Health: Risks of unexplained kidney disease

Prof Swaminathan Sundararaman

Unexplained kidney disease among agricultural workers has become a significant public health challenge across continents, mirroring patterns first observed in Central America and later in South Asia.

In the 1990s, doctors in Central America reported numerous sugarcane workers with end-stage kidney disease, initially in El Salvador. Studies soon revealed high CKD (chronic kidney disease) rates among agricultural workers from Guatemala to Panama, often without typical causes like diabetes or hypertension.

Around the same time, Sri Lankan physicians described similar CKD among middle-aged male rice paddy workers. Over the past two decades, Uddanam in Andhra Pradesh has shown comparable prevalence among coconut, cashew, and rice farmers.

Kidney disease in Uddanam, which dates to the 1980s, was first formally reported at the 2012 World Congress of Nephrology in Hong Kong. According to a study by Dr Ravi Raju Tatapudi, the rates of incidence were much higher than those in other Indian regions. Most patients had no traditional risk factors, and biopsies showed tubular inflammation and damage—now termed chronic kidney disease of unknown aetiology (CKDu).

In 2012, Dr Y J Anupama (Shivamogga, Karnataka) found CKD in one in 20 villagers across three villages—40 per cent without diabetes or hypertension—suggesting CKDu. Similar findings have since appeared in Tamil Nadu, Chhattisgarh, and Odisha.

The George Institute for Global Health, led by Prof Vivekanand Jha, has since studied disease burden, comorbidities, mortality, and community perception. Prof Prabir Roy-Chaudhury, Co-Director of the UNC Kidney Centre and President of the American Society of Nephrology, calls it a “twofold tragedy” affecting young, impoverished workers with no known cause or cure. Dr Sreejith Parameswaran (JIPMER, Puducherry) observes that one-third of patients with hypokalemic paralysis (characterised by acute muscle weakness) showed CKDu features, indicating its long-standing presence in Tamil Nadu. This aligns with Dr Mani’s 1993 report, describing chronic interstitial nephritis—now recognised as CKDu—as a frequent incidental finding that is still common at JIPMER.

Certain villages were found to be affected, while adjacent ones remained unaffected, as noted by Dr Manikandanesan Sakthivel (Isaac Centre for Public Health, IISc, Bengaluru).To assess global trends, the DEGREE Collaborative Study analysed kidney function in 60,964 people across 43 sites in 14 countries. The study found rural men in Uddanam and northwest Nicaragua were most affected.

Heat stress

Dr Nathan Raines (Beth Israel Deaconess, USA) emphasises the strong evidence linking occupational heat stress to CKDu in certain Central American populations. Research by the La Isla Network found that preventing heat stress among sugarcane cutters reduces both acute kidney injury (AKI) and acute kidney disease (AKD), which are associated with chronic kidney dysfunction. Separately, Boston University found that a genetic variant associated with heat-stress resilience protects against CKDu in Nicaraguans, further supporting the notion that heat is a key driver.

A study in Odisha found 14 per cent of farmers had chronic kidney disease linked to heat stress and dehydration. Between 2017 and 2020, a survey of Tamil Nadu salt pans revealed that nearly 90 per cent of workers faced unsafe heat conditions and inadequate hydration. Professor Ben Caplin (UCL, London) opines that heat stress can exacerbate any pre-existing kidney diseases. With heatwaves becoming increasingly frequent in India, the impact of heat on kidney health is becoming increasingly important, says Dr Vivekanand Jha.

Agrochemicals

The high prevalence of CKDu in farming communities has raised concerns about agrochemicals, such as glyphosate and Paraquat. Dr Shuchi Anand (Stanford University) and Dr Nishantha Nanayakkara (Kandy, Sri Lanka) observed faster CKDu progression among farmers relying on wells, where toxins concentrate, compared with those using a different water source, such as RO water.  Although heavy metals can harm the kidneys, no clear link to CKDu has been established. Dr Anupama’s study in Shivamogga also found no association.

Other theories, including infections like leptospirosis, lack solid evidence. Genetic factors are proposed but unproven. The disease may start before or at birth, as low-birth-weight children have fewer nephrons to handle environmental stress—making this hypothesis relevant in countries with high low-birth-weight rates.

Lack of early detection

Since CKDu is not associated with common causes such as hypertension, diabetes, or other known illnesses, its progression is primarily monitored through regular assessment of kidney function using estimated glomerular filtration rate (eGFR). Professor Caplin notes the absence of reliable biomarkers for early detection.He cautions that relying on elevated creatinine levels for surveillance delays recognition, as exposure-related causes and important causal exposures may occur months or years before eGFR becomes abnormal. Creatinine, moreover, is an imperfect indicator of GFR. Regardless, early avoidance of nephrotoxic drugs and heat exposure remains essential.

The NIH-funded CURE Research Consortium unites experts to identify causes and risk factors driving CKDu in agricultural communities. Prof Prabhdeep Kaur (Isaac Centre for Public Health, IISc, Bengaluru) stresses the need for sustained research funding on chronic diseases in India. Prof Prabir advocates a multifaceted approach integrating geographic, environmental, and multiomic (a holistic approach to biology) analyses. Dr Sreejith notes multiple causal factors and the need for interdisciplinary collaboration.

(Prof. Swaminathan Sundararaman is Inaugural Chair and Professor Department of Nephrology, Division of Medical Sciences, IISc, Bengaluru. Dr Praveen Kumar Kaudlay is a consultant haemato-oncologist with a special interest in stem cell transplantation at Royal Wolverhampton NHS Trust, UK. He can be reached at [e-mail].)