What are the causes of aristolochic acid nephropathy?

Studies have found that the cause of aristolochic acid nephropathy is simple, mainly due to excessive intake of aristolochic acid. Aristolochic acid is a precious Chinese medicinal material. It is often used to make Fukefenqing Pills, Dahuangqingwei Pills, Shujinhuoxue Pills, etc. The therapeutic effect is very significant, but once taken in excess, it will cause aristolochic acid nephropathy. Therefore, experts remind patients to take the medicine according to the doctor's instructions and never make decisions on their own.

1. Causes of Aristolochic Acid Nephropathy

Excessive intake of aristolochic acid is the main cause of aristolochic acid nephropathy. Aristolochic acid and its derivatives are mainly found in plants of the genus Aristolochia in the family Aristolochiaceae. This type of plant is widely distributed, with more than 350 species in the world and 40 to 50 species in my country. Among them, more than 20 species are commonly used as medicine, including Aristolochia affine (Akebia trifoliata) and Aristolochia stephaniae (Aristolochia fangji). There are more than 100 kinds of Chinese patent medicines and prescriptions containing aristolochic acid in my country. Among them, Longdan Xiegan Pills (Decoction), Paishi Chongji, Fuke Fenqing Pills, Ganlu Xiaodu Pills, etc. have been clinically reported to cause aristolochic acid nephropathy, with Longdan Xiegan Pills being the most common (Table 3). In addition, Jinsha Wulin Pills, Juhe Pills, Daochi Pills, Dahuang Qingwei Pills, Anyang Refined Paste, Xindi Powder, Xiaoji Yinzi, Bazheng Powder, Shujin Huoxue Pills, Shixiang Fansheng Pills, Chunyang Zhengqi Pills, Zhisou Huatan Pills, Twenty-five Flavors Songshi Pills, Xungufeng Injection, Fufang Dihu Decoction, Kouyanning and Yangyin Xiaoyan Decoction all contain aristolochic acid.

Aristolochic acid nephropathy is mainly related to excessive or long-term use of the above-mentioned drugs. For example, the pharmacopoeia stipulates that the commonly used dosage of Aristolochia chinensis is 3 to 6 g, while clinical reports of Aristolochia chinensis poisoning patients often show dosages of tens or even hundreds of grams. For example, Longdan Xiegan Pills and Ganlu Xiaodu Pills were originally only suitable for short-term use, but most cases of poisoning involved long-term use. However, the occurrence of aristolochic acid nephropathy varies depending on physical constitution. In some individual cases, acute aristolochic acid nephropathy may still occur even if a small dose of aristolochic acid is ingested. Patients with underlying renal disease are more likely to develop aristolochic acid nephropathy.

2. Diagnosis and differential diagnosis of aristolochic acid nephropathy

Clinical diagnosis of aristolochic acid nephropathy generally requires the following conditions:

① It is clear that herbal medicines containing aristolochic acid (especially Aristolochia strychnifolia) have been taken, or aristolochic acid has been detected in the medicines taken, or aristolochic acid is found in the patient's blood.

② Clinical manifestations include renal insufficiency, severe anemia and renal tubular dysfunction (low molecular weight proteinuria, renal glucosuria, aminoaciduria or Fanconi syndrome), with no or small amounts of erythrocytes in the urine (but when aristolochic acid nephropathy occurs on the basis of glomerular disease, proteinuria and hematuria may still occur).

③Pathological changes in kidney. In addition to extensive or patchy necrosis of tubular epithelial cells, exposure of tubular basement membrane and absence of tubular cell regeneration are relatively characteristic lesions in acute aristolochic acid nephropathy. The prominent manifestations of chronic aristolochic acid nephropathy are extensive interstitial fibrosis in the cortical area or at the corticomedullary junction and a decrease in the number of renal tubules without obvious cellular infiltration.

④Exclude tubulointerstitial diseases caused by other reasons, such as drugs, autoimmune diseases, monoclonal immunoglobulin deposition disease, renal ischemia, etc.

Aristolochic acid-induced acute tubular necrosis must be differentiated from toxic acute tubular necrosis caused by other reasons. Combined with the history of medication or exposure to poisons and the characteristics of renal tubular function damage, renal pathology shows that the renal tubular basement membrane is exposed without cell regeneration, and differential diagnosis is generally not difficult.