While we are concentrating on chronic kidney disease caused by diabetes, hypertension and glomerular disease what is awaiting our attention? In a review article entitled Chronic Kidney Disease of Unknown Cause in Agricultural Communities, ( May 9, 2019 N Engl J Med 2019; 380:1843-1852
DOI: 10.1056/NEJMra1813869) the authors, Richard J. Johnson, M.D., Catharina Wesseling, M.D., Ph.D., and Lee S. Newman, M.D. talk about diseases with names like MESOAMERICAN NEPHROPATHY, SRI LANKAN NEPHROPATHY, UDDANAM NEPHROPATHY and there are reports of high rates of chronic kidney disease in other hot regions of the world (e.g., among rural farmers in Tierra Blanca, Veracruz State, Mexico, where the major crops are sugarcane, cantaloupe, papaya, and rice). Two reports suggest that the disease may also be present in southern Egypt and the Sudan. There are reports from the Indian subcontinent of similar disorders and those of us who practice there encounter both acute and chronic renal failure in people exposed to extremely hot weather, lack of adequate drinking water, long and harsh working hours who have lost renal function for no identifiable disease. I think that we should also look at “Loss of renal function when earning dirhams for your family” in the labourers in the building and other labor intensive industries in the Middle East.
It was noted that sugarcane workers were losing their kidneys to CKD in the 1990s in South America. An upsurge was noted in El Salvador in 2002. Within a short time, multiple reports confirmed higher-than-expected rates of chronic kidney disease among sugarcane workers and other agricultural workers who were laboring in the fields along the Pacific Coast of Central America, from Guatemala to Panama, and the name Mesoamerican nephropathy was proposed for the disorder. Though noted in the sugarcane workers the condition can be seen in in cotton farmers, the shrimp industry, the construction industry and has probably been going on for much longer with some cases being seen in the 1970’s.
What seemed to be required for causing this loss of kidneys was hot humid climate as workers in the coffee plantations at a higher elevation were not affected. Those affected were usually men who had worked for two or more seasons, were between 20 and 50 years old, were asymptomatic initially but later anorexia, nausea, anemia and symptoms of chronic uremia developed. They had normal or only slightly elevated blood pressure and normal blood glucose levels. The urinalysis showed no or minimal proteinuria (<1 g per 24 hours), small numbers of red cells and leukocytes, and occasionally amorphous urate crystals. Serum electrolyte abnormalities included hypokalemia, hyponatremia, and hypomagnesemia in association with increased urinary electrolyte losses. Hyperuricemia was common but not required for the diagnosis. Women and children were affected in fewer numbers. In some cases sensorineural hearing loss and vascular lesions on the legs were noted.
What was happening? In some workers the serum creatinine was noted to be higher at the end of the shift thought to be related to dehydration, others had poorer renal function i.e. eGFR, at the end of the harvest, and many affected seasonal workers had not recovered renal function when they came to work next year.
What did the renal biopsy show?
Kidney-biopsy specimens from workers with established Mesoamerican nephropathy showed chronic interstitial disease, tubular atrophy, inflammation, and interstitial fibrosis. Glomeruli were characterized by focal wrinkling of the glomerular basement membrane, a finding that is consistent with ischemia, and global glomerulosclerosis was common. Immune deposits and changes characteristic of diabetes were not observed, and signs of hypertensive disease were minimal or absent.
SRI LANKAN NEPHROPATHY
A spate of chronic kidney disease of unknown origin was also identified in the North Central Province of Sri Lanka. The disease, which was first described in the 1990s, affects persons working in the rice paddies in rural regions. Men were more commonly affected than women, with an average age at presentation of 40 to 50 years. The similarities to Mesoamerican nephropathy are noteworthy, with most patients presenting with asymptomatic elevations of serum creatinine levels, low-grade or no proteinuria, and chronic interstitial nephritis with variable glomerulosclerosis in patients who undergo renal biopsy. Some patients presented with fever, leukocytosis, back pain, and arthralgias; urine specimens from such persons contained leukocytes and red cells despite minimal proteinuria, and renal biopsy showed an acute lymphocytic interstitial nephritis.
Numerous cases of chronic kidney disease have been reported among rural farmers in India, especially in Central India in the states of Andhra Pradesh, Odisha, Chhattisgarh, and Maharashtra. Known as Uddanam nephropathy (named after a village in Andhra Pradesh), chronic kidney disease in India was first noted in the 1990s, as it was in Sri Lanka, and its prevalence has increased during the past two decades. The disease is seen in hot, rural areas where farmers grow coconuts, cashew nuts, or rice. Affected patients usually present with normal blood pressure, low-grade or no proteinuria, and a relatively bland urinary sediment with occasional red cells and leukocytes. Renal biopsy, when performed, shows chronic interstitial disease with variable glomerulosclerosis.
What is causing all this?
Shallow wells for drinking water may concentrate toxins. A high concentration of glyphosate pesticides may be a causative factor, heavy metals such as lead, cadmium and arsenic in the drinking water may be a factor.
More recently, silica has been considered as a cause, especially in Central America and in India. Silica is commonly present in airborne material in burnt sugarcane fields. Respiratory exposure to silica has been associated with chronic kidney disease, and silica administration causes chronic interstitial nephritis in experimental animal models.
Other potential causes of chronic kidney disease include infectious diseases that can lead to tubulointerstitial injury, such as leptospirosis and hantavirus infection. Leptospirosis is common in sugarcane workers and may lead to chronic kidney disease. However, to date there is little support for these infections as causative agents in wells in India where Uddanam nephropathy has been reported.
Are there any genetic factors?
Genetic variants may also explain why kidney disease develops in some but not all persons in at-risk workforces and why renal function has improved in some workers but declined in others during the harvest season. Indeed, initial studies identified polymorphisms in SLC13A3 (sodium-dependent dicarboxylate transporter member 3)58 and KCNA10 (a voltage-gated potassium channel) that were associated with Sri Lankan nephropathy.
Physically demanding work in a hot environment and, as in the case of sugarcane workers, the lack of shade in the fields seem to be the precipitating factors. Heat stress and dehydration could potentiate toxin-mediated kidney injury by enhancing reabsorption of toxins in the context of volume contraction. It has been suggested that climate change may be a causative factor for this heat related stress.
How can we prevent CKD related to labour intensive jobs?
Shorter working hours can be advised and timed for cool hours of the day. Safe drinking water must be provided. At least 10 liters of water with two packets of electrolyte solution should be advised. Glyphosate pesticide should be banned. Workers should be weighed before and after shifts to ensure that significant loss of weight caused by dehydration does not occur. Laws should be formulated and enforced to prevent this loss of health and life in the most vulnerable workers and probably the most valuable workers in the food chain.
This is a preventable occupation related CKD and we should all be aware of it and try to prevent it.