How a mysterious epidemic of kidney disease is killing thousands of young men

Repeated damage from extreme heat over time seems to be a leading factor causing kidneys to fail

For years, Oscar has greeted dawn with the rhythmic swing of his machete as he chops sugar cane in fields near his home in El Salvador. On a typical morning, the 33-year-old begins work long before sunrise in a futile attempt to escape the suffocating heat and humidity. But one morning in December, Oscar clutched his wife’s hand instead of his steel machete. The pair sat in a waiting room of a clinic in the small town of Tierra Blanca. Oscar, a pseudonym being used to protect his privacy, had gone with his wife to find out whether his kidneys were failing.

Beginning in the late 1990s, a mysterious epidemic of chronic kidney disease began emerging in Bajo Lempa, a region on the Pacific coast of El Salvador where Tierra Blanca is located. The disease, which researchers have dubbed chronic kidney disease of unknown cause (CKDu), often affects people between the ages of 20 and 50. Many are agricultural workers or labourers without other known risk factors for kidney disease. As many as one in four adult men in Bajo Lempa have kidney disease, whether CKDu or another form, compared with an estimated one in ten men globally. Roughly 17% of men in Bajo Lempa live with kidney failure¹.

Although the epidemic of this perplexing kidney disease was first recognized in this region, more than half a dozen hotspots have since appeared elsewhere in Central America and around the world. Hard data on the number of people with CKDu globally have yet to be tallied. However, occupational-medicine specialist Emmanuel Jarquín says that tens of thousands of people have probably died from the disease, and the number continues to grow.

“This is the biggest story in the world about kidney disease,” says Jarquín, who is on the front line of the epidemic in El Salvador. In 2007, Jarquín founded the Agency for Development and Agricultural Health (AGDYSA), a scientific research organization based in San Salvador that aims to protect agricultural workers from kidney disease and other work-related conditions. There were so many cases of kidney failure in the district of Bajo Lempa that AGDYSA opened a satellite office in Tierra Blanca in 2023.

“People here are aware of their illness, but when they reach for treatment, they don’t receive anything,” says Jarquín. Not prevention, not dialysis, not anything. As a result, people get sicker, and fast. “It’s a vicious cycle,” he says.

Although the cause of the epidemic hasn’t been definitively determined, most scientists agree that, at least among sugar-cane workers, intense labour in extreme heat is one of the major drivers of this condition. Elsewhere, CKDu shows up among other labourers, including rice farmers, construction workers and miners.

Many researchers expect the effects of climate change to increase the prevalence of chronic kidney disease, which is already a growing health concern globally. In May, the governing body of the World Health Organization adopted a resolution to recognize kidney disease as a major cause of death and disability and to strengthen disease-prevention efforts.

Kidney disease is an example of the damage that prolonged, incessant heat can do to the body, says Ollie Jay, a heat physiologist at the University of Sydney in Australia. For the epidemic of CKDu, the agricultural workers of Bajo Lempa were an early warning sign.

An emerging epidemic

More than two decades ago, when otherwise healthy young men in Bajo Lempa began to grow fatigued and anaemic, they chalked it up to long hours of intense and exhausting work. Sugar-cane cutters are “marathon workers”, says Fabiano Amorim, a physiologist at the University of New Mexico in Albuquerque. Furthermore, “they sometimes don’t have the proper food for the work they are doing. They don’t have water available.”

Taking time off to rest wasn’t an option. The men depended on their work to provide food and shelter for their families. So the workers swallowed ibuprofen and got back to their machetes.

But for many, the fatigue worsened until they could no longer get out of bed. With local physicians unable to help, some of the men managed to make the two-hour drive to Rosales National Hospital in San Salvador. When they arrived, the men learnt that their kidneys had failed. Their bodies could no longer filter certain types of toxin, such as uric acid, from the blood or eliminate excess water. When this happens, fluid accumulates in the body until the lungs can no longer fill with air and the heart struggles to beat. Without dialysis to clean and filter the blood, death is inevitable.

Sugar-cane cutters in Nicaragua wear dust monitors as part of an effort to evaluate labour practices and reduce the effects of heat stress.Credit: Ed Kashi/VII/Redux/eyevine

When the men arrived at Rosales National Hospital, nephrologist Ricardo Leiva and his then-trainee Ramón García-Trabanino were puzzled about why these seemingly healthy young men’s kidneys had abruptly crashed. The textbooks that both physicians had pored over in medical school taught them that kidney failure was usually the result of untreated diabetes and high blood pressure or certain rare autoimmune and genetic conditions. The men from Bajo Lempa had none of these.

“They were so young … I had no answers,” says García-Trabanino, who now helps to run a private dialysis clinic in San Salvador. “It was a massacre.”

Yet, with the hospital flooded with people from Bajo Lempa, neither had much time to work it out. “I started work at 5 a.m. every day,” Leiva says. “And I didn’t get home until after it was dark.”

When Leiva, García-Trabanino and a team of researchers published the first account of the mysterious kidney disease in a public-health journal in 2002², the condition seemed like a local kidney anomaly — what biologists call an endemic nephropathy. But then papers began identifying other hotspots of CKDu, including in the sugar-cane-growing region of Nicaragua³.

“Nobody believed us that we were seeing a new form” of chronic kidney disease, says Marvin Gonzalez Quiroz, a physician and epidemiologist from Nicaragua, who is now at the University of Texas at San Antonio. “Nobody believed the prevalence that we were reporting.” Other research documented similar problems in Mexico, Costa Rica, Panama, India and Sri Lanka⁴.

None of the early studies could pin down a cause, but several leading hypotheses have emerged, including exposure to pesticides and heavy metals, as well as pathogens, the use of non-steroidal anti-inflammatory drugs and chronic heat stress. Researchers now say that CKDu could have multiple causes that vary between individuals, and across locations and time. Still, epidemiological and animal studies point to heat stress as an important factor.

How we keep cool

Humans maintain their core body temperature in a narrow range of 36–37 °C, says Daniel Vecellio, a biometeorologist at the University of Nebraska Omaha, and expend a lot of energy to keep it there. When our bodies heat up, blood vessels in the limbs and extremities dilate in a process called vasodilation, shunting blood away from major organs and to the surface of the skin, allowing heat to dissipate. As the core body temperature creeps up, glands in the skin begin pumping out sweat, further cooling the body. A fan or breeze amplifies this cooling; high humidity makes the process less effective, says Vecellio. When vasodilation and sweating are inadequate and the body temperature gets too high, muscles cramp, nausea takes hold and people can become confused and faint. In extreme cases, seizures and death can follow.

The kidneys are some of the first organs to feel the strain as body temperature rises. Sending more blood to the body’s surface means that the kidneys and other major organs receive less oxygen and nutrients. This often happens while water is lost through sweating, forcing the kidneys to kick into overdrive to preserve the body’s fluid balance. That effort can lead to drops in kidney function, even in healthy adults.

The entire heat response is a finely tuned physiological symphony that leaves little room for error, says Catharina Giudice, an emergency-medicine physician at Harvard University in Boston, Massachusetts. “The kidneys are more vulnerable than other organs. They have a very intense metabolic demand, so small changes in blood flow tend to be more harmful,” she says.

In Sri Lanka, exposure to pesticides could be behind an epidemic of chronic kidney disease.Credit: Ed Kashi/VII/Redux/eyevine

People working in construction and agriculture don’t just get hot from being outside in the Sun — they also generate heat through physical labour. Sweating a lot can leave them dangerously dehydrated at the end of a workday, even if they drink water as usual, says Giudice.

Except in the most severe cases, researchers thought that the kidneys could quickly bounce back from heat stress with no long-term damage. The emergence of CKDu instead hints that small, repeated injuries — even those that don’t result in a hospital visit — can build up over time. Compounded and amplified by other exposures, these small insults can lead to end-stage kidney failure, says Giudice.

“You’re having this acute kidney injury day after day,” she says. “Then you progress to a state where the cells can’t recover fully.”

Biopsies from people with CKDu show damage to specific parts of the kidney called the tubules, which reabsorb and return water and other useful substances to the blood. The problem, says Zachary Schlader, a physiologist at Indiana University Bloomington, is working out how to detect this damage before kidney function drops drastically. Typical tests spot a problem only when there are elevated levels of a waste product called creatinine in the blood and protein in the urine.

Nearly ten years ago, Schlader decided to look for molecular distress signals that could be early indicators of declines in kidney function. In one study of sugar-cane cutters in Nicaragua, Schlader and his colleagues found that markers of tubule injury changed as blood creatinine increased throughout the harvest season⁵. Another study by some of the same researchers, looking at workers during harvest, found that increased levels of white blood cells in urine (a marker of inflammation) and a decrease in haemoglobin in red blood cells (the production of which depends on the hormone erythropoietin secreted by the kidneys) could predict declines in kidney function across the harvest season⁶.

“The hotter people got, the more dehydrated people got, these signals went up,” says Schlader. Importantly, he says, there are biomarkers that can be measured easily, and can be detected before more commonly used markers of kidney injury, such as creatinine.

“And it’s not just the kidney that’s being affected; the whole body is,” says Schlader. “Heat stress causes systemic inflammation, and CKDu is likely some combination of what’s happening within the kidneys and what’s happening systemically.”

Research by Schlader’s team and others has shown that kidney damage can accumulate much more quickly than anyone thought.

“It affirmed a lot of what we hear anecdotally, which is that people start working when they’re young, they’re healthy. They have good kidney function, and then bang, they have stage-four kidney disease and will need dialysis soon,” says Madeleine Scammell, an environmental-health scientist at Boston University in Massachusetts, who studies CKDu.