Cause of CKD among Agricultural Workers in Central America Unknown

During the past two or three decades, a large number of young workers in the sugarcane fields in Central America have been diagnosed with end-stage renal disease (ESRD). During the same time period (2002), researchers in El Salvador also reported an upsurge in chronic kidney disease (CKD). A key finding of the report was that the patients with CKD and/or ESRD did not have any of the comorbidities known to cause CKD or ESRD, including diabetes, hypertension, or glomerular disease. Shortly following the 2002 report, others confirmed that the rates of CKD among sugarcane workers, as well as among other agricultural workers along the Pacific Coast of Central America, from Guatemala to Panama, were higher than expected. The disorder was given the name Mesoamerican nephropathy.

Richard J. Johnson, MD, Catharina Wesseling, MD, PhD, and Lee S. Newman, MD, recently published a review of the clinical presentation and epidemiology of CKD that is endemic among agricultural workers; the researchers also explored possible causes of the condition. The review in the New England Journal of Medicine was edited by Julie R. Ingelfinger, MD [2019;380(19):1843-1852].

The disease, common among sugarcane workers, is also seen in other poor agricultural communities such as cotton and corn workers and workers at shrimp farms; it is also seen in construction sites and mines. Sugarcane workers working at sea level are more apt to develop the disease than those working at higher elevations and is nearly absent among workers at coffee plantations at higher elevations. Women and children in the region have presented with milder and less frequent kidney disease.

Sugarcane workers usually have elevated serum creatinine levels at screening prior to working on a seasonal harvest. The condition is found most often in men who have worked for ≥2 seasons, are 20 to 50 years of age, are asymptomatic, and have normal or only slightly elevated blood pressure as well as normal levels of blood glucose. Results of urinalysis show no or minimal proteinuria, small amounts of red cells and leukocytes, and sometimes amorphous urate crystals. Hyperuricemia is common but not required for the diagnosis.

In some workers in sugarcane fields, levels of serum creatinine increase during the work shift, commonly accompanied by mild elevations in muscle enzyme levels. Changes in the creatinine level during the work shift may represent injury to the kidneys; if repetitive, the kidney injury may lead to a predisposition to CKD. One report suggested an association between episodes of acute kidney injury (AKI) during the work shift and a trend toward worsening of kidney function over the course of the harvest season. Another found that some sugarcane workers with new elevations in serum creatinine at the end of the harvest season did not fully recover during the following year; one third of that population was diagnosed with CKD (estimated glomerular filtration rate [eGFR], <60 mL/min/1.73 m2). It is unclear whether CKD is the result of repetitive AKI or is a chronic disease process in which fluctuations in renal function over the course of a workday are exaggerated responses to changes in hydration status.

Workers with established Mesoamerican nephropathy show chronic interstitial disease, tubular atrophy, inflammation, and interstitial fibrosis. At the time of diagnosis, CKD is advanced to stage 3 or 4 (eGFR 15 to 60 mL/min/1.73 m²), with subsequent decline in eGFR of 3.8 to 4.4 ml/min/1.73 m² per year. Patients are initially asymptomatic; however, over a period of several years, signs and symptoms of ESRD (anemia, anorexia, nausea, and progressive uremia) often develop. Adequate dialysis programs may not be readily available in that part of the world. It is unknown whether earlier identification of affected patients would make it feasible to reverse the disease.

The review also addressed CKD of unknown origin in the North Central Province of Sri Lanka that affects individuals working in rice paddies in rural regions, as well as cases of CKD reported among rural families in Central India in the states of Andhra Pradesh, Odisha, Chhattisgarh, and Maharashtra. Both instances of disease were initially noted in the 1990s, with prevalence increasing during the past two decades. Other parts of the world that report high rates of CKD among rural farmers include Tierra Blanca, Veracruz State, Mexico; two reports indicate the disease may also be present in southern Egypt and the Sudan.

The cause of the upsurge in CKD is unknown; various possible causes are currently under investigation. Avenues being examined include the use of agrochemicals, particularly the herbicide glyphosate; and exposure to lead, cadmium, arsenic, or silica, particularly in Central America and India. Other possibilities include infectious diseases that can lead to tubulointerstitial injury (e.g., leptospirosis and hantavirus infection); genetic factors may also play a role.

The authors noted that the regions of interest tend to be the hottest regions in the various countries. Preventive policies and treatment in Central America have focused on reducing heat and sun exposure and improving hydration with safe water and electrolytes. The Worker Health and Efficiency Program implemented a hydration and shade intervention that included a provision for tents for shade, refillable water containers, an increased number of breaks, and other preventive measures. Those changes tended to slow the decline in eGFR during the harvest, but the difference was not significant.

In Sri Lanka, preventive efforts have focused on obtaining safe drinking water and eliminating potential neurotoxins in the environment. There was also political action in El Salvador against pesticides to address CKD in that country. In 2013, the Congress of El Salvador approved the prohibition of 53 pesticides, including nephrotoxic paraquat and glyphosate; the ban, however, was never enacted into law.

In summary, the authors said, “A spate of chronic kidney disease is occurring in several regions of the world, affecting manual workers in hot, agricultural communities. The causes remain unclear but may involve a complex interplay of environmental exposures, infections, genetic factors, and heat. Preventive measures have included programs to ensure safe drinking water, adequate hydration, rest, and shade for workers at risk, as well as to reduce exposure to toxins. However, proof that these interventions are reducing the incidence of chronic kidney disease has yet to be provided. International collaborative research efforts would help accelerate the search for causes and provide adequate prevention and treatment in resource-poor countries with little or no access to renal replacement therapy.”

Takeaway Points

1. There has been an increase in the prevalence of kidney disease among agricultural workers in various parts of the world. Most of the cases of kidney disease among sugarcane workers, as well as other members of poorer agricultural communities, in Central America are not associated with the classic causes (diabetes, hypertension, and glomerular disease).
2. The disorder, Mesoamerican nephropathy, is seen along the Pacific Coast of Central America, from Guatemala to Panama; it is most prevalent among workers in the hottest regions at the lowest elevations.
3. The causes of the disease remain unknown; possible preventive interventions include availability of safe drinking water, and adequate hydration, rest and shade for workers at risk.