End-stage renal disease and low level exposure to lead, cadmium and mercury; a population-based, prospective nested case-referent study in Sweden

A total of 118 cases who later in life developed end-stage renal disease, and 378 matched (sex, age, area, and time of blood sampling) referents were identified among participants in two population-based prospective cohorts (130,000 individuals). Cd, Pb, and Hg concentrations were determined in prospectively collected samples.Erythrocyte lead was associated with an increased risk of developing end-stage renal disease (mean in cases 76 μg/L; odds ratio (OR) 1.54 for an interquartile range increase, 95% confidence interval (CI) 1.18-2.00), while erythrocyte mercury was negatively associated (2.4 μg/L; OR 0.75 for an interquartile range increase, CI 0.56-0.99). For erythrocyte cadmium, the OR of developing end-stage renal disease was 1.15 for an interquartile range increase (CI 0.99-1.34; mean Ery-Cd among cases: 1.3 μg/L). The associations for erythrocyte lead and erythrocyte mercury, but not for erythrocyte cadmium, remained after adjusting for the other two metals, smoking, BMI, diabetes, and hypertension. Gender-specific analyses showed that men carried almost all of the erythrocyte lead and erythrocyte cadmium associated risks.Erythrocyte lead is associated with end-stage renal disease but further studies are needed to evaluate causality. Gender-specific analyses suggest potential differences in susceptibility or in exposure biomarker reliability.Chronic kidney disease and development of end-stage renal disease is of increasing public health concern worldwide. In Sweden, the number of patients treated for end-stage renal disease is increasing, and diabetes and nephrosclerosis due to hypertension are the most common causes of end-stage renal disease [1]. A higher prevalence of obesity, resulting in an increase of diabetes and hypertension contribute [2]. Obesity, per se, is also associated with the development of chronic kidney disease in both diabetic and non-diabetic renal disease [3-5]. Other risk factors for chronic kidney disease in the general population are