Is everyday low-level cadmium exposure linked to kidney damage?
In ordinary US adults, higher cadmium levels well below occupational safety limits went along with more albumin leaking into the urine, though urinary cadmium was not linked to reduced kidney filtration.
Source
Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006
Study at a glance
- Design
- Cross-sectional — Secondary analysis of four pooled NHANES cycles (1999-2006) in US adults; blood and urinary cadmium compared with eGFR-defined CKD and albuminuria using survey-weighted logistic regression adjusted for age, sex, race/ethnicity and BMI, plus ROC curves.
- N
- N=5426 · 5426 adults aged 20 or over from the NHANES urine subsample with both cadmium and kidney measures; pregnant or menstruating women excluded.
- Population
- Non-institutionalised US civilian adults aged 20 years and over in NHANES 1999-2006.
- Outcome
- Chronic kidney disease (eGFR below 60 mL/min/1.73 m2) and albuminuria (raised urinary albumin-to-creatinine ratio).
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What they did
The authors pooled four cycles of the US National Health and Nutrition Examination Survey (1999-2006) and analysed 5426 adults who had cadmium measured in both blood (a marker of recent exposure) and urine (a marker of long-term body burden). They defined chronic kidney disease as an estimated glomerular filtration rate below 60 and albuminuria as a raised albumin-to-creatinine ratio in urine. Survey-weighted logistic regression adjusted for age, sex, race/ethnicity and body mass index compared people above and below 1 unit of cadmium, and ROC curves tested how well cadmium levels separated people with and without kidney problems.
What they found
Blood cadmium above 1 mcg/L was linked to higher odds of both CKD (odds ratio 1.48) and albuminuria (odds ratio 1.41). Urinary cadmium above 1 mcg/g was linked to albuminuria (odds ratio 1.63) but not to CKD (odds ratio 0.70, not significant). Smokers had roughly double the cadmium levels of non-smokers, and cotinine correlated with blood cadmium. As a screening marker cadmium was weak: the area under the ROC curve for CKD was only 0.62 for urinary and 0.60 for blood cadmium.
The limits
What it doesn't show
Because NHANES measures everyone once, the study cannot show that cadmium caused the kidney changes; reduced kidney function could itself alter cadmium handling, and albuminuria was usually measured only once so it may not be chronic. The regression did not adjust for smoking even though smoking is a major cadmium source, and there was no adjustment for diabetes or hypertension. Urinary cadmium levels were close to the detection limit, and classic markers of cadmium tubular damage such as beta-2-microglobulin were not available. The AUROC values around 0.6 mean cadmium is a poor individual-level predictor.
Key terms
- Albuminuria
- Abnormal amounts of the protein albumin in the urine, an early marker of kidney damage measured here as the urinary albumin-to-creatinine ratio.
- Estimated glomerular filtration rate (eGFR)
- An estimate of how much blood the kidneys filter per minute, calculated from serum creatinine, age, sex and race; below 60 defines chronic kidney disease in this study.
- Biomarker of exposure
- A measurable substance in the body that reflects contact with a toxin; blood cadmium reflects recent exposure whereas urinary cadmium reflects cadmium stored in the kidney over years.
- Area under the ROC curve (AUROC)
- A summary of how well a measure separates people with and without a condition, from 0.5 (no better than chance) to 1.0 (perfect).
- Cross-sectional study
- A study that measures exposure and outcome at the same point in time, so it can show association but not which came first.
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Quiz yourself
Which cadmium measure best reflects long-term accumulation in the kidney?
Common questions
Why measure cadmium in both blood and urine?
Blood cadmium rises quickly after exposure and mostly reflects the last few months, while urinary cadmium mirrors the amount built up in the kidney over many years, so the two capture different time scales of exposure.
If urinary cadmium was linked to albuminuria but not CKD, what might that mean?
The authors suggest low-level cadmium may first disturb the kidney tubules' handling of small proteins, showing up as albumin in the urine, before any measurable fall in filtration; the blood-cadmium link to CKD might partly reflect short-term blood-pressure effects.
Does this mean cadmium testing could screen for kidney disease?
No. The areas under the ROC curves were only around 0.6, so cadmium levels separate people with and without kidney problems only slightly better than chance.
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