Intranasal Administration of Sugarcane Ash Causes Chronic Kidney Disease in Rats.

Background. Silica nanoparticles found in sugarcane ash have been postulated to be a toxicant contributing to chronic kidney disease of unknown etiology (CKDu). However, while the administration of manufactured silica nanoparticles is known to cause chronic tubulointerstitial disease in rats, the effect of administering sugarcane ash on kidney pathology remains unknown. Here we investigate whether sugarcane ash can induce CKD in rats. Methods. Sugarcane ash was administered for 13 weeks into the nares of rats (5 mg/day for 5d/week), and blood, urine and kidney tissues were collected at 13 weeks (at the end of ash administration) and in a separate group of rats at 24 weeks (11 weeks after stopping ash administration). Kidney histology was evaluated, and inflammation and fibrosis (collagen deposition) measured. Results. Sugarcane ash exposure led to the accumulation of silica in the kidneys, lungs, liver and spleen of rats. Mild proteinuria developed although renal function was largely maintained. However, biopsies showed focal glomeruli with segmental glomerulosclerosis, and tubulointerstitial inflammation and fibrosis that tended to worsen even after the ash administration had been stopped. Staining for the lysosomal marker, LAMP-1, showed decreased staining in ash administered rats consistent with lysosomal activation. Conclusion. Sugarcane ash containing silica nanoparticles can cause CKD in rats.

Urinary concentrations of metals before and after volcanic eruption: a natural experiment surrounding the eruption of Volcán de Fuego, 2018.

Volcanic eruptions increase environmental heavy metal concentrations, yet little research has been performed on their extrapulmonary human health effects. We fortuitously collected biological samples in a cohort of Guatemalan sugarcane cutters in the area surrounding Volcán de Fuego before and after the June 2018 eruption. We sought to determine whether stratovolcanic activity was associated with changes in urinary concentrations of heavy metals in a cohort of sugarcane workers. In this exploratory analysis, we found significant increases in urinary arsenic, (ß = 1.46, P < 0.0001), cadmium (ß = 1.03, P < 0.0001), and lead (ß = 0.87, P = 0.003) in participants with residential proximity to Volcán de Fuego as compared to participants farther away, suggesting that volcanic activity could be associated with acute heavy metal exposures. This natural experiment is, to our knowledge, the first of its kind and suggests a need for more research into heavy metal exposure-related health impacts of volcanic eruptions.

Inhaled silica nanoparticles cause chronic kidney disease in rats.

Silica nanoparticles (SiNPs) released during the burning of sugarcane have been postulated to have a role in chronic kidney disease of unknown etiology. We tested the hypothesis that pristine SiNPs of the size present in sugarcane might cause chronic kidney injury when administered through the lung in rats. We administered 200- or 300-nm amorphous SiNPs twice weekly (4 mg/dose), or vehicle by oropharyngeal aspiration for 13 wk to rats followed by euthanasia after an additional 13 wk (26 wk total). Tissues were evaluated for the presence of SiNPs and evidence of histological injury. Both sizes of SiNPs caused kidney damage, with early tubular injury and inflammation (at week 13) that continued to inflammation and chronic fibrosis at week 26 despite discontinuation of the SiNP administration. Both sizes of SiNPs caused local inflammation in the lung and kidney and were detected in the serum and urine at week 13, and the 200-nm particles were also localized to the kidney with no evidence of retention of the 300-nm particles. At week 26, there was some clearance of the 200-nm silica from the kidneys, and urinary levels of SiNPs were reduced but still significant in both 200- and 300 nm-exposed rats. In conclusion, inhaled SiNPs cause chronic kidney injury that progresses despite stopping the SiNP administration. These findings support the hypothesis that human exposure to amorphous silica nanoparticles found in burned sugarcane fields could have a participatory role in chronic kidney disease of unknown etiology.NEW & NOTEWORTHY Inhalation of silica nanoparticles (SiNPs) released during the burning of sugarcane has been postulated to have a role in chronic kidney disease of unknown etiology (CKDu). We administered 200- and 300-nm amorphous SiNPs to rats by aspiration and observed kidney damage with tubular injury and inflammation that persisted even after stopping the SiNP exposure. These findings support the hypothesis that human exposure to SiNPs found in sugarcane ash could have a participatory role CKDu.

Association of Copeptin, a Surrogate Marker of Arginine Vasopressin, with Decreased Kidney Function in Sugarcane Workers in Guatemala.

BACKGROUND: Vasopressin is elevated in response to heat and dehydration and has been postulated to have a role in the chronic kidney disease of unknown origin being observed in Central America. The aims of this study were to examine whether the vasopressin pathway, as measured by copeptin, is associated with the presence of kidney dysfunction, and to examine whether higher fluid intake is associated with lower circulating copeptin and thereby preserves kidney health among sugarcane workers exposed to hot conditions. METHODS: Utilizing a longitudinal study of 105 workers in Guatemala, we examined relationships between hydration indices, plasma copeptin concentrations, and kidney function markers at 3 times during the 6-month harvest. We also examined whether baseline copeptin concentrations increased the odds of developing an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS: Copeptin concentrations were positively associated with serum creatinine (ß 1.41, 95% CI 0.88-2.03) and negatively associated with eGFR (ß -1.07, 95% CI -1.43 to -0.70). In addition, as workers improved their hydration (measured by increases in fluid balance), copeptin concentrations were reduced, and this reduction was associated with an improvement in kidney function. CONCLUSIONS: Results suggest that copeptin should be studied as a potential prognostic biomarker.

Increase of core temperature affected the progression of kidney injury by repeated heat stress exposure.

An epidemic of chronic kidney disease of unknown etiology (Mesoamerican nephropathy) has emerged in hot regions of Central America. We have demonstrated that dehydration associated with recurrent heat exposure causes chronic kidney disease in animal models. However, the independent influence of core body temperature on kidney injury has not been explored. In the present study, we tested the hypothesis that kidney injury could be accelerated by increasing body temperature independent of external temperature. Wild-type mice were exposed to heat (39.5°C, 30 min, 2 times daily) with or without the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) for 10 days. Core temperature, renal function, proteinuria, and renal histological and biochemical analyses were performed. Isolated mitochondria markers of oxidative stress were evaluated from kidney tissue. DNP increased body core temperature in response to heat by 1°C (42 vs. 41°C), which was transient. The mild increase in temperature correlated with worsening albuminuria (R = 0.715, P < 001), renal tubular injury, and interstitial infiltration of monocytes/macrophages. Tubular injury was marked in the outer medulla. This was associated with a reduction in kidney tissue ATP levels (nonheated control: 16.71 ± 1.33 nmol/mg and DNP + heat: 13.08 ± 1.12 nmol/mg, P < 0.01), reduced mitochondria, and evidence for mitochondrial oxidative stress. The results of the present study suggest that kidney injury in heat stress is markedly worsened by increasing core temperature. This is consistent with the hypothesis that clinical and subclinical heat stroke may play a role in Mesoamerican nephropathy.

Climate Change and the Kidney.

The worldwide increase in temperature has resulted in a marked increase in heat waves (heat extremes) that carries a markedly increased risk for morbidity and mortality. The kidney has a unique role not only in protecting the host from heat and dehydration but also is an important site of heat-associated disease. Here we review the potential impact of global warming and heat extremes on kidney diseases. High temperatures can result in increased core temperatures, dehydration, and blood hyperosmolality. Heatstroke (both clinical and subclinical whole-body hyperthermia) may have a major role in causing both acute kidney disease, leading to increased risk of acute kidney injury from rhabdomyolysis, or heat-induced inflammatory injury to the kidney. Recurrent heat and dehydration can result in chronic kidney disease (CKD) in animals and theoretically plays a role in epidemics of CKD developing in hot regions of the world where workers are exposed to extreme heat. Heat stress and dehydration also has a role in kidney stone formation, and poor hydration habits may increase the risk for recurrent urinary tract infections. The resultant social and economic consequences include disability and loss of productivity and employment. Given the rise in world temperatures, there is a major need to better understand how heat stress can induce kidney disease, how best to provide adequate hydration, and ways to reduce the negative effects of chronic heat exposure.

Evaluation of heat stress and cumulative incidence of acute kidney injury in sugarcane workers in Guatemala.

OBJECTIVE: Agricultural workers worldwide exposed to heat stress could be at the risk of kidney injury, which could lead to chronic kidney disease of an unknown origin (CKDu). Hydration has been promoted as a key measure to reduce kidney injury. In the presence of a hydration intervention, the incidence of acute kidney injury (AKI) was calculated in a sugarcane worker population in Guatemala and several risk factors were evaluated. METHODS: We measured kidney function at the beginning and end of the work shift at three time points in 517 sugarcane workers. We defined AKI as an increase in serum creatinine of 26.5 µmol/L or 50% or more from the pre-shift value. Associations between AKI and risk factors were examined, including interactions with hydration status. RESULTS: The prevalence of dehydration post-shift (> 1.020 specific gravity) was 11% in February, 9% in March, and 6% in April. Cumulative incidence of AKI was 53% in February, 54% in March, and 51% in April. AKI was associated with increasing post-shift specific gravity, a dehydration marker, (OR 1.24, 95% CI 1.02-1.52) and with lower electrolyte solution intake (OR 0.94, 95% CI 0.89-0.99). CONCLUSIONS: Dehydration and insufficient electrolyte consumption are risk factors for AKI. However even well-hydrated sugarcane workers routinely experience AKI. While hydration is important and protective, there is a need to understand other contributors to risk of AKI and identify prevention strategies with these workers.

Organophosphorus pesticide residue levels in homes located near orchards.

Organophosphorus pesticides (OPs) are commonly applied to agricultural crops. Families living in these communities may have higher exposure to OPs due to take home exposures and close proximity to agricultural fields. The objectives of this study were to measure OP concentrations in home carpet dust in agricultural and non-agricultural households and examine factors that may impact OP concentrations such as occupation, housing characteristics, and resident behaviors. Agricultural households had at least one parent who worked in agriculture during the previous 5 years. Carpet dust samples were collected at two time points from 278 households in an agricultural community located in the Pacific Northwest from 2008-2011. Samples were analyzed for four types of OPs: azinphos-methyl, phosmet, malathion, and chlorpyrifos. Overall, OP detection frequencies and concentrations were higher in agricultural households compared to non-agricultural households. Factors associated with higher OP concentrations in home carpet dust were identified and included: (1) homes with two or more agricultural workers living in the home, (2) homes located in close proximity to an agricultural field or orchard, (3) having an entry floor mat, and (4) frequently vacuuming the house. Having air conditioning in the home had a protective effect with OP concentrations. While the use of these four OPs is restricted or limited for residential use in the United States, results show that they were still found in the indoor environment. The understanding of the impact of agricultural work and other factors that elevate levels of OPs in the home is crucial to mitigating pesticide exposure in agricultural communities.

Exposome and Metabolome Analysis of Sugarcane Workers Reveals Predictors of Kidney Injury.

Introduction: Sugarcane workers are exposed to potentially hazardous agrochemicals, including pesticides, heavy metals, and silica. Such occupational exposures present health risks and have been implicated in a high rate of kidney disease seen in these workers. Methods: To investigate potential biomarkers and mechanisms that could explain chronic kidney disease (CKD) among this worker population, paired urine samples were collected from sugarcane cutters at the beginning and end of a harvest season in Guatemala. Workers were then separated into 2 groups, namely those with or without kidney function decline (KFD) across the harvest season. Urine samples from these 2 groups underwent elemental analysis and untargeted metabolomics. Results: Urine profiles demonstrated increases in silicon, certain pesticides, and phosphorus levels in all workers, whereas heavy metals remained low. The KFD group had a reduction in estimated glomerular filtration rate (eGFR) across the harvest season; however, kidney injury marker 1 did not significantly change. Cross-harvest metabolomic analysis found trends of fatty acid accumulation, perturbed amino acid metabolism, presence of pesticides, and other known signs of impaired kidney function. Conclusion: Silica and certain pesticides were significantly elevated in the urine of sugarcane workers with or without KFD. Future work should determine whether long-term occupational exposure to silica and pesticides across multiple seasons contributes to CKD in these workers. Overall, these results confirmed that multiple exposures are occurring in sugarcane workers and may provide insight into early warning signs of kidney injury and may help explain the increased incidence of CKD among agricultural workers.

A longitudinal assessment of heat exposure and biomarkers of kidney function on heat shock protein 70 and antibodies among agricultural workers.

Background: Exposure to extreme heat impacts millions of people worldwide and outdoor workers are among the populations most affected by high temperatures. Heat stress induces several biological responses in humans, including the production of heat shock proteins (HSP) and antibodies against HSP (anti-HSP) which may play a central role in the body's cellular response to a hot environment. Objective: This longitudinal study investigated the impact of high temperatures and humidity on the presence of HSP70 and anti-HSP70 and examined relationships with markers of kidney function in an at-risk workforce under conditions of extreme heat and exertion in Guatemala. Methods: We collected ambient temperature and relative humidity data as well as biomarkers and clinical data from 40 sugarcane workers at the start and the end of a 6-month harvest. We used generalized mixed-effects models to estimate temperature effects on HSP70 and anti-HSP70 levels. In addition, we examined trends between HSP70 and anti-HSP70 levels and markers of kidney function across the harvest. Results: At the end of the harvest, temperatures were higher, and workers had, on average, higher levels of HSP70 and anti-HSP70 compared to the beginning of the season. We observed significant increasing trends with temperature indices and HSP70 levels. Maximum temperature was associated with HSP70 increments after controlling for age, systolic and diastolic blood pressure (ß: 0.21, 95% Confidence Interval: 0.09, 0.33). Kidney function decline across the harvest was associated with both higher levels of anti-HSP70 levels at the end of the harvest as well as greater increases in anti-HSP70 levels across the harvest. Conclusions: These results suggest that workplace heat exposure may increase the production of HSP70 and anti-HSP70 levels and that there may be a relationship between increasing anti-HSP70 antibodies and the development of renal injury. HSP70 holds promise as a biomarker of heat stress in exposed populations.

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.

Latin American Agricultural Workers' Job Demands and Resources and the Association With Health Behaviors at Work and Overall Health.

In the present study, we describe the job demands and job resources (JD-R) experienced by agricultural workers in three Latin American countries and their relationship to proactive health behaviors at work and overall health. Following previous research on the JD-R model, we hypothesized that job demands (H1) would be negatively related to agricultural workers' self-reported overall health. On the other hand, we hypothesized that job resources (H2) would be positively related to agricultural workers' overall health. Furthermore, we hypothesized (H3) that workers' engagement in jobsite health promotion practices via their proactive health behaviors at work would partially mediate the relationship between workers' job resources and job demands and overall health. We also had a research question (R1) about whether there were differences by type of job held. The sample of workers who participated in this study (N = 1,861) worked in Mexico, Guatemala, and Nicaragua for one large agribusiness that produces sugar cane. They worked in two distinct areas: company administration and agricultural operations. We administered employee health and safety culture surveys using survey methods tailored to meet the needs of both types of workers. Stratified path analysis models were used to test study hypotheses. In general, we found support for hypotheses 1 and 2. For example, operations workers reported more physically demanding jobs and administrative workers reported more work-related stress. Regardless, the existence of high job demands was associated with poorer overall health amongst both types of workers. We found that workers in more health-supportive work environments perform more proactive health behaviors at work, regardless of their role within the organization. However, hypothesis 3 was not supported as proactive health behaviors at work was not associated with overall health. We discuss future research needs in terms of evaluating these hypotheses amongst workers employed by small- and medium-sized agribusinesses as well as those in the informal economy in Latin America. We also discuss important implications for agribusinesses seeking to develop health promotion programs that meet the needs of all workers.

Environmental metal exposures and kidney function of Guatemalan sugarcane workers.

BACKGROUND: Exposure to environmental metals can cause nephrotoxicity. There is an international epidemic of chronic kidney disease of unknown cause (CKDu). Whether metal exposures contribute to kidney dysfunction in populations at risk for CKDu remains unresolved. OBJECTIVE: Urinary metals (arsenic, cadmium, nickel, and uranium) were examined in 222 sugarcane cutters in Guatemala at three time points over 1 year. METHODS: We explored the relationships between metal concentrations and markers of kidney function using multivariable linear mixed-effect models. RESULTS: Arsenic, cadmium, and nickel were detected in the majority of the 340 urine samples and were generally within limits previously considered to be nonnephrotoxic. Nevertheless, higher urine cadmium was inversely associated with estimated glomerular filtration rate (eGFR) (ß: -4.23, 95% confidence interval [CI]: -6.92, -1.54) and positively associated with neutrophil gelatinase-associated lipocalin (NGAL) (ß: 2.92, 95% CI: 1.20, 4.64). Higher urine arsenic was also inversely associated with eGFR (ß: -4.36, 95% CI: -7.07, -1.64). SIGNIFICANCE: Our findings suggest that exposures to metals, including cadmium and arsenic, might contribute to kidney toxicity seen in workers at risk for CKDu. These findings are consistent with the potential for metal nephrotoxicity at lower than expected levels in the setting of manual work in a very hot environment.

Cross-sectional study examining the accuracy of self-reported smoking status as compared to urinary cotinine levels among workers at risk for chronic kidney disease of unknown origin in Guatemala.

OBJECTIVES: There is a lack of information on cotinine levels in rural populations in low-income and middle-income countries like Guatemala. Therefore, there is a need to explore smoking status and biomarkers of tobacco use in epidemiological research in rural, low-income populations, in particular those at-risk for chronic kidney disease of unknown origin (CKDu). DESIGN: We evaluated self-reported smoking status against urinary cotinine levels, the gold standard biomarker of tobacco smoke exposure, among agricultural workers at four separate cross-sectional time points. SETTING: Guatemala. PARTICIPANTS: 283 sugarcane workers. PRIMARY OUTCOME MEASURES: Compared self-reported smoking status and urinary cotinine levels in two agricultural worker studies. RESULTS: Self-reported smoking prevalence was 12% among workers. According to cotinine levels (≥50 ng/mL), the smoking prevalence was 34%. Self-reported smoking status had 28% sensitivity and 96% specificity. Urinary cotinine levels show that smoking prevalence is underestimated in this worker population. CONCLUSIONS: According to our findings, smoking status should be objectively measured with biomarkers rather than self-reported in CKDu epidemiological research. Self-reported smoking status is likely an underestimate of the true smoking prevalence among agricultural workers. Research on the CKDu epidemic in Central America and other parts of the world might be underestimating tobacco exposure as a potential contributor to the development of CKDu.

Body Composition, Anemia, and Kidney Function among Guatemalan Sugarcane Workers.

Rates of anemia among agricultural workers, who are also at risk for kidney injury and chronic kidney disease of unknown cause (CKDu), are unknown. We evaluated body composition through the sum of three skinfolds among 203 male sugarcane cutters and assessed the relationship of variables related to nutrition, anemia (hemoglobin < 13 g/dL), and elevated hemoglobin A1c (HbA1c ≥ 5.7%) with estimated glomerular filtration rate (eGFR) using linear regression. Eleven percent of workers were at the level of essential body fat (2-5%). Anemia was present among 13% of workers, 70% of which were normochromic normocytic, a type of anemia suggesting potential underlying chronic disease. Anemia was more common among those with lower BMI and fat free mass. The prevalence of elevated HbA1c was 21%. A moderate negative correlation was found between hemoglobin and HbA1c (Pearson's r = -0.32, p <0.01) which suggests that HbA1c values should be interpreted with caution in populations that have high rates of anemia. Twelve percent of workers had reduced kidney function with an eGFR < 90 mL/min/1.73 m2. On average, the eGFR was 18 mL/min per 1.73 m2 lower [(95% CI:-24, -12), p <0.01)] for those with anemia than those without, and 8 mL/min per 1.73 m2 lower among those with elevated HbA1c [(95% CI: -13, -2), p < 0.01]. Results will inform future studies examining the role of anemia in the evaluation of CKDu and interventions to improve nutrition for workers in low-resource settings.

Sugarcane Workweek Study: Risk Factors for Daily Changes in Creatinine.

INTRODUCTION: Agricultural workers laboring in thermally stressful environments are at increased risk for kidney injury and chronic kidney disease of unknown origin (CKDu), and their environmental and occupational exposures have been considered to be important risk factors. This study examined the effects of repeated kidney stress from the simultaneous strain of work and other factors experienced by workers in Guatemala during a typical workweek. METHODS: We collected data from 107 sugarcane workers across 7 consecutive work shifts. Data included information on daily occupational, meteorological, environmental, and lifestyle factors. We used multivariable linear mixed models to evaluate associations of these factors with percent change in creatinine. RESULTS: We observed that increasing wet bulb globe temperature (ß = 2.5%, 95% confidence interval [CI] = 0.3%, 4.7%) and increasing diastolic blood pressure (ß = 6.2%, 95% CI = 0.9%, 11.6%) were associated with increases in creatinine across the shift, whereas consumption of water from chlorinated dormitory tanks as compared to artesian well water (ß = -17.5%, 95% CI = -29.6%, -5.4%) and increasing number of rest breaks (ß = -5.8%, 95% CI = -9.0%, -2.6%) were found to be protective against increases in creatinine. Workers reporting drinking tank water had lower concentrations of urine creatinine-corrected arsenic, lead, uranium, and glyphosate compared to workers reporting the use of well water or municipal water. CONCLUSION: These results reinforce the need to focus on preventive actions that reduce kidney injury among this worker population, including strategies to reduce heat stress, managing blood pressure, and examining water sources of workers for nephrotoxic contaminants.

International Total Worker Health: Applicability to Agribusiness in Latin America.

Total Worker Health® (TWH) is a framework for integrating worker and workplace safety, health, and well-being, which has achieved success in European and US settings. However, the framework has not been implemented in Latin America or in agricultural sectors, leaving large and vulnerable populations underrepresented in the implementation and evaluation of these strategies to improve safety and promote health and well-being. This study presents a case study of how a TWH approach can be applied to a multinational Latin American agribusiness. We describe the process and adaptation strategy for conducting a TWH assessment at multiple organizational levels and in multiple countries. We follow this with a description of a TWH leadership training that was conducted based on the results of the assessment. Finally, we describe our methods to make corporate recommendations for TWH policies and programs that were informed by the TWH assessment and leadership trainings. With this case study we aim to demonstrate the importance and feasibility of conducting TWH in Latin America.

Creatinine Fluctuations Forecast Cross-Harvest Kidney Function Decline Among Sugarcane Workers in Guatemala.

BACKGROUND: Chronic kidney disease of unknown origin (CKDu) is an epidemic that disproportionately affects young agriculture workers in hot regions. It has been hypothesized that repeated acute kidney injury (AKI) may play a role in the development of disease. METHODS: Latent class mixed models were used to identify groups of Guatemalan sugarcane harvesters based on their daily changes in creatinine over 6 consecutive days in 2018. Exponential smoothing state space models were used to forecast end-of-season creatinine between the identified groups. Percent change in estimated glomerular filtration rate (eGFR) across the harvest was compared between groups. RESULTS: Twenty-nine percent (n = 30) of the 103 workers experienced repeated severe fluctuations in creatinine across shift. The model with multiplicative error, multiplicative trend, and multiplicative seasonality was able to accurately forecast end-of-season creatinine in the severe group (mean percentage error [MPE]: -4.7%). eGFR of workers in the severe group on average decreased 20% across season compared to 11% decline for those in the moderate group (95% confidence interval for difference: -17% to 0%). CONCLUSIONS: Daily fluctuations in creatinine can be used to forecast end-of-season creatinine in sugarcane harvesters. Workers who experience repeat severe daily fluctuations in creatinine, on average, experience a greater reduction in kidney function across the season.