Thousands ill from mysterious kidney disease, but what’s the cause?

For decades, thousands of farmers in tropical hot spots around the world have suffered from a disease that destroys their kidneys. Their eyes can become yellow, their bodies swollen and their muscles continuously cramping as their kidneys become irreversibly damaged – until they die.

These are some of the end-stage symptoms of chronic kidney disease, known as CKD, a painful disease typically resulting from severe hypertension or diabetes, the most common causes of the condition worldwide.

But in these farmers, such lifestyle diseases are not the issue, and more than 20 years into their epidemic, public health officials remain baffled as to the cause. It remains a mystery.

“Globally, no one knows,” said Neil Pearce, professor of epidemiology and biostatistics at the London School of Hygiene and Tropical Medicine.

The numbers are highest in four equatorial regions around the world – Central America, Sri Lanka, India and Egypt – and only recently have the regional epidemics been recognized for their similarities in this unique form of the condition, called chronic kidney disease of unknown etiology, or CKDu.

Rates of the disease in Central America are fairly widely acknowledged, with 46% of male deaths in the region of Chichigalpa, Nicaragua, over the past decade thought to be caused by CKDu, according to La Isla Foundation.

“(But) even there, we don’t know how extensive it is,” Pearce said.

The concern in Sri Lanka is equally high, with 2.9 million people estimated to be at high risk (PDF) of developing the deadly disease, congregated mostly in the country’s North Central Province – but the scale of this epidemic has remained more hidden internationally.

“What we do know is it looks like the same thing is happening … but it’s also not known if it’s the same disease,” Pearce said.

The Sri Lankan government has had enough of the mystery, convening experts from around the world last week to find answers, in collaboration with the World Health Organization. Approximately 45 global experts from a range of organizations, academic institutions and disciplines took part in the consultation.

“The problem is being taken very seriously here,” said Pearce, who attended the meeting to push the need for a standardized research protocol to be used in each of the hot spots. “Until we’ve (done) that, it’s hard to say how big the problem is.”

Pearce’s team at the London School of Hygiene and Tropical Medicine is conducting a survey in Nicaragua, looking for clues or insight into any patterns there.

What are the clues?

CKDu has mainly affected coastal farmers, mostly men, working in extremely hot climates but also in lowland areas with increased humidity levels. In Central America, those most affected have been men farming sugar cane, whereas rice farmers on the paddy fields are at most risk in Sri Lanka.

“When you go into the highlands, you don’t find any CDKu,” said Tewodros Rango, an environmental researcher at Duke University.

Rango, like many experts, believes the working environment could be to blame. The intense heat could be causing farmers to sweat excessively and become extremely dehydrated while they are exposed to intense moisture in the atmosphere and with inadequate access to water.

“One thing they all have in common is, they are hot,” Pearce added.

Farm work in these equatorial regions, particularly among sugar cane farmers, is considered to be the most strenuous work in the world, with the average sugarcane worker drinking 7 liters of water and losing 5½ pounds (2½ kilograms) of weight per day-long shift, according to Pearce.

“This is the most plausible hypothesis,” Rango agreed. “We want to quantify the dehydration.”

But it’s not so simple.

Lifestyle factors could also be playing a role, such as the consumption of alcohol and tobacco, which can also lead to dehydration and damage the kidneys over time. In interviews with almost 30 patients with CKDu, Rango found that most of them smoked and drank alcohol regularly.

“I think this and the working environment account for the cause,” he said.

What were the suspects?

Until now, a range of causes has been thought to be to be behind the disease, including pesticides, agrochemicals and heavy metals in drinking supplies.

“Increasingly, the finger is being pointed at water,” said Herath Manthrithilake, head of Sri Lanka programs at the International Water Management Institute. He has witnessed the epidemic progress and grow into other regions of Sri Lanka, with tens of thousands now estimated to have been affected, according to studies.

“It was thought that cadmium and arsenic (in the water) were to blame, but there was no conclusive evidence for either of them,” he said.

In 2013, Rango conducted a study in Sri Lanka, in partnership with the water institute, testing water supplies in affected and nonaffected regions for traces of these heavy elements. It found levels to be extremely low – in both the water and urine samples.

“We couldn’t link these trace elements with CKDu,” Rango said.

But this hasn’t taken water out of the running as a suspect, as experts including Manthrithilake believe it still has a role to play. “We are zeroing in on groundwater,” he said.

With the majority of people in Sri Lanka’s affected regions relying on wells as their source of water, Manthrithilake now hypothesizes that fluoride and calcium in rock at the bottom of these wells could be inadvertently consumed when water is pumped out.

“We need to test the water coming out of these wells,” he said.

However, Pearce doesn’t believe the case for water is strong enough. “(This wouldn’t) explain why the disease is more common in men than women,” he said.

What can be done?

The debate will continue, both in the meeting this week and into the future, but for now, experts agree on two things: that there’s a need for a comparable survey and that the answer to the mystery is still years away.

Until then, the priorities include earlier diagnosis and improved working conditions in such intense heat. Initial symptoms of the disease are nondistinct, such as tiredness and appetite loss, meaning people are usually diagnosed late, when damage to the kidney is extensive and irreversible. The only option at this stage is dialysis, which is not always available or accessible.

This timing of visiting health care services is also delayed when families rely on the income from workers.

“The farmers only go to the hospital once they can’t function very well,” Rango said. “But early diagnosis can be done at the community level.”

As the Sri Lankan government debates its approach, the real help will need to come from expanded resources to enable treatment, while the detectives continue their investigations.

“Emphasis is placed on preventive action, provision of services and care, social interventions as well as research,” WHO spokeswoman Karen Reidy said. “The recommendations generated from the (meeting) highlight all of these areas and represent the priority interventions for implementation.”