Organic solvent exposure may increase the risk of glomerular nephropathies with chronic renal failure.
ABSTRACT Several studies have suggested that exposure to organic solvents is associated with glomerular nephropathies (GN), but this relationship remains controversial.
A case-control study of 298 biopsy-proven cases and 298 hospital controls, matched for year of birth, sex, origin, and place of residence, was conducted between 1989 and 1991 in five hospitals in the Paris area: 82 cases of membranous glomerulopathy were included; 100, nephrotic syndrome with either minimal change nephropathy or focal and segmental hyalinosis (MCN/FSH); and 116, IgA nephropathy (IgA N). Subjects were interviewed about their lifelong occupational and non-occupational activities. A 'blind' assessment of type, level, and duration of solvent exposure was carried out by two industrial hygienists. Human leucocyte antigen (HLA) phenotypes were determined.
Among males, a clear association, which was not explained by social class, was observed between chronic renal failure and high exposure to solvents for both MCN/FSH (OR = 7.7, 95% CI: 1.4-41.6) and IgA N (OR = 3.5, 95% CI: 1.0-11.8). The odds ratios increased with duration of exposure. No relationship was observed between such exposure and GN cases with normal renal function. No evidence was found that the HLA phenotype plays a role in the association between solvent exposure and the disease.
These results support the hypothesis of a causal relationship between high solvent exposure, which concerned 15% of the males in this study, and the development of GN with chronic renal failure.
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ABSTRACT: To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD) rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF) in the ratio of 2∶2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16) and 25% (4/16), respectively. Urinary N-Acetyl-β-(D)-Glucosaminidase (NAG) activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM). Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.PLoS ONE 01/2012; 7(9):e45873. · 3.73 Impact Factor
- Nephrology Dialysis Transplantation 01/2008; 22(12):3681-90. · 3.37 Impact Factor
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ABSTRACT: It has been shown that all-solvent exposure is associated with the progression of primary glomerulonephritis to end-stage renal disease (ESRD), but little is known about the type of solvents that are high risk. The aim of this study was to investigate the role of solvents by occupation, product and type. Using a retrospective cohort design, the authors studied 269 patients with non-end-stage and biopsy-proven primary glomerulonephritis diagnosed between 1994 and 2001 in Paris and its suburbs. Two industrial hygienists evaluated patients' exposures from lifetime occupational histories collected by interview from 2002-4, and using a list of the 30 most common solvents. The studied outcome was ESRD, defined as glomerular filtration rate <15 ml/mn/1.73 m(2) or dialysis. It was recorded during a mean follow-up of five years. Cox models were used to estimate adjusted hazard ratios (HR) of ESRD related to exposures. Eighteen per cent of the patients had ever been exposed to solvents. Those with the highest risk of progression to ESRD were exposed machinery fitters and machine assemblers (HR 4.7, 95% CI 1.2 to 17.4) and plumbers/welders (HR 4.2, 95% CI 1.3 to 13.6), as compared to never exposed patients, as well as those who ever handled printing inks and petroleum products (HR 12.6 (95% CI 1.7 to 94.9) and 3.2 (95% CI 1.4 to 7.2), respectively). Among solvents, the highest risks were found for: toluene/xylene (HR 5.1, 95% CI 1.8 to 14.8), gasoline, fuel and gas-oil (HR 8.6, 95% CI 2.7 to 27.4), and ketones (HR 13.3, 95% CI 1.4 to 123.5). This study highlights the potential nephrotoxicity of several solvents. Intervention to promote screening for proteinuria in exposed workers may prevent the progression of glomerulonephritis to ESRD.Occupational and Environmental Medicine 06/2007; 64(12):843-8. · 3.22 Impact Factor