Arsenic and CKD: Is There a Link?

While long-term arsenic exposure is a global health problem, is arsenic related to worsening of kidney disease or proteinuria? How does arsenic cause chronic kidney damage? A recent original investigation published in the American Journal of Kidney Diseases showed that increased urinary arsenic concentrations were cross-sectionally associated with increased albuminuria in a rural US population with a high burden of diabetes and obesity. Dr. Ana Navas-Acien (ANA), corresponding author, discusses this study with Dr. Kenar Jhaveri (eAJKD), eAJKD Blog Editor.

eAJKD: What prompted this investigation?

ANA: For a number of years, I’ve been interested in the long-term health effects of chronic exposure to arsenic at low to moderate levels. The health endpoints that we’ve been looking at include cardiovascular disease and diabetes. Relatively little is known about the potential role for arsenic in kidney diseases. Does arsenic play a major factor in inducing or worsening proteinuria? This is what we wanted to explore and study further.

eAJKD: What is the mechanism of inorganic arsenic injury? How might it be interacting with our bodies to potentially cause CKD and proteinuria?

ANA: How arsenic causes kidney injury is not completely clear. We know that arsenic plays an important role in inducing stress and inflammation. Those mechanisms may lead to endothelial dysfunction, and ultimately cardiovascular and kidney diseases. Arsenic is different from other metals. Lead and cadmium are known to be nephrotoxicants. For arsenic, we don’t have that type of evidence yet since the research studies have just not been done. There is some evidence of association of kidney disease and arsenic from Taiwan. Kidney disease and mortality improved after implementation of some measures for cleaning arsenic from the drinking water.

eAJKD: Arsenic trioxide is used for treatment of acute promyelocytic leukemia (APL), and initial phase 2 and 3 trails showed kidney complications. Also, there are older case reports suggesting arsenic as a tubular toxin. This is supported by other basic science data. So there is some data that high levels of exposure may lead to tubular damage.Could arsenic exposure be a second hit in the population you studied (diabetic and hypertensive patients) for kidney disease?

ANA: I think so, especially in susceptible populations. These groups of individuals also have a high burden of obesity, and are the ones exposed to relatively high levels of arsenic as compared to other populations around the United States.

eAJKD: Are there other parts of United States with such high levels of arsenic exposure?

ANA: There are many populations exposed to arsenic levels similar to those measured in the Strong Heart Study, but in general, it’s the rural population that is most exposed to mild-moderate chronic levels. In urban cities, we use surface water as opposed to the ground water used in rural settings. Even when ground water is used in urban areas, treatment systems remove arsenic from the water. We need additional public health interventions to reduce arsenic levels in rural communities.

eAJKD: Your study showed a strong association between arsenic levels and a urine protein-to-creatinine ratio greater than 30 mg/g in younger participants and those with a higher education levels. Why is that?

ANA: One possibility for the younger populations is that sometimes it’s easier to see a relationship in younger groups because as people age, there are more cardiovascular events. Age is such an important risk factor itself that if you restrict your analysis to older people, one generally tends to see weaker associations with well-known risk factors. For education, we don’t have a good explanation for that trend.

eAJKD: What research questions remain for you? What future studies are you preparing in this field?

ANA: We are interested in what happens with even lower arsenic exposures. If you’re not raised in a rural community where arsenic may be present in the drinking water, then your arsenic exposure will be at a much lower level. Those lower levels come from rice and grains, and sometimes from drinks like juice. So one question would be are these health effects observed at the low levels? Other questions involve socioeconomic status and genetic and epigenetic mechanisms. Could low-moderate arsenic exposure induce chronic diseases? Through which mechanisms? These are the open questions that are all interesting and intriguing.

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