Health burden of sugarcane burning on agricultural workers and nearby communities.

Sugarcane is the most widely cultivated crop in the world, with equatorial developing nations performing most of this agriculture. Burning sugarcane is a common practice to facilitate harvest, producing extremely high volumes of respirable particulate matter in the process. These emissions are known to have deleterious effects on agricultural workers and nearby communities, but the extent of this exposure and potential toxicity remain poorly characterized. As the epidemicof chronic kidney disease of an unknown etiology (CKDu) and its associated mortality continue to increase along with respiratory distress, there is an urgent need to investigate the causes, determine viable interventions to mitigate disease andimprove outcomes for groups experiencing disproportionate impact. The goal of this review is to establish the state of available literature, summarize what is known in terms of human health risk, and provide recommendations for what areas should be prioritized in research.

Decreasing incidence of hospital diagnosed CKD/CKDu in North Central Province of Sri Lanka: is it related to provision of drinking water reverse osmosis plants?

BACKGROUND: We assessed the possible impact of provision of reverse osmosis (RO) water on the incidence of hospital diagnosed CKD/CKDu in North Central Province (NCP) of Sri Lanka. METHODS: An ecological study was conducted on data from 2010-2020 on the incidence of hospital diagnosed CKD/CKDu, CKD/CKDu screening and provision of drinking water RO plants in NCP. Analysis was conducted using descriptive statistics, ANOVA and chi-square test. RESULTS: The annual incidence of hospital diagnosed CKD/CKDu (per 100 000 population) in 2010-2013, 2014-2016 and 2017-2020 periods in Anuradhapura district were 129.07, 331.06 and 185.57 (p = 0.002) while in Polonnaruwa district these were 149.29, 326.12 and 296.73 (p = 0.04) respectively. In NCP provision of RO plants commenced after 2011 and the decline in the incidence of hospital diagnosed CKD/CKDu was seen in 25 of the 29 Divisional Secretary Divisions when more than 20% of the families received access to drinking RO water projects. CONCLUSIONS: The annual incidence of hospital diagnosed CKD/CKDu increased in NCP from 2010 to 2016 and continuously decreased thereafter. Continuous declining of CKD/CKDu incidence was seen after more than 20% of the families received access to drinking water RO plants.

Tubulointerstitial nephropathy is the predominant finding in men in a review of more than 3000 renal biopsies over a 10-year period from Sri Lanka.

BACKGROUND: Chronic kidney disease (CKD) is a significant clinical challenge in Sri Lanka. The present study presents histopathological diagnoses from native renal biopsies in Kandy District, 2011-2020. METHODS: Reports of 5,014 renal biopsies principally performed at Kandy Teaching Hospital over 2011-2020 were reviewed. After exclusions for post-kidney transplant biopsies (1,572) and those without evident pathology (347), 3,095 biopsies were included. The predominant histopathological entities were grouped and categorised according to diagnosis and stratified by age and sex. RESULTS: The main histopathological entities (all biopsies) were tubulointerstitial nephropathy (TIN) 25% (n = 760), glomerulonephritis (GN) 15% (467), lupus nephropathy 14% (429), focal segmental glomerular sclerosis (FSGS) 10% (297), and IgA nephropathy (IgAN) 8% (242). For adult women ≥ 15 years, the main histopathological entities were lupus nephropathy 24% (325), TIN 17% (228), and GN 16% (217). For adult men ≥ 15 years, the main histopathological entities were TIN 34% (449), GN 14% (180), and IgAN 10% (125). The proportion of TIN in the present study was higher than international studies of a similar size. CONCLUSION: This is the largest study of renal biopsies reported from Sri Lanka to date. TIN was the most common diagnosis in adults ≥ 15 years at 25%. Notable sex differences showed TIN was the most common histopathology in men (34%) but not in women (17%). No previously published similar study of this size has found TIN as the predominant diagnosis amongst renal biopsies in men. Further research is required into the possible causes of these observations in Sri Lanka. CLINICAL TRIAL NUMBER: Not applicable.

Heavy metal association with chronic kidney disease of unknown cause in central India-results from a case-control study.

BACKGROUND: Chronic Kidney Disease of unknown cause (CKDu) a disease of exclusion, and remains unexplained in various parts of the world, including India. Previous studies have reported mixed findings about the role of heavy metals or agrochemicals in CKDu. These studies compared CKDu with healthy controls but lacked subjects with CKD as controls. The purpose of this study was to test the hypothesis whether heavy metals, i.e. Arsenic (As), Cadmium (Cd), Lead (Pb), and Chromium (Cr) are associated with CKDu, in central India. METHODS: The study was conducted in a case-control manner at a tertiary care hospital. CKDu cases (n = 60) were compared with CKD (n = 62) and healthy subjects (n = 54). Blood and urine levels of As, Cd, Pb, and Cr were measured by Inductively Coupled Plasma- Optical Emission Spectrometry. Pesticide use, painkillers, smoking, and alcohol addiction were also evaluated. The median blood and urine metal levels were compared among the groups by the Kruskal-Wallis rank sum test. RESULTS: CKDu had significantly higher pesticide and surface water usage as a source of drinking water. Blood As levels (median, IQR) were significantly higher in CKDu 91.97 (1.3-132.7) µg/L compared to CKD 4.5 (0.0-58.8) µg/L and healthy subjects 39.01 (4.8-67.4) µg/L (p < 0.001) On multinominal regression age and sex adjusted blood As was independently associated with CKDu[ OR 1.013 (95%CI 1.003-1.024) P < .05].Blood and urinary Cd, Pb, and Cr were higher in CKD compared to CKDu (p > .05). Urinary Cd, Pb and Cr were undetectable in healthy subjects and were significantly higher in CKDu and CKD compared to healthy subjects (P = < 0.001). There was a significant correlation of Cd, Pb and Cr in blood and urine with each other in CKDu and CKD subjects as compared to healthy subjects. Surface water use also associated with CKDu [OR 3.178 (95%CI 1.029-9.818) p < .05). CONCLUSION: The study showed an independent association of age and sex adjusted blood As with CKDu in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were found to have significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu subjects had significantly higher pesticide and surface water usage, which may be the source of differential As exposure in these subjects.

Metabolome evidence of CKDu risks after chronic exposure to simulated Sri Lanka drinking water in zebrafish.

It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease.

Chemical characteristics and water stability evaluation of groundwater in the CKDu Zone of Sri Lanka.

Groundwater is the main source of drinking water for the rural population in the chronic kidney disease of unknown etiology (CKDu) zone of the North Central Province (NCP) in Sri Lanka. In this study, a total of 334 groundwater samples (311 dug wells, 21 tube wells and 2 springs) during the wet season from two aquifers in the NCP were collected, and investigated their chemical characteristics and evaluate their water quality, including groundwater chemistry, main ion sources, the corrosion and scaling potential of groundwater. The results showed that the two hydrochemical types of groundwater in the NCP were mainly of the Ca-HCO3, Na·Ca-HCO3 types, with the main HCO3-, Na+ and Ca2+ ions in both types of groundwater originating from silicate and evaporite salt dissolution and influenced by alternating cation adsorption, while the presence of NO3- was mainly anthropogenic. Evaluation of water stability using namely Langelier saturation index (LSI), Ryznar stability index (RSI), Puckorius scaling index (PSI) and Larson-Skold index (LS), indicated that most groundwater presents corrosion potential and has corrosion behavior tendency of metals to some degrees. The water quality of Polonnaruwa was better than that of Anuradhapura in the NCP, and when the groundwater was worse than the "good" grade, which must be properly treated before it is used as drinking water.

Clinical findings and kidney morphology in chronic kidney disease of unknown cause in India.

BACKGROUND: Chronic kidney disease of unknown cause (CKDu) is an emerging health problem in India and other countries worldwide. However, clinical descriptions, including kidney pathology, are scarce. METHODS: This is a descriptive case series of patients with CKDu from an endemic region in India, with a focus on clinical and biochemical characteristics, kidney biopsy findings, and environmental exposure. Patients with suspected CKDu, aged 20-65, and eGFR 30-80 mL/min/1.73 m2 from rural areas with endemic prevalence of CKDu were included. The exclusion criteria were diabetes mellitus, uncontrolled hypertension, proteinuria >1 g/24 h, or other known kidney diseases. The participants underwent kidney biopsies, and blood and urine samples were collected. RESULTS: Fourteen participants (3 females, 11 males) with a mean eGFR of 53 (range 29-78) mL/min/1.73 m2 were included. Kidney biopsies showed a combination of chronic tubulointerstitial damage, glomerulosclerosis, and glomerular hypertrophy, with varying degrees of interstitial inflammation. Eight participants had polyuria (diuresis ≥ 3 L/day). The urinary sediments were bland, with no haematuria. Serum potassium and sodium levels were, in most cases, normal but within the lower reference interval. CONCLUSION: The kidney morphology and clinical characteristics in patients with CKDu in India were similar to those described for CKDu in Central America and Sri Lanka.

The politics of glyphosate regulation: lessons from Sri Lanka's short-lived ban.

BACKGROUND: Glyphosate is the world's most used herbicide and a central component of modern industrial agriculture. It has also been linked to a variety of negative health and environmental effects. For instance, the International Agency for Research on Cancer classified glyphosate as "probably carcinogenic to humans" in 2015. This has motivated widespread political demands for stricter glyphosate regulation but so far few governments have followed through. METHODS: We conduct a case study of Sri Lanka, which in 2015 became the first and so far only country in the world to adopt and implement a complete glyphosate ban. But this ban proved to be short-lived, as it was partially reversed in 2018 (and later fully revoked in 2022). To explain the political causes of Sri Lanka's pioneering glyphosate ban and its subsequent reversal, we employ process tracing methods drawing on publicly available documents. Our analysis is theoretically guided by the multiple streams framework and the concept of self-undermining policy feedback. RESULTS: Glyphosate regulation rose to the top of the Sri Lankan political agenda in 2014 when a local scientist linked glyphosate exposure to an epidemic of Chronic Kidney Disease of Unknown Origin (CKDu). A glyphosate ban was eventually adopted in June 2015 by the newly elected government of Maithripala Sirisena. The ban was a political commitment made to the Buddhist monk Rathana Thero and his party, which had supported Sirisena during his presidential campaign. The ban's partial reversal in 2018, implemented through sectoral exceptions, was the result of continued lobbying by export-oriented plantation industries and increased political concerns about potential negative effects on the large and structurally powerful tea sector. The reversal was further aided by the scientific community's failure to corroborate the hypothesized link between glyphosate and CKDu. CONCLUSIONS: The case of Sri Lanka suggests that strict glyphosate regulation becomes more likely when coupled with locally salient health risks and when decision-making authority is de-delegated from regulatory agencies back to the political executive. Meanwhile, the short-lived nature of the Sri Lankan ban suggests that strict glyphosate regulation faces political sustainability threats, as the apparent lack of cost-effective alternative herbicides motivates persistent business lobbying for regulatory reversal.

Kidney disease characteristics, prevalence, and risk factors in León, Nicaragua: a population-based study.

BACKGROUND: CKD of unknown etiology (CKDu) disproportionately affects young people in Central America who lack traditional CKD risk factors (diabetes and hypertension) and has instead been variably linked to heat stress, occupational and environmental exposures, nephrotoxic medications, and/or genetic susceptibility. This study aimed to estimate the prevalence of CKD and identify risk factors for traditional CKD and CKDu in Nicaragua. METHODS: Surveys and assessment for CKD markers in urine and serum were performed in 15-59 year olds in households of the León municipality of Nicaragua. The survey included questions on demographics, health behaviors, occupation, and medical history. Participants with CKD were subdivided into traditional CKD and suspected CKDu based on history of diabetes, hypertension, or other specified conditions. A multinomial logistic regression model was used to identify factors associated with traditional CKD and suspected CKDu, compared to the non-CKD reference group. RESULTS: In 1795 study participants, CKD prevalence was 8.6%. Prevalence in males was twofold higher than females (12% vs 6%). Of those with CKD, 35% had suspected CKDu. Both traditional CKD and CKDu were associated with male sex and increasing age. Traditional CKD was associated with a family history of CKD, history of urinary tract infections, and lower socioeconomic status, while CKDu was associated with drinking well water and a lower body mass index. CONCLUSIONS: Both traditional CKD and CKDu are significant burdens in this region. Our study supports previous hypotheses of CKDu etiology and emphasizes the importance of CKD screening.

Association of Single Nucleotide Polymorphisms in KCNA10 and SLC13A3 Genes with the Susceptibility to Chronic Kidney Disease of Unknown Etiology in Central Indian Patients.

Global rise in the prevalence of endemic chronic kidney disease of unknown etiology (CKDu) possess major health issues. The prevalence of CKDu is also rising in the Indian population. Besides environmental factors, genetic factors play an important role in the predisposition to CKDu. In the present study, we have analyzed the association of single nucleotide polymorphisms (SNPs) in three genes with the susceptibility to CKDu. This was a case-control study with a total of 180 adult subjects (CKD = 60, CKDu = 60, Healthy = 60) from central India. We performed KASP genotyping assay to determine the allele frequency of SNP genotypes. We used the odds ratio (OR) to assess the association of individual SNPs, rs34970857 of KCNA10, rs6066043 of SLC13A3, and rs2910164 of miR-146a with CKDu and CKD susceptibility. In the case of rs34970857 of the KCNA10 gene, we noted a significantly increased OR for CKDu versus healthy control (Dominant model; CKDu versus control, CT + CC versus TT, OR = 3.96, p = 0.004). In the recessive and homozygous model, we observed significantly increased OR for rs6066043 of SLC13A3 gene, CKDu versus healthy control {(Recessive model; CKDu versus control, GG versus AA + GA, OR = 2.41, p = 0.03; homozygous model, GG versus AA, OR = 3.54, p = 0.04)}. CC genotype of rs34970857 of the KCNA10 gene and the GG genotype of the SLC13A3 gene are significantly associated with the susceptibility of CKDu.

Fluorescence characteristics and source analysis of DOM in groundwater during the wet season in the CKDu zone of North Central Province, Sri Lanka.

The dissolved organic matter (DOM) should be purified for safe drinking water due to disinfection by-products (DBPs) produced by disinfectants reaction with DOM. Current research on groundwater in the chronic kidney disease with unknown etiology (CKDu) zone of the North Central Province (NCP) in Sri Lanka has focused mainly on aquatic chemistry, with limited attention paid to the spatial distribution, compositional sources and factors of DOM. Therefore, the structure, composition, source and spatial distribution of the DOM of two kinds of groundwater samples collected from dug well and tube well in the NCP during the wet season were determined, compared and analyzed by analytical tools such as parallel factor analysis (PARAFAC). Results show that the average concentrations of TOC in these two groundwater samples are generally higher than 5.0 mg/L, and the concentration of TOC in the groundwater of the shallow weathered aquifer is higher than that of the deep hard rock aquifer, while its distribution of the two aquifers are on contrary. The DOM in the dug well has three types and four components, including humus-like component C1 (33.36%) and C2 (38.60%), protein-like component C3 (13.09%) and heterogeneous organic component C4 (14.95%). In the tube well, two types and two components of the DOM are determined, including humus-like component CⅠ (69.80%) widely existing in natural water and soluble microbial by-product CⅡ (30.20%) produced by microbial community activities. In the dug well, DOM is mainly exogenous input, the higher ion concentration in water affected the fluorescence intensity of humus and protein components. And in the tube well, DOM has obvious endogenous characteristics, and higher pH value may inhibit the production of protein like fluorescent substances to a certain extent.

Food-mediated exposure of Hofmeister ions in Oryza sativa (Rice) from selected CKDu endemic regions in Sri Lanka.

The objectives of this study were to determine selected Hofmeister anions and cations that are important for kidney health, in raw rice samples from selected Chronic Kidney Disease of unknown etiology (CKDu) endemic and non-endemic areas in Sri Lanka and their intake. The anions and cations were analyzed by Ion Chromatography and Microwave Plasma Atomic Emission Spectrometry (MP-AES), respectively, after alkaline and acid digestion in thirty raw rice samples each from CKDu endemic and non-endemic areas, and the dietary intake was estimated. The mean concentrations of fluoride (F-), chloride (Cl-), phosphate (PO43-), sulfate (SO42-), sodium (Na+), magnesium (Mg2+), potassium (K+), and calcium (Ca2+) in raw rice in CKDu endemic areas were 53.317, 1515.3, 2799.6, 2704.9, 30.603, 300.76, 1001.3, and 90.075 mg/kg, respectively. The mean concentration of the anions and cations in raw rice from CKDu non-endemic areas were 22.850, 947.52, 4418.7, 6080.2, 23.862, 364.45, 955.78, and 96.780 mg/kg, respectively. Significantly higher differences (p < 0.05) were reported in the mean concentration of F-, Cl-, and Na+ in raw rice from CKDu endemic areas in comparison with the samples from non-endemic areas. The aggregated estimated daily intake (EDI) and cumulative EDI of F- via consumption of cooked non-traditional samba rice from CKDu endemic areas for adults were the highest (0.155 and 0.172 mg/kg bw/d, respectively), which were higher than the recommended tolerable upper intake value (0.15-0.2 mg/kg bw/d). In contrast, the traditional rice from CKDu non-endemic areas for adolescents, reported the lowest values (0.0210 and 0.0470 mg/kg bw/d, respectively). Adults who consume non-traditional samba rice from CKDu endemic areas were at health risk, while children were the most vulnerable group due to their low body weight. These results indicate that the consumption of rice rich in Hofmeister ions may contribute to the total intake and act as risk factors to negatively affect weak kidneys in CKDu endemic areas. Further research to analyze Hofmeister ions in cooked rice and rice from different countries is recommended.

Rising of a global silent killer: critical analysis of chronic kidney disease of uncertain aetiology (CKDu) worldwide and mitigation steps.

Chronic kidney disease of uncertain aetiology (CKDu) is an advanced version of chronic kidney disease (CKD) which bears a high burden on the world health economy. More than 200 articles were analysed to understand the disease responsible for more than 30,000 deaths per year. CKDu is a non-communicable occupational disease that has a progressive deterioration of the kidney in the absence of CKD risk factors such as hypertension, diabetes and glomerulonephritis, while the diagnosis is only possible at the later stages when kidney function is no longer effective. Published evidence for the existence of CKDu was found for around 35 countries. This is a growing health issue in Asia, Central America, Africa and Middle East with identified hot spots. Despite many research studies over decades, the exact root causes are still uncertain. Six main suspected causative factors are identified. Those are heat stress, strenuous labour, dehydration, use of agrochemicals, exposure to heavy metals and the use of polluted water and agricultural lands. This review summarizes four key areas which are CKDu and its general medical background, worldwide prevalence, suspected causative factors and potential circumventing steps to mitigate against CKDu. The importance of further studies addressing early detection and surveillance methods, contribution of nephrotoxins in environmental health, soil chemistry on transporting nephrotoxins, geological parameters which influence the prevalence of the disease and other related sectors to overcome the mysterious nature is highlighted. Mitigation steps to lessen the burden of CKDu are also identified.

Significance of Mg-hardness and fluoride in drinking water on chronic kidney disease of unknown etiology in Monaragala, Sri Lanka.

The epidemic of chronic kidney disease of unknown etiology (CKDu) that contributes significantly to morbidity and mortality rates among dry-zonal farming communities has become a public health priority in Sri Lanka. Though a large number of hypotheses were introduced as causative factors, none of them have been confirmed so far. As drinking water quality is among the most suspected causative factors for the emergence of CKDu, a detailed hydro-geochemical investigation was carried out concurrently with the population screening in the Monaragala district of Sri Lanka where high incidences of CKDu are reported. A population screening was performed selecting 46,754 people using both dipstick proteinuria test and Albumin-Creatinine Ratio (ACR). The results revealed that the disease prevalence is about 6.7 % in the district. A total of 60 groundwater samples, 30 each, were collected from CKDu-prevalent locations and control locations where there are no CKDu cases reported. The samples were analyzed to identify any possible linkage between water quality and disease prevalence. Concentrations of hardness, F-, Na+, and Mg2+ in groundwater revealed a statistically significant difference between CKDu and control wells at a confident level of p = 0.05. The study revealed that alkali (Na++K+) and alkaline earth cations (Mg2+, Ca2+, Sr2+, Ba2+) were relatively higher in drinking water sources used by CKDu patients, compared to the well waters used by healthy individuals. Nearly 87 % of the wells used by CKDu cases showed higher fluoride levels that exceed the threshold level (1.0 mg L-1). Contents of nephrotoxic trace elements such as As, Cd, and Pb were found to be comparable in both types of wells and were well below the WHO permissible levels, thus negating their prime influence on the CKDu prevalence. It is obtrusive that the elevated fluoride levels together with water hardness associated with higher Mg2+ levels have a possible relation with CKDu and may influence the disease progression.

Dietary heavy metal(loid)s exposure and prevalence of chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka.

Intake of heavy metals and metalloids through the diet is posing a big research challenge in Sri Lanka due to the increasing occurrence of chronic kidney disease of unknown aetiology (CKDu) among the farming communities pursuing their livelihoods in the North Central Province (NCP). Duplicated diet studies were conducted on a sample of 62 individuals comprising adult males, adult females, boys, and girls who were selected following a demographic survey in an area of the NCP where there was a high incidence of CKDu. A health risk assessment was made by analysing the heavy metal(loid)s content in the diet samples, by means of inductively coupled plasma mass spectrometry. Rice and vegetables constituted the main diet in the CKDu prevalent areas, with all gender and age categories adhering to similar daily diet patterns. Results of the heavy metal(loid) analysis of duplicated food intake samples indicated that the amounts of Pb in rice, As and Pb in vegetables, and Cd in fish exceeded the recommended daily limits. Because consumption of rice was much higher than the other food items, the estimated daily intake of Pb exceeded the permissible daily intake of 3.5 µg/kgBW/day. There were no significant differences between the age and gender categories in respect of estimated daily intake of Pb, which suggested that the entire population of the study area faced the risk of a high level of Pb exposure. Further, the hazard quotient of Pb was greater than 1. Influence of heavy metal(loid)s on the prevalence of CKDu cannot be understated, and as such interventions are required as a matter of urgency to reduce the local population's dietary exposure to heavy metal(loid)s.

Major and trace elements in rice paddy soils in Sri Lanka with special emphasis on regions with endemic chronic kidney disease of undetermined origin.

Environmental exposure to trace elements has been widely suspected as an etiological factor for the emergence of chronic kidney disease of undetermined origin (CKDu) that prevails in certain districts of the dry zone areas of Sri Lanka. Contaminated rice can be act as a host for potentially toxic trace elements that ultimately led to health hazards; thus, rice soils were investigated in detail, giving particular attentions to identified CKDu hotspots. A total of 102 rice soil samples were collected from main climatic zones viz. wet and dry zones including CKDu hotspots. In addition to pH, electrical conductivity and cation exchange capacity, acid extracted major and trace element contents in rice soils were determined by using ICP-MS. Significant differences were observed for Mn, Ni, Cu, Zn, and Pb contents between climatic zones. Arsenic and Pb contents in soils were lower than the levels reported in soils from other regions of the world, though significantly higher contents were observed in CKDu regions compared to non-endemic wet zone regions. Calculation of enrichment factor revealed that soils in both dry and wet zones were moderately enriched with As, Cd, and Pb, suggesting an influence of anthropogenic processes. Twenty percent of the wet zone samples showed significant enrichment of Ni, Cu, and Zn. Geo-accumulation index assorted that the studied soil samples were uncontaminated to moderately contaminated, implying that rice soils in both climatic zones are not alarmingly contaminated with toxic trace elements. However, regular and continuous monitoring of rice soil quality is extremely important.

Urine tungsten and chronic kidney disease in rural Colorado.

BACKGROUND: Chronic kidney disease (CKD) is a cause of global morbidity and mortality in agricultural communities. The San Luis Valley (SLV) is a rural agricultural community in southern Colorado with geographic and sociodemographic risk factors for CKD, including a water supply contaminated by heavy metals. METHODS: We obtained pre-existing sociodemographic, clinical, and urine trace metal data for 1659 subjects from the San Luis Valley Diabetes Study, a prospective cohort study. We assessed prospective associations between urine tungsten (W) and time-to-CKD using accelerated failure time models (n = 1659). Additionally, logistic models were used to assess relationships between urine W and renal injury markers (NGAL, KIM1) using Tobit regression (n = 816), as well as epidemiologically-defined CKD of unknown origin (CKDu) using multiple logistic regression (n = 620). RESULTS: Elevated urine W was strongly associated with decreased time-to-CKD, even after controlling for hypertension and diabetes. Depending on how CKD was defined, a doubling of urine W was associated with a 27% (95% CI 11%, 46%) to 31% (14%, 51%) higher odds of developing CKD within 5 years. The relationship between urine W and select renal injury markers was not significant, although urine NGAL was modified by diabetes status. Elevated (>95%ile) urinary W was significantly associated with CKDu (OR 5.93, 1.83, 19.21) while adjusting for known CKD risk factors. CONCLUSIONS: Our data suggest that increased exposure to W is associated with decreased time-to-CKD and may be associated with CKDu. Given persistence of associations after controlling for diabetes and hypertension, W may exert a primary effect on the kidney, although this needs to be evaluated further in future studies.

Pilot study determining the feasibility of implementing the Disadvantaged Populations eGFR Epidemiology Study (DEGREE) protocol, point-of-care field measurements and a new module on risk factors for chronic kidney disease of unknown origin in Hispanic outdoor workers.

BACKGROUND: To field test the Disadvantaged Populations eGFR Epidemiology (DEGREE) protocol, outdoor point-of-care (POC) testing for serum creatinine, and a new risk factor module on chronic kidney disease of undetermined origin (CKDu) in U.S. outdoor Hispanic workers. METHODS: Fifty workers were interviewed in Houston (TX). DEGREE and CKDu questionnaires were completed indoors. Anthropometrics and paired blood samples for POC and laboratory assay were completed outdoors over two periods (November-December 2017, April-May 2018). RESULTS: Administration of DEGREE and CKDu questionnaires averaged 10 and 5 min, respectively, with all questions easily understood. We observed high correlations between POC and IDMS creatinine (r = 0.919) and BUN (r = 0.974). The POC device would disable testing when outdoor temperatures were above 85 °F or below 65 °F; this was adjustable. CONCLUSIONS: Implementation of DEGREE and the new CKDu module was straightforward and well understood. The POC device performed well in the field, with some adjustment in methods when temperature readings were out of range.

CKD and CKDu in northern Peru: a cross-sectional analysis under the DEGREE protocol.

BACKGROUND: This study estimated the prevalence and risk factors for decreased estimated glomerular filtration rate (eGFR) in those without known hypertension, type 2 diabetes mellitus, or heavy proteinuria as a surrogate marker for chronic kidney disease of unknown cause (CKDu) among adults in the North of Peru. METHODS: A cross-sectional study was conducted following the Disadvantaged Populations eGFR Epidemiology (DEGREE) Study protocol. Low eGFR was defined based on a single eGFR ≤60 mL/min/1.7m2 estimated using the CKD-EPI equation. Environmental conditions related to CKDu (i.e., work in agriculture or sugarcane, water source, heat intolerance, and pesticide exposure) were evaluated, in addition to traditional risk factors for CKD (i.e., smoking, heavy drinking, physical activity, hypertension, type 2 diabetes mellitus, urolithiasis, among others). RESULTS: A total of 1514 subjects were included in the study, mean age 45.1 (SD: 16.4), and 55.2% were females. Overall, only 26 cases (1.7%; 95%CI: 1.1-2.5%) had an eGFR < 60 mL/min/1.7m2 compatible with CKD definition; when those with hypertension and type-2 diabetes or heavy proteinuria were excluded, according to the DEGREE protocol, the estimate fell to 0.9% (95%CI: 0.4-1.5%). Low physical activity levels (OR = 1.99; 95%CI: 1.18-3.34), hypertension (OR = 2.07; 1.26-3.41), and urolithiasis (OR = 1.97; 95%CI: 1.18-3.27) were factors associated with low eGFR. CONCLUSIONS: A low population-based prevalence of low eGFR (as a surrogate for CKDu), both in rural and urban settings areas, in the Northern Peru, was found. Low physical activity levels, hypertension and urolithiasis were factors associated with low eGFR. Interventions to prevent CKD cases may be focused on well-known CV risk factors and urolithiasis.

An ecological study of chronic kidney disease in five Mesoamerican countries: associations with crop and heat.

BACKGROUND: Mesoamerica is severely affected by an epidemic of Chronic Kidney Disease of non-traditional origin (CKDnt), an epidemic with a marked variation within countries. We sought to describe the spatial distribution of CKDnt in Mesoamerica and examine area-level crop and climate risk factors. METHODS: CKD mortality or hospital admissions data was available for five countries: Mexico, Guatemala, El Salvador, Nicaragua and Costa Rica and linked to demographic, crop and climate data. Maps were developed using Bayesian spatial regression models. Regression models were used to analyze the association between area-level CKD burden and heat and cultivation of four crops: sugarcane, banana, rice and coffee. RESULTS: There are regions within each of the five countries with elevated CKD burden. Municipalities in hot areas and much sugarcane cultivation had higher CKD burden, both compared to equally hot municipalities with lower intensity of sugarcane cultivation and to less hot areas with equally intense sugarcane cultivation, but associations with other crops at different intensity and heat levels were not consistent across countries. CONCLUSION: Mapping routinely collected, already available data could be a first step to identify areas with high CKD burden. The finding of higher CKD burden in hot regions with intense sugarcane cultivation which was repeated in all five countries agree with individual-level studies identifying heavy physical labor in heat as a key CKDnt risk factor. In contrast, no associations between CKD burden and other crops were observed.