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Published On Sep 08, 2016

Clinical Research

A Killing Heat

Warming temperatures may be causing a global wave of kidney disease.

In the Chichigalpa region of northwest Nicaragua, male sugarcane workers have been dying at such alarming rates that locals have named the region the “land of widows.” The culprit is chronic kidney disease (CKD). But while CKD is most commonly caused by hypertension and diabetes—both of which can damage the delicate filters the kidneys rely on to remove waste from the body—most of the victims there don’t suffer from either condition.

This epidemic isn’t confined within Nicaraguan borders. In the past two decades, CKD has killed an estimated 20,000 people throughout Central America, and has also claimed victims in Southeast Asia, Africa and the Middle East. Some researchers believe that the common denominator is intense heat and dehydration, according to an assessment report in the Clinical Journal of the American Society of Nephrology in May 2016. The reason for the sudden uptick in deaths, the authors say, may be a warming planet.

“We are seeing a new type of CKD and climate change appears to be exacerbating the issue,” says Richard J. Johnson, a nephrologist at the University of Colorado Hospital Anschutz Medical Campus in Aurora, Colo., and a co-author of the report. “CKD may well be one of the first epidemics because of global warming.”

Nephrologist Ramón García-Trabanino, another co-author of the report, first caught wind of the connection in 1998, when he was working at Rosales National Hospital in San Salvador. El Niño had brought searing heat and crippling drought that year to the countries of the tropical Pacific. “The hospital was absolutely full of kidney patients,” García-Trabanino says. But the physicians at Rosales didn’t understand why agricultural workers in the nearby region of Bajo Lempa were particular victims of this “silent massacre.”

The treatment available for these workers was limited—dialysis or kidney transplants were beyond the hospital’s means—but García-Trabanino resolved to find the cause. His first suspicion was toxic pesticides, which can stress the kidneys. But when he and a team from a local community organization analyzed similar laborers who worked inland, 500 meters above sea level, CKD was almost nonexistent. “They were working the same crops and using the same chemicals, but they were not getting sick,” García-Trabanino says.

He continued to investigate, teaming up with Johnson in 2012. In studies conducted over the next couple of years, the researchers found only one common theme among the CKD deaths: the dehydration of workers in hot temperatures. 

Johnson took this theory to the lab, where his team put mice in heat chambers and allowed them to drink only in the evenings. The mice developed CKD within five weeks. During the day, the loss of salt and water caused the mice to produce high levels of fructose, which in turn activated an enzyme that caused kidney damage. The researchers also found that crystals of uric acid would sometimes form as water levels dropped in the urine, causing further damage.

When Johnson and his team studied groups of sugarcane workers in Nicaragua and El Salvador in 2013, all of whom were dehydrated on a daily basis, they found high uric acid levels in the morning and increasing levels throughout the day. “Some patients just had sheets of uric acid crystals in their urine,” Johnson says. On the hottest day of the study, every worker they tested had levels higher than the critical threshold for developing CKD.

The connection between CKD and global warming as a reason for the uptick in cases holds promise, although Johnson cautions that the authors’ proposal that heat stress and dehydration cause CKD is still a hypothesis, and “we need to do more studies to verify this.” The preliminary data, however, is telling. Although climate change has led to an overall increase in temperature of only about 1.5°F globally during the past century, it has led to a greater number of extreme heat events, where temperatures either exceed 104°F or are 9°F to 11°F higher than the normal maximum temperature of the region. Johnson collaborated with climate scientists at the National Oceanic and Atmospheric Administration to look at the relationship between the disease patterns and global temperatures. “The areas with the highest solar radiation levels and numbers of heat waves overlap the places where the epidemics are,” Johnson says.

And Johnson notes that the evidence goes beyond such observations. “There are experimental models and animal models,” he says. “The hypothesis has temporality. It has epidemiology.” Fellow researchers are finding escalating CKD cases among outdoor laborers in India, the Americas, Africa and the Middle East—all regions where the temperatures are hot and rising. 

What impact will this possible mechanism for kidney disease have in the United States? Currently 13.2% of adults 30 years or older have CKD, a number that is expected to increase to 16.7% by 2030. But extreme dehydration is unlikely to be a major factor here. “While there are high rates of kidney disease in the South, is that climate related, or related to the regional variation of diet, poverty and other factors?” asks Joseph Vassalotti, chief medical officer at the National Kidney Foundation. Unlike the sugarcane workers in Nicaragua, higher rates of diabetes and hypertension are more likely factors.

In California’s Central Valley, however, there have been recent studies indicating that farmworkers may be developing acute kidney injury and CKD at higher rates than currently expected. “If we can demonstrate that CKD is related to climate change then it could affect all countries sooner or later,” García-Trabanino says.

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