Chinese-herbs nephropathy

Kl. Kabanda, A., Jadoul, M., Lauwerys, R., Bernard, A., and van Ypersele de Strihou, C., Low molecular weight proteinuriain Chinese herbs nephropathy. Kidney Int. 48(5), 1571-1576(1995). 

Several adulterants added to nonherbal supplements, vitamins, and herbal medicine preparations can cause renal dysfunction and renal failure. Aristolochic acid is used as a herbal remedy for weight loss and has been reported to cause Chinese herb nephropathy characterized by extensive interstitial fibrosis with tubular atrophy and loss. Herbal medicine preparations produced in South Asia contain potentially harmful levels of lead, mercury, and/or arsenic which can lead to renal toxicity. 

In the UK, the long-term (2 and 6 years) use of Aristolochia species in Chinese herbal mixtures, taken as an oral medication or herbal tea, resnlted in Chinese-herb nephropathy with end-stage renal insnfficiency (1). In reaction to these reports, the erstwhile Medicines Control Agency banned all Aristolochia species for medicinal use in the UK. 

Aristolochic acid is a potent carcinogen and can cause serious kidney damage, Chinese herb nephropathy, which can be fatal (10). Renal fibrosis has also been reported (11). 

A 58-year-old Japanese woman with CREST syndrome (calcinosis, Raynaud s syndrome, esophageal sclerosis, sclerodactyly, and telangiectasia) developed progressive renal dysfunction (16). Renal biopsy showed changes typical of Chinese herb nephropathy. Analyses of Chinese herbs she had taken for several years demonstrated the presence of aristolochic acid. Oral prednisolone improved her renal function and anemia. 

A 59-year-old man developed renal insufficiency after self-medication for 5 years with a Chinese herbal remedy to treat his hepatitis (17). Renal biopsy showed signs characteristic of Chinese herb nephropathy. Analysis of the remedy proved the presence of aristolochic acids I and II. 

In Japan two cases of Chinese herb nephropathy were associated with chronic use of Aristolochia manchuriensis (Kan-mokutsu) (24). The diagnosis was confirmed by renal biopsy and the toxic constituents were identified as aristolochic acids I, II, and D. 

Taiwanese authors have reported 12 cases of suspected Chinese herb nephropathy, confirmed by renal biopsy (25). Renal function deteriorated rapidly in most patients, despite withdrawal of the Aristolochia. Seven patients underwent dialysis and the rest had slowly progressive renal insufficiency. One patient was subsequently found to have a bladder carcinoma. Other cases have been reported from mainland China (26) and Taiwan (27). 

Because of fear of malignancies the Belgian researchers who first described the condition have advocated prophylactic removal of the kidneys and ureters in patients with Chinese herb nephropathy. Of 39 patients who agreed to this, 18 (46%) had urothelial carcinoma, 19 of the others had mild to moderate urothelial dysplasia, and only two had normal urothelium (28). All tissue samples contained... 

Animal experiments have shed more light on Chinese herb nephropathy (29). Salt-depleted male Wistar rats were regularly injected with two different doses of aristolochic acid or with vehicle only for 35 days. The histological signs of Chinese herb nephropathy were demonstrated only in animals that received the high dose of 10 mg/kg. The authors presented this as an animal model for studying the pathophysiology of Chinese herb nephropathy. 

When 19 kidneys and urethras removed from 10 patients with Chinese herb nephropathy who required kidney transplantation were examined histologically, there were conclusive signs of neoplasms in 40% (30). 

One patient who had a urothehal malignancy 6 years after the onset of Chinese herb nephropathy later developed a breast carcinoma that metastasised to the liver (31). The urothelial mahgnancy contained aristolochic acid-DNA adducts and mutations in the p53 gene, and the same mis-sense mutation in codon 245 of exon 7 of p53 was found in DNA from the breast and liver tumors. However, DNA extracted from the urothelial tumor also showed a mutation in codon 139 of exon 5, which was not present in the breast and liver. 

Tamaki K, Okuda S. Chinese herbs nephropathy a variant form in Japan. Intern Med 2001 40(4) 267-8. 

GiUerot G, Jadoul M, Arlt VM, van Ypersele De Strihou C, Schmeiser HH, But PP, Bieler CA, Cosyns JP. Aristolochic acid nephropathy in a Chinese patient time to abandon the term Chinese herbs nephropathy Am J Kidney Dis 2001 38(5) E26. 

Martinez MC, Nortier J, Vereerstraeten P, Vanherweghem JL. Progression rate of Chinese herb nephropathy impact of Aristolochia fangchi ingested dose. Nephrol Dial Transplant 2002 17(3) 408-12. 

Tanaka A, Nishida R, Maeda K, Sugawara A, Kuwahara T. Chinese herb nephropathy in Japan presents adult-onset Fanconi syndrome could different components of aristolochic acids cause a different type of Chinese herb nephropathy Clin Nephrol 2000 53(4) 301-6. 

Cosyns JP, Jadoul M, Squifflet JP, Wese FX, van Ypersele de Strihou C. Urothelial lesions in Chinese-herb nephropathy. Am J Kidney Dis 1999 33(6) 1011-17. 

Schmeiser HH, Bieler CA, Wiessler M, van Ypersele de Strihou C, Cosyns JP. Detection of DNA adducts formed by aristolochic acid in renal tissue from patients with Chinese herbs nephropathy. Cancer Res 1996 56(9) 2025-8. 

Vanherweghem JL, Abramowicz D, Tielemans C, Depierreux M. 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 27(2) 209-15. 

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

Figure 1. Pathological aspect of Chinese herb nephropathy. Paucicellular interstitial fibrosis around atrophic tubules ( ). Fibrous thickening of the arteriolar walls (arrow). No glomerular lesion. H E staining, original magnification 300x. By courtesy of Dr. M. Depierreux.

Meyer MM, Chen TP, Bennett WM. Chinese herb nephropathy. Proc (Bayi Univ Med Cent) 2000 13 334-337... 

Kabanda A, Jadoul M, Lauwerys R, Bernard A, van Ypersele de Strihou C. Low molecular weight proteinuria in Chinese herbs nephropathy. Kidney Int 1995 48 1571-1576... 

Nortier JL, Deschodt-Lanckman MM, Simon S,Thielemans NO, de Prez EG, Depierreux MF,Tielemans CL, Richard C, Lauwerys RR, Bernard AM, Vanherweghem JL. Proximal tubular injury in Chinese herbs nephropathy monitoring by neutral endopeptidase... 

Vanherweghem JL. Association of valvular heart disease with Chinese-herb nephropathy. Lancet 1997 350 1858 (letter)... 

Reginster F, Jadoul M, van Ypersele de Strihou C. Chinese herbs nephropathy presentation, natural history and fate after transplantation. Nephrol DialTransplant 1997 12 81-86... 

Unger P, Nortier J, Muniz Martinez MC, Plein D, Vandenbossche JL, Vereerstraeten P, Vanherweghem JL. High prevalence of fenfluramine-related aortic regurgitation in women with end-stage renal disease secondary to Chinese herb nephropathy. Nephrol Dial Transplant 2003 18 906-910... 

Vanherweghem JUTielemans C, Simon J, Depierreux M. Chinese herbs nephropathy and renal pelvic carcinoma. Nephrol Dial Transplant 1995 10 270-273... 

MalakJ. Chinese herb nephropathy is not a (dex)fenfluramine nephropathy but a serotonin nephropathy. JAItern Complement... 

Colson CR, De Greef KE, DuymelinckC, Simoens PJ, Verpooten GA, De Broe ME. Role of serotonin in the development of Chinese herbs nephropathy Nephrol Dial Transplant 1999 14 SuppI 4 16 (abstract)... 

Debelle F, Nortier J, Arit VM, De Prez E, Vienne A, Salmon I, Phillips DH, Deschodt-Lanckman M, Vanherweghem JL. Effects of dexfenfluramine on aristolochic acid nephrotoxicity in a rat model for Chinese-herb nephropathy. Arch Toxicol 2003 77 218-226... 

Aristolochic acid and its salts, originated from a weed, Aristolochia clematitis, have toxic and carcinogenic effects to the kidneys and urothelium [45], respectively. Ivic [46] postulated that this plant may be a cause of Balkan nephropathy, but failed to provide convincing evidence from field surveys. Evidence that A. clematitis played a central role in the etiology of Chinese herb nephropathy [47-49], a condition similar to Balkan nephropathy, initiated a second look at this previously abandoned hypothesis and it gained a lot of weight by recent data on the association between DNA adduct formation derived from AA, mutation pattern and tumour development in BEN [50] (see also chapter 33). 

Recently similarity of Balkan nephropathy and nephropathy induced by Chinese herbs used in slimming diets have been suggested [48]. Nevertheless, Chinese herb nephropathy is rapid progressive tubulointerstitial diseases with pronounced fibrosis and progression towards end-stage renal disease within few years, clearly different from the protracted clinical course of Balkan nephropathy. 

Cosyns JP, Jadoul M, Squifflet JP et al. Chinese herbs nephropathy a clue to Balkan endemic nephropathy Kidny Int. 1994 45(6) 1680-8. 

Cosyns JP, Dehoux JP, Guiot Y, Goebbels RM, Robert A, Bernard AM, van Ypersele de Strihou C. Chronic aristolochic acid toxicity in rabbits a model of Chinese herbs nephropathy Kidney Int. 2001 59(6) 2164-73... 

Europe was stunned with the outbreak of Chinese herb nephropathy. There have been no reports from Africa and - because of the superb epidemiological... 

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