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Nephrology Times:
doi: 10.1097/01.NEP.0000413836.42434.43
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In Central America's Kidney Disease Epidemic, Risk Varies with Altitude

Coleman, Matthew

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An epidemic of kidney disease is ravaging the Pacific coast of Central America, with young male sugarcane workers particularly affected. In El Salvador, the mortality rate from chronic kidney disease (CKD) increased 10-fold between 1984 and 2005.

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While the cause of this surge is unknown, a popular hypothesis looks to sweltering heat and volume depletion. This theory gains additional credence from the recent observation that, in El Salvador, sugarcane and cotton plantation workers in lower coastal regions had an increased prevalence of reduced kidney function, while sugarcane workers and subsistence farmers at higher altitudes did not. These findings, from a cross-sectional, population-based survey, were published online ahead of print by the American Journal of Kidney Diseases.

“Why did we see this only in the coastal areas?” said study coauthor Catharina Wesseling, MD, PhD, of the Central American Institute for Studies on Toxic Substances, National University, Heredia, Costa Rica. “We really see that it is hotter there.

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“We strongly suspect that bouts of dehydration or volume depletion could cause CKD in the long term, and I think it is almost irrefutable that dehydration or chronic bouts of dehydration are part of this disease.”

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Five Communities

The study, which was requested by the Salvadoran health authorities, included 256 men and 408 women age 20 to 60 from five communities in El Salvador. Sandra Peraza, MSc, of the University of El Salvador, was the lead author.

Two of the communities—one rural and one semirural—were located at sea level and depended on sugarcane production as the dominant economic activity, with a past reliance on cotton production. End-stage renal disease previously had been reported in men in these communities.

For the remaining three communities, there was no prior information about kidney problems. They were selected to represent different economic activities and altitudes.

One community also had an economy based on sugarcane production but was located 500 m above sea level (masl), with average temperatures during the 1987–2000 harvest seasons that were about 4 C lower than those at sea level.

“A community with heavy coffee production was chosen as an example of another agricultural activity at high altitude (1,650 masl),” the authors wrote. “The final community was an urban neighborhood at 650 masl with a service-oriented economy, assumed to reflect the background distribution of SCr [serum creatinine] levels in El Salvador.”

The study was funded by the Swedish International Development Coordination Agency, through the SAREC project of Bilateral Research Cooperation with National Autonomous University of Nicaragua at León, and through a grant administered by SALTRA, the Program on Work and Health in Central America.

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Elevated Serum Creatinine

The prevalence of elevated serum creatinine level differed significantly among the communities, both in men and in women, with the highest prevalence in the rural coastal sugarcane community (men, 28%; women, 16%) and the semirural coastal sugarcane community (men, 32%; women, 13%), and a much lower prevalence in the high-altitude sugarcane (men, 4%; women, 5%) and coffee communities (men, 0%; women, 2%). The urban community had an intermediate prevalence (men, 9%; women, 11%).

Strikingly, coastal young men age 20 to 29 had a higher prevalence of elevated serum creatinine than did higher-altitude men age 50 to 60—13% versus 10%.

The prevalence of estimated glomerular filtration rate less than 60 mL/min/1.73 m2, calculated using the Modification of Diet in Renal Disease study equation, also was highest in the two coastal sugarcane communities (men, 19% and 18%; women, 8% in both communities) and much lower in the high-altitude sugarcane (men, 2%; women, 3%), coffee (men, 0%; women, 1%), and urban communities (men, 0%; women, 2%).

“Picture the low-altitude communities and imagine the hottest and humid day in Houston or Florida,” said Daniel Weiner, MD, MS, Assistant Professor at Tufts University School of Medicine.

“Now imagine going out into the fields where there is no shade, taking a sickle, and manually chopping down sugarcane all day. People become volume depleted rapidly, and when you attenuate these effects by lowering temperature at higher altitudes, it may just have much less stress on the body.”

In the study, proteinuria was infrequent and mostly low grade.

“This is compatible with kidney disease originating in tubulointerstitial rather than glomerular damage,” the researchers wrote. “Glomerulonephritis is unlikely as a dominant cause of CKD in this region also because diabetes and hypertension did not emerge as important risk factors.”

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Other regions have also seen a spike in kidney disease prevalence that is not explained by traditional risk factors.

“There seem to be pockets worldwide of similar clinical presentations,” Dr. Weiner said. “There is a small region in India and areas in Sri Lanka with similar manifestations.”

Back in Central America, a CKD epidemic has been confirmed in Nicaragua, where a team of researchers that includes Dr. Weiner has been studying the problem and searching for its cause.

“In Nicaragua, all the sugarcane companies' growing areas are at low altitude,” said research team leader Daniel Brooks, MPH, DSc, Associate Professor of Epidemiology at the Boston University School of Public Health.

“In El Salvador, this was the first time someone compared the same industry using basically the same approaches, work practices, chemicals, and so forth, so this was a really nice comparison.”

Steven Cuadra, MD, Head of the Section of Epidemiology and Biostatistics in the Department of Preventive Medicine at the National Autonomous University of Nicaragua, believes there must be additional forces driving the study results, he said.

“I don't think the small temperature difference is enough to explain the extreme differences between high- and low-altitude sugarcane communities.”

Dr. Wesseling commented on the temperature of the higher-altitude areas.

“It's also hot, just not as hot. I would say there is maybe a threshold. It is hotter down the coast—that's for sure. Is that enough of an explanation? I would not dare to say 100 percent yes.”

Dr. Brooks expressed a similar perspective.

“I don't necessarily think this could be the only cause,” he said. “It is just a hypothesis, and we have to look more.”

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Pesticides Unlikely Player

While Dr. Wesseling does not think that pesticides are behind the uptick in kidney disease in these areas, they cannot be ruled out as a hypothetical cause, she said.

“Pesticide use is out of control in Central America, and there are huge effects in many health aspects in many populations. While in this case I don't see that pesticides have a role, it cannot be completely discarded.

“This is because pesticides are a very diverse group of toxic substances—we are talking about hundreds of substances. If you go from the south of Mexico up to Panama, where there are reports of kidney disease, it is hard to believe that one chemical or pesticide can be used and so many exposed to cause so many sick people and death. It doesn't fit in the equation.”

Dr. Brooks' team found that kidney disease in Nicaragua is not only rampant among sugarcane workers but also in industries that don't use pesticides.

“Stevedores working at the ports, miners, and construction workers have shown a high prevalence of kidney disease,” Dr. Brooks said, though he stressed that even with this knowledge, pesticides cannot be eliminated as a potential contributor.

“It seems the most consistent thing between different occupations that have high levels of kidney disease has something to do with strenuous manual labor being performed outside in hot conditions.”

Pesticides have not been shown as a common cause of kidney disease, Dr. Weiner said.

“While there are definitely heavy metals that can cause kidney disease, not many herbicides, pesticides, or fungicides primarily affect the kidney. We certainly do not know every effect of these chemicals, but isolated kidney disease is not something commonly reported with various agricultural agents.”

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Working Conditions

In terms of interventions to stem the swell of kidney disease in these areas, working conditions must be the focus of preventive measures.

“We need to make sure that workers are being adequately hydrated while they are working,” Dr. Weiner said. “Many employers in the region have been taking steps to do this.”

Another area of improvement is education, especially when it comes to appropriate use of medicines.

“There is use of anti-inflammatory drugs that may exacerbate effects of volume depletion—medicines like ibuprofen,” Dr. Weiner said. “There is a lot of use of antibiotics for vague urinary symptoms, and these may also cause kidney disease or exacerbate effects of volume depletion.”

More research is crucial, such as a large interdisciplinary study focusing not only on the biological aspects of the problem but the social, Dr. Wesseling said.

Close follow-up is also needed.

“I believe we should follow people for a couple of years to see if they have accumulating damage and whether this varies by industry, type of job, and how hard the job is, and at the same time we should also look at agri-chemicals and other possible occupational exposures,” Dr. Brooks said.

Future work should be informed by the evolving understanding of acute kidney injury (AKI), Dr. Weiner noted.

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“In terms of studies that can be done in the future, I think we recently have learned that when you have AKI this can have chronic manifestations, and the question is, are these patients having repeated clinical episodes of AKI, and, if so, can this manifest with a chronic, nonproteinuric fibrotic kidney disease?” he said. “We don't know this for certain.

“The next study that we would like to do is to specifically look at kidney injury markers before and after a day or week of work—are there direct impacts of conditions of the region with those engaged in active agricultural work as well as those who are in more sedentary work—and see if similar kidney injury markers are presenting.”

© 2012 Lippincott Williams & Wilkins, Inc.

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