Glyphosate and Chronic Kidney Disease - Sri Lanka
Jayasumana et al. propose a hypothesis that glyphosate herbicide combines with kidney-toxic metals in the diet to form some type of glyphosate-metal complex which is transported into the body and ultimately ends up in the kidney, contributing to chronic kidney disease.
There has been no evidence of any connection between the exposure of glyphosate-based products and chronic kidney disease (CKDu). The authors state that they “have hypothesized” this relationship which has “not been given any serious consideration by investigators for the last two decades.” While speculative theories have a place in science, they need to be investigated and proven to be of practical use. No new data are provided to support this theory, and there are many alternative hypotheses- previous studies have associated employment as a farmer, use of pesticides, dehydration, cadmium exposure, and other factors with the occurrence of renal dysfunction.
The CKDu National Research Project Team in Sri Lanka has been working for several years to understand and address chronic kidney disease of uncertain etiology (CKDu), supported by the Sri Lanka Ministry of Health and the World Health Organization. Their recent report states “the results of this cross-sectional study indicate that multiple agents may play a role in the pathogenesis of CKDu,” citing lead, arsenic and especially cadmium exposures as well as ground water use, excessive fluoride intake, selenium deficiency, genetic predisposition, female gender, age, and the previously recognized associations with farming and pesticide exposure. It is not clear whether the pesticide association is a causal relationship, or simply a marker for farming and associated exposures.
Brief Technical Comments:
1) Chronic Kidney Disease of Uncertain Etiology (CKDu) has been reported from multiple locations over the past century, with many instances predating the discovery and use of glyphosate (1974). CKDu is generally believed to be multi-factorial. Contributing factors (Soderland et al) include heavy metals, plant toxins, infections, and dehydration. Farm employment, pesticide use, alcohol consumption, urinary tract infection, non-steroidal anti-inflammatory medication, low selenium intake, high fluoride intake, volcanic ash exposure, snake bite, hard water, and family history have also been identified as risk factors for CKDu. Causal relationships in CKDu are difficult to untangle as many factors are intimately related (ex- farming, pesticide use, dehydration, and snakebite).
2) The allegations by Jayasumana et al. regarding glyphosate and kidney disease are entirely theoretical. They speculate that metals in hard water in conjunction with some other unknown factor, “compound X,” may be the cause of CKDu. The authors assume that this factor must be an agricultural chemical, bind to (chelate) heavy metals, result in increased uptake of the metal(s), and transport metal(s) to the kidney, where it accumulates and induces renal disease. No evidence to support this hypothesis is provided and, despite the illustrations created by Jayasumana et al, there is no evidence for the existence of large, stable complexes of metals with glyphosate.
3) Plants contain a large number of compounds capable of chelating metals more effectively than glyphosate. Naturally occurring dietary compounds are far more likely candidates for complexation with heavy metals (Harris 2012).
4) For further information on glyphosate safety see the 2004 review by the World Health Organization. Glyphosate was formally evaluated in the EU in 2002 and is currently under review. The conclusions of the 2002 EU assessment have been confirmed in the draft assessment from the German Rapporteur (BfR).
5) Reported urine glyphosate (and AMPA) levels in CKDu cases (Jayatilake et al) are far below levels suggesting an exposure capable of inducing chronic toxic effects in animals, and 96.5 % of CKDu cases had glyphosate levels below the stated reference limit in urine. Also notable in this study, work in rice paddies was negatively associated with CKDu, counter to allegations that work in rice agriculture may explain CKDu. Deficiency in selenium and family history of renal failure are risk factors for CKDu, suggesting nutritional and hereditary factors. Recent research (Nanayakkara), also supported by WHO, has demonstrated the existence of an important genetic variant (single nucleotide polymorphism [SNP]) which is a significant risk factor for CKDu.
6) Water concentrations of arsenic reported in affected regions (Nanayakkara et al) were higher than found in uncontaminated areas of Europe and North America but “much lower than the reported concentrations in As-contaminated countries such as Bangladesh and Taiwan.” 75-80 percent of arsenic appears as arsenobetaine (non-toxic). Notably, while areas of Bangladesh have much higher exposure to inorganic arsenic and have overt manifestations of clinical arsenic intoxication and alterations in renal function, CKDu is not reported in these populations.
7) Nanayakkara et al. also studied concentrations of 18 metals and confirmed the absence of nephrotoxic metal elevations in drinking water. Metal concentrations (unadjusted) in urine were not elevated in cases vs controls. The absence of any clear causal relationship between CKDu and metals in urine does not support the concept of glyphosate-metal complexes accumulating in the kidney
Last update: 27 January 2015