Aristolochia Nephropathy

from: Deutsche Zeitschrift für Akupunktur 43(2000), 187-197
Axel Wiebrecht

Abstract

The possible harmful effects of traditional Chinese remedies to the kidney have attained broader public attention in Germany due to publications in the Deutsches Aerzteblatt and the SPIEGEL magazine and their subsequent echo in various papers and announcements. These reports revealed a strange mixture of truth, hoaxes, confusions, misinterpretations and ignorance. The present article suggests that the tragic cases of terminal kidney failure following a Belgian weight reduction program can not simply be attributed to Chinese herbs, even if they are involved. On the other hand it will be argued that Aristolochia species applied in the context of Traditional Chinese Medicine can cause severe nephropathy. The widely used term "Chinese herb nephropathy (CHN)" makes no sense as nephropathy is not a special characteristic of Chinese herbs, but one of aristolochic acid and Aristolochia species containing this substance, which appears in China as well as in Western and other countries. An estimate pertaining to France calculated a frequency of two cases of nephropathy in 1000 patients treated with remedies containing aristolochic acid. In the meantime similar reports have emerged in many countries.

In Germany all remedies containing aristolochic acid, i.e. all varieties of the Aristolochia species and preparations made from these as well were banned in 1981 because aristolochic acid is carcinogenic. The carcinogenic effect was also evident in the Belgian cases, and was brought to the attention of the international public by a report in the New England Journal of Medicine in June of 2000. The nephro­toxic effects were well known since the fifties. A dose evaluation shows that as a result of TCM treatment, a dosage of up to 7956 mg aristolochic acid may accumulate after three months, or as much as 63.650 mg after two years. These amounts exceed by far those attained in the West, when Herba aristolochiae clematidis or pure aristolochic acid (up to about 162 mg) was used. On these grounds the therapeutic use of Aristolochia species should definitely be rejected regardless of the ban in Germany and other countries. Pharmacies and pharmaceutical wholesalers should be held to higher quality standards to avoid confusion or errors pertaining to drugs, as well as to prevent contamination by heavy metals, pesticides or even pharmaceutical agents. Herbs that can be mistaken for Aristolochia species, such as Stephania tetrandra, should definitely be examined for the absence of aristolochic acid. Powders or other preparations from these herbs should be avoided. mg mg/d common daily dos

  mg mg/d common daily dose
Capsule A (3 per day, orally):           
     
Fenfluramin 17-25 42-75 60(-120)1
Diethylpropion 17-25 42-75 60-752
Meprobamat 0-50 0-150 600-16002

Capsule B (3 per day, orally):
     
Cascara powder 20-150 60-600 250-10003
Acetazolamid 24-45 72-135 75-5002
Belladonna extract 1-2 3-6 extract dependant
Stephania tetrandra 100-200 300-600(powder) 3000-9000 (drug)4
Magnolia officinalis 100-200 300-600(powder) 3000-9000 (drug)4

intradermal injections (1 per week):
     
Artichoke extract (Chophytol S) 0,2    
Euphyllin 0,5    
1 according to (40)  2 according to (10)  3 according to (71)  4 acoording to (5)
Tab. 1: Medication used in the Belgian slimming clinic from May, 1990 to May, 1992 (70)
Pharmaceutical Name Botanical Species Chinese Name TCM Category
Cort. Magnoliae Officinalis Magnolia officinalis Hou Po transf. dampness
Rad. Stephaniae Tetrandrae Stephania tetrandra- (Han) Fang Ji drain dampness
Rad. Aristolochiae seu Cocculi Aristolochia fangchi+ Guang Fang Ji drain dampness
  Cocculus trilobus-    
Caul. Mutong Aristolochia manshuriensis+ (Guan) Mu Tong drain dampness
  Akebia trifoliata    
  Akebia quinata-    
  Clematis armandii-- (Chuan) Mu Tong  
  Clematis montana-- (Chuan) Mu Tong  
Fruct./Rad. Aristolochiae Aristolochia debilis+ Ma Dou Ling(Fruct.) relieve cough
  Aristolochia contorta Qing Mu Xiang(Rad.)  
+ with evidence of aristolochic acid I und II (31)
- with no evidence of aristolochic acid I/II (31)
-- with no evidence of aristolochic acid (12)

Tab. 2: Compilation of pharmaceutical, botanical and Chinese names of the herbs and the categories to which they belong in the Traditional Chinese-pharmacotherapy according to (5, 52). 

   Belgium  France  Tardolyt®  TCM  Jackson et al.
 DD of herb [mg] 300-600   (270)-540  3000-90001    
 AA [mg/g herb]  0,65-1,56  3  1,07-9,822    
 DD AA [mg]  0,195-0,936  1,62  0,45-0,93  3,2-88,4  70-1404
 treatment period [d]  540  90-450  28-3605  7206  1-227
TD [mg] 110-505 146-729 25-162 2304-63650 140-4208
1 3-15g(5) or 4,5-9g(52) are quoted for Aristolochia fangchi , 3-9g(5) or 3-6g(52) for Aristolochia manshuriensis   2 according to (31)
3 according to(8)   4 body weight supposed as 70kg
5 according to (33) and (29)   6 treatment period of the English cases was 2 -6 years (36)
7 one case 45 days   8 one case 1029mg
DD = daily dose   AA = aristolochic acid   TD = total dose (cumulated)
Tab. 3: Estimation of doses of aristolochic acid given in the Belgium slimming clinic, of the French cases, of Tardolyt®, of Aristolochia fangchi or Aristolochia manshuriensis doses commonly used in TCM and of cases with acute application according to Jackson et al. (35). For Belgium and France the data from Stengel and Jones was used (57) giving a conservative estimation with 540mg powder as a maximum daily dose for France.