Abstract
Chronic kidney disease of unknown etiology (CKDu) is a global epidemic. Sri Lanka has experienced a doubling of the disease every 4 or 5 years since it was first identified in the North Central province in the mid-1990s. The disease primarily affects people in agricultural regions who are missing the commonly known risk factors for CKD. Sri Lanka is not alone: health workers have reported prevalence of CKDu in Mexico, Nicaragua, El Salvador, and the state of Andhra Pradesh in India. A global search for the cause of CKDu has not identified a single factor, but rather many factors that may contribute to the etiology of the disease. Some of these factors include heat stroke leading to dehydration, toxic metals such as cadmium and arsenic, fluoride, low selenium, toxigenic cyanobacteria, nutritionally deficient diet and mycotoxins from mold exposure. Furthermore, exposure to agrichemicals, particularly glyphosate and paraquat, are likely compounding factors, and may be the primary factors. Here, we argue that glyphosate in particular is working synergistically with most of the other factors to increase toxic effects. We propose, further, that glyphosate causes insidious harm through its action as an amino acid analogue of glycine, and that this interferes with natural protective mechanisms against other exposures. Glyphosate’s synergistic health effects in combination with exposure to other pollutants, in particular paraquat, and physical labor in the ubiquitous high temperatures of lowland tropical regions, could result in renal damage consistent with CKDu in Sri Lanka.
Highlights
Starting in the early 1990s, an epidemic of chronic kidney disease (CKD) was discovered among rice paddy farmers, primarily young men, in the North Central province of Sri Lanka [1,2]
As it becomes increasingly clear that Chronic kidney disease of unknown etiology (CKDu) is a multifactorial disease, the complexity of possibilities can be narrowed by an understanding of local environmental health conditions and resulting disease processes in the people that live and work there
We have proposed a plausible mechanism of toxicity for glyphosate that involves substitution for the coding amino acid glycine during protein synthesis, and we have shown theoretically how this could lead to increased toxicity of multiple other factors associated with CKDu
Summary
Starting in the early 1990s, an epidemic of chronic kidney disease (CKD) was discovered among rice paddy farmers, primarily young men, in the North Central province of Sri Lanka [1,2]. In a more recent study, Wijkström et al (2018) [13] found that the morphology and biochemical characteristics of CKDu patients in Sri Lanka have many resemblances with the MeN epidemic in Central America, indicating a similar diagnostic entity and possibly a similar etiology With these fairly consistent pathological findings of chronic interstitial nephritis and glomerular sclerosis, there is enough agreement that the Sri Lankan CKDu is a toxic nephropathy [11,14,15,16,17,18,19]. Most of the research in Sri Lanka that has been conducted on CKDu during the past decade has resulted in multiple hypotheses These hypotheses include arsenic, cadmium, nephrotoxic pesticides, fluoride, the use of cheap aluminum vessels, cyanobacteria, ayurvedic treatments, snake bites, and the use of nonsteroidal anti-inflammatory medications as possible causes of CKDu [36,46,47,48]. To chelate and transport metals to the kidneys [12,56]
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