The long-term effects of uranyl nitrate on the structure and function of the rat kidney

Haley, Diane P.; Bulger, Ruth Ellen; Dobyan, Dennis C.

doi:10.1007/bf02890280

Cited by 58 publications

(31 citation statements)

References 6 publications

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“…Chez le rongeur, que l'exposition soit due à une injection sous-cutanée (10 mg/kg de nitrate d'uranyle) ou intra-péritonéale (0,66 ou 1,32 mg/kg de fluorure d'uranyle), les lésions rénales touchent préférentiellement les deux tiers distaux du tube contourné proximal (TCP) (Diamond et al, 1989 ;Haley et al, 1982 Histologiquement, l'uranium induit une perte focale de la bordure en brosse ainsi qu'une induction de vacuoles du TCP dès la première heure consécutive à l'injection sous-cutanée de nitrate d'uranyle (10 mg/kg) (Haley, 1982). Chez le rat, cinq jours après le traitement, l'apparition de foyers nécrotiques est notée.…”

Section: Atteinte Histologiqueunclassified

“…Le caractère réversible de la lésion tubulaire est montré à travers différents modèles lors d'une exposition relativement faible et pour lesquels un arrêt de l'exposition a été étudié (Diamond et al, 1989 ;Haley et al, 1982 ;Kobayashi et al, 1984). Malgré une régénération tubulaire, une fibrose interstitielle et une infiltration de cellules mononuclées indiquent des conséquences chroniques de l'atteinte rénale .…”

Section: Atteinte Histologiqueunclassified

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Données nouvelles sur la néphrotoxicité de l’uranium

Guéguen

Rouas

2012

Radioprotection

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RÉSUMÉL'uranium est un radioélément ainsi qu'un métal lourd auquel l'homme peut être exposé du fait de sa présence dans l'environnement ou des activités humaines. Il exerce principalement une toxicité chimique au niveau du tubule contourné proximal du rein après exposition aiguë ou chronique. Après exposition à une forte dose d'uranium, la néphrite tubulaire aiguë est révélée par une protéinurie ainsi qu'une diminution du débit de filtration glomérulaire. Plus récemment, l'utilisation de marqueurs d'intégrité tissulaire telle que la béta 2-microglobuline ou des enzymes tissulaires a pu être corrélée aux altérations histopathologiques des tubules contournés proximaux. Lors d'exposition chronique à de faible niveau, l'utilisation de marqueurs plus spécifiques et plus sensibles s'avère nécessaire lorsque les lésions sont faibles. Des études expérimentales développées au laboratoire ont montré la pertinence de certains de ces biomarqueurs tel que Kim-1 pour détecter de faibles altérations rénales. L'uranium exerce sa cytotoxicité au niveau des cellules épithéliales des tubules contournés proximaux probablement du fait de son entrée dans la cellule où il s'accumule préférentiellement dans le noyau cellulaire, lorsqu'il n'est pas sous forme de précipités. Les mécanismes conduisant à la mort des cellules ne sont pas encore totalement élucidés mais le stress oxydant semble y jouer un rôle important. ABSTRACT New data on uranium nephrotoxicity.Uranium is an element and also a heavy metal to which humans can be exposed due to its natural presence or human activities. It has mainly a chemical toxicity on the proximal convoluted tubules of the kidney after acute or chronic exposure. At high dose exposure, acute tubular nephritis is observed, as indicated by proteinuria and a decreased glomerular filtration rate. More recently, the use of structural biomarkers such as beta 2-microglobuline or tubular enzymes has been correlated with histopathological injury of the proximal convoluted tubules. During chronic exposure at a low level, the use of some of these sensitive and specific biomarkers would be necessary, particularly when the injury is slight. Recent experimental studies in the laboratory have shown the relevance of such new biomarkers as Kim-1 to detect slight renal injury. Uranium exerts its toxicity on epithelial tubular cells in which it accumulates mainly in the nucleus when it is not precipitated. The mechanisms leading to cell death are not totally elucidated but oxidative stress seems to play an important role.

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Section: Atteinte Histologiqueunclassified

Données nouvelles sur la néphrotoxicité de l’uranium

Guéguen

Rouas

2012

Radioprotection

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“…Very high doses of uranium (10-25 mg/kg body weight) cause an acute renal failure (8,9,17,18), and lower exposure levels induce morphologic and functional changes in kidneys (10,12,19). The primary target is the proximal convoluted tubule, and the damage at higher doses is irreversible (8)(9)(10).…”

Section: Calcium Fractional Excretion (%)mentioning

confidence: 99%

“…Both functional and histologic damage to the proximal tubulus has been demonstrated (8)(9)(10)(11)(12)(13). Little is known about the effects of long-term environmental uranium exposure in humans.…”

mentioning

confidence: 99%

Renal effects of uranium in drinking water.

Kurttio

Auvinen²,

Salonen³

et al. 2002

Environ Health Perspect

366

211

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Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L.

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“…The nephrotoxic effects of uranium are known from the uranium industry around the world from human 95,96 and animal studies 97 . Biologically soluble uranium compounds such as uranyl nitrate [UO 2 (NO 3 ) 2 ] and ammonium diuranate (NH 3 -UO 3 -H 2 O) are filtered rapidly through the renal glomeruli and are toxic to the renal proximal tubules.…”

Section: Uraniummentioning

confidence: 99%

Renal cell carcinoma: Review of etiology, pathophysiology and risk factors

Petejová¹,

Martínek²

2016

BIOMED PAP

119

101

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Background and Aims. The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm. Methods. A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015. Results and Conclusions. Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways.

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The long-term effects of uranyl nitrate on the structure and function of the rat kidney

Cited by 58 publications

References 6 publications

Données nouvelles sur la néphrotoxicité de l’uranium

Données nouvelles sur la néphrotoxicité de l’uranium

Renal effects of uranium in drinking water.

Renal cell carcinoma: Review of etiology, pathophysiology and risk factors

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