Ethical considerations for genetic research in low-income countries: perceptions of informed consent, data sharing, and expectations in Nicaragua.

Genetic research presents numerous ethical, legal, and social implications (ELSI), particularly when the research involves collaborations between investigators in high and low-income countries. Some ELSI issues are universal, and others are specific to context and culture. This study investigates perceptions of genetic research in Nicaragua, Central America, where local and U.S. based researchers have collaborated for over a decade. A total of 43 residents from northwestern Nicaragua, a region with high mortality rates attributed to chronic kidney disease of non-traditional causes (CKDnt), were interviewed, including research participants in ongoing studies (n = 36), health professionals (n = 3), labor leaders (n = 2), and family members of research participants (n = 2). Questions focused on informed consent, data-sharing, and post-study expectations. Audio recordings of interviews conducted in Spanish were transcribed and translated into English. English transcripts were coded and analyzed using NVivo 12 software. The lack of familiarity with terms in the consent form presented a barrier to participant comprehension of key elements of the genetic research study, raising concerns about the validity of informed consent. Research participants often viewed their participation as access to health care. Health professionals emphasized the importance of long-term partnerships between foreign-based researchers and local health institutions. Leaders and family members recommended that they be informed of research studies and allowed the opportunity to consent, as they felt the benefits and risks of research also apply to them. Our findings identified genetic research practices to be improved upon in order to be more responsive to the contextual realities of collaborators living in low-resource settings.

Heat stress and heat strain among outdoor workers in El Salvador and Nicaragua.

BACKGROUND: There is growing attention on occupational heat stress in Central America, as workers in this region are affected by a unique form of chronic kidney disease. Previous studies have examined wet bulb globe temperatures and estimated metabolic rates to assess heat stress, but there are limited data characterizing heat strain among these workers. OBJECTIVE: The aims were to characterize heat stress and heat strain and examine whether job task, break duration, hydration practices, and kidney function were associated with heat strain. METHODS: We used data from the MesoAmerican Nephropathy Occupational Study, a cohort of 569 outdoor workers in El Salvador and Nicaragua who underwent workplace exposure monitoring, including continuous measurement of core body temperature (Tc), heart rate (HR), physical activity, and wet bulb globe temperature (WBGT), over the course of three days in January 2018 - May 2018. Participants represented five industries: sugarcane, corn, plantain, brickmaking, and construction. RESULTS: Median WBGTs were relatively high (>27 °C) at most sites, particularly when work shifts spanned the afternoon hours (e.g., 29.2 °C among plantain workers). Sugarcane workers, especially cane cutters in both countries and Nicaraguan agrichemical applicators, had the highest estimated metabolic rates (medians: 299-318 kcal/hr). Most workers spent little time on break (<10% of the shift), as determined by physical activity data. Overall, sugarcane workers-particularly those in Nicaragua-experienced the highest Tc and HR values. However, a few workers in other industries reached high Tc (>39 °C) as well. Impaired kidney function (estimated glomerular filtration rate <90 mL/min/1.73 m2) was associated with higher Tc and HR values, even after adjustment. SIGNIFICANCE: This is the largest study to-date examining heat stress and strain among outdoor workers in Central America. Workers at sugar companies regularly experienced Tc > 38°C (76.9% of monitored person-days at Nicaraguan companies; 46.5% at Salvadoran companies). Workers with impaired kidney function had higher measures of Tc and HR. IMPACT STATEMENT: This study examined levels of occupational heat stress and heat strain experienced among outdoor workers in five industries in El Salvador and Nicaragua. We characterized heat stress using wet bulb globe temperatures and estimated metabolic rate and heat strain using core body temperature and heart rate. Sugarcane workers, particularly cane cutters and Nicaraguan agrichemical applicators, performed more strenuous work and experienced greater levels of heat strain. Impaired kidney function was associated with higher heart rates and core body temperatures.

Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (n = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (n = 78); Nicaraguans performing non-agricultural work (n = 102); and agricultural workers in Spain (n = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (p = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings.

Point-of-Care Testing in Chronic Kidney Disease of Non-Traditional Origin: Considerations for Clinical, Epidemiological, and Health Surveillance Research and Practice.

Purpose: As the prevalence of chronic kidney disease of non-traditional origin (CKDnt) rises in low-resource settings, there is a need for reliable point-of-care creatinine testing. The purpose of this analysis was to assess the accuracy of two commonly used point-of-care creatinine devices, the i-STAT handheld (Abbott, Princeton, NJ, USA) and the StatSensor Creatinine (Nova Biomedical, Waltham, MA, USA) in comparison to venipuncture serum creatinine measures. The affordability, sensitivity, specificity, ease of use, and other considerations for each device are also presented. Methods: Three paired data sets were compared. We collected 213 paired i-STAT and venipuncture samples from a community study in Nicaragua in 2015-2016. We also collected 267 paired StatSensor Creatinine and venipuncture samples, including 158 from a community setting in Nicaragua in 2014-2015 and 109 from a Guatemala sugarcane worker cohort in 2017-2018. Pearson correlation coefficients, Bland-Altman plots, and no intercept linear regression models were used to assess agreement between point-of-care devices and blood samples. Results: The i-STAT performed the most accurately, overestimating creatinine by 0.07 mg/dL (95% CI: 0.02, 0.12) with no evidence of proportional bias. The StatSensor Creatinine performed well at low levels of creatinine (Mean (SD): 0.87 (0.19)). Due to proportional bias, the StatSensor Creatinine performed worse in the Nicaragua community setting where creatinine values ranged from 0.31 to 7.04 mg/dL. Discussion: Both devices provide acceptable sensitivity and specificity. Although adequate for routine surveillance, StatSensor Creatinine is less accurate as the values of measured creatinine increase, a consideration when using the point-of-care device for screening individuals at risk for CKDnt. Research, clinical, and screening objectives, cost, ease of use, and background prevalence of disease must all be carefully considered when selecting a point-of-care creatinine device. Conclusion: POC testing can be more accessible in resource-limited settings. The selection of the appropriate device will depend on the use-case.

High prevalence of chronic kidney disease of unknown etiology among workers in the Mesoamerican Nephropathy Occupational Study.

BACKGROUND: Mortality from chronic kidney disease of unknown etiology (CKDu) is extremely high along the Pacific coast of Central America, particularly among sugarcane workers. The Mesoamerican Nephropathy Occupational Study (MANOS) is a prospective cohort study of CKDu among agricultural and non-agricultural workers in El Salvador and Nicaragua. The objective of this manuscript is to describe the MANOS cohort recruitment, baseline data collection, and CKDu prevalence after two rounds. METHODS: Workers with no known diabetes, hypertension, or CKD were recruited from sugarcane, corn, plantain, brickmaking, and road construction industries (n = 569). Investigators administered questionnaires, collected biological samples, and observed workers for three consecutive workdays at the worksite. Serum specimens were analyzed for kidney function parameters, and used to calculate estimated glomerular filtration rate (eGFR). At six months, serum was collected again prior to the work shift. CKD at baseline is defined as eGFR ≤ 60 ml/min/1.73m2 at both timepoints. Age-standardized prevalence was calculated by industry, country, and demographic measures. Kidney function parameters were compared by CKD status. RESULTS: Prevalence of CKD at baseline was 7.4% (n = 42). Age-standardized prevalence was highest in Salvadoran sugarcane (14.1%), followed by Salvadoran corn (11.6%), and Nicaraguan brickmaking (8.1%). Nicaraguan sugarcane had the lowest prevalence, likely due to kidney function screenings prior to employment. CONCLUSION: Despite efforts to enroll participants without CKD, our identification of prevalent CKD among agricultural and non-agricultural workers in the MANOS cohort indicates notable kidney disease in the region, particularly among sugarcane workers.

Climate Trends at a Hotspot of Chronic Kidney Disease of Unknown Causes in Nicaragua, 1973-2014.

An ongoing epidemic of chronic kidney disease of uncertain etiology (CKDu) afflicts large parts of Central America and is hypothesized to be linked to heat stress at work. Mortality rates from CKDu appear to have increased dramatically since the 1970s. To explore this relationship, we assessed trends in maximum and minimum temperatures during harvest months between 1973 and 2014 as well as in the number of days during the harvest season for which the maximum temperature surpassed 35 °C. Data were collected at a weather station at a Nicaraguan sugar company where large numbers of workers have been affected by CKDu. Monthly averages of the daily maximum temperatures between 1996 and 2014 were also compared to concurrent weather data from eight Automated Surface Observing System Network weather stations across Nicaragua. Our objectives were to assess changes in temperature across harvest seasons, estimate the number of days that workers were at risk of heat-related illness and compare daily maximum temperatures across various sites in Nicaragua. The monthly average daily maximum temperature during the harvest season increased by 0.7 °C per decade between 1973 and 1990. The number of days per harvest season with a maximum temperature over 35 °C increased by approximately five days per year between 1974 and 1990, from 32 days to 114 days. Between 1991 and 2013, the number of harvest days with a maximum temperature over 35 °C decreased by two days per year, and the monthly average daily maximum temperature decreased by 0.3 °C per decade. Comparisons with weather stations across Nicaragua demonstrate that this company is located in one of the consistently hottest regions of the country.

Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy.

OBJECTIVES: Nicaraguan sugarcane workers, particularly cane cutters, have an elevated prevalence of chronic kidney disease of unknown origin, also referred to as Mesoamerican nephropathy (MeN). The pathogenesis of MeN may include recurrent heat stress, crystalluria, and muscle injury with subsequent kidney injury. Yet, studies examining the frequency of such events in long-term, longitudinal studies are limited. METHODS: Using employment and medical data for male workers at a Nicaraguan sugarcane company, we classified months of active work as either work as a cane cutter or other sugarcane job and determined occurrence of dysuria, heat events and muscle events. Work months and events occurred January 1997 to June 2010. Associations between cane cutting and each outcome were analyzed using logistic regression based on generalized estimating equations for repeated events, controlling for age. RESULTS: Among 242 workers with 7257 active work months, 19.5% of person-months were as a cane cutter. There were 160, 21, and 16 episodes of dysuria, heat events, and muscle events, respectively. Compared with work months in other jobs, cane cutting was associated with an elevated odds of dysuria [odds ratio 2.40 (95% confidence interval 1.56-3.68)]. The number of heat and muscle events by cane cutter and other job were limited. CONCLUSIONS: Working as a cane cutter compared with other jobs in the sugarcane industry was associated with increased dysuria, supporting the hypothesis that cane cutters are at increased risk of events suspected of inducing or presaging clinically evident kidney injury.

Urinary Metals Concentrations and Biomarkers of Autoimmunity among Navajo and Nicaraguan Men.

Metals are suspected contributors of autoimmune disease among indigenous Americans. However, the association between metals exposure and biomarkers of autoimmunity is under-studied. In Nicaragua, environmental exposure to metals is also largely unexamined with regard to autoimmunity. We analyzed pooled and stratified exposure and outcome data from Navajo (n = 68) and Nicaraguan (n = 47) men of similar age and health status in order to characterize urinary concentrations of metals, compare concentrations with the US National Health and Nutrition Examination Survey (NHANES) male population, and examine the associations with biomarkers of autoimmunity. Urine samples were analyzed for metals via inductively coupled plasma mass spectrometry (ICP-MS) at the US Centers for Disease Control and Prevention. Serum samples were examined for antinuclear antibodies (ANA) at 1:160 and 1:40 dilutions, using an indirect immunofluorescence assay and for specific autoantibodies using enzyme-linked immunosorbent assay (ELISA). Logistic regression analyses evaluated associations of urinary metals with autoimmune biomarkers, adjusted for group (Navajo or Nicaraguan), age, and seafood consumption. The Nicaraguan men had higher urinary metal concentrations compared with both NHANES and the Navajo for most metals; however, tin was highest among the Navajo, and uranium was much higher in both populations compared with NHANES. Upper tertile associations with ANA positivity at the 1:160 dilution were observed for barium, cesium, lead, strontium and tungsten.

Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane Workers.

Background: An epidemic of CKD in Central America predominantly affects males working in certain industries, including sugarcane. Urinary tract infections are commonly diagnosed among men in Nicaragua, who often receive antibiotics and nonsteroidal anti-inflammatory drugs for urinary symptoms. Methods: We followed 251 male Nicaraguan sugarcane workers in seven job tasks over one harvest and measured urine dipstick parameters, kidney injury biomarkers, and eGFR. We administered a questionnaire about urinary symptoms, health-related behaviors, and medication history. We cultured urine in a subset of workers. Results: The study population was composed of factory workers (23%), cane cutters (20%), irrigators (20%), drivers (16%), agrichemical applicators (12%), seeders/reseeders (6%), and seed cutters (4%). The mean age of participants was 33.9 years, and mean employment duration was 10.1 years. Cane cutters reported higher proportions of urinary-related symptoms compared with agrichemical applicators, irrigators, and seeders/reseeders. Seed cutters were more likely to take antibiotics (22%), whereas drivers and seeders/reseeders were more likely to take pain medications (27% and 27%, respectively). Proteinuria was uncommon, whereas dipstick leukocyte esterase was relatively common, especially among cane cutters, seed cutters, and seeders/reseeders (33%, 22%, and 21% at late harvest, respectively). Dipstick leukocyte esterase at late harvest was associated with a 12.9 ml/min per 1.73 m2 (95% CI, -18.7 to -7.0) lower mean eGFR and 2.8 times (95% CI, 1.8 to 4.3) higher mean neutrophil gelatinase-associated lipocalin. In general, workers who reported urinary-related symptoms had higher mean kidney injury biomarker levels at late harvest. None of the workers had positive urine cultures, including those reporting urinary symptoms and/or with positive leukocyte esterase results. Amoxicillin, ibuprofen, and acetaminophen were the most commonly used medications. Conclusions: Job task is associated with urinary symptoms and dipstick leukocyte esterase. Urinary tract infection is misdiagnosed based on leukocyte esterase, which may be an important predictor of kidney outcomes.

Investigating Possible Infectious Causes of Chronic Kidney Disease of Unknown Etiology in a Nicaraguan Mining Community.

A chronic kidney disease of unknown etiology (CKDu) has been killing workers in Central America. Occupational heat stress is thought to play an important role. Leptospirosis and hantavirus have been suggested as additional possible risk factors. In a case-control study in a Nicaraguan mining community, a structured survey was administered to adults, and biological measurements and specimens were taken. Serum was analyzed for antibodies to Leptospira and hantavirus. Before statistical analysis, a board-certified nephrologist determined final case and control status based on serum creatinine and other laboratory values. Multivariable analysis was by logistic regression. In sensitivity analyses, cases were restricted to those diagnosed with CKDu in the previous 3 years. Of 320 eligible participants, 112 were classified as presumptive cases, 176 as controls and 32 as indeterminant. The risk of CKDu in those ever having worked in mining or construction was 4.4 times higher than in other participants (odds ratio = 4.44, 95% CI: 1.96-10.0, P = 0.0003). Eighty-three (26%) of the 320 participants were seropositive for at least one tested strain of Leptospira. No evidence of a causal link between leptospirosis or hantavirus and CKDu was found. The sensitivity analyses provide some evidence against the hypotheses that leptospirosis or hantavirus leads to CKDu within a few years. A major limitation was the impossibility of determining the absolute or relative timing of infection and CKDu onset. A prospective cohort design, with repeated collection of specimens over several years, could yield clearer answers about infections as potential etiologic agents in CKDu.

Prevalence and Risk Factors for CKD Among Brickmaking Workers in La Paz Centro, Nicaragua.

RATIONALE & OBJECTIVE: In Central America, there is a high prevalence of chronic kidney disease (CKD) of nontraditional etiology often observed among agricultural workers. Few studies have assessed CKD prevalence among workers in nonagricultural occupations, which was the objective of this investigation. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Male and female workers (n = 224) employed by artisanal brickmaking facilities in La Paz Centro, Nicaragua. PREDICTORS: Age, sex, education, smoking status, body mass index, alcohol consumption, water consumption, first-degree relative(s) with CKD, years worked, hours worked per week, job category, study visit (baseline and follow-up), and self-reported hypertension and diabetes. OUTCOMES: CKD defined as estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m2 at 2 time points 4 months apart and CKD stage. ANALYTICAL APPROACH: A linear mixed-effects model with an unstructured covariance matrix was used to evaluate the association between demographics, occupational risk factors, and eGFR at baseline. The interaction between risk factors and time with change in eGFR was also evaluated. Multivariable logistic regression models were used to evaluate predictors of CKD. RESULTS: The CKD prevalence was 12.1% (n = 27), 100% of cases were male, 30% had stage 5 CKD (eGFR < 15mL/min/1.73m2), and 22% were younger than 35 years. Proportions of participants with eGFRs < 60mL/min/1.73m2 at baseline and follow-up were 13.8% and 15.2%, respectively. Linear regression analysis demonstrated significant predictors of lower kidney function at baseline including oven work, older age, lack of education, and having an immediate family member with CKD. Predictors of CKD identified using logistic regression analysis included oven work and lack of education. LIMITATIONS: Crude job classification measures, loss to follow-up, self-reported exposures. CONCLUSIONS: The prevalence of CKD is high in this population of brick workers, suggesting that the epidemic of CKD affecting Mesoamerica is not limited to agricultural workers. These results are consistent with the hypothesis that occupational heat exposure is a risk factor for kidney disease in this region.

Acute Kidney Injury in Sugarcane Workers at Risk for Mesoamerican Nephropathy.

RATIONALE & OBJECTIVE: Mesoamerican nephropathy (MeN), a form of chronic kidney disease (CKD) of unknown cause in Central America, affects young individuals working in physically strenuous occupations. Repeated episodes of work-related kidney injury may lead to CKD in this setting. We aimed to better understand the burden and natural history of acute kidney injury (AKI) in workers at risk for MeN. STUDY DESIGN: Cross-sectional study of active sugarcane workers, followed by prospective follow-up of individuals with AKI. SETTING & PARTICIPANTS: 326 sugarcane workers with normal preharvest serum creatinine (Scr) values and no history of CKD in an MeN hotspot in Nicaragua near the end of the harvest, and prospective follow-up of workers with AKI. PREDICTOR: AKI during the harvest, as defined by Scr level increase ≥ 0.3mg/dL over baseline to a level ≥ 1.3mg/dL. OUTCOMES: Kidney function trajectory and development of CKD over 12 months. ANALYTICAL APPROACH: Linear regression models were used to analyze the association between job category and kidney function. For workers with AKI, the effect of time on Scr level was evaluated using linear mixed effects. RESULTS: 34 of 326 participants were found to have AKI, with a median late-harvest Scr level of 1.64mg/dL in the AKI group. Workers without AKI had a median Scr level of 0.88mg/dL. AKI was more common among cane cutters compared with other field workers. Participants with AKI had variable degrees of kidney function recovery, with median 6- and 12-month Scr values of 1.25 and 1.27mg/dL, respectively (P < 0.001 for each follow-up value compared to late-harvest Scr). When we compared workers' kidney function before the AKI episode to their kidney function at last follow-up, 10 participants with AKI developed de novo estimated glomerular filtration rate < 60mL/min/1.73m2 and 11 had a >30% decrease in estimated glomerular filtration rate. LIMITATIONS: Follow-up limited to 1 year and some loss to follow-up in the prospective component of the study. Broad definition of AKI that includes both acute and subacute kidney injury. CONCLUSIONS: In a group of sugarcane workers with normal preharvest kidney function, newly decreased kidney function developing during the harvest season was common. Of those with kidney injury, nearly half had established CKD 12 months later.

Leptospira seropositivity as a risk factor for Mesoamerican Nephropathy.

BACKGROUND: Leptospirosis is postulated as a possible cause of Mesoamerican Nephropathy (MeN) in Central American workers. OBJECTIVES: Investigate job-specific Leptospira seroprevalence and its association with kidney disease biomarkers. METHODS: In 282 sugarcane workers, 47 sugarcane applicants and 160 workers in other industries, we measured anti-leptospiral antibodies, serum creatinine, and urinary injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and N-acetyl-D-glucosaminidase (NAG). RESULTS: Leptospira seroprevalence differed among job categories and was highest among sugarcane cutters (59%). Seropositive sugarcane workers had higher NGAL concentrations (relative mean: 1.28; 95% CI: 0.94-1.75) compared to those who were seronegative, with similar findings among field and non-field workers. CONCLUSIONS: Leptospira seroprevalence varied by job category. There was some indication that seropositivity was associated with elevated biomarker levels, but results were inconsistent. Additional studies may help establish whether Leptospira infection plays any role in MeN among Central American workers.

Characterization of Mesoamerican Nephropathy in a Kidney Failure Hotspot in Nicaragua.

BACKGROUND: Mesoamerican nephropathy (MeN) is a kidney disease of unknown cause that mainly affects working-age men in Central America. Despite being a major cause of morbidity and mortality in this region, its clinical characteristics have not been well defined. STUDY DESIGN: Cross-sectional family-based study. SETTING & PARTICIPANTS: 266 members of 24 families with high chronic kidney disease (CKD) burdens in a MeN hotspot in Northwestern Nicaragua. We compared clinical and biochemical characteristics of affected individuals first with their unaffected relatives and then with NHANES (National Health and Nutrition Examination Survey) participants with CKD in order to reveal identifying features of MeN. PREDICTOR: CKD defined as serum creatinine level ≥ 1.5mg/dL in men and ≥1.4mg/dL in women. OUTCOMES: Clinical and biochemical parameters, including serum sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, and uric acid. RESULTS: Hyperuricemia, in many cases severe, was common among patients with MeN. Uric acid levels in patients with MeN were higher than those in NHANES participants (mean, 9.6 vs 7.4mg/dL for men in each group) despite more frequent use of uric acid-lowering medications in Nicaraguan individuals (71.7% vs 11.2%). In multivariable linear mixed-effects regression analysis, uric acid levels were 2.0mg/dL (95% CI, 1.0-3.0; P<0.001) higher in patients with MeN compared with their NHANES counterparts after adjusting for age, estimated glomerular filtration rate, and uric acid-lowering therapies. In contrast to prior reports, hyponatremia and hypokalemia were not common. LIMITATIONS: CKD defined by single serum creatinine measurement; population likely not representative of full MeN phenotype spectrum across Central America; major differences between MeN and NHANES groups in important characteristics such as age, ancestry, and recruitment method. CONCLUSIONS: Hyperuricemia out of proportion to the degree of decreased kidney function was common among Nicaraguan patients with MeN. Our results suggest that rather than being solely a consequence of CKD, hyperuricemia may play a role in MeN pathogenesis, a hypothesis that deserves further study.

Urine biomarkers of kidney injury among adolescents in Nicaragua, a region affected by an epidemic of chronic kidney disease of unknown aetiology.

BACKGROUND: An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recognized by health authorities as a public health priority in Central America. Previous studies have identified strenuous manual work, agricultural activities and residence at low altitude as potential risk factors; however, the aetiology remains unknown. Because individuals are frequently diagnosed with CKD in early adulthood, we measured biomarkers of kidney injury among adolescents in different regions of Nicaragua to assess whether kidney damage might be initiated during childhood. METHODS: Participants include 200 adolescents aged 12-18 years with no prior work history from four different schools in Nicaragua. The location of the school served as a proxy for environmental exposures and geographic locations were selected to represent a range of factors that have been associated with CKD in adults (e.g. altitude, primary industry and CKD mortality rates). Questionnaires, urine dipsticks and kidney injury biomarkers [interleukin-18, N-acetyl-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and albumin-creatinine ratio] were assessed. Biomarker concentrations were compared by school using linear regression models. RESULTS: Protein (3.5%) and glucose (1%) in urine measured by dipstick were rare and did not differ by school. Urine biomarkers of tubular kidney damage, particularly NGAL and NAG, showed higher concentrations in those schools and regions within Nicaragua that were defined a priori as having increased CKD risk. Painful urination was a frequent self-reported symptom. CONCLUSIONS: Although interpretation of these urine biomarkers is limited because of the lack of population reference values, results suggest the possibility of early kidney damage prior to occupational exposures in these adolescents.

Biomarkers of Kidney Injury Among Nicaraguan Sugarcane Workers.

BACKGROUND: In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: 284 sugarcane workers in 7 jobs were recruited from one company in northwestern Nicaragua. Blood and urine samples were collected before and near the end of the 6-month harvest season. PREDICTORS: Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake. OUTCOMES & MEASUREMENTS: Changes in levels of urinary kidney injury biomarkers normalized to urine creatinine level, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-ß-d-glucosaminidase (NAG), and albumin; serum creatinine-based estimated glomerular filtration rate (eGFR). RESULTS: Mean eGFR was 113 mL/min/1.73 m(2) and <5% of workers had albuminuria. Field workers had increases in NGAL and IL-18 levels that were 1.49 (95% CI, 1.06 to 2.09) and 1.61 (95% CI, 1.12 to 2.31) times as high, respectively, as in non-field workers. Cane cutters and irrigators had the greatest increases in NGAL levels during the harvest, whereas cane cutters and seeders had the greatest increases in IL-18 levels. Electrolyte solution consumption was associated with lower mean NGAL and NAG levels among cane cutters and lower mean IL-18 and NAG levels among seed cutters; however, there was no overall effect of hydration among all workers. On average, workers with the largest increases in NGAL and NAG levels during the harvest had declines in eGFRs of 4.6 (95% CI, 1.0 to 8.2) and 3.1 (95% CI, -0.6 to 6.7) mL/min/1.73 m(2), respectively. LIMITATIONS: Surrogate exposure measure, loss to follow-up. CONCLUSIONS: Results are consistent with the hypothesis that occupational heat stress and volume depletion may be associated with the development of kidney disease, and future studies should directly measure these occupational factors. The presence of urine tubular injury markers supports a tubulointerstitial disease that could occur with repeated tubular injury.

Changes in kidney function among Nicaraguan sugarcane workers.

BACKGROUND: There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers. OBJECTIVES: To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the potential role of hydration, and measure proteinuria. METHODS: We recruited 284 Nicaraguan sugarcane workers performing seven distinct tasks. We measured urine albumin and serum creatinine and estimated glomerular filtration rate (eGFR). RESULTS: eGFR varied by job and decreased during the harvest in seed cutters (-8·6 ml/min/1·73 m(2)), irrigators (-7·4 ml/min/1·73 m(2)), and cane cutters (-5·0 ml/min/1·73 m(2)), as compared to factory workers. The number of years employed at the company was negatively associated with eGFR. Fewer than 5% of workers had albumin-to-creatinine ratio (ACR) >30 mg/g. CONCLUSIONS: The decline in kidney function during the harvest and the differences by job category and employment duration provide evidence that one or more risk factors of CKD are occupational.