The current chronic kidney disease epidemic, the major health issue in the rice paddy farming areas in Sri Lanka has been the subject of many scientific and political debates over the last decade. Although there is no agreement among scientists about the etiology of the disease, a majority of them has concluded that this is a toxic nephropathy. None of the hypotheses put forward so far could explain coherently the totality of clinical, biochemical, histopathological findings, and the unique geographical distribution of the disease and its appearance in the mid-1990s. A strong association between the consumption of hard water and the occurrence of this special kidney disease has been observed, but the relationship has not been explained consistently. Here, we have hypothesized the association of using glyphosate, the most widely used herbicide in the disease endemic area and its unique metal chelating properties. The possible role played by glyphosate-metal complexes in this epidemic has not been given any serious consideration by investigators for the last two decades. Furthermore, it may explain similar kidney disease epidemics observed in Andra Pradesh (India) and Central America. Although glyphosate alone does not cause an epidemic of chronic kidney disease, it seems to have acquired the ability to destroy the renal tissues of thousands of farmers when it forms complexes with a localized geo environmental factor (hardness) and nephrotoxic metals.

The chronic kidney disease of unknown etiology (CKDu) among paddy farmers in was first reported in 1994 and has now become most important public health issue in dry zone of Sri Lanka. The objective was to identify risk factors associated with the epidemic in an area with high prevalence. A case control study was carried out in Padavi-Sripura hospital in Trincomalee district. CKDu patients were defined using health ministry criteria. All confirmed cases (N = 125) fulfilling the entry criteria were recruited to the study. Control selection (N = 180) was done from people visiting the hospital for CKDu screening. Socio-demographic and data related to usage of applying pesticides and fertilizers were studied. Drinking water was also analyzed using ICP-MS and ELISA to determine the levels of metals and glyphosate. Majority of patients were farmers (N = 107, 85.6%) and were educated up to ‘Ordinary Level’ (N = 92, 73.6%). We specifically analyzed for the effect modification of, farming by sex, which showed a significantly higher risk for male farmers with OR 4.69 (95% CI 1.06-20.69) in comparison to their female counterparts. In the multivariable analysis the highest risk for CKDu was observed among participants who drank well water (OR 2.52, 95% CI 1.12-5.70) and had history of drinking water from an abandoned well (OR 5.43, 95% CI 2.88-10.26) and spray glyphosate (OR 5.12, 95% CI 2.33-11.26) as a pesticide. Water analysis showed significantly higher amount of hardness, electrical conductivity and glyphosate levels in abandoned wells. In addition Ca, Mg, Ba, Sr, Fe, Ti, V and Sr were high in abandoned wells. Surface water from reservoirs in the endemic area also showed contamination with glyphosate but at a much lower level. Glyphosate was not seen in water samples in the Colombo district. The current study strongly favors the hypothesis that CKDu epidemic among farmers in dry zone of Sri Lanka is associated with, history of drinking water from a well that was abandoned. In addition, it is associated with spraying glyphosate and other pesticides in paddy fields. Farmers do not use personnel protective equipments and wears scanty clothing due to heat when spraying pesticides.

Chronic Kidney Disease of unknown etiology (CKDu) has escalated into an epidemic in North Central Province (NCP) and adjacent farming areas in the dry zone of Sri Lanka. Studies have shown that this special type of CKD is a toxic nephropathy and arsenic may play a causative role along with a number of other heavy metals. We investigated the hypothesis that chemical fertilizers and pesticide could be a source of arsenic. 226 samples of Fertilizers and 273 samples of pesticides were collected and analyzed using atomic absorption spectrometry and inductively coupled plasma mass spectrometry for arsenic and other heavy metals in two university laboratories. Almost all the agrochemicals available to the farmers in the study area are contaminated with arsenic. The highest amount was in triple super phosphate (TSP) with a mean value of 31 mg/kg. Also TSP is a rich source of other nephrotoxic metals including Cr, Co, Ni, Pb and V. Annually more than 0.1 million tons of TSP is imported to Sri Lanka containing approximately 2100 kg of arsenic. The next highest concentration was seen in the rock phosphate obtained from an open pit mine in NCP (8.56 mg/kg). Organic fertilizer contained very low amounts of arsenic. Arsenic contamination in pesticides varied from 0.18 mg/kg to 2.53 mg/kg although arsenic containing pesticides are banned in Sri Lanka. Glyphosate the most widely used pesticide in Sri Lanka contains average of 1.9 mg/kg arsenic. Findings suggest that agrochemicals especially phosphate fertilizers are a major source of inorganic arsenic in CKDu endemic areas. Organic fertilizer available in Sri Lanka is comparatively very low in arsenic and hence the farmers in CKDu endemic areas in Sri Lanka should be encouraged to minimize the use of imported chemical fertilizer and use organic fertilizers instead.

Sri Lankan Agricultural Nephropathy (SAN), a new form of chronic kidney disease among paddy farmers was first reported in 1994. It has now become the most debilitating public health issue in the dry zone of Sri Lanka. Previous studies showed SAN is a tubulo-interstitial type nephropathy and exposure to arsenic and cadmium may play a role in pathogenesis of the disease. Urine samples of patients with SAN (N = 10) from Padavi-Sripura, a disease endemic area, and from two sets of controls, one from healthy participants (N = 10) from the same endemic area and the other from a non-endemic area (N = 10; Colombo district) were analyzed for 19 heavy metals and for the presence of the pesticide- glyphosate. In both cases and the controls who live in the endemic region, median concentrations of urinary Sb, As, Cd, Co, Pb, Mn, Ni, Ti and V exceed the reference range. With the exception of Mo in patients and Al, Cu, Mo, Se, Ti and Zn in endemic controls, creatinine adjusted values of urinary heavy metals and glyphosate were significantly higher when compared to non-endemic controls. Creatinine unadjusted values were significant higher for 14 of the 20 chemicals studied in endemic controls and 7 in patients, compared to non-endemic controls. The highest urinary glyphosate concentration was recorded in SAN patients (range 61.0-195.1 μg/g creatinine). People in disease endemic area exposed to multiple heavy metals and glyphosate. Results are supportive of toxicological origin of SAN that is confined to specific geographical areas. Although we could not localize a single nephrotoxin as the culprit for SAN, multiple heavy metals and glyphosates may play a role in the pathogenesis. Heavy metals excessively present in the urine samples of patients with SAN are capable of causing damage to kidneys. Synergistic effects of multiple heavy metals and agrochemicals may be nephrotoxic.

Objective Chronic Interstitial Nephritis in Agricultural Communities (CINAC) causes major morbidity and mortality for farmers in North-Central province (NCP) of Sri Lanka. To prevent the CINAC, reverse osmosis (RO) plants are established to purify the water and reduce the exposure to possible nephrotoxins through drinking water. We assessed RO plant maintenance and efficacy in NCP. Methods We have interviewed 10 RO plant operators on plant establishment, maintenance, usage and funding. We also measured total dissolved solids (TDS in ppm) to assess the efficacy of the RO process. Results Most RO plants were operated by community-based organizations. They provide clean and sustainable water source for many in the NCP for a nominal fee, which tends to be variable. The RO plant operators carry out RO plant maintenance. However, maintenance procedures and quality management practices tend to vary from an operator to another. RO process itself has the ability to lower the TDS of the water. On average, RO process reduces the TDS to 29 ppm. Conclusions The RO process reduces the impurities in water available to many individuals within CINAC endemic regions. However, there variation in maintenance, quality management, and day-to-day care between operators can be a cause for concern. This variability can affect the quality of water produced by RO plant, its maintenance cost and lifespan. Thus, uniform regulation and training is needed to reduce cost of maintenance and increase the efficacy of RO plants.