1 Department of Medical Epidemiology, Karolinska Institutet, Stockholm, 2 Department of Renal Medicine, Huddinge University Hospital, Huddinge, Sweden, 3 The International Epidemiology Institute, Rockville, MD and 4 Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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Abstract |
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Methods. All native residents from May 1996 to May 1998, aged 1874 years, formed the source population. Cases (n=926) were incident patients with chronic renal failure in a pre-uraemic stage. Control subjects (n=998) were randomly selected within the source population. Exposures were assessed at personal interviews and relative risks were estimated by odds ratios (OR) in logistic regression models, with adjustment for age, sex, body mass index (BMI), smoking, alcohol consumption and regular analgesics use.
Results. In families with unskilled workers only, the risk of chronic renal failure was increased by 110% [OR=2.1; 95% confidence interval (CI), 1.14.0] and 60% (OR=1.6; 95% CI, 1.02.6) 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% (OR=1.3; 95% CI, 1.01.7) higher risk compared with those with a university education. The excess risk was of similar magnitude regardless of underlying renal disease.
Conclusions. Low socio-economic status is associated with an increased risk of chronic renal failure. The moderate excess was not explained by age, sex, BMI, smoking, alcohol or analgesic intake. Thus, socio-economic status appears to be an independent risk indicator for chronic renal failure in Sweden.
Keywords: case-control study; education; kidney failure, chronic; occupations; risk factors; socio-economic factors
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Introduction |
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A gradient by socio-economic status (SES) has been observed in a wide range of diseases [5]. SES represents an important risk indicator for cardiovascular disease, but evidence linking low SES to renal disease is scant. Earlier studies have shown an inverse association between income and treated ESRD [69]. The income-earning capacity, however, is often reduced among ESRD patients and low income may be a consequence, rather than a cause, of ESRD.
To shed light on the possible associations between SES and the risk of CRF, we analysed this exposure in relation to incident pre-uraemic disease in a nation-wide, population-based case-control study in Sweden. An occupational-based socio-economic classification scale and educational level were used as measures of SES.
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Subjects and methods |
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Subjects
Monthly lists of all serum creatinine measurements were provided by medical laboratories covering essentially all inpatient and outpatient care in Sweden. Eligible as cases were patients in the source population whose serum creatinine level for the first time, and permanently, exceeded 300 µmol/l (3.4 mg/dl) for men or 250 µmol/l (2.8 mg/dl) for women, the increase being due to renal causes. Case patient eligibility was determined in collaboration with local physicians. Patients with pre-renal causes (e.g. severe heart failure) or post-renal causes (e.g. outlet obstruction) of the serum creatinine elevation were not eligible. Diagnoses of underlying conditions were based on routine clinical work-up.
Control subjects, frequency-matched to the case patients by age and sex, were randomly selected from the National Population Register on three occasions during the ascertainment period.
All regional ethics committees and the Swedish Data Inspection Board approved the study protocol. Each study subject provided informed consent before inclusion.
Data collection
The study subjects received a mailed self-administered questionnaire about number of years of education, highest educational degree, marital status, anthropometrical measures, weekly alcohol intake and lifetime tobacco use. Information on every occupation held for more than a year was obtained during subsequent face-to-face interviews by professional interviewers from Statistics Sweden. In addition, occupations of spouses and parents were recorded to assess household SES. A detailed history of lifetime use of non-narcotic analgesics was also obtained during the interview, as described elsewhere [4]. The interviewers could not be kept blinded to the case control status of the interviewees, but they were unaware of the study hypotheses, and they were trained to treat both categories in a strictly equal manner. The mailed questionnaire was checked during the interview and supplemented when needed.
Statistical analysis
Occupation and educational level were used independently to estimate SES. The SES associated with reported occupations was derived from the official Swedish socio-economic classification scheme (SEI), and the scores were aggregated into the following classes: (i) unskilled and semi-skilled manual workers; (ii) skilled manual workers; (iii) assistant non-manual employees; (iv) intermediate non-manual employees; (v) employed or self-employed professionals, higher civil servants and executives. A sixth group of self-employed (other than professionals) and farmers was analysed separately. Each subject was grouped according to the highest SEI score obtained from the occupational history. The spouse with the highest score determined the household SES. Students were classified according to the SES of their parents. Educational level was grouped into three categories based on the number of years of education (09, 1012 and 13 years or more).
Multivariate unconditional logistic regression models estimated relative risks [odds ratios (OR)] as measures of the association between SES and CRF, along with their 95% confidence intervals (CI). Co-variates were considered if they were known or suspected a priori to be confounding factors, or if they were associated with both CRF and SES in the data. We initially considered height, body-mass index (BMI; the weight in kilograms divided by the square of the height in metres), number of siblings, cigarette smoking, weekly alcohol consumption and cumulative lifetime dose of analgesics during regular use. Smoking and alcohol consumption were grouped in quartiles according to the distribution among control subjects.
The final analysis model, assessed using the likelihood ratio test, contained terms for age, sex, BMI, cigarette smoking, alcohol consumption and ever vs never regular use of aspirin or paracetamol use. A simple indicator variable (ever vs never) of regular use was found to sufficiently control for possible confounding by aspirin or acetaminophen in relation to SES. Regular use of an analgesic was defined as use at least twice a week for 2 months or longer. In our modelling, we excluded 37 case patients (4.0%) and 48 control subjects (4.8%) with missing information for one or more co-variates. Analysis of variance was used to investigate the relation between SES and glomerular filtration rate.
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Results |
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Characteristics of the participating case patients and control subjects are shown in Table 1. There were about twice as many men as women. As expected from the frequency-matched design, the mean age was identical among case patients and control subjects. Further, the mean age was similar among men (58 years) and women (57 years). Patients and control subjects did not differ materially with regard to number of reported occupations (median=3 in both groups). Thirty-one percent of the case patients were classified as having diabetic nephropathy, 24% had a glomerulonephritis diagnosis, 15% renal vascular disease, 11% a hereditary renal disease, 9% a systemic disease or vasculitis and 11% any other renal disease diagnosis. A majority of the patients were in the pre-uraemic stage, in no need of renal replacement therapy. The median value of the estimated glomerular filtration rate (GFR) was 21 ml/min (interquartile range, 1726 ml/min). Among patients in the unskilled manual workers group, 27% had a GFR in the lowest quartile, 24% in the second quartile, 27% in the third and 21% had a GFR in the highest quartile. The corresponding distribution of the GFR values among patients in the professionals group were 20% in the lowest quartile, 25% in the second, 23% in the third and 33% in the highest quartile. No statistically significant differences in GFR between patients in the different SES groups were found (P=0.07).
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Discussion |
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The strengths of our study include the well-defined study base, which permitted strict random sampling of control subjects, the unique and comprehensive organization for case finding that ensured identification of all new case patients occurring in the study base, the objective diagnostic criteria that defined CRF before its end-stage, minimizing selective loss of patients with rapid disease progression and early death, and the relatively large sample size.
Weaknesses include an element of judgmental categorization inherent in occupation-based SES classification, possible biases due to differential detection or case ascertainment in different SES strata, possible differential willingness to participate among cases and controls across SES categories, and possible differential recall among case patients and control subjects. Detection bias, if any, would probably result in earlier diagnosis among socio-economically privileged people, thus counteracting the observed inverse relationship. We found no significant relation between SES and estimated GFR at time of inclusion. Ascertainment bias is unlikely, given the equal access for everyone to Swedish health care, and the essentially complete coverage by our case-finding organization. It should be noted that serum creatinine testing was carried out for overt symptoms in routine clinical practice and not as a screening effort among symptomless people. This should allay concerns about possible selective recruitment from a pool of subjects with prevalent disease. Since non-participation, particularly that attributed to active refusal, may be unevenly distributed across SES strata, selection bias may have been introduced, since the refusal rate was higher among our control subjects than among our case patients. Although this may have inflated the observed association between SES and CRF, the difference in participation rates between case patients and control subjects is not large enough to entirely explain our finding. Likewise, we regard the possibility of misclassification of SES level following incomplete recollection of previous occupations unlikely.
Data from the USA indicate that the incidence of ESRD is 34-fold greater in African Americans and Indians than in whites [10]. However, this association may be the result of joint effects of both race and SES. Our study was confined to ethnically homogeneous native Swedes, precluding confounding by race.
Prior studies have been limited to the association between SES and renal replacement therapy among ESRD patients [69]. Rate of progression, therapeutic decisions and changes in SES due to reverse causation may have affected the results of these studies. To our knowledge, our study is the first to examine the influence of SES on CRF before end-stage. Moreover, as opposed to some past studies, which used aggregated SES indices such as area-based measures of education and income or current income, which may have changed because of the renal or predisposing disease, we classified our subjects individually, according to the highest SES attained during a lifetime. Evaluations of the SEI scheme have shown that it performs well in comparison with other classifications [11].
The reason why attained education was associated with a less marked risk gradient than the occupational-based SES is not entirely clear. In an American case-control study, risk varied 7-fold with attained education [8]. One explanation for this apparent discrepancy is that the lowest educational category in our study encompasses a considerable variation, which is partly concealed by the fact that 9 years of schooling became compulsory in the 1960s. Before then, only 6 years were required. The gradient might have been greater if the cut-off point for the reference category had been set lower. But SES-related health gradients for several other diseases have also been generally less pronounced in countries such as Sweden, with its more egalitarian socio-economic policies [5]. Notwithstanding, it was recently suggested that morbidity, assessed through national health interview surveys, according to occupational class is very similar among men from Sweden, Denmark, the UK, The Netherlands, Germany, Switzerland and France, implying that our results may be applicable to other European countries [12].
SES per se does not plausibly affect renal function and cannot be regarded as a specific exposure but a marker for general material and cultural circumstances. Associated biologically meaningful exposures are likely to explain most or all of the relationship with CRF. Individuals with low SES may not receive the same medical attention to predisposing diseases as persons with higher SES. However, the gradient was similar for glomerulonephritis, which is not preceded by any known predisposing disease, as it was for diabetic nephropathy. Previous studies in the USA indicate that mechanisms other than limited access to health care are involved in the association of income with ESRD [8]. Furthermore, in Sweden there is a strong commitment to equity of health care access and use.
Control for several factors with known or suspected impact on renal function did not cancel the inverse relationship between SES and CRF. Other factors that may explain the association include other chronic diseases, diet and occupational exposures. Although the prevalence of hypertension and type 2 diabetes mellitus was higher among low SES individuals in some studies [13,14], these ailments were essentially evenly distributed across SES strata in our study, thus practically ruling out any important confounding role. A diet low in fruit and vegetables has been implicated in the aetiology of diseases of the cardiovascular system and may conceivably also affect the kidneys [15]. Occupational exposure to nephrotoxins such as heavy metals and solvents occurs more often in occupations associated with lower SES [2]. In a recent review, the meta-analysis shows an association between exposure to organic solvents and glomerulonephritis [16]. The heterogeneous design among the 14 case-control studies included in the analysis and the methodological limitations of several of the included studies, however, preclude firm conclusions. Moreover, most evidence weighed against no important role of solvent exposure in the strongest study published so far [17]. Accordingly, our findings cannot simply be explained by a possible socio-economic gradient in solvent exposure. Non-occupational exposure to cadmium, a well-known risk factor for renal disease, has increased in modern times [18], thus possibly cancelling some of the excess noted previously among job-exposed workers. Further, the fact that household SES tended to be more strongly linked to CRF risk than was individual SES, might indicate that the association can be attributed more to issues related to lifestyle and cultural factors than to occupational exposures. Socio-economic disparities in fetal environmental factors and pregnancy outcome are other conceivable factors that warrant further studies [19]. Moreover, accumulating evidence suggests that social status itself, regardless of associated material and economic advantages, may confer health benefits possibly via psychosocial mechanisms [20].
In conclusion, notwithstanding generally negligible inequalities with regard to access to health care in Sweden, and a tentatively limited range of exposure to SES-related factors with a potential impact on renal function, SES appears to represent an independent risk indicator for CRF in Sweden. Thus, the underlying mechanisms warrant further studies to identify possibly preventable risk factors of renal disease. SES should be considered in all aetiological research on renal failure.
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Acknowledgments |
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Notes |
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References |
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