Effects on household income and earnings from chronic kidney disease of non-traditional origins: PREP project findings from Chichigalpa, Nicaragua.

OBJECTIVE: Our purpose with this study is to examine the socioeconomic outcomes associated with chronic kidney disease not related to well-known risk factors (CKDnt) in four communities in Chichigalpa, Nicaragua that are home to a substantial number of sugarcane workers. METHODS: We employed a cluster-based systematic sampling design to identify differences in outcomes between those households affected directly by CKDnt and those that are not. RESULTS: Overall, we find that approximately one-third of households surveyed had a household member diagnosed with CKDnt. 86% of CKDnt households reported that the head of the household had been without work for the last 6 months or more, compared with 53% of non-CKDnt households. Non-CKDnt households took in more than double the earnings income on average than CKDnt households ($C52 835 and $C3120, respectively). Nonetheless, on average, CKDnt households' total income exceeded that of non-CKDnt households due to Nicaragua's national Instituto Nicaraguense de Seguridad Social Social Security payments to CKDnt households, suggestive of a substantial economic burden on the state resulting from the disease. Households headed by widows or widowers who are widowed as a result of CKDnt demonstrate distinct deficits in total income when compared with either non-widowed households or to households widowed by causes other than CKDnt. CONCLUSIONS: Despite strong similarities in terms of demographic characteristics and despite residing in the same communities with similar access to the available resources, households experiencing CKDnt exhibit distinct and statistically significant differences in important socioeconomic outcomes when compared to non-CKDnt households.

Association Between Acute Kidney Injury Hospital Visits and Environmental Heat Stress at a Nicaraguan Sugarcane Plantation.

BACKGROUND: Mesoamerican sugarcane cutters are at a high risk of chronic kidney disease of non-traditional origin, a disease likely linked to heat-related acute kidney injury (AKI). Studies in general populations have described a positive association between high environmental temperatures and clinically assessed kidney outcomes, but there are no studies in occupational settings. METHOD: We accessed routine records of clinically diagnosed AKI (AKI-CD) and wet bulb globe temperatures (WBGT) at a large Nicaraguan sugarcane plantation and modeled the relationship between these using negative binomial regression. A rest-shade-hydration intervention was gradually enhanced during the study period, and efforts were made to increase the referral of workers with suspected AKI to healthcare. RESULTS: Each 1°C WBGT was associated with an 18% (95% confidence interval [CI]: [4, 33%]) higher AKI-CD rate on the same day and a 14% (95% CI [-5, 37%]) higher rate over a week. AKI-CD rates and severity, and time between symptoms onset and diagnosis decreased during the study period, that is, with increasing rest-shade-hydration intervention. Symptoms and biochemical signs of systemic inflammation were common among AKI-CD cases. DISCUSSION: Occupational heat stress, resulting from heavy work in environmental heat, was associated with a higher rate of clinically diagnosed AKI in a population at risk of CKDnt. Promoting rest-shade-hydration may have contributed to reducing AKI rates during the study period. Occupational health and safety personnel have key roles to play in enforcing rest, shade, and hydration practices, referring workers with suspected AKI to healthcare as well as collecting and analyzing the data needed to support workplace heat stress interventions.

Impact of heat and a rest-shade-hydration intervention program on productivity of piece-paid industrial agricultural workers at risk of chronic kidney disease of nontraditional origin.

OBJECTIVES: Assess the impact of environmental heat and a rest-shade-hydration (RSH) intervention against heat stress on productivity of piece-paid Mesoamerican sugarcane cutters. These workers are at a high risk of chronic kidney disease of non-traditional origin (CKDnt), from the severe heat stress they experience due to heavy work under hot conditions. RSH interventions in these populations improve kidney health outcomes, but their impact on productivity has yet to be examined. METHODS: We accessed routine productivity data from seed (SC, N = 749) and burned (BCC, N = 535) sugarcane cutters observed over five harvest seasons with increasing RSH intervention at a large Nicaraguan sugarcane mill. Hourly field-site wet-bulb globe temperature (WBGT) was recorded by mill staff and summarized as a daily mean. Mixed linear regression was used to model daily productivity, adjusting for age (18-29, 30-44, and >45 years), sex, WBGT (<28, 28-29, 29-30, 30-31, and >31 °C) on the same and preceding day, harvest season (2017-18 to 2021-22), month, and acclimatization status (<1, 1-2, and >2 weeks). RESULTS: There was an inverse dose-response relationship between SC productivity and WBGT on the same and preceding days, decreasing by approximately 3%/°C WBGT. Productivity increased during the study period, i.e. coinciding with RSH scale-up, by approximately 19% in SC and 9% in BCC. CONCLUSION: Agricultural worker productivity was expected lower on hotter days, strengthening the interest in all stakeholders to mitigate increasing global temperatures and their impact. Despite decreasing the total time allocated for work each day, an RSH intervention appears to result in increased productivity and no apparent loss in productivity.

Impact of heat on emergency hospital admissions related to kidney diseases in Texas: Uncovering racial disparities.

BACKGROUND AND OBJECTIVE: While impact of heat exposure on human health is well-documented, limited research exists on its effect on kidney disease hospital admissions especially in Texas, a state with diverse demographics and a high heat-related death rate. We aimed to explore the link between high temperatures and emergency kidney disease hospital admissions across 12 Texas Metropolitan Statistical Areas (MSAs) from 2004 to 2013, considering causes, age groups, and ethnic populations. METHODS: To investigate the correlation between high temperatures and emergency hospital admissions, we utilized MSA-level hospital admission and weather data. We employed a Generalized Additive Model to calculate the association specific to each MSA, and then performed a random effects meta-analysis to estimate the overall correlation. Analyses were stratified by age groups, admission causes, and racial/ethnic disparities. Sensitivity analysis involved lag modifications and ozone inclusion in the model. RESULTS: Our analysis found that each 1 °C increase in temperature was associated with a 1.73 % (95 % CI [1.43, 2.03]) increase in hospital admissions related to all types of kidney diseases. Besides, the effect estimates varied across different age groups and specific types of kidney diseases. We observed statistically significant associations between high temperatures and emergency hospital admissions for Acute Kidney Injury (AKI) (3.34 % (95 % CI [2.86, 3.82])), Kidney Stone (1.76 % (95 % CI [0.94, 2.60])), and Urinary Tract Infections (UTI) (1.06 % (95 % CI [0.61, 1.51])). Our research findings indicate disparities in certain Metropolitan Statistical Areas (MSAs). In Austin, Houston, San Antonio, and Dallas metropolitan areas, the estimated effects are more pronounced for African Americans when compared to the White population. Additionally, in Dallas, Houston, El Paso, and San Antonio, the estimated effects are greater for the Hispanic group compared to the Non-Hispanic group. CONCLUSIONS: This study finds a strong link between higher temperatures and kidney disease-related hospital admissions in Texas, especially for AKI. Public health actions are necessary to address these temperature-related health risks, including targeted kidney health initiatives. More research is needed to understand the mechanisms and address health disparities among racial/ethnic groups.

Occupational Heat Stress and Kidney Health in Salt Pan Workers.

Introduction: Work in heat affects millions of workers. Although kidney function in agricultural workers is increasingly researched, nonagricultural studies are scarce. In coastal salt pans, the absence of occupational exposures to pesticides and other toxicants allows assessment of heat stress alone. Methods: Seven Indian salt pans were surveyed from 2017 to 2020. Job-specific workload was assessed. Heat stress was characterized as exceeding the wet bulb globe temperature (WBGT)-threshold limit value (TLV) for high and moderate workloads. Preshift and postshift heart rates (HRs), tympanic temperatures, and urine specific gravity (USG) were measured for 352 workers, as were sweat rates (SwR), serum creatinine (SCr), serum uric acid, and urine dipstick. Estimated glomerular filtration rate (eGFR; ml/min per 1.73 m2) was computed. Heat-strain symptoms were assessed using questionnaires. Results: The mean WBGT was 30.5 ± 1.3 °C (summer) and 27.8 ± 1.9 °C (winter). Water intake during the workday was low, median was one Litre, and most workers (87%) exceeded the TLV for heat stress. Dehydration-related symptoms were frequent in those with high-heat stress, as were cross-shift increases in temperature (≥1°C; 15%), a high USG (≥1.020; 28%), and a high SwR (≥1 l/h; 53%). An eGFR of 60 to 89 ml/min per 1.73 m2 was observed in 41% of all workers examined, and 7% had eGFR below 60 ml/min per 1.73 m2. The odds ratio for eGFR <90 ml/min per 1.73 m2 in workers exceeding the TLV, compared to workers below this limit, adjusted for age and gender was 2.9 (95% CI: 1.3-6.4). Conclusion: Workplace interventions to prevent heat stress and dehydration in the salt pans and other at-risk industries are urgently required. The findings strengthen the notion that high-heat stress and limited hydration is a risk factor for kidney dysfunction.

An explorative study of inflammation-related proteins associated with kidney injury in male heat-stressed workers.

Chronic kidney disease of non-traditional origin (CKDnt) and acute kidney injury (AKI) often affect heat-stressed Mesoamerican manual workers. Inflammation occurs concurrently with AKI in this population, but its role remains unknown. To explore links between inflammation and kidney injury in heat stress, we compared levels of inflammation-related proteins in cutters with and without increasing serum creatinine levels during sugarcane harvest. These sugarcane cutters have previously been identified to be repeatedly exposed to severe heat stress during the five month harvest season. A nested case-control study was conducted among male Nicaraguan sugarcane cutters in a CKDnt hotspot. Cases (n = 30) were defined as having an increase in creatinine of ≥0.3 mg/dL across the five-month harvest. Controls (n = 57) had stable creatinine levels. Ninety-two inflammation-related proteins in serum were measured before and after harvest using Proximity Extension Assays. Mixed linear regression was used to identify differences in protein concentrations between cases and controls before harvest, differential trends during harvest, and association between protein concentrations and the urine kidney injury markers Kidney Injury Molecule (KIM)-1, Monocyte Chemoattractant Protein (MCP)-1 and albumin. One protein, chemokine (C-C motif) ligand 23 (CCL23), was elevated among cases at pre-harvest. Changes in seven inflammation-related proteins (CCL19, CCL23, colony-stimulating factor 1 [CSF1], hepatocyte and fibroblast growth factors [HGF and FGF23], and tumor necrosis factor beta [TNFB] and TNF-related activation-induced cytokine [TRANCE]) were associated with case status and at least two out of three urine kidney injury markers (KIM-1, MCP-1 and albumin). Several of these have been implicated in myofibroblast activation, which likely is an important step in kidney interstitial fibrotic disease such as CKDnt. This study provides an initial exploration of immune system determinants of, and activation during, kidney injury experienced during prolonged heat stress.

Climate change and nephrology.

Climate change should be of special concern for the nephrologist, as the kidney has a critical role in protecting the host from dehydration, but it is also a favorite target of heat stress and dehydration. Here we discuss how rising temperatures and extreme heat events may affect the kidney. The most severe presentation of heat stress is heat stroke, which can result in severe electrolyte disturbance and both acute and chronic kidney disease (CKD). However, lesser levels of heat stress also have multiple effects, including exacerbating kidney disease and precipitating cardiovascular events in subjects with established kidney disease. Heat stress can also increase the risk for kidney stones, cause multiple electrolyte abnormalities and induce both acute and chronic kidney disease. Recently there have been multiple epidemics of CKD of uncertain etiology in various regions of the world, including Mesoamerica, Sri Lanka, India and Thailand. There is increasing evidence that climate change and heat stress may play a contributory role in these conditions, although other causes, including toxins, could also be involved. As climate change worsens, the nephrologist should prepare for an increase in diseases associated with heat stress and dehydration.

Targeting workload to ameliorate risk of heat stress in industrial sugarcane workers.

OBJECTIVE: The aim of this study was to quantify the physiological workload of manual laborers in industrial sugarcane and assess the effect of receiving a rest, shade, and hydration intervention to reduce heat stress exposure risk. METHODS: In an observational study, physiological workload was evaluated for burned cane cutters (BCC), seed cutters (SC) and drip irrigation repair workers (DIRW) using heart rate (HR) recorded continuously (Polar®) across a work shift. Workers' percentage of maximal HR (%HRmax), time spent in different HR zones, and estimated core temperature (ECTemp) were calculated. The effect of increasing rest across two harvests was evaluated for BCC and SC. RESULTS: A total of 162 workers participated in this study [52 BCC (all male), 71 SC (13 female) and 39 DIRW (16 female)]. Average %HRmax across a work shift was similar between BCC and SC (BCC: 58%, SC: 59%), but lower in DIRW (51%). BCC and SC spent similar proportions of work shifts at hard/very hard intensities (BCC: 13%, SC: 15%), versus DIRW who worked mostly at light (46%) or light-moderate (39%) intensities. SC maximum ECTemp reached 38.2°C, BCC 38.1°C; while DIRW only reached 37.7°C. Females performed at a higher %HRmax than males across work shifts (SC 64% versus 58%; DIRW 55% versus 49%). An additional rest period was associated with a lower average %HRmax across a work shift in BCC. CONCLUSION: In this setting, BCC and SC both undertake very physiologically demanding work. Females maintained a higher workload than male co-workers. Regulated rest periods each hour, with water and shade access, appears to reduce physiological workload/strain.

Point-of-care biomarkers for prediction of kidney function trajectory among sugarcane cutters: a comparative test accuracy study.

OBJECTIVES: Heat-stressed Mesoamerican workers, such as sugarcane cutters, suffer from high rates of chronic kidney disease of non-traditional origin (CKDnt). We aimed to identify easily available early markers of rapid kidney function decline in a population at high risk of CKDnt. DESIGN: The accuracy of different biomarkers measured during harvest for prediction of cross-harvest kidney function decline were assessed in an exploratory study group, and the performance of the most promising biomarker was then assessed in an independent confirmation group. SETTING: Male sugarcane cutters in El Salvador and Nicaragua. PARTICIPANTS: 39 male Salvadoran sugarcane cutters sampled fortnightly at ≤9 occasions before and after work shift during harvest. 371 male Nicaraguan sugarcane cutters were sampled as part of routine monitoring during two harvests. Cutters worked at high physical intensity at wet-bulb globe temperatures mostly above 29°C for 6-8 hours per day 6 days a week during the 5-6 months harvest season. PRIMARY OUTCOMES: Change in estimated glomerular filtration rate (CKD Epidemiology Collaboration) across the harvest season (ΔeGFRcross-harvest). RESULTS: Dipstick leukocyturia after work shift in the El Salvadoran group was the most promising marker, explaining >25% of ΔeGFRcross-harvest variance at 8/9 occasions during harvest. Leukocyturia was associated with experiencing fever, little or dark urine, cramps, headache, dizziness and abdominal pain in the preceding 2-week period. Decreasing blood haemoglobin (Hb) and eGFR during harvest were also predictive of ΔeGFRcross-harvest. In the Nicaraguan confirmation dataset, those having ≥++ leukocyturia at any sampling during harvest had a 13 mL/min/1.73 m2 (95% CI 10 to 16 mL/min/1.73 m2) worse ΔeGFRcross-harvest than those without recorded leukocyturia. CONCLUSION: Leukocyturia and Hb, both measurable with point-of-care methods, may be early indicators for kidney injury and risk for eGFR decline among heat-stressed male workers, thereby facilitating individual-level prevention and research aiming to understand the causes of CKDnt.

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.

Workplace Intervention for Heat Stress: Essential Elements of Design, Implementation, and Assessment.

Heat stress is associated with numerous health effects that potentially harm workers, especially in a warming world. This investigation occurred in a setting where laborers are confronted with occupational heat stress from physically demanding work in high environmental temperatures. Collaboration with a major Nicaraguan sugarcane producer offered the opportunity to study interventions to prevent occupational heat-stress-related kidney disease. Two aims for this study of a rest-shade-water intervention program were: (1) describe the evolving intervention, summarize findings that motivated proposed improvements, assess impact of those improvements, and identify challenges to successful implementation and (2) extract primary lessons learned about intervention research that have both general relevance to investigations of work-related disease prevention and specific relevance to this setting. The learning curve for the various stakeholders as well as the barriers to success demonstrate that effectiveness of an intervention cannot be adequately assessed without considerations of implementation. Designing, effectively implementing, and assessing both health impacts and implementation quality is a resource-intensive endeavor requiring a transdisciplinary approach. Both general and specific lessons learned are presented for decisions on study design and study elements, implementation assessment, and management engagement in understanding how productivity and health can be successfully balanced and for building effective communication between investigators and all levels of management.

Markers of kidney tubular and interstitial injury and function among sugarcane workers with cross-harvest serum creatinine elevation.

OBJECTIVES: Serum creatinine (SCr) is a routine marker of kidney injury but also increases with dehydration and muscular work. This study was to elucidate whether increase in SCr is associated with more specific markers of kidney tubular and interstitial injury and function, during prolonged heat stress among workers at high risk of chronic kidney disease of non-traditional origin (CKDnt). METHODS: Urine monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), calbindin, glutathione S-transferase-π (GST-π), clusterin, interleukin 18 and albumin, fractional excretion of potassium (FEK), blood haemoglobin, serum potassium, ferritin and erythropoietin were measured before and after harvest in a sample of 30 workers with a ≥0.3 mg/dL SCr increase across harvest (cases), and 53 workers with stable SCr (controls). RESULTS: Urine MCP-1 (p for differential cross-harvest trend <0.001), KIM-1 (p=0.002), calbindin (p=0.02), GST-π (p=0.04), albumin (p=0.001) and FEK (p<0.001) increased in cases, whereas blood haemoglobin (p<0.001) and serum erythropoietin (p<0.001) decreased. CONCLUSION: Several markers of tubular and interstitial injury and function changed as SCr increased across a harvest season, supporting the use of SCr as an indicator of kidney injury in physically active workers regularly exposed to heat stress. Repeated injury similar to that described here, and continued work under strenuous and hot conditions with similarly elevated injury markers is likely to worsen and possibly initiate CKDnt.

The Prevention of Occupational Heat Stress in Sugarcane Workers in Nicaragua-An Interpretative Phenomenological Analysis.

Background: Chronic kidney disease of non-traditional origin (CKDnt) is an ongoing epidemic that has taken the lives of tens of thousands of people in Mesoamerica, also affecting other tropical geographies. Occupational heat stress, which will increase worldwide as climate change persists, has been identified as a primary trigger of kidney injury and reduced renal function. At Nicaragua's largest sugarcane mill, the water, rest, and shade (WRS) intervention has proven to reduce the risk of heat stress and kidney injury effectively as assessed by the research and policy NGO La Isla Network (LIN) and their academic partners, who have worked with the sugar mill to improve the design of their intervention system. However, discrepancies between intervention design and implementation have been found. This study explores the perceptions of the WRS intervention in the company from the perspective of positions responsible for the workers' environment and heat stress prevention implementation. Methods: A qualitative design was used in the study. Twenty-one key informants of low and middle management, field assistants, and two members from LIN took part in the study. Semi-structured interviews were used to collect the data. Interviews' transcriptions were analyzed using interpretative phenomenological analysis (IPA). Results: Four main themes were developed in the analysis of the data: "A worthwhile struggle," "Culture of care", "Traditional production culture Vs. Culture of care," and "The importance of the formalization of care." Each theme contained sub-themes, all of which were further discussed in the light of organizational psychology. Conclusion and Implications: Discretionary differences resulting in low and middle management prioritizing production over health protection appeared to relate to a fair part of the implementation challenges and indicate that more efforts are needed to align operations' production and health goals. Education enhancement might be necessary, while further focus on health metrics for performance assessment might offer an opportunity to level perceived incentives and value of health and production.

Occupational heat exposure and the risk of chronic kidney disease of nontraditional origin in the United States.

Occupational heat exposure is linked to the development of kidney injury and disease in individuals who frequently perform physically demanding work in the heat. For instance, in Central America, an epidemic of chronic kidney disease of nontraditional origin (CKDnt) is occurring among manual laborers, whereas potentially related epidemics have emerged in India and Sri Lanka. There is growing concern that workers in the United States suffer with CKDnt, but reports are limited. One of the leading hypotheses is that repetitive kidney injury caused by physical work in the heat can progress to CKDnt. Whether heat stress is the primary causal agent or accelerates existing underlying pathology remains contested. However, the current evidence supports that heat stress induces tubular kidney injury, which is worsened by higher core temperatures, dehydration, longer work durations, muscle damaging exercise, and consumption of beverages containing high levels of fructose. The purpose of this narrative review is to identify occupations that may place US workers at greater risk of kidney injury and CKDnt. Specifically, we reviewed the scientific literature to characterize the demographics, environmental conditions, physiological strain (i.e., core temperature increase, dehydration, heart rate), and work durations in sectors typically experiencing occupational heat exposure, including farming, wildland firefighting, landscaping, and utilities. Overall, the surprisingly limited available evidence characterizing occupational heat exposure in US workers supports the need for future investigations to understand this risk of CKDnt.

Prevalence Studies on CKDu Need Stringent Reporting on Outcomes to Enhance Comparability.

Prevalence studies on Chronic Kidney Disease of unknown etiology (CKDu) need stringent reporting on outcomes following existing guidelines. Only by doing so, the much-needed comparisons between occupations, regions and climates for the elucidation of the etiology/etiologies of CKDu, and subsequently for its prevention, are possible. We, here, comment on methodological issues in a recently published study on rice farmers from West Java, Indonesia.

Pathophysiological Mechanisms by which Heat Stress Potentially Induces Kidney Inflammation and Chronic Kidney Disease in Sugarcane Workers.

BACKGROUND: Chronic kidney disease of non-traditional origin (CKDnt) is common among Mesoamerican sugarcane workers. Recurrent heat stress and dehydration is a leading hypothesis. Evidence indicate a key role of inflammation. METHODS: Starting in sports and heat pathophysiology literature, we develop a theoretical framework of how strenuous work in heat could induce kidney inflammation. We describe the release of pro-inflammatory substances from a leaky gut and/or injured muscle, alone or in combination with tubular fructose and uric acid, aggravation by reduced renal blood flow and increased tubular metabolic demands. Then, we analyze longitudinal data from >800 sugarcane cutters followed across harvest and review the CKDnt literature to assess empirical support of the theoretical framework. RESULTS: Inflammation (CRP elevation and fever) and hyperuricemia was tightly linked to kidney injury. Rehydrating with sugary liquids and NSAID intake increased the risk of kidney injury, whereas electrolyte solution consumption was protective. Hypokalemia and hypomagnesemia were associated with kidney injury. DISCUSSION: Heat stress, muscle injury, reduced renal blood flow and fructose metabolism may induce kidney inflammation, the successful resolution of which may be impaired by daily repeating pro-inflammatory triggers. We outline further descriptive, experimental and intervention studies addressing the factors identified in this study.