A Mysterious Epidemic and its Relationship to Global Health

By Richard J Johnson MD
DrRichardJohnson.com

Chronic kidney disease is not uncommon in the United States, with as many as 15 percent of all adults manifesting some decrease in kidney function.  Some of the more common causes are diabetes and high blood pressure, but chronic kidney disease, or CKD as it is often referred to, is also common as we age and especially in those who have obesity and prediabetes (the metabolic syndrome).  Other causes can include kidney stones, anatomic problems and hereditary conditions.

So, a surprise developed a couple of decades ago when a kidney disease of an unknown cause was identified in some of the hotter countries in the world where it was manifesting in those working manually outside under the hot sun.  One of the major sites where this disease was observed was along the Pacific coast of Central America where it was primarily affecting young, male sugarcane workers. What was scary was that it was occurring in epidemic proportions, that the individuals affected were often poor and disadvantaged, and that dialysis and kidney transplantation were often not available.  Among some regions the disease occurred in epidemic proportions, and those afflicted were often only in their twenties. In these areas the mysterious “CKD of unknown etiology” was one of the most common causes of death among young men, and over 60,000 deaths were recorded.

What was equally scary was that similar epidemics of CKD of unknown etiology were identified in other places of the world, including India, Sri Lanka, Mexico, and Thailand. Again, it often affected sugarcane workers and individuals working rice paddies, but it could also affect construction workers and others spending a lot of time in the sun. More recently, there are reports of kidney damage occurring in individuals working manually outside in California, Texas and Florida, bringing home to those of us living in the USA that this disease appears capable of occurring anywhere it is very hot.

Initially everyone thought it might relate to chemicals used in agriculture—indeed, there is evidence that many individuals are exposed to agrochemicals and insecticides, such as glyphosate (round-up) or paraquat. However, most studies have not been able to confirm a role for chemicals.

Another thought was that heat stress might be involved. Evidence supporting this was found when workers were tested before and after being in the sugarcane fields.  There was clear evidence that working in the sun could lead to both dehydration and overheating, and the degree this happened correlated with the risk of developing kidney injury that could occur while they were working.

Our group also did a very interesting study.  Led by Carlos Roncal, we exposed laboratory mice to heat by placing them in a heat chamber, and each day for 5 weeks they would be put in a chamber for 30 minutes at a time for 6 to 8 times per day. Each time they came out of the heat chamber they were allowed to rest for 30 minutes. One group, however, were allowed to drink water whenever they came out of the heat chamber, while the others had to wait till the end of the day.  Interestingly, the mice that had to wait ended up drinking exactly the same amount of water as the group that could drink it immediately.  Despite drinking the same amount of water, the group that had a delay in being rehydrated developed CKD, while the others who hydrated immediately were protected.  This study provided key evidence that heat stress and inadequate hydration were important causes of the CKD, and has led to a change in practice in which workers are provided more breaks, access to shade, and better hydration.

The reason for the epidemic was unclear however.  Initially many felt climate change was unlikely, as overall mean temperature has increased by only about 1 degree in the last 50 years.  However, this viewpoint has changed since it is really not about mean temperatures, but extreme temperatures like heat waves.  Of interest, climate change is responsible for 75 percent of the heat waves today, and we have been able to link the heat waves with the development of kidney damage. Indeed, by looking at maps showing heat wave patterns, one can predict where this kidney disease can be found.

There is an additional twist.  Recently it has become apparent that, while hydration and shade can dramatically reduce the development of kidney disease in the sugarcane worker, that some kidney damage is still occurring. So, it seems like there may be another cause.  One observation has been that if individuals hydrate with soft drinks, that tends to make the kidney disease worse, which is not so surprising given how bad soft drinks are as it relates to causing obesity and diabetes.

One curious thing about sugarcane is that many owners will burn the sugarcane fields a few days before the sugarcane is harvested. The fire tends to burn away the leaves but the cane remains intact which can then be cut more easily. This results in higher yields of sugar. However, a problem with burning the sugarcane is that it can cause tons of soot and ash to go into the atmosphere, and also the workers all become drenched in soot and also breathe in the ash as the process of cutting the freshly burned cane releases the ash into the air.  Rice paddies are also often burned at the end of the season as it can act as a fertilizing process.

Again, our group wondered if the breathing or drinking of ash-contaminated water might also cause kidney disease.  Analysis of the ash showed that the major component was silica in the form of nanoparticles.  Crystalline silica, such as is released from sand blasting, can cause lung disease (silicosis) if it is inhaled.  However, nanoparticle silica such as present in sugarcane ash was thought to be safer, and in fact it can pass through the lung, into the blood, and be excreted in the urine.  But when we gave either sugarcane ash or silica nanoparticles to laboratory rats, they also developed CKD that looked similar to that occurring in the sugarcane workers. Furthermore, in initial studies we have been able to find silica nanoparticles in the kidneys of sugarcane workers who developed this mysterious kidney disease.

There is a lesson here, and that is that burning sugarcane fields is a terrible thing to do.  Indeed, there is a movement to eliminate sugarcane burning in many countries, such as Brazil. Nevertheless, there are many places in the world where it is still done.  But think of what we can do if we could stomp this out.  It would be the Trifecta!

First, it would save lives of the workers, as they would no longer be exposed to sugarcane ash. So we would help the workers.

Second, it would reduce pollution and the emissions of the carbon-particle containing ash that has been shown to contribute to climate change.  So we would help the planet.

Finally, it might force the price of sugar to go up, which would translate into less obesity, diabetes, fatty liver and high blood pressure.  This would help the general population.

So, lets make a better world—stay hydrated, give yourself plenty of shade, avoid soft drinks, and lets try to stomp out the practice of burning the sugarcane fields and rice paddies.  We can help make the difference.

References

1 Roncal Jimenez, C. A. et al. Fructokinase activity mediates dehydration-induced renal injury. Kidney Int 86, 294-302 (2014). https://doi.org:10.1038/ki.2013.492

2 Johnson, R. J., Wesseling, C. & Newman, L. S. Chronic Kidney Disease of Unknown Cause in Agricultural Communities. N Engl J Med 380, 1843-1852 (2019). https://doi.org:10.1056/NEJMra1813869

3 Garcia-Trabanino, R. et al. Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador–A cross-shift study of workers at risk of Mesoamerican nephropathy. Environ Res 142, 746-755 (2015). https://doi.org:10.1016/j.envres.2015.07.007

4 Rogers, K. L. et al. Silica Nanoparticles and Mesoamerican Nephropathy: A Case Series. Am J Kidney Dis 83, 420-423 (2024). https://doi.org:10.1053/j.ajkd.2023.06.010

5 Roncal-Jimenez, C. et al. Heat Stress Nephropathy From Exercise-Induced Uric Acid Crystalluria: A Perspective on Mesoamerican Nephropathy. Am J Kidney Dis 67, 20-30 (2016). https://doi.org:10.1053/j.ajkd.2015.08.021

6 Stem, A. D., Gibb, M., Roncal-Jimenez, C. A., Johnson, R. J. & Brown, J. M. Health burden of sugarcane burning on agricultural workers and nearby communities. Inhal Toxicol, 1-16 (2024). https://doi.org:10.1080/08958378.2024.2316875