During the past two decades mysterious kidney failure has killed more than 20,000 farmers on Central America’s Pacific coast. The chronic kidney disease continues to afflict those in the region, most of whom either worked or still work on sugarcane or cotton plantations and are men between the ages of 20 and 40.

Chronic kidney disease typically affects older people60 is the average age. Patients usually exhibit symptoms like swelling and itchiness for years, some of which are compounded by other chronic diseases, such as diabetes and hypertension.

But the Central American cases are different. In addition to attacking people in a younger age bracket, the disease, dubbed chronic kidney disease of non-traditional causes (CKDnT), creeps up quickly: Patients do not notice anything wrong in the early and middle stages of the disease; by the time they notice of any symptoms and are diagnosed it is often too late. At that point their kidneys are so deteriorated that the only possible treatments are either dialysis or an organ transplant. “There’s nothing in common between the chronic kidney disease we know so well and the CKDnT,” says Ramón García-Trabanino, a nephrologist at Rosales National Hospital, in San Salvador, El Salvador who for the past 16 years has been involved in finding an explanation of this phenomenon.

CKDnT has afflicted workers in Nicaragua, Costa Rica, El Salvador, Panama, Honduras and some parts of Mexico. In Costa Rica, for instance, there is evidence the disease was already affecting people in the 1970s and has been growing fast. In Guanacaste, a northwestern province where the illness has been observed almost exclusively, mortality rates have risen from 4.4 people for every 100,000 in 1970 to 38.5 per 100,000 in 2012. In the rest of the country the disease’s advance has been slower, going from 3.6 to 8.4 for every 100,000 inhabitants for the same time period, according to a study published July 21 in Occupational & Environmental Medicine.

Pinpointing the cause of the disease has proved to be one of the most difficult parts of the crisis. When, for the first time in 1999, scientists in El Salvador started noticing CKDnT, they thought the chemicals and pesticides used to maintain crops—and known to cause acute kidney damage—were to blame for the outbreak. They also considered water and soil contamination caused by heavy metals as potential causes. All of these hypotheses, though, were soon dismissed. Renal disease caused by these agents has been very well documented and, so far, researchers have not been able to find evidence that would link them.

But since 2004 scientists have started to pay more attention to factors related to the work environment of farmers in those regions. People affected by this disease typically work an average of 12 hours a day outdoors, often in high temperatures. “By measuring their metabolic rate, we now know that the work they do equals to running half a marathon every day,” García-Trabanino says. Tests confirm that the conditions are hard on a body. Most of the urine samples taken from patients contain high levels of uric acid, a waste product of a protein called purine. This acid is processed in the bloodstream and travels to the kidneys where it is expelled from the body via urination. “Physical exhaustion and heat can provoke excessive production of uric acid, and if the person cannot get rid of it on time, the acid develops into uric acid crystals that are held temporarily in the kidneys’ filters,” explains Richard Johnson, a nephrologist at the University of Colorado Anschutz Medical Campus. “This produces dehydration and [it] is then when renal damage begins.” Johnson is also the co-author of an article published October 8 in American Journal of Kidney Diseases that links CKDnT to high temperatures.

For the analysis, his team measured the concentration of uric acid in the urine samples from 189 sugarcane workers from El Salvador before and after their shifts in the field. They found that uric acid levels were lower before the shift began and increased as the day went on. He also conducted the study with 29 Nicaraguan farmers and was met with similar results. The studies also found that renal damage, expressed in concentration and crystallization of uric acid, was more significant during hotter days.

As average global temperatures rise and extreme heat days become more prevalent, some scientists suspect the incidence of renal damage could be on the rise, although at this point the link is speculative. “There is evidence that global warming is responsible for 75 percent of the daily records for extreme high temperature in continental areas,” Johnson says. “We believe there could be a relation between that and CKDnT.”

This idea gained credence when scientists observed the impact of temperatures on farmers performing similar physical activities at different altitudes. In a 2005 study published in Nefrologia 45.7 percent of farmers working in coastal areas had higher than normal uric acid levels in their urine whereas only 12.9 percent of farmers in higher altitudes showed greater than normal levels. All things being equal, temperatures are typically lower at higher altitude. “They [those in higher altitudes] do not suffer from this disease with the same high incidence as those living near the coastline,” García-Trabanino adds. “That is why we think heat is a crucial factor.”

Virginia Weaver, a researcher at the Welch Center for Prevention, Epidemiology and Clinical Research at Johns Hopkins University cautions that given the limited information about CKDnT in the affected areas, it is not clear that the origin of the disease is the same in all locations, however. The disease has also been reported in other corners of the world such as in Sri Lanka, Egypt and Andhra Pradesh Province in India. “None of the elements we’ve studied on their own gives us an answer about the origins of this disease, so we believe that it could be a combination of multiple factors and the effects of extreme heat and physical exertion are currently being considered as the potential cause,” says Weaver, who is also co-author of a commentary published in the August 19, BMC Nephrology, which summarizes much of the known information known about the illness.

But even though the origins of this CKDnT outbreak remain unknown, scientists think that simple precautions, such as ensuring workers are taking regular breaks in the shade and staying properly hydrated without sugary drinks (very popular in the affected regions), could make a big difference.

Efforts to diagnose the disease before renal damage has taken a toll are also important. “Funding is needed in order to take basic public health measures, which are also known to be cost-effective,” Weaver says, adding “resources to identify the disease early on and during more treatable phases are also necessary.” García-Trabanino agrees: “In my experience, and even not knowing the cause of the disease, if the person gets to us early enough, we can offer a drug treatment that will help slow down the illness, and this has an annual cost of no more than $200.”

In contrast, the monthly costs of dialysis in Central America ranges between $355 and $2,249, according to the Pan American Health Organization (PAHO). An investment in early diagnosis would financially benefit the citizens of El Salvador, where the gross domestic product per capita in 2014 barely reached $3,826. The situation of its neighboring countries, also affected by the epidemic, is not all that different, according to data from The World Bank.

More research to find the cause is also needed. In July PAHO updated a resolution originally published in 2013 that promoted research and treatment efforts on renal disease in Central America’s agricultural communities. Also, this month at the Second International Research Workshop on Mesoamerican Nephropathy in San Jose, Costa Rica, researchers will share their latest finding about the intriguing disease.