and in vivo. Int J Toxicol 30:35–46

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Wu H, Liao P et al (2006) NMR-based metabonomic study on the subacute toxicity of aristolochic acid in rats. Food Chem Toxicol 44:1006–1014

    Article  CAS  PubMed  Google Scholar 

  • Zhao Z, Yuen JP, Wu J et al (2006) A systematic study on confused species of Chinese materia medica in the Hong Kong market. Ann Acad Med Singap 35:764–769

    PubMed  Google Scholar 

References cited in Tables 13.1 to 13.5

  • Adesunloye BA (2003) Acute renal failure due to the herbal remedy CKLS. Am J Med 115:506–507

    Article  PubMed  Google Scholar 

  • Averbukh Z, Modai D, Leonov Y et al (1989) Rhabdomyolysis and acute renal failure induced by paraphenylenediamine. Hum Toxicol 8:345–348

    Article  CAS  PubMed  Google Scholar 

  • Bandara V, Weinstein SA, White J et al (2010) A review of the natural history, toxinology, diagnosis and clinical management of Nerium oleander (common oleander) and Thevetia peruviana (yellow oleander) poisoning. Toxicon 56:273–281

    Article  CAS  PubMed  Google Scholar 

  • Benjamin SP, Fernando ME, Jayanth JJ et al (2006) Cleistanthus collinus poisoning. J Assoc Physicians India 54:742–744

    CAS  PubMed  Google Scholar 

  • Boubaker K, Ounissi M, Brahmi N et al (2013) Acute renal failure by ingestion of Euphorbia paralias. Saudi J Kidney Dis Transpl 24:571–575

    Article  PubMed  Google Scholar 

  • Bourquia A, Jabrane AJ, Ramdani B et al (1988) Systemic toxicity of paraphenylenediamine. 4 cases. Presse Med 17:1798–1800

    CAS  PubMed  Google Scholar 

  • Brncic N, Viskovic I, Peric R et al (2001) Accidental plant poisoning with Colchicum autumnale: report of two cases. Croat Med J 42:673–675

    CAS  PubMed  Google Scholar 

  • Brvar M, Ploj T, Kozelj G et al (2004) Case report: fatal poisoning with Colchicum autumnale. Crit Care 8:R56–R59

    Article  PubMed  PubMed Central  Google Scholar 

  • Bunawan NC, Rastegar A, White KP et al (2014) Djenkolism: case report and literature review. Int Med Case Rep J 7:79–84

    PubMed  PubMed Central  Google Scholar 

  • Chen CL, Fang HC, Chou KJ et al (2001) Acute oxalate nephropathy after ingestion of star fruit. Am J Kidney Dis 37:418–422

    Article  CAS  PubMed  Google Scholar 

  • Chou WC, Wu CC, Yang PC et al (1995) Hypovolemic shock and mortality after ingestion of Tripterygium wilfordii hook F.: a case report. Int J Cardiol 49:173–177

    Article  CAS  PubMed  Google Scholar 

  • Chrispal A (2012) Cleistanthus collinus poisoning. J Emerg Trauma Shock 5:160–166

    Article  PubMed  PubMed Central  Google Scholar 

  • Conz PA, La Greca G, Benedetti P et al (1998) Fucus vesiculosus: a nephrotoxic alga? Nephrol Dial Transplant 13:526–527

    Article  CAS  PubMed  Google Scholar 

  • Daniele C, Dahamna S, Firuzi O et al (2005) Atractylis gummifera L. poisoning: an ethnopharmacological review. J Ethnopharmacol 97:175–181

    Article  CAS  PubMed  Google Scholar 

  • Das S, Hamide A, Mohanty MK et al (2014) Fatal Cleistanthus collinus toxicity: a case report and review of literature. J Forensic Sci 59:1441–1447

    Article  CAS  PubMed  Google Scholar 

  • Diamond JR, Pallone TL (1994) Acute interstitial nephritis following use of tung shueh pills. Am J Kidney Dis 24:219–221

    Article  CAS  PubMed  Google Scholar 

  • Djibo A, Bouzou SB (2000) Acute intoxication with “sobi-lobi” (Datura). Four cases in Niger. Bull Soc Pathol Exot 93:294–297

    CAS  PubMed  Google Scholar 

  • Ernst E (2002) St. John’s wort supplements endanger the success of organ transplantation. Arch Surg 137:316–319

    Article  CAS  PubMed  Google Scholar 

  • Fang HC, Lee PT, Lu PJ et al (2008) Mechanisms of star fruit-induced acute renal failure. Food Chem Toxicol 46:1744–1752

    Article  CAS  PubMed  Google Scholar 

  • Haller CA, Benowitz NL (2000) Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 343:1833–1838

    Article  CAS  PubMed  Google Scholar 

  • Hilepo JN, Bellucci AG, Mossey RT (1997) Acute renal failure caused by “cat’s claw” herbal remedy in a patient with systemic lupus erythematosus. Nephron 77:361

    Article  CAS  PubMed  Google Scholar 

  • Horoz M, Gok E, Genctoy G et al (2008) Crataegus orientalis associated multiorgan hypersensitivity reaction and acute renal failure. Intern Med 47:2039–2042

    Article  PubMed  Google Scholar 

  • Hsu HY, Lin CC, Chen JY et al (1998) Toxic effects of Erycibe obtusifolia, a Chinese medicinal herb, in mice. J Ethnopharmacol 62:101–105

    Article  CAS  PubMed  Google Scholar 

  • Huang HH, Yen DH, Wu ML et al (2006) Acute erycibe henryi prain (“Ting Kung Teng”) poisoning. Clin Toxicol (Phila) 44:71–75

    Article  Google Scholar 

  • Huang GZ, Li L, Liu L (2009) Pathological study on autopsy died of tripterygium intoxication – report of 4 cases. Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi Chin J Integr Tradit West Med/Zhongguo Zhong Xi Yi Jie He Xue Hui Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban 29:165–168

    CAS  Google Scholar 

  • Jha V (2010) Herbal medicines and chronic kidney disease. Nephrology (Carlton) 15(Suppl 2):10–17

    Article  Google Scholar 

  • Jha V, Parameswaran S (2013) Community-acquired acute kidney injury in tropical countries. Nat Rev Nephrol 9:278–290

    Article  CAS  PubMed  Google Scholar 

  • Kang K-S, Heo ST (2015) A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba. Yonsei Med J 56:304–306

    Article  PubMed  Google Scholar 

  • Kim CS, Kim SM, Choi JS et al (2012) Dioscorea quinqueloba induces acute kidney injury. Clin Toxicol (Phila) 50:80

    Article  Google Scholar 

  • Kim HY, Kim SS, Bae SH et al (2014) Acute interstitial nephritis induced by Dioscorea quinqueloba. BMC Nephrol 15:143

    Article  PubMed  PubMed Central  Google Scholar 

  • Klintschar M, Beham-Schmidt C, Radner H et al (1999) Colchicine poisoning by accidental ingestion of meadow saffron (Colchicum autumnale): pathological and medicolegal aspects. Forensic Sci Int 106:191–200

    Article  CAS  PubMed  Google Scholar 

  • Kwan TH, Tong MK, Leung KT et al (2006) Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones. Hong Kong Med J 12:394–397

    CAS  PubMed  Google Scholar 

  • Kwan LP, Mok MM, Ma MK et al (2014) Acute drug toxicity related to drinking herbal tea in a kidney transplant recipient. Ren Fail 36:309–312

    Article  CAS  PubMed  Google Scholar 

  • Lee JJ, Chen HC (2006) Flavonoid-induced acute nephropathy by Cupressus funebris Endl (mourning cypress). Am J Kidney Dis 48:e81–e85

    Article  PubMed  Google Scholar 

  • Li FK, Lai CK, Poon WT et al (2004) Aggravation of non-steroidal anti-inflammatory drug-induced hepatitis and acute renal failure by slimming drug containing anthraquinones. Nephrol Dial Transplant 19:1916–1917

    Article  CAS  PubMed  Google Scholar 

  • Light TD, Light JA (2003) Acute renal transplant rejection possibly related to herbal medications. Am J Transplant 3:1608–1609

    Article  PubMed  Google Scholar 

  • Lin CC, Chen JC (2002) Medicinal herb Erycibe henri Prain (“Ting Kung Teng”) resulting in acute cholinergic syndrome. J Toxicol Clin Toxicol 40:185–187

    Article  PubMed  Google Scholar 

  • Lin JL, Ho YS (1994) Flavonoid-induced acute nephropathy. Am J Kidney Dis 23:433–440

    Article  CAS  PubMed  Google Scholar 

  • Logan JL, Ahmed J (2003) Critical hypokalemic renal tubular acidosis due to Sjogren’s syndrome: association with the purported immune stimulant echinacea. Clin Rheumatol 22:158–159

    Article  CAS  PubMed  Google Scholar 

  • Luyckx VA, Ballantine R, Claeys M et al (2002) Herbal remedy-associated acute renal failure secondary to Cape aloes. Am J Kidney Dis 39:E13

    Article  PubMed  Google Scholar 

  • Mueller BA, Scott MK, Sowinski KM et al (2000) Noni juice (Morinda citrifolia): hidden potential for hyperkalemia? Am J Kidney Dis 35:310–312

    Article  CAS  PubMed  Google Scholar 

  • Mullins RJ, Heddle R (2002) Adverse reactions associated with echinacea: the Australian experience. Ann Allergy Asthma Immunol 88:42–51

    Article  PubMed  Google Scholar 

  • Neto MM, Silva GE, Costa RS et al (2009) Star fruit: simultaneous neurotoxic and nephrotoxic effects in people with previously normal renal function. NDT Plus 2:485–488

    PubMed  PubMed Central  Google Scholar 

  • Popat A, Shear NH, Malkiewicz I et al (2001) The toxicity of Callilepis laureola, a South African traditional herbal medicine. Clin Biochem 34:229–236

    Article  CAS  PubMed  Google Scholar 

  • Powell T, Hsu FF, Turk J et al (1998) Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis 32:153–159

    Article  CAS  PubMed  Google Scholar 

  • Prakash J (1999) Acute renal failure in epidemic dropsy. Ren Fail 21:707–711

    Article  CAS  PubMed  Google Scholar 

  • Prakash S, Hernandez GT, Dujaili I et al (2009) Lead poisoning from an Ayurvedic herbal medicine in a patient with chronic kidney disease. Nat Rev Nephrol 5:297–300

    Article  PubMed  Google Scholar 

  • Rhidian R (2011) Running a risk? Sport supplement toxicity with ephedrine in an amateur marathon runner, with subsequent rhabdomyolysis. BMJ Case Rep 2011, doi:10.1136/bcr.11.2011.5093

    Google Scholar 

  • Sandler B, Aronson P (1993) Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome. Urology 41:343–345

    Article  CAS  PubMed  Google Scholar 

  • Schwarz A (1993) Beethoven’s renal disease based on his autopsy: a case of papillary necrosis. Am J Kidney Dis 21:643–652

    Article  CAS  PubMed  Google Scholar 

  • Seedat YK (1993) Acute renal failure in the black population of South Africa. Int J Artif Organs 16:801–802

    CAS  PubMed  Google Scholar 

  • Seedat YK, Hitchcock PJ (1971) Acute renal failure from Callilepsis laureola. S Afr Med J 45:832–833

    CAS  PubMed  Google Scholar 

  • Segasothy M, Samad S (1991) Illicit herbal preparation containing phenylbutazone causing analgesic nephropathy. Nephron 59:166–167

    Article  CAS  PubMed  Google Scholar 

  • Segasothy M, Swaminathan M, Kong NC et al (1995) Djenkol bean poisoning (djenkolism): an unusual cause of acute renal failure. Am J Kidney Dis 25:63–66

    Article  CAS  PubMed  Google Scholar 

  • Sharma BD, Malhotra S, Bhatia V et al (1999) Epidemic dropsy in India. Postgrad Med J 75:657–661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shemesh IY, Mishal Y, Baruchin AM et al (1995) Rhabdomyolysis in paraphenylenediamine intoxication. Vet Hum Toxicol 37:244–245

    CAS  PubMed  Google Scholar 

  • Sir Hashim M, Hamza YO, Yahia B et al (1992) Poisoning from henna dye and para-phenylenediamine mixtures in children in Khartoum. Ann Trop Paediatr 12:3–6

    Article  CAS  PubMed  Google Scholar 

  • Smith AY, Feddersen RM, Gardner KD Jr et al (1994) Cystic renal cell carcinoma and acquired renal cystic disease associated with consumption of chaparral tea: a case report. J Urol 152:2089–2091

    CAS  PubMed  Google Scholar 

  • Snow A, Halpenny D, McNeill G et al (2012) Life-threatening rupture of a renal angiomyolipoma in a patient taking over-the-counter horse chestnut seed extract. J Emerg Med 43:e401–e403

    Article  PubMed  Google Scholar 

  • Stahl CE, Borlongan CV, Szerlip M et al (2006) No pain, no gain – exercise-induced rhabdomyolysis associated with the performance enhancer herbal supplement ephedra. Med Sci Monit 12:Cs81–Cs84

    PubMed  Google Scholar 

  • Steenkamp V, Stewart MJ (2005) Nephrotoxicity associated with exposure to plant toxins, with particular reference to Africa. Ther Drug Monit 27:270–277

    Article  CAS  PubMed  Google Scholar 

  • Stewart MJ, Steenkamp V (2000) The biochemistry and toxicity of atractyloside: a review. Ther Drug Monit 22:641–649

    Article  CAS  PubMed  Google Scholar 

  • Talasaz AH, Abbasi MR, Abkhiz S et al (2010) Tribulus terrestris-induced severe nephrotoxicity in a young healthy male. Nephrol Dial Transplant 25:3792–3793

    Article  PubMed  Google Scholar 

  • Terris MK, Issa MM, Tacker JR (2001) Dietary supplementation with cranberry concentrate tablets may increase the risk of nephrolithiasis. Urology 57:26–29

    Article  CAS  PubMed  Google Scholar 

  • Vachvanichsanong P, Lebel L (1997) Djenkol beans as a cause of hematuria in children. Nephron 76:39–42

    Article  CAS  PubMed  Google Scholar 

  • Vanderperren B, Rizzo M, Angenot L et al (2005) Acute liver failure with renal impairment related to the abuse of senna anthraquinone glycosides. Ann Pharmacother 39:1353–1357

    Article  PubMed  Google Scholar 

  • Vanholder R, De Smet R, Lesaffer G (1999) p-cresol: a toxin revealing many neglected but relevant aspects of uraemic toxicity. Nephrol Dial Transplant 14:2813–2815

    Article  CAS  PubMed  Google Scholar 

  • Watson AR, Coovadia HM, Bhoola KD (1979) The clinical syndrome of Impila (Callilepis laureola) poisoning in children. S Afr Med J 55:290–292

    CAS  PubMed  Google Scholar 

  • Weisbord SD, Soule JB, Kimmel PL (1997) Poison on line – acute renal failure caused by oil of wormwood purchased through the Internet. N Engl J Med 337:825–827

    Article  CAS  PubMed  Google Scholar 

  • Wong JS, Ong TA, Chua HH et al (2007) Acute anuric renal failure following jering bean ingestion. Asian J Surg 30:80–81

    Article  PubMed  Google Scholar 

  • Wood R, Mills PB, Knobel GJ et al (1990) Acute dichromate poisoning after use of traditional purgatives. A report of 7 cases. S Afr Med J 77:640–642

    CAS  PubMed  Google Scholar 

  • Wu MS, Hong JJ, Lin JL et al (1996) Multiple tubular dysfunction induced by mixed Chinese herbal medicines containing cadmium. Nephrol Dial Transplant 11:867–870

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Su T, Li XM et al (2011) Aristolochic acid nephropathy: variation in presentation and prognosis. Nephrol Dial Transplant 27:292–298

    Google Scholar 

  • Zhang WX, Zhang ZM, Zhang ZQ et al (2014) Andrographolide induced acute kidney injury: analysis of 26 cases reported in Chinese literature. Nephrology (Carlton) 19:21–26

    Article  CAS  Google Scholar 

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  1. Nephrology Department, Erasme Hospital and Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles, 808 route de Lennik, 1070, Brussels, Belgium

    Thomas Baudoux MD & Joëlle L. Nortier MD, PhD

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  1. Thomas Baudoux MD
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  2. Joëlle L. Nortier MD, PhD
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Correspondence to Joëlle L. Nortier MD, PhD .

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  1. Department of Pharmacology & Toxicology, University of Oulu, Oulu, Finland

    Olavi Pelkonen

  2. Service de Chimie Thérapeutique et de Pharmacognosie, University of Mons, Mons, Belgium

    Pierre Duez

  3. Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

    Pia Maarit Vuorela

  4. Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

    Heikki Vuorela

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Baudoux, T., Nortier, J.L. (2017). Nephrotoxicity of Herbal Products. In: Pelkonen, O., Duez, P., Vuorela, P., Vuorela, H. (eds) Toxicology of Herbal Products. Springer, Cham. https://doi.org/10.1007/978-3-319-43806-1_13

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