Pam Harrison

August 18, 2017

This story is also available in Spanish and Portuguese.

MADRID — A lethal epidemic of chronic kidney disease not associated with any of the usual risk factors, such as hypertension and diabetes, is claiming the lives of relatively young men who work outdoors in hot spots around the world, and some experts are blaming the phenomenon on long hours spent in high temperatures without proper rehydration.

An estimated 50,000 people have already died, Richard Johnson, MD, from the University of Colorado Hospital in Aurora, reported at the European Renal Association and European Dialysis and Transplant Association 54th Congress.

From the podium in Madrid, Dr Johnson questioned whether "global warming and water shortage" might be contributing to the problem.

"Of course, it's possible that toxins are involved, but we now think that the disease might be driven by repeated bouts of acute injury to the kidney," he told Medscape Medical News.

"Over time, this worsens kidney function, and patients can then develop classical signs of kidney failure with nausea, poor appetite, and high blood pressure," he explained. "And since dialysis is rarely available in these areas, the disease can progress, leading to death."

One of the hardest-hit areas is Central America, where it is estimated that 20,000 people working in sugarcane fields have died from kidney failure.

In Central America, the illness has been dubbed Mesoamerican nephropathy. It is also referred to as heat stress nephropathy and chronic kidney disease of unknown etiology.

Most strikingly, the disease does not appear to be due to any of the common causes of end-stage renal disease.

Dr Johnson described a mouse model of recurrent dehydration that he and his colleagues developed to study the possible mechanism for the disease (Kidney Int. 2014;86:294-302).

Ermando de Jesus Hernandez from El Salvador, age 39, suffers from heat stress nephropathy. Both his father and brother died from the disease. Hernandez continues to cut sugarcane to provide for his family, earning $2.26 per ton cut. (Tom Laffay)

Typically, young men present with an asymptomatic rise in serum creatinine in association with low-grade or no proteinuria, explained Carlos Roncal-Jimenez, MS, from the University of Colorado Denver in Aurora.

Some people complain of "sandy urine" that causes dysuria, but when urine cultures are tested, no infection is seen, Roncal-Jimenez, Dr Johnson, and their colleagues report in a recent review on the topic (Blood Purif. 2016;41:135-138).

"Most strikingly, the disease does not appear to be due to any of the common causes of end-stage renal disease," the researchers point out.

Investigators recently assessed kidney function in a group of nearly 300 agricultural workers who harvest crops in the Central Valley of California (Occup Environ Med. 2017;74:402-409). In a single shift, 12% of workers evaluated had acute kidney injury. Investigators identified both heat strain and piece-rate work that incentivizes workers to maximize their efforts as risk factors.

Virginia Weaver, MD, from the Johns Hopkins University Bloomberg School of Public Health in Baltimore, suggests that if physicians see a patient who has had an episode of acute kidney injury from an unknown cause, "it is worth asking them what they do for work."

Dr Johnson said he agrees, and recommends that physicians tell patients to stay hydrated, rest, seek shade, and not work outside when it is extremely hot, if at all possible.

"Patients also need to avoid taking nonsteroidal anti-inflammatory agents, like ibuprofen, as they can worsen kidney damage," he said. "And drinking soft drinks and other beverages with high sugar content is also not recommended, as soft drinks themselves are dehydrating."

Global Hot Spots

"This disease has affected way more people" than previous epidemics of kidney disease related to environmental exposure, Dr Weaver explained. "It's a huge factor in morbidity and mortality in countries where there are no other employment opportunities, so it's devastating in the communities where it's occurring."

Because agricultural work is the only job option for many workers around the world, efforts to reduce heat stress nephropathy must focus on early detection and prevention.

Epidemics that are clinically similar are being seen elsewhere; some 100,000 rice farmers in the northern (and hottest) provinces of Sri Lanka have been affected by impaired kidney function (Environ Health Prev Med. 2015;20:152-157).

The problem has probably been around for decades, but Dr Johnson said that as the world heats up and water shortages loom, outdoor workers are likely to be increasingly affected unless clear measures are taken to curtail it.

Heat stress and recurrent dehydration might not be the only factors driving the epidemic of chronic kidney disease in outdoor workers. However, none of the usual occupational or environmental toxins implicated in previous outbreaks of nephropathy have been identified as risk factors in the current outbreaks and novel risk factors must be considered, as Dr. Weaver emphasized.

It's devastating in the communities where it's occurring.

"It's important that we don't overlook other factors that could be contributing to this disease, such as environmental pesticides, and even the quality of water itself, because it might be more than just heat stress and dehydration that's causing it," Dr Weaver told Medscape Medical News.

"We see this chronic kidney disease of unknown etiology in occupations other than just agricultural workers, so this makes it more challenging to identify exposure to any one chemical as a risk factor," she added.

Water, Rest, Shade Plan

Jason Glaser, president of the La Isla Foundation advocacy group, has worked on occupational interventions that companies can introduce to reduce the risk for heat stress nephropathy and improve the lot of at-risk workers.

"The thing to remember is that sugar was the focus in Central America because it is such a dominant crop in areas that possess all the identified risks, but we are sure to see this disease in other industries in which people are exposed to heat stress, dehydration, and potential toxins," Glaser told Medscape Medical News.

In El Salvador, for example, the La Isla network WE program encourages sugarcane workers to adopt a "water, rest, shade" strategy to reduce heat stress and the risk for dehydration.

Workers in the fields are provided with hydration backpacks so they can quench their thirst while working, diminishing the risk for dehydration and its consequences for the kidneys. Workers are also encouraged to take frequent rest breaks in shade tents placed around the fields so they can get out of the sun.

And experts have developed a machete that reduces the energy needed to cut sugarcane and increases productivity. The custom-made blade also reduces the common repetitive-strain injuries experienced by workers.

"Worldwide, we have a long way to go," Glaser acknowledged, "although there are hopeful signs, with some companies beginning to study whether chronic kidney disease is affecting their workforce."

Dr Johnson is a member of the Colorado Research Partners, which is developing inhibitors of fructose metabolism, is a member of the scientific board, and has shares in XORT Therapeutics. Dr Weaver, Mr Roncal-Jimenez, and Mr Glaser have disclosed no relevant financial relationships.

European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 54th Congress. Presented June 5, 2017.

Follow Medscape Nephrology on Twitter @MedscapeKidney

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