Fanconi's syndrome and subsequent progressive renal failure caused by a Chinese herb containing aristolochic acid

Lee, Sang-Ho; Lee, Taewon; Lee, Byungcheol; Choi, Hyuckjai; Yang, Moon Ho; Ihm, Chun-Gyoo; Kim, Myungjae

doi:10.1111/j.1440-1797.2003.00232.x

Cited by 62 publications

(28 citation statements)

References 10 publications

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“…After an outbreak of AAN in Belgium, there were also reports about renal toxicity of AA from other Asian and European countries and the USA [11,12,13]. However, the possible different susceptibility within the same species and among various species to AA’s renal toxicity had been suggested in an animal study [7, 14], and the different response to AA’s renal toxicity had been noticed in the Belgian study and our study.…”

Section: Introductioncontrasting

confidence: 40%

Cytotoxicity of Phenanthrenes Extracted from <i>Aristolochia contorta</i> in Human Proximal Tubular Epithelial Cell Line

Wen

Tang

et al. 2006

Nephron Exp Nephrol

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Background/Aims:Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is predominantly a result of aristolochic acid I (AA-I) intoxication. However, other unidentified phytotoxins have indeed been postulated as the cause of this unique interstitial nephropathy. The purpose of this study was to investigate the cytotoxicity of other phenanthrene derivatives extracted from Aristolochia contorta in the human proximal tubular epithelial cell line HK-2. Methods: After HK-2 cells were incubated with an indicated concentration of test compounds for 24 h, cell viability was assessed by lactate dehydrogenase (LDH) leakage assay (cell membrane damage) in combination with MTT assay (metabolic capability). Cellular morphologic assessments were performed with a phase-contrast inverted microscope and transmission electron microscope. Results: In all test compounds at 5 µg/ml, AA-I, 7-methoxy-aristololactam IV and aristololactam IVa showed cytotoxic activity in HK-2 cells in both MTT assay and LDH leakage assay (p < 0.01). At high concentration (5–80 µg/ml), these three compounds caused a dose-dependent decrease in MTT reduction and a dose-dependent increase in LDH leakage compared to non-treated cells (p <0.01). In LDH leakage assay, 40 µg/ml 7-methoxy-aristololactam IV induced a 1.58-fold LDH leakage compared to AA-I at the same concentration (p < 0.01). Moreover, the IC₅₀of these three compounds were 16.675 µg/ml for AA-I, 4.535 µg/ml for 7-methoxy-aristololactam IV, and 30.244 µg/ml for aristololactam IVa in MTT assay. The cellular morphologic assessments suggest interactions with cell membrane and intracellular structures such as lysosome and mitochondria are likely to be involved in cell injury induced by these three compounds. Conclusion: The potency of cytotoxic activity of aristololactam IVa and 7-methoxy-aristololactam IV extracted from A. contorta is similar to or even stronger than that of AA-I.

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Section: Introductioncontrasting

confidence: 40%

Cytotoxicity of Phenanthrenes Extracted from <i>Aristolochia contorta</i> in Human Proximal Tubular Epithelial Cell Line

Wen

Tang

et al. 2006

Nephron Exp Nephrol

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“…This mistake had been made because of the similarity of the Chinese names fangchi and fangji [4]. Since that time, nephropathy caused by Chinese herb medicines has been reported in both western countries and Asian areas [5].…”

Section: Discussionmentioning

confidence: 99%

Fanconi’s syndrome, interstitial fibrosis and renal failure by aristolochic acid in Chinese herbs

Hong

Chung

et al. 2006

Pediatr Nephrol

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Aristolochic acid-associated nephropathy (AAN) has been identified as a separate entity of progressive tubulo-interstitial nephropathy. Its characteristic pathological findings, including hypocellular interstitial fibrosis, intimal thickening of interlobular and afferent arterioles with glomeruli sparing or mild sclerosis, have been identified. Many cases of AAN in adults have been reported in Taiwan as well as throughout the world, but it has seldom been described in children. We report on a 10-year-old boy who presented with severe anemia, Fanconi's syndrome, and progressive renal failure. Renal biopsy revealed typical findings of AAN. Aristolochic acids I and II were identified from a Chinese herb mixture ingested by the boy. AAN was diagnosed after other etiologies had been excluded. The case demonstrates the hazards of Chinese herbs with regard to children's health in Taiwan and suggests that more attention should be paid to this issue.

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“…Cardinal symptoms and signs in children with FS are polyuria, metabolic acidosis, rickets and severe growth failure if left untreated. FS is a constellation of laboratory findings displayed by many different inherited diseases [2] or due to a multitude of exogenous agents such as antibiotics, antiviral agents, chemotherapeutics, bisphosphonate, aristolochic acid that is contained in some Chinese herbs [3], valproate [4], immunosuppressive, antiviral and X-ray contrast agents [5,6].…”

Section: Introductionmentioning

confidence: 99%

Urinary proteome pattern in children with renal Fanconi syndrome

Drube

Schiffer

Mischak

et al. 2009

Nephrology Dialysis Transplantation

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Background. The renal Fanconi syndrome (FS) is characterized by renal glucosuria, loss of electrolytes, bicarbonate and lactate, generalized hyperaminoaciduria and low-molecular-weight proteinuria. We studied the urinary low-molecular-weight proteome to identify excreted peptides indicative of a pathogenetic mechanism leading to tubular dysfunction. Methods. We established a urinary proteome pattern using capillary electrophoresis mass spectrometry (CE-MS) of 7 paediatric patients with cystinosis and 6 patients with ifosfamide-induced FS as the study group, and 54 healthy volunteers and 45 patients suffering from other renal diseases such as lupus nephritis (n = 8), focal segmental glomerulosclerosis (n = 27), minimal change disease (n = 7) and membranous glomerulonephritis (n = 3) as controls. Consequently, we conducted a blinded study consisting of 11 FS patients and 9 patients with renal disease other than FS. Additionally, we applied this pattern to 294 previously measured samples of patients with different renal diseases. Amino acid sequences of some marker proteins were obtained. Results. Specificity for detecting FS was 89% and sensitivity was 82%. The marker peptides constituting the proteome pattern are fragments derived from osteopontin, uromodulin and collagen alpha-1. Conclusions. CE-MS can be used to diagnose FS in paediatric patients and might be a future tool for the non-invasive diagnosis of FS. The reduced amount of the marker proteins osteopontin and uromodulin indicates loss of function of tubular excretion in all patients suffering from FS regardless of the underlying cause. In addition, the six different fragments of the collagen alpha-1 (I) chain were either elevated or reduced in the urine. This indicates a change of proteases in collagen degradation as observed in interstitial fibrosis. These changes were prominent irrespectively of the stages of FS. This indicates fibrosis as an early starting pathogenetic reason for the development of renal insufficiency in FS patients.

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Fanconi's syndrome and subsequent progressive renal failure caused by a Chinese herb containing aristolochic acid

Cited by 62 publications

References 10 publications

Cytotoxicity of Phenanthrenes Extracted from <i>Aristolochia contorta</i> in Human Proximal Tubular Epithelial Cell Line

Cytotoxicity of Phenanthrenes Extracted from <i>Aristolochia contorta</i> in Human Proximal Tubular Epithelial Cell Line

Fanconi’s syndrome, interstitial fibrosis and renal failure by aristolochic acid in Chinese herbs

Urinary proteome pattern in children with renal Fanconi syndrome

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