Effects of aristolochic acid I and/or hypokalemia on tubular damage in C57BL/6 rat with aristolochic acid nephropathy

BACKGROUND/AIMS: This study was designed to investigate the roles of aristolochic acid I (AA-I) and hypokalemia in acute aristolochic acid nephropathy (AAN). METHODS: After an adaptation period (1 week), a total of 40 C57BL/6 mice (male, 8 weeks old) were divided into four groups: I (control group), II (low potassium [K] diet), III (normal K diet with administration of AA-I [10 mg/kg weight]), and IV (low K diet with AA-I). After collecting 24 hours of urine at 2 weeks, the mice were sacrificed, and their blood and kidneys were obtained to perform immunochemical staining and/or Western blot analysis. RESULTS: Proteinuria, glycosuria, and increased fractional excretion of sodium and K were prominent in groups III and IV (p < 0.05). Diffuse swelling and poor staining of collecting duct epithelial cells were evident in the medullas of group II. Typical lesions of toxic acute tubular injury were prominent in the cortices of groups III and IV. Α-Smooth muscle actin (α-SMA) was higher in the cortices of the mice in groups III and IV versus group II (p < 0.05), and higher in the medullas of group IV than groups I and III (p < 0.05). E-cadherin was higher in the cortices of groups III and IV compared to group I (p < 0.05). The F4/80 value was higher in the cortices and medullas of groups II, III, and IV compared to group I (p < 0.05), particularly in the case of group II. CONCLUSIONS: AA-I can induce acquired Fanconi syndrome in the acute stage of AAN. Macrophages appear to play a key role in the pathogenesis of AAN and hypokalemic nephropathy. It remains uncertain whether hypokalemia plays any role in AAN and hypokalemia.

Silica Nephropathy

Occupational exposure to heavy metals, organic solvents and silica is associated with a variety of renal manifestations. Improved understanding of occupational renal disease provides insight into environmental renal disease, improving knowledge of disease pathogenesis. Silica [SiO[2]] is an abundant mineral found in sand, rock, and soil. Workers exposed to silica include sandblasters, miners, quarry workers, masons, ceramic workers and glass manufacturers. New cases of silicosis per year have been estimated in the US to be 3600-7300. Exposure to silica has been associated with tubulointerstitial disease, immune-mediated multisystem disease, chronic kidney disease and end-stage renal disease. A rare syndrome of painful, nodular skin lesions has been described in dialysis patients with excessive levels of silicon. Balkan endemic nephropathy is postulated to be due to chronic intoxication with drinking water polluted by silicates released during soil erosion. The mechanism of silica nephrotox-icity is thought to be through direct nephrotoxicity, as well as silica-induced autoimmune diseases such as scleroderma and systemic lupus erythematosus. The renal histopathology varies from focal to crescentic and necrotizing glomerulonephritis with aneurysm formation suggestive of polyarteritis nodosa. The treatment for silica nephrotoxicity is non-specific and depends on the mechanism and stage of the disease. It is quite clear that further research is needed, particularly to elucidate the pathogenesis of silica nephropathy. Considering the importance of diagnosing exposure-related renal disease at early stages, it is imperative to obtain a thorough occupational history in all patients with renal disease, with particular emphasis on exposure to silica, heavy metals, and solvents

Rim e hipertensão / Kidney and hypertension

O rim participa do controle da pressão arterial normal e anormalidades da capacidade renal de excretar sódio desempenham papel importante na manutenção de todos os tipos de hipertensão. Existem evidências de que pelo menos alguns casos de hipertensão essencial tenham sua origem em distúrbios dos mecanismos renais de eliminar sódio. Por outro lado, quase todos os pacientes com doença renal apresentam hipertensão em algum momento de sua evolução. Nesse contexto, a hipertensão acelera a evolução da nefropatia e das lesões extra-renais, enquanto o controle da pressão arterial melhora o prognóstico renal e diminui a mortalidade desses pacientes. Controle rígido da pressão arterial é fundamental para reduzir a incidência de insuficiência renal e a progressão e a mortalidade associadas a doenças renais...

Genetic Toxicity of Ochratoxin A in Chinese Hamster Lung and VERO Cells, ddY Mice, and Drosophila melanogaster

Ochratoxin A is a natural contaminant of mouldy food and feed, which is produced by Penicillium and Aspergillus, and is suspected of being one of the etiological agents responsible for Balkan endemic nephropathy and the associated urinary tract tumors. For evaluation of the mutagenicity of ochratoxin A, we performed in vitro chromosome aberration tests using Chinese hamster lung fibroblast cells (CHL cells) and monkey kidney cells (VERO cells), in vivo micronueleus tests using ddY mouse bone marrow cells and somatic mutation and recombination tests (SMART) using Drosophila melanogaster. The results of chromosome aberration tests in CHL cells showed no incidence of increased structural and numerical aberrations regardless of metabolic activation, while in VERO cells treated with 2.0, 1.0, 0.5, 0.3 ug/ml of ochratoxin A showed significant increase of structural aberrations without metabolic activation. Aspartame and-phenylalanine, structural analogs of ochratoxin A, didn't affect the chromosome aberrations induced by ochratoxin A. The in vivo induction of micronucleated polychromatic erythrocytes were measured in bone marrows of ddY mice treated with 10.0, 5.0, 2.5mg/kg/10ml of ochratoxin A through intraperitoneal route once. At 24 and 48 hours after treatment, ochratoxin A didn't induce micronuclei in bone marrows of ddY mice. And at the concentration of 40, 20, 10 ug/ml of ochratoxin A, which was administered by feeding to larvae of Drosophila melanogaster, showed no incidence of increased multiple wing hairs and flares. Summarizing all results, we concluded that ochratoxin A is a kidney cell specific direct genotoxicant.

Genotoxicite de l'ochratoxine A, relation avec la tumeur renale

Ochratoxin A [OTA] is a mycotoxin which has been implicated in Balkan Endemic Nephropathy [BEN], a disease characterized by tubulonephritis and may be involved in the high incidence of urinary tract tumors associated to BEN. The prevalence of human ochratoxicosis is being determined in Tunisia. 100% of people suffering from chronic interstitial nephropathy of unknown etiology were ochratoxin A positive. These nephropathies are similar to Balkan Endemic Nephropathy. We prove an OTA genotoxic effects in patient suffering from this kind of nephropathy. OTA-DNA adducts formation has been detected in DNA of kidney tissues [biopsy]. DNA adducts which are covalent complex between OTA and DNA base [Guanine], constitute first steps of the carcinogenesis process

Nitrate content of well water and the endemic Balkan nephropathy

A hypothesis on the role of a high nitrate content in drinking water as a cause of Balkan nephropathy was tested by a follow-up study of 366 inhabitants of an endemic village. During a 12-year period [1974-1985], 28 of them were classified as Balkan nephropathy cases. These consumed water from 24 out of 85 wells used by the cohort members. Comparison of "affected" and "healthy" wells did not reveal any difference regarding the nitriate content of water