Mysterious Kidney Disease Devastates Rural Farming Communities

Health Letter, June 2016

By Sammy Almashat, M.D., M.P.H.

Kesava Rao, 45, was a healthy man who worked all of his life in construction and coconut harvesting, and had hardly ever seen a doctor in his home state of Andhra Pradesh, India.[1] That all changed when he sought medical attention for a fever and was diagnosed with a devastating kidney ailment, the cause of which continues to baffle experts around the world.

The condition is known by several names, including chronic kidney disease of unknown etiology (CKDu), chronic kidney disease of nontraditional causes (CKDnT) and Mesoamerican nephropathy.[2],[3] Like others stricken with the condition, Rao had no obvious cause for his kidney disease, such as diabetes or high blood pressure.

The ailment, first detected in Central America, has now been found across the world, including in Egypt, India and Sri Lanka.[4] In some regions, it has reached epidemic levels. Experts and advocates are urgently looking to uncover the causes of and find solutions to the disease.

Scale of the outbreak

Because experts have not yet agreed on a precise definition for CKDu,[5] it is difficult to determine how many people have been affected. Within Central America, Nicaragua and El Salvador have been hit the hardest, with death rates from kidney disease in males 60 years old and younger far exceeding those of other countries in North and Central America.[6] Studies of five communities in El Salvador found that 13 to 21 percent of the population had chronic kidney disease, with most cases of unknown cause.[7]

Because they are generally otherwise healthy and display no early symptoms, CKDu patients often are diagnosed in late stages of the disease, when kidney damage is severe and only dialysis or a kidney transplant will save their lives.[8] The La Isla foundation, which is devoted to finding solutions to the epidemic, reports that in Chichigalpa, Nicaragua, 75 percent of deaths in people ages 35 to 55 are due to chronic kidney disease.[9] Some estimate that CKDu already has killed at least 20,000 people in Central America.[10]

Elusive causes

CKDu patients from different regions of the world have been found to share several characteristics. While more common types of chronic kidney disease are mainly due to diabetes or high blood pressure and occur in elderly men and women, CKDu has afflicted otherwise healthy rural farmworkers, mostly men, in their 30s to 50s.[11] In patients with CKDu, unlike those with other forms of kidney disease, there is typically no protein found in the urine.[12] This is a key indicator that the form of kidney damage in CKDu is distinct from that in more common types of kidney disease.

The editors of the journal MEDICC have dubbed CKDu a “perfect storm” because it is thought to have several potential causes that, when occurring together, damage the kidneys.[13]

First, there is the heat. The regions where CKDu has been seen (Central America, Egypt, southern India and Sri Lanka) have hot climates. Heat stress is a major hazard for agricultural and other workers. In the U.S. alone, hundreds of workers in recent decades have died and tens of thousands have been injured from severe heat exposure, with farmworkers at the highest risk.[14] Far more workers who do not display overt signs of heatstroke nevertheless suffer dehydration from long hours in the fields without adequate water and electrolyte intake. Intensive labor under hot and humid conditions may result in repeated bouts of acute dehydration and kidney damage.[15] It is thought that enough instances of short-term kidney damage eventually may result in irreversible long-term damage and CKDu. One study of an affected region in El Salvador showed higher rates of kidney disease in warmer coastal communities than in the higher-altitude, cooler areas.[16]

But heat clearly cannot be the only cause, as unaffected workers around the world labor in conditions as hot as or hotter than those where CKDu has taken hold. Exposures to the mineral silica,[17] various toxic metals — such as cadmium, lead and arsenic — and to a naturally occurring chemical in plants known as aristolochic acid may be other potential risk factors.[18] However, evidence is lacking that any of these substances could, on its own, lead to CKDu. It is possible, however, that when these exposures occur in combination with heat- and labor-induced dehydration, long-term kidney damage may result.[19] Other experts point to pesticide exposure and intake of high-sugar drinks, non-steroidal anti-inflammatory drugs and alcohol as potential contributors to CKDu.[20]

The MEDICC editors point to a further, more insidious factor at play when concluding that “social determinants [of health] such as deep-rooted poverty appear to combine synergistically with harsh, sometimes inhuman, working conditions and exposure to environmental toxins to produce a silent killer.”[21]

Solutions urgently needed

Rao, the CKDu patient in India, now needs dialysis every week in order to survive.[22] His eldest son, only 20, stopped his schooling after high school in order to provide for the family. And Rao is one of the lucky ones who can get lifesaving treatment. The Pan American Health Organization (PAHO) noted in a July 2015 update on CKDu in Central America that dialysis costs anywhere from $355 to $2,249 per patient per month, while the monthly cost of anti-rejection drugs for patients fortunate enough to receive kidney transplants is $725 to $4,250.[23] With the exception of Sri Lanka,[24] none of the countries where CKDu is prevalent provide universal access to health care, making these costs prohibitive for most poor CKDu patients and their families.

Noting the importance of ensuring access to life-saving treatments for kidney disease, PAHO concluded that the countries in the region “should urgently analyze the comprehensive response to [chronic kidney disease] in light of the agreed commitment to advance toward universal access to health and universal health coverage.”[25] Even were these nations to expand access, however, the costs of dialysis and post-transplant drugs would be daunting for poor Central American nations, where just $144 to $951 is spent on health care per person per year.[26]

In a 2015 paper, researchers from Johns Hopkins University reminded readers that, while experts continue the search for the cause or causes of CKDu, funding for “basic public health measures that are known to be cost effective and also address potential CKDu risk factors” should be urgently undertaken.[27] These measures include provision of uncontaminated drinking water, prevention of dehydration in workers, and safer use of agricultural chemicals, such as pesticides.

Like universal health care, these measures will benefit workers (and their families) above and beyond the hoped-for reduction of CKDu cases. These commonsense interventions must be implemented while research is pursued to unlock the mystery of CKDu.


References

[1] Chatterjee R. Mysterious kidney disease goes global. Science. April 1, 2016. http://www.sciencemag.org/news/2016/03/mysterious-kidney-disease-goes-global. Accessed May 17, 2016.

[2] Ibid.

[3] Correa-Rotter R, Wesseling C, Johnson RJ. CKD of unknown origin in Central America: the case for a Mesoamerican nephropathy. Am J Kidney Dis. 2014;63(3):506-520.

[4] Chatterjee R. Mysterious kidney disease goes global. Science. March 31, 2016. http://www.sciencemag.org/news/2016/03/mysterious-kidney-disease-goes-global. Accessed April 15, 2016.

[5] Pan American Health Organization. 54th Directing Council: 67th Session of the Regional Committee of WHO for the Americas. Provisional Agenda Item 7.5. E. Chronic Kidney Disease in Agricultural Communities in Central America. July 10, 2015. http://www.paho.org/hq/index.php?option=com_content&view=article&id=11087%3A2015-54th-directing-council&catid=8080%3A54th-session-28-sep-2-oct&Itemid=41537&lang=en. Accessed May 17, 2016.

[6] Ordunez P, Saenz C, Martinez R, et al. The epidemic of chronic kidney disease in Central America. Lancet Glob Health. 2014;2(8):e440-441.

[7] Almaguer M, Herrera R, Orantes CM. Chronic kidney disease of unknown etiology in agricultural communities. MEDICC Rev. 2014;16(2):9-15.

[8] Ibid.

[9] Chatterjee R. Mysterious kidney disease goes global. Science. May 17, 2016. http://www.sciencemag.org/news/2016/03/mysterious-kidney-disease-goes-global. Accessed April 15, 2016.

[10] Ibid.

[11] Ibid.

[12] Almaguer M, Herrera R, Orantes CM. Chronic kidney disease of unknown etiology in agricultural communities. MEDICC Rev. 2014;16(2):9-15.

[13] CKDu: A perfect storm. MEDICC Rev. 2014;16(2):3.

[14] Public Citizen. Petition for a heat standard. https://www.citizen.org/sites/default/files/petition-for-a-heat-standard-090111.pdf. Accessed May 17, 2016.

[15] Almaguer M, Herrera R, Orantes CM. Chronic kidney disease of unknown etiology in agricultural communities. MEDICC Rev. 2014;16(2):9-15.

[16] Peraza S, Wesseling C, Aragon A, et al. Decreased kidney function among agricultural workers in El Salvador. Am J Kidney Dis. 2012;59(4):531-540.

[17] Chatterjee R. Mysterious kidney disease goes global. Science. March 31, 2016. http://www.sciencemag.org/news/2016/03/mysterious-kidney-disease-goes-global. Accessed May 17, 2016.

[18] 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 Nephrol. 2015;16:145.

[19] Ibid.

[20] Ordunez P, Saenz C, Martinez R, et al. The epidemic of chronic kidney disease in Central America. Lancet Glob Health. 2014;2(8):e440-441.

[21] CKDu: A perfect storm. MEDICC Rev. 2014;16(2):3.

[22] Chatterjee R. Mysterious kidney disease goes global. Science. March 31, 2016. http://www.sciencemag.org/news/2016/03/mysterious-kidney-disease-goes-global. Accessed May 17, 2016.

[23] Pan American Health Organization. 54th Directing Council: 67th Session of the Regional Committee of WHO for the Americas. Provisional Agenda Item 7.5. E. Chronic Kidney Disease in Agricultural Communities in Central America. July 10, 2015. http://www.paho.org/hq/index.php?option=com_content&view=article&id=11087%3A2015-54th-directing-council&catid=8080%3A54th-session-28-sep-2-oct&Itemid=41537&lang=en. Accessed May 17, 2016.

[24] Sri Lanka’s healthcare challenges. The Economist. November 24, 2014. http://country.eiu.com/article.aspx?articleid=1502512534&Country=Sri%20Lanka&topic=Economy&subtopic=Forecast. Accessed May 17, 2016.

[25] Pan American Health Organization. 54th Directing Council: 67th Session of the Regional Committee of WHO for the Americas. Provisional Agenda Item 7.5. E. Chronic Kidney Disease in Agricultural Communities in Central America. July 10, 2015. http://www.paho.org/hq/index.php?option=com_content&view=article&id=11087%3A2015-54th-directing-council&catid=8080%3A54th-session-28-sep-2-oct&Itemid=41537&lang=en. Accessed May 17, 2016.

[26] Ibid.

[27] 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 Nephrol. 2015;16:145.