End-stage renal disease and low level exposure to lead, cadmium and mercury; a population-based, prospective nested case-referent study in Sweden.
BACKGROUND
Cadmium (Cd), lead (Pb), and mercury (Hg) cause toxicological renal effects, but the clinical relevance at low-level exposures in general populations is unclear. The objective of this study is to assess the risk of developing end-stage renal disease in relation to Cd, Pb, and Hg exposure.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, Umea University, Umea, Sweden. Johan.N.Sommar@envmed.umu.se
Johan Nilsson
JN
Sommar
Maria K
MK
Svensson
Bodil M
BM
Björ
Sölve I
SI
Elmståhl
Göran
G
Hallmans
Thomas
T
Lundh
Staffan M I
SM
Schön
Staffan
S
Skerfving
Ingvar A
IA
Bergdahl
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002104:Cadmium / Q000097:blood* / Q000633:toxicity; D016022:Case-Control Studies; D004781:Environmental Exposure; D004784:Environmental Monitoring; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000453:epidemiology; D007854:Lead / Q000097:blood* / Q000633:toxicity; D008297:Male; D013058:Mass Spectrometry; D008628:Mercury / Q000097:blood* / Q000633:toxicity; D008875:Middle Aged; D011446:Prospective Studies; D013054:Spectrophotometry, Atomic; D013548:Sweden / Q000453:epidemiology
D015415:Biomarkers; D002104:Cadmium; D007854:Lead; D008628:Mercury