May 26, 2009 (Milan, Italy) — Exposure to cadmium, even at low levels, can increase the risk of developing chronic kidney disease (CKD), according to an analysis of nearly 17,000 subjects in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006.

The study, presented here at the World Congress of Nephrology, a Joint Meeting of the European Renal Association–European Dialysis and Transplant Association and the International Society of Nephrology, by Italian investigators, was selected as a "Top 20% Abstract" at the meeting.

"Data from this large general population show that low-level exposure to cadmium is associated with kidney dysfunction and can help explain the epidemic of CKD," said principal investigator Pietro Manuel Ferraro, MD, from Columbus-Gemelli University Hospital and Catholic University in Rome, Italy.

Experimental and epidemiologic evidence suggest that chronic heavy-metal exposure can cause renal proximal tubular damage and progressive fibrosis. The current study zeroed in on 1 particular metal — cadmium — to examine whether it plays a role in CKD.

Cadmium, a byproduct of zinc production, is relatively abundant in the environment. Because of health and environmental concerns, its use has been decreasing, although it is still the key component in nickel-cadmium batteries. It is also present in cigarettes in amounts that vary according to brand, according to Dr. Ferraro.

"Cigarette smoking, which is also linked to cardiovascular disease, may, in fact, be the origin of such exposure to cadmium," he said, based on analyses not presented at this meeting.

In the analysis of 16,838 NHANES subjects, 9% were determined to have CKD, defined as a glomerular filtration rate of less than 60 mL/min per 1.73 m2, and 17% had albuminuria, defined as an albumin-to-creatinine ratio of 17 mg/g of more for males and 25 mg/g or more for females.

Compared with people without CKD, these subjects were found to have higher levels of cadmium in serum and urinary samples, the study found.

The NHANES subjects were stratified in quartiles, according to serum cadmium levels, and a multivariate analysis was performed to test the association between cadmium levels, presence of CKD, and presence of albuminuria after adjustment for age, sex, high blood pressure, diabetes, smoking, and serum lead levels.

Median serum cadmium levels were 0.62 ± 0.48 μg/dL in CKD subjects, compared with 0.55 ± 0.57 μg/dL in people without CKD (P < .001). Median urinary cadmium levels were 0.50 ± 0.39 μg/dL and 0.39 ± 0.36 μg/dL, respectively (P < .001).

People with the highest serum cadmium levels had a 48% risk for CKD (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.17 - 1.86; P = .001) and a 46% increased risk for albuminuria (OR, 1.46; 95% CI, 1.28 - 1.66; P < .001), compared with those in the lowest quartile, Dr. Ferraro reported.

An interaction was also observed between serum cadmium and lead exposure, with the combination producing the highest risk. People with the greatest exposure to both cadmium and lead (approximately 10% of the population) had a 24% higher risk for albuminuria than those in the highest cadmium quartile (OR, 1.24; 95% CI, 1.04 - 1.48; P = .017).

"Taking the first quartile as a reference, and adjusting for all risk factors for CKD, persons with the highest serum cadmium levels were at significantly higher risk for CKD and proteinuria. And we showed, in a separate analysis, that persons in the highest quartiles of both cadmium and lead had a risk that was almost double that of patients in the lowest quartiles," Dr. Ferraro said. "We believe cadmium exposure is an independent risk factor for CKD, and that there is an interaction between cadmium and lead."

Commenting on the poster, Steven McDonald, MD, from Queen Elizabeth Hospital in Adelaide, Australia, said the findings raise a red flag for him.

"It's been known that high levels of cadmium are related to CKD, but here, in this general population, even low levels were associated," he noted. "The relevance to my own practice is that there is a large lead smelter 2 hours away. I am going to want to see if my patients with lead exposure also have high cadmium levels, because this raises their risk even more."

World Congress of Nephrology 2009: A Joint Meeting of the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) and the International Society of Nephrology (ISN): Poster 182 (CK). Presented May 23, 2009.

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