When Climate Change Kills: Chronic Kidney Disease of Unknown Origin (CKDu)

Stéphanie Lavaud

September 02, 2019

Has global warming caused a new disease? This is what scientists seem to believe when faced with a rising death toll from chronic kidney disease of unknown origin (CKDu), which is killing agricultural workers in different countries around the world. Without being able to completely rule out pesticides and other factors, scientists are contemplating another environmental cause – the increasingly elevated temperatures farm workers experience in the fields.

A special edition of the New England Journal of Medicine (NEJM) this month is dedicated to the links between health and climate.

Dr Cecilia Sorensen of the Department of Emergency Medicine at the University of Colorado, US, and her colleague Dr Ramon Garcia-Trabanino of the Haemodialysis Centre in San Salvador, El Salvador, see the symptomatic illness CKDu as a "sentinel disease in the era of climate change".

They call for better awareness by health professionals of climate change risks, writing in the NEJM that "we can learn from this epidemic and choose a wiser path forward".

First Described in 1990 in El Salvador

Scarcely covered in the mainstream media, but reported in scientific literature, this mysterious renal pathology has emerged in different areas of the globe in recent years. It was described for the first time in the 1990s in El Salvador, when an unusually high number of agricultural workers were dying from irreversible renal failure. Then similar disease patterns were observed elsewhere in Central America and in North and South America, the Middle East, Africa, and India. "In Central America, CKD has become a leading cause of hospitalisation and death, owing in large part to CKDu", the authors write. "Over the past decade, the death toll from CKD rose 83% in Guatemala, and CKD is now the second leading cause of death in both Nicaragua and El Salvador."

The United States has also been affected, with cases reported in Florida, California, and the San Luis Valley in Colorado. US experts have said this is not the usual kidney disease they see that's caused by high blood pressure or diabetes.

A Renal Pathology That Does Not Involve Diabetes or Hypertension

What is it? In 2015, Dr Virginia Weaver and colleagues  from Johns Hopkins University in Baltimore, US, described the main characteristics of the CKDu "epidemic" in BMC Nephrology . They stated that the disease affects young and middle aged adult patients and leads to substantial morbidity and mortality in the absence of known causes of CKD such as diabetes or hypertension. Men seem more at risk, at least for the most severe cases, and very poor rural areas where agricultural work is the main occupation are more affected. "Poverty with lack of access to health care makes determining clinical characteristics of CKDu difficult," the authors wrote.

"CKDu may have been present for a significant period of time but not identified due to absence of diagnostic testing."

Although CKDu does not present in exactly the same way in each part of the globe, the disease has characteristics that suggest a common cause. Many possible causes have been investigated, like cadmium, arsenic, or lead, viruses, pesticides and other agricultural chemicals - none of which can be totally ruled out as contributory. Suspicions have turned towards extreme fatigue from heavy labour, along with dehydration and heat stress induced by high temperatures.

Enigmatic Illness Linked to Heat Exposure

Thirty years after the first descriptions, "the causation of CKDu remains enigmatic", write Drs Sorensen and Garcia-Trabanino. "What we do know for certain is that CKDu is related to heat exposure and dehydration, although exposure to agrochemicals, heavy metals, and infectious agents, as well as genetic factors and risk factors related to poverty, malnutrition, and other social determinants of health may also contribute."

In Central America, sugar cane workers have very high rates of CKDu and have become the subject of scientific research.

These farmers carry 5 to 6 tons (4.5 – 5.4 tonnes) of sugar cane per day, whilst heavily clothed, in temperatures that frequently exceed 40°C. The authors write: "There is increasing evidence that such heat exposure can cause daily subclinical acute kidney injury (ischemia, temperature-induced oxidative stress, and decreasing intracellular energy stores), which may cumulatively impair kidney function and result in CKD either directly or by exacerbating renal insults caused by other environmental exposures — or both. Indeed, recurrent exposure to heat stress and dehydration induces chronic inflammation and tubular injury in mice, similar to that seen in CKDu."

Physiological Limitation Impairment

Experts are increasingly assuming that CKDu is a result of global warming, since numerous geographical locations affected by this wave of renal disease have seen substantial changes in temperature in recent decades. "While average global temperatures have risen nearly 1°C, there has been a more drastic increase in heat waves accompanied by increased humidity; together, these factors drive up the heat index, with direct consequences for health." Drs Sorensen and Garcia-Trabanino postulate that we may now have reached "a physiological limit, in terms of heat exposure, at which acclimatisation and behavioural modifications can no longer overcome the biologic stressors of unsafe working conditions and environmental exposures in these hot spot communities".

They warn: "We are now living in an era when climate change is no longer a distant, existential threat. It is happening now, and it is affecting human health in profound ways.

"The combined effect of increasing heat extremes and water shortages is creating a new era of climate-health crises, in which known diseases are being exacerbated and new diseases are arising. CKDu is likely to be just one of many heat-sensitive illnesses that will be unmasked and accelerated by climate change."

Heat is known to exacerbate chronic diseases, particularly in older people.

Drs Sorensen and Garcia-Trabanino comment: "Whether knowingly or not, we have all most likely cared for patients who were adversely affected by climate change."

Diseases Associated With Climate Change

Their message to doctors is that diseases associated with climate change will pose challenges for medicine in the future. Firstly, CKDu prevalence increases with heat exposure. Secondly, such climate-sensitive diseases are more prevalent in disadvantaged areas of the world where people do not have access to high quality medical care. Thirdly, CKDu disproportionately affects the poorest and most vulnerable populations, often leading to exclusion from the agricultural workforce of the primary earners for their families, taking "an enormous toll on the social fabric of the family and community".

In fact, the World Bank believes that climate change could lead to more than 100 million people living in poverty by 2030.

Changing the Future?

In their conclusions, the authors take a clear position: "By using our trusted voices, we can also increase awareness within our communities and support climate-health literacy in medical schools and residencies to prepare the next generation of clinicians to handle the dynamic challenges of the future, including widespread emerging diseases such as CKDu. Furthermore, we can educate our patients to take health-protective and health-promoting actions that benefit their own personal health as well as the health of the planet.

"As stewards of community health, we take the pulse of humanity daily and see the casualties of climate change first hand. We believe that physicians have the opportunity to change the course of the future."

More on CKDu

To find out more about CKDu, visit La Isla Network, a site dedicated solely to this disease. The name of the foundation comes from a Nicaraguan community where so many men have died from CKDu that the locals have named it 'La Isla de Viudas', or 'The Island of Widows'.

Translated and adapted from Medscape French Edition.

Sorensen C, Garcia-Trabanino R. A New Era of Climate Medicine — Addressing Heat-Triggered Renal Disease, N Engl J Med 2019; 381:693-696. DOI: 10.1056/NEJMp1907859

Weaver VM, Fadrowski JJ, Jaar BG. Global dimensions of chronic kidney disease of unknown etiology (CKDu): a modern era environmental and/or occupational nephropathy? BMC Nephrology 2015, Volume 16, Article number: 145.

Quantitative risk assessment of the effects of climate change on selected causes of death, 2030s and 2050s. Geneva: World Health Organization, 2014.


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