Kidney Damage Causd by Fraditional Chinese Medicine

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Preface

kidney is an important organ for eliminating drugs from the body. Most drugs after being absorbed into the body, go through metabolic processes, including glomerulous filtration, active tubule secretion and re-absorption in the kidneys before excretion. These processes cause the kidney to become more susceptible to drug toxin. Also kidney is the most blood profuse organ, if there are nephrotoxic substances in the blood, they can easily damage the kidney tissues. The countercurrent flow of blood in the kidney increases the concentration of the drugs in the medullary and papillary portions of the kidney, and results in necroses.

 

Now, doctors have better understanding of the nephrotoxic side effects of some frequently used drugs, like nephrotoxic antibiotics, analgesics, contrast mediums, diuretics and immunosuppressives. Physicious are more cautious when prescribing these drugs, in order to prevent the side effects and kidney toxin. While most people believe that traditional Chinese herbal medicine have fewer side effects, they overlooked the facts that some Chinese herbs can cause kidney toxin as well. With Chinese herbal medicine becoming more popular and widely used, more renal failure cases have been reported. There is an incident in Belgium, in which hundreds of people have suffered from acute progressive renal failure due to the use of Chinese herbs containing aristolochic acid.

This article summarizes the reports of journals from Taiwan and around the world to bring to the reader's attention to the renal failure caused by consumption of some Chinese herbs.

 

The Causes of kidney Failure

1. Insufficient knowledge of Chinese herbs?toxic side medicine

In Chinese tradition, many Chinese medicines containing nephrotoxins have been known for their toxicity. According to the Pharmacopoeia of the PeopleÕs Republic of China, drug toxicity can be classified into four levels: slight toxicity level, comprising herbs like Radix seu Folium Claoxyli Indici and Radix Aristolochia Fangchi; moderate toxicity level , containing herbs such as Semen Pharbitidis, Fructus Xanthii, Fructus Quisqualis, Fructus Coriariae, Radix et Herba, Plumbaginis Zeylanicae and Fructus Papaveris Deseminatus; strong toxicity level,including herbs like Radix Tripterygii, Pseudobulbus Cremastrae Appendiculatae, Semen Strychni and Radix Aconiti kusnezoffii, and finally the acute toxicity level,including herbs such as Mylabris. Many nephropathy clinical reports associated with the consumption of Radix Tripterygii, Radix Aconiti kusnezoffii and Herba Leonuri are due to over-dosage of these drugs and the prolonged treatment.

2. Inaccurate Diagnosis and Prolonged treatment

Accurate diagnosis plays an important role in traditional Chinese medicine treatment. However, most clinical case reports related to kidney toxicity are due to incorrect diagnosis by Chinese medicial practitioners, and the blind use or the prolonged consumption of drugs by patients themselves. According to a quantitative analysis of kidney toxicity clinical reports, approximately 33.33% of nephropathy cases are linked to the misuse of fringe medicine, while 93.255% are related to the use of high-dosed drugs over a short period of time.

3. Misusing Herbs

The misuse of similar herb species can lead to kidney damage as well. For example, the misuse of Aristolochia fangchi for Stephania tetrandra caused a terrible kidney toxicity incident in Belgium, in which 11 out of a total of 12 lots of products were inspected and found to contain aristolochic acid. In addition, the two kidney failure cases reported in England were due to the misuse of Clematis armandii in place of Aristolochia manshuriensis.

4. Lack of Awareness to the Risk Factors

There are several identified risks factors that can increase the risk of kidney damage. When using Chinese medicine in the presence of these risk factors, the chance of developing kidney damage is higher. Theses risk factors are the following:

a.  Elderly patients. 

b.  Diabetics and chronic kidney disease patients.

c.  People allergic to drugs or prone to allergies.

d.  Combined use of drugs containing kidney toxin, especially combined use of chemicals with herbal medicines.

5.  Poor  TCM  Manufacturing Process and Quality Control

Tripterygium polyglycoside is widely used for kidney and rheumatic disease treatment. However, the products manufactured by different companies appear to have different ingredient amounts of tripterygium polyglycoside, resulting in different side effects and toxicity. The inconsistent tripterygium polyglycoside amount can easily cause confusion in clinical drug application, which can lead to kidney damage.

Prevention Plan

1. Education

Promote the proper use of traditional Chinese medicine, correct the public concept that traditional Chinese medicine is natural medicine with no toxicity or side effects, and implement an instant reporting system of kidney toxicity incidents to increase public awareness of the relationship between traditional Chinese medicine and kidney damage to prevent kidney damage from happening.

2. Proper use of TCM

a. Understand TCM toxicity and side effects, familiarize with the metabolic process, dosage amount and correct use (Such as Aconitum kusnezoffii Reichb and Xanthii Fructus) of herb drugs. Do not prescribe to pregnant women, elderly, children and people allergic to drugs.

b. Strictly control drug dosage and practice TCM principles. Use drugs only under the doctors?directions in prescriptions.

c. Understand the risks factors relating to renal failures.

3. Speed Up TCM Standardization and modernizating Manufacturing Process.

Make every effort to use safe and correct herbs, insist on product quality consistency and emphasize correct dosage efficient use of drugs.

research into drug toxicity and pharmaco-  kinetics, and abide by the operation procedures.

4.  Further Investigating Diuretics and Auti-heumatic Drugs.

Treatment length of kidney diseases and rheumatism usually takes a long time. The drugs for rheumatism treatment are the ones most frequently used in treating kidney diseases, which accounts for most of the clinical cases of reported kidney toxicity. So far, the pathological research on rheumatism is insufficient; it only focuses on the urinary function and efficacy of the drug but not on the relationship between its long-term use and kidney toxicity. The kidney damage linked to the use of rheumatism drugs containing aristolochic acid has been studied and paid attention to. The Health Department in Taiwan has come to an initiative decision to ban five Chinese herbs containing aristolochic acid, including Guang Fan Gji, Guan Mu Tong, Ma Dou Ling, Tian Xian Teng and Chuan Mu Xian as well as other harmonizing formulas related to them

5.  Analysing the Content of Aristolochic Acid(AA)

Using LC/PDA/MS Method to analyse the AA contents, the result can assist the doctors and patients to use products not containing AA or with only limited amount to avoid renal failure.

The approximate amount of aristolochic acid in different aristolochia species are: more than 1000 ppm in Ma Dou Ling. 700?800 ppm in Tian Xian Teng and Chuan Mu Xi and 400 ppm in Guang Fan Ji and Guan Mu Tong. Guang Fan Ji and Guan Mu Tong are frequently and widely used in traditional Chinese medicine and comparatively easier to induce more instances of kidney damage. According to Chinese Pharmacopoeia, both Gang Fang Ji and Han Fang Ji are classified as certified Fang Ji plant species whereas Guan Mu Tong and Chuan Mu Tong are classified as certified Mu Tong plant species (refer to Attachment 1). However, for both instances, the latter ones do not count as one of the Aristolochia species since they don't contain any aristolochic acid. Therefore, we suggest that only Han Fang Ji and Chuan Mu Tong be permitted for prescription use in order to protect public health.

Xi Xin is a plant categorized under the Xi Xin genus of the Aristolochiaceae family. According to Chinese Pharmacopoeia, the whole herb of Asarum sieboldii, A. heterotropoides var. mandshuricum and A. sieboldii var. seoulense are supplied as certified Xi Xin articles; whereas according to Japanese Pharmacopoeia, only the root portion of A. sieboldii and A. heterotropoides var. mandshuricum are identified as certified Xi Xin. All the plants of the family of Aristolochiaceae contain aristolochic acid except for the Xi Xin genus, which only contain a small amount, particularly those certified ones mentioned above.  An analysis of 16 plants containing aristolochic acid for medical use by K.HASHIMOTO showed that seven of them, identified as part of the Xi Xin genus, were detected to have no aristolochic acid independent of the places of production. Another analysis of 9 species of Xi Xin genus plants around the world (Japan, Liao Ning province,China, Ji Ling province,China , Si Chuan province ,China , Jiang Su province ,China or South and North Korea) by T.T. Jong showed that the amount of aristolochic acid was highest in A. cripulatum (3376ug/g), followed by A. forbesi (105.9ug/g); whereas all the others were below 85ug/g; and only 3.3ug/g were found in A. sieboldii. Qualitative analysis revealed that the amount of aristolochic acid in the root of Xi Xin was slightly lower than that in the herb , and this may explain the different results of the two studies mentioned above. Also, it's worthy to mention that the amount of aristolochic acid in the certified medical plants recorded in Pharmacopoeia is all below 4ug/g.

We analyzed the root of 40 certified medical plants of the Xi Xin genus and found that 20 of them identified no detectable level of aristolochic acid (The maximum detected value was 0.2 ppm); 30 of them had a value around 2ug/g; and 7 of them were around 3ug/g.  In addition, we examined 14 traditional Chinese herbal extract preparations containing Xi Xin manufactured by Sun Ten Pharmaceuticals Co. Ltd.and found that all had aristolochic acid amounts falling within the maximum range of detection. So far, certified species of Xi Xin have not been proven to be interchangeable with other medical plants. However, since the amount of aristolochic acid that Xi Xin contains is very slight compared with the amount of dosage that can cause toxicity and prove to be carcinogenic, we suggest the establishment of strict upper limits for the use of aristolochic acid in pharmaceutical preparations rather than prohibiting the use of all aristolochic species. U.S and most European countries follow the specification made by FAD for the maximum acceptable amount of aristolochic acid , that is below 0.5 ppm. In Japan, the upper limit of aristolochic acid is set as Ònot detectable?by HPLC(about 1ppm) whereas in Singapore , the upper limit of time length for the use of pharmaceutical preparations containing aristolochic acid is 2 weeks. Therefore, perhaps an upper limit of 1 ppm and less than 2 weeks duration of drug use is the most reasonable and safe standard to be established.