A new kidney disease is striking down labourers in what could be one of the first epidemics caused by global warming.
It’s 10am in the sugarcane fields outside the town of Tierra Blanca, El Salvador, and the mercury is already pushing 31°C.
The workers arrived at dawn wearing thick jeans, long-sleeved shirts and face scarves to prevent being scorched by the sun’s rays. They are moving quickly between rows of cane, preparing for the harvest. In the scant shade, old Pepsi and Fanta bottles full of water swing from tree branches, untouched. Gulping only the thick air, the workers won’t stop until noon, when their shift is over.
Among them is 25-year-old Jesús Linares. His dream was to be a language teacher but, like many Salvadoran children, he went to work to help support his family. Aged eight, he learned to hide in the cane whenever the police sought out underage workers. Since then he’s tended sugarcane from dawn to noon and then pigs until dusk. In the evenings, he tries to listen to English audio programmes or read a language book, but for the past year he’s been too tired to concentrate, so tired that a few months ago he visited the Tierra Blanca clinic. Blood tests revealed that Linares was in the early stages of chronic kidney disease.
It’s a familiar story here in the Bajo Lempa region in southeast El Salvador, where studies suggest that up to 25% of its nearly 20 000 inhabitants have chronic kidney disease. Nationally, kidney failure is the leading cause of adult hospital deaths. Chronic kidney disease is most commonly caused by hypertension and diabetes, but two-thirds of patients in Bajo Lempa don’t have either of those conditions, and the cause of their illness remains uncertain.
Scientists have identified certain key themes. The majority of people with the unexplained disease are men and it strikes predominantly in hot regions where people engage in strenuous outdoor labour. Dehydration, which seems an obvious factor, causes acute kidney disease that is easily reversed by drinking water, rather than this chronic form. This has left two questions: What causes this new form of kidney disease and will it spread as the world gets warmer?
“This is really a silent massacre,” says Ramón García-Trabanino, a Salvadoran kidney specialist.
The patients at the Hospital Nacional Rosales in San Salvador all have the same story: until three months ago they were perfectly fine. Most of them had never seen a doctor in their life and had ignored any signs of ill health. The turning point came only when they were too sick to work.
Working hard lies at the heart of Salvadoran culture. During the 1980–1992 civil war, the armed forces carried out a scorched-earth strategy, targeting the civilian population in the countryside to remove any possible support base for the rebels. Tens of thousands died and a quarter of the populace fled. When peace finally came, rural people returned to their land and worked hard to overcome difficulties that peace could not resolve.
In keeping with this work ethic, many agricultural labourers don’t admit to getting ill. But kidney disease is a sneaky opponent. It can destroy one kidney while the person remains blissfully unaware of this. Only in the final stages of the disease do workers get a hint that all is not well, and by the time they arrive at the emergency ward, they are dying.
García-Trabanino started at the Rosales hospital in 1998. He had expected to be treating the full gamut of medical conditions. Instead, all he encountered were men dying from kidney failure. They came in such numbers that they overwhelmed the beds and spilt into the corridors.
“Sometimes, even with [our] obsolete dialysis techniques, we managed to get some of them to survive a night. A day. A week,” he says.
Most died within a month, and no one seemed interested in finding out why, or even how many cases there were. So García-Trabanino and a colleague started counting them until, after a few months, their count reached more than 200. The ministry of health didn’t follow up on their findings, but it did grant the doctors a medal.
Today, the hospital has 1 000 cases of chronic kidney disease, with more than 30 new patients arriving each month. “But we only have resources for half of them,” says Ricardo Leiva, head of the nephrology unit. By the time the new victims arrive they typically need dialysis to remove waste, salt and extra water from the body. The waiting list is long.
Early last year, 32-year-old José Luis Morales, a healthy-looking man with a footballer’s physique, became so weak he couldn’t pick up a glass of water. Morales works as a truck driver in Chalatenango, a humid lowland area in northern El Salvador and another hotspot for chronic kidney disease. Unable to work, he went to San Salvador to see García-Trabanino.
“He had the classic picture of this disease,” García-Trabanino says. “He is not diabetic; he is not hypertensive. He is young without any past medical history.”
Currently in stage two of the disease, Morales will need to take life-long medication. “We can’t revive or bring back to life the lost kidney tissue, but we can take care of what is left,” says García-Trabanino.
Chronic kidney disease destroys kidney tissue until it can no longer filter waste from the blood. Without dialysis, this can lead to high blood pressure, weakness and a host of other symptoms.
Diabetic kidney disease damages the glomeruli, the tiny units that clean the blood, but the new form destroys the renal tubules, where urine is made and transported, and the interstitium, which surrounds the other structures in the kidneys and helps to maintain the right balance of fluid.
This is the same pattern of damage caused by some toxins, and because the new disease hit agricultural communities so heavily, García-Trabanino suspected that exposure to herbicides and insecticides might be to blame. However, García-Trabanino and a team of researchers found almost no cases of the mysterious disease among farm workers from higher altitudes.
“They were working the same crops and using the same chemicals, but they were not getting sick,” he says. “We were clueless.”
Physicians began to wonder whether the problem was instead confined to the country’s Bajo Lempa region. However, a subsequent study found high levels of chronic kidney disease in outdoor labourers stretching from Mexico to Nicaragua.
“We realised the problem was bigger than we thought, and it was all across Central America and southern Mexico,” says García-Trabanino.
A deadly alchemy gives rise?
Richard J Johnson, a University of Colorado kidney specialist, learned about the new form of chronic kidney disease spreading through Central America in 2011 and began to think about possible causes.
Johnson’s research focused on the sugar fructose and its role in obesity, high blood pressure and heart disease. When a person eats fructose, the liver bears most of the brunt, but some of the sugar ends up in the kidneys. With each meal, fructose enters the kidney tubules, where it is metabolised into uric acid and causes oxidative stress, both of which can damage the kidney.
Then Johnson discovered that, under certain conditions, the body processes regular carbohydrates to make its own fructose. And one of the triggers of this deadly alchemy is dehydration.
Until that point, nephrologists thought dehydration caused only acute kidney injury, but Johnson’s findings put a new spin on the role of insufficient water intake.
Could chronic dehydration be causing continuous fructose overproduction that, in turn, could be leading to long-term kidney damage?
Johnson tested his theory in the lab, where his team exposed mice to hours of heat. One group of mice was allowed to drink water throughout the experience, whereas a second group had water only in the evenings.
Within five weeks the mice with a restricted water intake developed chronic kidney disease. During the day, loss of salt and water caused the mice to produce high levels of fructose, and crystals of uric acid would sometimes form as water levels dropped in their urine. When the scientists disabled the gene that metabolises fructose and repeated the experiment, neither group developed chronic kidney disease.
The results caught García-Trabanino’s attention: “I was astonished. His animal models were absolutely in line with our findings.”
The two investigated the effects of dehydration on Salvadoran field workers and found that levels of uric acid started high in the morning and increased throughout the day.
Johnson now believes that heat stress and dehydration drive the production of fructose and the hormone vasopressin, which also damages the kidneys. “At this stage, that heat stress and dehydration might be causing this problem is still a hypothesis,” Johnson admits, “although it is a strong one.”
For 57-year-old former farm worker Santos Coreas, the money he receives from his sons working in the United States is the difference between life and death. It pays for his weekly haemodialysis, although that still falls short of the recommended three-times-a-week regime.
In El Salvador, the government provides healthcare to about 70% of the population, according to García-Trabanino. From 2004 to 2013, in this area, 271 patients reached end-stage renal disease, the point at which the only options are dialysis or death.
Only a third of them received dialysis, a quarter of these relying on El Salvador’s largest source of income: relatives sending money home from abroad.
Of the 235 patients who relied on the public health system, many didn’t have access to dialysis or were afraid of outdated techniques that are associated with a high death toll. Only 12 of these people were alive one year after diagnosis.
But dialysis isn’t the only line of defence if you can act early enough. In 2006, the nongovernmental organisation Emergency Social Fund for Health began collecting blood samples from locals. In 6 000 samplings since, it found the disease in 1 500 people, but only 100 have died, and these were workers already in the final stage. For the others, early diagnosis and medication can keep the end stages of the disease at bay for decades.
But this requires funding, and the organisation relies on donations. Meanwhile, the number of people who need such treatment has continued to rise.
For Johnson, a clue to why the epidemic is escalating came from his fieldwork with García-Trabanino. One day, when researchers were measuring uric acid levels, only seven workers showed up for work. “But they all had uric acid crystals in their urine. It was bad news for these seven,” Johnson says.
He found out that it had been the hottest day of the year at the study location: “Suddenly a really, really big heatwave came in, and the workers weren’t ready.”
Johnson began to pore over global maps of climate and solar radiation. The rise in average temperatures over the past few years in Central America had been incremental, but the number of extreme events had gone up disproportionately.
“The areas that have the highest solar radiation and heatwaves are overlapping with the places right where the epidemics are.”
Climate experts at the National Oceanic and Atmospheric Administration in Boulder, Colorado, verified his discovery and published a report in May 2016, which suggested a connection between climate change and the epidemic. Johnson says it “may well be one of the first epidemics because of global warming”.
Climate change brings dire predictions of extreme weather but it is affecting the world’s most vulnerable now, he says. Our kidneys, with their role in keeping vital nutrients within the normal range and blood volume stable, may be on the front line of attack.
“We predict the kidney is going to be one of the prime targets as heat increases,” Johnson warns.
Researchers classify the new form of chronic kidney disease as “climate-sensitive”, which means that climate is one ingredient contributing to the epidemic.
As temperatures continue to rise, many such climate-sensitive ?diseases will become climate-driven, and monitoring and bringing attention to them will become even more crucial.
For the people of El Salvador, climate change is yet another life-threatening obstacle to overcome amid the constant threat from not only frequent earthquakes and the volcanoes that dot the countryside, but also gang violence, political unrest and poverty.
But for García-Trabanino, the country’s perilous existence under towering volcanoes has come to symbolise what it means to be Salvadoran: “We have survived the civil war, earthquakes and volcanoes, but Salvadorans fight, and they will fight again.”
This is an edited version of an article that was first published by Wellcome on Mosaic. It is republished here under a Creative Commons licence.