OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

The renal toxicity and mutagenicity of aristolochic acid (AA) as well as its carcinogenicity on upper urinary tract transitional epithelial cells have been widely known. Since 2003, drug regulatory departments have successively cancelled the quality standards for AA-containing medicines such as Aristolochiae Radix, Aristolochiae Manshuriensis Caulis and Aristolchiae Fangchi Radix, and adopted measures for strengthening regulation and revising package insert or quality standards for other AA-containing medicines, including Aristolochia Cinnabarina Radix, Aristolochiae Fructus, Aristolochiae Mollissimae Herba, in order to control its safety risk. In recent years, domestic and foreign studies on AA have mainly involved action mechanism and clinical performance of AA toxicity, early-stage diagnosis and treatment method. In this paper, authors gave a brief summary and evaluation on risk factors for using AA-containing medicines, and offered measures and suggestions for preventing and controlling AA toxicity.
Animals ; Aristolochia ; adverse effects ; chemistry ; Aristolochic Acids ; analysis ; therapeutic use ; toxicity ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; analysis ; therapeutic use ; toxicity ; Humans

Aristolochic acid nephropathy (AAN), a progressive renal interstitial fibrosis frequently resulting in end stage renal disease, still remains a common chronic interstitial nephropathy in China. Therefore, great attention should be paid to AAN. This review summarized recent research progress of AAN in terms of in vivo aristolochic acid metabolism, epithelial mesenchymal transition, proteomics, immunity-inflammation, and autophagy, which will help to further understand the pathogenesis of AAN, and to search effective intervention targets.
Animals ; Aristolochic Acids ; adverse effects ; metabolism ; Autophagy ; Drugs, Chinese Herbal ; adverse effects ; Epithelial-Mesenchymal Transition ; Humans ; Inflammation ; Kidney Diseases ; chemically induced ; Proteomics

BACKGROUNDThe research of cancer in patients on hemodialysis (HD) in China has not been reported. The aim of this study was to investigate the clinical and histological features and outcomes of cancer in Chinese HD patients.

METHODSThe study subjects were 49 cancer patients (1.4%) out of 3448 end stage renal disease (ESRD) patients maintained on HD at China-Japan Friendship Hospital from October 1997 to July 2011.

RESULTSUrinary tract cancer (74%) was the most common followed by gastrointestinal tract cancer (12%), breast cancer (6%), lung cancer (4%), thyroid cancer (2%), and hematologic cancer (2%). Thirty-three patients (67%) had urinary tract transitional cell carcinoma (TCC) and 29 of them had aristolochic acid nephropathy (AAN) as underlying disease. Death occurred in eight patients out of 49, and the survival rate of HD patients with cancer was similar to those without cancer (P = 0.120).

CONCLUSIONThe urinary tract TCC is the most common cancer in HD patients with AAN in one of the centers of northern China.

Adult ; Aged ; Aged, 80 and over ; Aristolochic Acids ; metabolism ; Carcinoma, Transitional Cell ; complications ; epidemiology ; metabolism ; China ; Female ; Humans ; Kidney Diseases ; epidemiology ; etiology ; metabolism ; Male ; Middle Aged ; Renal Dialysis ; adverse effects ; Retrospective Studies ; Urologic Neoplasms ; complications ; epidemiology ; metabolism

Aristolochic Acids ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Infant, Newborn ; Kidney Diseases ; chemically induced ; Kidney Tubular Necrosis, Acute ; chemically induced ; Magnoliopsida ; adverse effects ; Male ; Retrospective Studies

OBJECTIVETo summarize the clinical characteristics and prognosis of newborn aristolochic acid nephropathy induced by akebia.

METHODRetrospective analysis of clinical manifestations, therapy and prognosis was made upon data of 3 newborn infants with renal function lesion induced by akebia.

RESULTThree infants who were fed with Chinese herbal medicines containing akebia trifoliate suffered from acute renal failure, renal glomerular and tubular injury, with symptoms of vomiting, diarrhea, and oliguria. Laboratory tests manifested hyperpotassemia, hyponatremia, elevation of serum creatinine and urea nitrogen, and metabolic acidosis. Renal glomerular lesion was mild, presented with proteinuria and increased serum β(2) microglobin. Renal dysfunction was manifested with alkaline urine, glucosuria, positiveness of urine glucose, ketone and aminoaciduria, and increased urine β(2) microglobin excretion. After symptomatic treatment for 3 to 4 weeks, the renal function of these infants recovered. Proteinuria, aminoaciduria and glucosuria turned negative within 5 to 8 months, 3 months to 1 year, and 9 months to 3 years, respectively. Urine pH decreased to 7.0 after 5.0 - 5.5 years. All cases took citric acid mixtures for 5.5 to 6 years. A 12-years follow-up demonstrated that serum creatinine of 3 cases were within normal range during the first 11 years of life, however recent follow-up showed increased serum creatinine of case 1 and case 2, except for serum creatinine of case 3 remained normal. The estimated glomerular filtration rate (eGFR) of all the 3 cases decreased. Among which, eGFR of case 1 and case 2 were lower than 90 [ml/(min·1.73 m(2))], and decreased 1.1 [ml/(min·1.73 m(2))] and 0.6 [ml/(min·1.73 m(2))] per year during recent six years, respectively. No obvious decrease of eGFR was observed in case 3. Blood gas analysis and urine routine were normal, yet blood and urine β(2) microglobin excretion were still high. Urinary N-acetyl-β-D-glucosaminidase increased again after having returned to normal.

CONCLUSIONNewborn aristolochic acid nephropathy induced by akebia might induce acute renal failure and renal tubules injury. Renal function could recover after symptomatic treatment in short-term. Nevertheless, glomerular filtration rate presents a slow descending tendency and renal tubules lesion lasted for many years, which requires a long-term follow-up.

Aristolochic Acids ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Infant, Newborn ; Kidney Diseases ; chemically induced ; Kidney Tubular Necrosis, Acute ; chemically induced ; Magnoliopsida ; adverse effects ; Male ; Retrospective Studies

Aristolochic Acids ; adverse effects ; Humans ; Kidney Diseases ; chemically induced

OBJECTIVETo observe the effect of bone morphogenetic protein-7 (BMP-7) on aristolchic acid induced renal tubular epithelial cell trans-differentiation to look for new therapeutic approach for aristolchic acid nephropathy (AAN).

METHODSIn vitro cultured human proximal renal tubular epithelial cell line HK-2 cells were treated with different concentrations of BMP-7 (75 ng/mL, 150 ng/mL and 300 ng/mL) after trans-differentiation of the cells was induced by AA (10 microg/mL). Levels of alpha-SMA mRNA and protein expressions were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting respectively.

RESULTSBMP-7 reversed the AA inducing alpha-SMA expressions in HK-2 cells in a dose-dependent manner.

CONCLUSIONBMP-7 can inhibit the trans-differentiation of human renal tubular epithelial cell induced by AA, thereby might be a new potential drug for AAN prevention and treatment.

Actins ; metabolism ; Aristolochic Acids ; adverse effects ; Bone Morphogenetic Protein 7 ; pharmacology ; Cell Line ; Cell Transdifferentiation ; drug effects ; Epithelial Cells ; cytology ; Humans ; Kidney Tubules, Proximal ; cytology

OBJECTIVETo investigate the effects of prostaglandin E1 (PGE1) on the progression of aristolochic acid nephropathy (AAN).

METHODSTwenty-four patients diagnosed as AAN with serum creatinine (Scr) between 1.5 mg/dL and 4 mg/dL during September 2001 to August 2003 were randomly divided into 2 groups. All patients had ingested long dan xie gan wan containing aristolochic acid (0.219 mg/g) for at least 3 months. Twelve patients were injected with Alprostadil (10 microg/d for 10 days in one month, summing up to 6 months). Except for PGE1, the other therapy was same in both groups. Renal function was assessed using reciprocal serum creatinine levels (1/Scr).

RESULTSThe level of Scr an d serum hemoglobin (Hgb) was similar in both groups prior to therapy. During follow-up, 1/Scr levels in PGE1 group were significantly higher than control group (P < 0.01), and Hgb levels in PGE1 group were significantly increased compared with control (P < 0.05).

CONCLUSIONPGE1 can slow the progression of renal failure and increase Hgb level of AAN patient.

Adult ; Alprostadil ; therapeutic use ; Aristolochic Acids ; adverse effects ; Creatinine ; blood ; Female ; Follow-Up Studies ; Hemoglobins ; metabolism ; Humans ; Kidney ; pathology ; Male ; Middle Aged ; Nephritis, Interstitial ; chemically induced ; drug therapy ; pathology

The article summarized the general situation of the study on the renal toxicity caused by aristolochic acids (AAs) and Chinese herbs containing AAs. The renal lesion induced by AAs and Chinese herbs containing AAs locates mainly in renal tubules, and glomeruluses have no obvious histological change. The short term administration of large doses causes acute renal epithelia denaturalization and tubular necrosis, but the long-term administration may result in chronically progressive interstitial fibrosis of the kidney. Renal failure may occur following both acute and chronic renal lesion. The renal function should be strictly monitored while one is using the Chinese herbs containing AAs, and the dosage and duration for the treatment must be limited to prevent renal toxicity.
Animals ; Aristolochiaceae ; chemistry ; Aristolochic Acids ; adverse effects ; isolation & purification ; toxicity ; Drugs, Chinese Herbal ; adverse effects ; isolation & purification ; toxicity ; Fibrosis ; Humans ; Kidney ; pathology ; Kidney Tubules ; pathology ; Nephritis, Interstitial ; chemically induced ; pathology ; Plants, Medicinal ; chemistry ; Renal Insufficiency ; chemically induced