Three Epidemics Across 10,000 Miles: Can We Connect the Dots?

Invited commentary by Dr. Veeraish Chauhan

Recently, the Center for Public Integrity, an investigative journalism organization, published an article on Mesoamerican Nephropathy (sometimes referred to as chronic kidney disease of undetermined etiology, or CKDu, in other parts of the world). The article discussed a possible link between this poorly understood kidney disease and pesticides. Mesoamerican Nephropathy was first described in a cross sectional study from El Salvador in 2002. However, some descriptions of the disease date back to the 1980s. Similar disease entities have been described in Sri Lanka and India.

This disease is classically seen in young farmers who work on sugarcane plantations in the low lying fertile regions of Guatemala, El Salvador, Nicaragua, and Costa Rica along the Pacific coast. It is characterized by progressive kidney failure, with biopsy features of tubular atrophy and interstitial fibrosis. The proteinuria is usually described as “low-grade,” even though global glomerulosclerosis seems to be a universal finding. A significant epidemiologic finding is that the prevalence of diabetes and hypertension is typically low in the affected populations.

The disease comes with significant morbidity and mortality. Per estimates from a recent analysis, Mesoamerican Nephropathy has killed 20,000 patients in Central America over the last twenty years. Over these two decades, the number of men dying from kidney disease has risen five-fold in El Salvador and Nicaragua, such that kidney disease now kills more men here than HIV/AIDS, diabetes, and leukemia combined. Today, El Salvador has the highest overall mortality attributed to kidney disease anywhere in the world!

The etiology of Mesoamerican Nephropathy is still not conclusively known. Still, common links have been described including pesticides and other agrochemicals. After a World Health Organization (WHO) led study submitted its findings regarding a possible role of cadmium and arsenic in causing CKDu in Sri Lanka, the government there banned three agrochemicals that were the purported sources of these heavy metals. Similarly, in what seems to be a knee jerk reaction, El Salvador’s legislative assembly has proposed an even more sweeping ban on up to 53 “suspect” agrochemicals. The ban and the bad press have been fiercely contested by agribusiness groups, and by companies like Monsanto and Dow Chemicals who make these pesticides and fertilizers. Meanwhile in India, ongoing research being conducted by Harvard University is examining the possible role of high silica levels in water as the cause of a similar CKDu. Silica exposure has already been associated with CKD.

Is there something common that can be postulated as a cause for this disease that is occurring 10,000 miles apart in sharply defined geographical regions? What are the etiologic agents involved, and are they even the same in Nicaragua, Sri Lanka, and India?

Blaming pesticides and fertilizers as the cause of Mesoamerican Nephropathy/CKDu certainly meets the criteria of “biologic plausibility,” but the link has not been definitively established. So what is wrong with the evidence here? For one, these very agrochemicals are used worldwide, but the specific disease is only known to be localized to certain geographic areas. Even in El Salvador where pesticide use/presence of heavy metals (cadmium and arsenic) in the environment was present in one heavily affected community, it was not the case elsewhere in other equally affected parts of the country.

Not only is there still no conclusive causal evidence to pin the blame on agrochemicals, the “tunnel-vision” emphasis serves to distract the attention from other equally plausible (if not, stronger) explanations. In fact, some of the strongest evidence points to the role of repeated episodes of dehydration and heat stress, possibly in combination with other factors. Yes, blaming dehydration and heat stress might not be as sexy (or a political hot-potato) as blaming Big Agro, but they, among others, are significant factors nevertheless! Dangerous work conditions (12-hour long workdays of brutal physical labor in 96 degrees heat- a temperature at which the US Occupational Safety and Health Administration calls for 45 minutes of rest for every 15 minutes of work) have been considered a possible causal link. Higher NSAID use by the men doing this labor is a suspect as well. Other competing hypotheses include genetic factors, alcohol use, use of herbal medications, and diet. Even if we assume that the culprit is indeed arsenic or cadmium, how do we know that its source is a tainted agrochemical, and not ground/well water (a known source of arsenic in certain locations) or the volcanic soil of Central America (a rich source or arsenic and cadmium)?

The only thing that can be concluded from these unanswered questions is that we have insufficient data to prove a causal link between CKDu/Mesoamerican Nephropathy and any specific chemical exposure. As more money gets pumped into research to find an answer, we hope that this heavily politicized disease that is devastating young communities across continents finds a cure.

Veeraish Chauhan, MD, FACP, FASN
Lakewood Ranch, Florida, USA

 

Note: Please visit AJKD.org for a recent report (subscription required) on the First International Research Workshop on the Mesoamerican Nephropathy.

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