Risk factors for the development of chronic renal failure : epidemiological studies on the role of analgesic use, occupational exposures and socioeconomic background

Abstract: Chronic renal failure is a severe condition that reduces life expectancy and typically progresses to end-stage renal disease and a need for renal replacement therapy. In a large proportion of cases, chronic renal failure evolves from known renal or systemic diseases, but in some cases the pathogenesis remains unknown. The aim of this thesis was to investigate whether the use of paracetamol and aspirin, occupation and workplace exposures, and socioeconomic status affect the development of chronic renal failure. We conducted a nation-wide population-based case-control study in Sweden. All 5.3 million native-born residents aged 18 to 74 years, living in the country during the period from May, 1996, through May, 1998, formed the study base. Personal interviews were performed with 926 patients with incident pre-uraemic chronic renal failure and 928 randomly selected control subjects. Regular use of either paracetamol or aspirin in the absence of the other was associated with a significant increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, and were increased for most disease-specific types of chronic renal failure. The associations were only slightly attenuated when the recent use of analgesics, which could have occurred in response to antecedents of renal disease, was disregarded. Our results are consistent with the existence of exacerbating effects of paracetamol and aspirin on chronic renal failure. Low socio-economic status was associated with an increased risk of chronic renal failure. In families with unskilled workers only, the risk of chronic renal failure was increased by 110% and 60% among women and men, respectively, relative to subjects living in families in which at least one member was a professional. Subjects with 9 years or less of schooling had a 30% higher risk compared with those with a university education. The excess risk was of similar magnitude regardless of underlying renal disease. The moderate excess was not explained by age, sex, body mass index, smoking, alcohol or analgesic intake. Thus, socioeconomic status appeared to be an independent risk indicator for chronic renal failure in Sweden. Our results did not support the hypothesis of an adverse effect of organic solvents on chronic renal failure development, in general. The overall risk for chronic renal failure among subjects ever exposed to organic solvents was virtually identical to that among never-exposed (odds ratio, 1.01; 95% Cl, 0.81-1.25). No dose-response relationships were observed for lifetime cumulative solvent exposure, average dose, or exposure frequency or duration. The absence of association pertained to all subgroups of chronic renal failure. Detrimental effects from subclasses of solvents or on specific renal diseases cannot be ruled out. Except for organic solvents and exhaust fumes, which were unrelated to risk of chronic renal failure, the exposure prevalence were low to the workplace exposure agents implicated in the literature. Silica and cadmium were associated with 39% (95% Cl, 0-94%) and 26% (95% Cl, -55-67%) excess risks, respectively, but apart from this, no striking excesses were found. There was an up to 2-fold variation in risk for chronic renal failure across occupational groups. This significant heterogeneity (P=0.001) in chronic renal failure risk among occupational groups could not be explained by studied lifestyle factors or workplace exposures.

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