Biomarkers of Kidney Injury Among Nicaraguan Sugarcane Workers

doi:10.1053/j.ajkd.2015.08.022

American Journal of Kidney Diseases

Volume 67, Issue 2, February 2016, Pages 209-217

https://doi.org/10.1053/j.ajkd.2015.08.022 Get rights and content

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-β-d-glucosaminidase (NAG), and albumin; serum creatinine–based estimated glomerular filtration rate (eGFR).

Results

Mean eGFR was 113 mL/min/1.73 m² 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 m², 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.

Section snippets

Study Design

The study design and population have been previously described.¹³ Briefly, the population included sugarcane workers employed by one company in northwestern Nicaragua. We enrolled participants (n = 1,249) prior to the harvest season (October 2010 to December 2010) at a screening conducted by the company, which aims to identify, so as not to hire, workers with serum creatinine levels ≥ 1.4 mg/dL. Four to 6 months later, near the end of the harvest season (March 2011 to May 2011), we resampled 506

Description of Study Population

Men constituted the majority of the study population (88%), with women employed as seeders, seed cutters, and factory workers only (Table 1). Mean age of workers was 33.6 (range, 18-63) years, whereas mean duration of employment at the company was 9.4 (range, <1-40) years. Workers reported drinking an average 5.1 L of water and 2.4 electrolyte solution packets while at work each day (Table 1).

Levels of biomarkers of kidney injury and function were normally distributed after natural log

Discussion

In a population of Nicaraguan sugarcane workers at risk for Mesoamerican Nephropathy, urinary levels of NGAL and IL-18, both biomarkers of kidney injury, increased during the harvest season in certain job tasks relative to others. These findings suggest that subclinical kidney injury is occurring in these workers during one harvest season, and the differences by job provide evidence that occupational exposures play a role. We found associations between increases in NGAL and NAG levels and

Acknowledgements

We would like to express gratitude to all of the study participants. We also thank Dr Alcides Gonzalez and the Nicaraguan Ministry of Health for contributions to the field investigation and laboratory support.

Support: The funds were provided by the Compliance Advisor/Ombudsman (CAO), the independent accountability mechanism for social and environmental issues of the International Finance Corporation (IFC)/Multilateral Investment Guarantee Agency (MIGA) of the World Bank Group, and the Comité

References (53)

C. Wesseling et al.
Resolving the enigma of the Mesoamerican nephropathy: a research workshop summary
Am J Kidney Dis
(2014)
S. Peraza et al.
Decreased kidney function among agricultural workers in El Salvador
Am J Kidney Dis
(2012)
C. Torres et al.
Decreased kidney function of unknown cause in Nicaragua: a community-based survey
Am J Kidney Dis
(2010)
R. Correa-Rotter et al.
CKD of unknown origin in Central America: the case for a Mesoamerican nephropathy
Am J Kidney Dis
(2014)
D.R. Brooks et al.
CKD in Central America: a hot issue
Am J Kidney Dis
(2012)
S.G. Coca et al.
Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review
Kidney Int
(2008)
Y. Liu et al.
Urinary interleukin 18 for detection of acute kidney injury: a meta-analysis
Am J Kidney Dis
(2013)
M. Bedford et al.
Acute kidney injury and CKD: chicken or egg?
Am J Kidney Dis
(2012)
P. Soderland et al.
Chronic kidney disease associated with environmental toxins and exposures
Adv Chronic Kidney Dis
(2010)
J. Wijkstrom et al.
Clinical and pathological characterization of Mesoamerican nephropathy: a new kidney disease in Central America
Am J Kidney Dis
(2013)

C.R. Parikh et al.

Urine stability studies for novel biomarkers of acute kidney injury

Am J Kidney Dis

(2014)

F.L. Nauta et al.

Effect of frozen storage on urinary concentration of kidney damage markers

Am J Kidney Dis

(2012)

O. Ramirez-Rubio et al.

Chronic kidney disease in Nicaragua: a qualitative analysis of semi-structured interviews with physicians and pharmacists

BMC Public Health

(2013)

O. Ramirez-Rubio et al.

An epidemic of chronic kidney disease in Central America: an overview

J Epidemiol Community Health

(2013)

D.E. Weiner et al.

The Central American epidemic of CKD

Clin J Am Soc Nephrol

(2013)

C. Wesseling et al.

The epidemic of chronic kidney disease of unknown etiology in Mesoamerica: a call for interdisciplinary research and action

Am J Public Health

(2013)

C.M. Orantes et al.

Epidemiology of chronic kidney disease in adults of Salvadoran agricultural communities

MEDICC Rev

(2014)

N. Raines et al.

Risk factors for reduced glomerular filtration rate in a Nicaraguan community affected by Mesoamerican nephropathy

MEDICC Rev

(2014)

J.K. O'Donnell et al.

Prevalence of and risk factors for chronic kidney disease in rural Nicaragua

Nephrol Dial Transplant

(2011)

C.M. Orantes et al.

Chronic kidney disease and associated risk factors in the Bajo Lempa region of El Salvador: Nefrolempa study, 2009

MEDICC Rev

(2011)

S.L. Sanoff et al.

Positive association of renal insufficiency with agriculture employment and unregulated alcohol consumption in Nicaragua

Ren Fail

(2010)

R.L. Laws et al.

Changes in kidney function among Nicaraguan sugarcane workers

Int J Occup Environ Health

(2015)

Global burden of disease: disease and injury country estimates. World Health Organization....

Cuadra SN, Jakobsson K, Hogstedt C, Wesseling C. Chronic kidney disease: assessment of current knowledge and...

P. Devarajan

Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease

Scand J Clin Lab Invest Suppl

(2008)

V.S. Vaidya et al.

Biomarkers of acute kidney injury

Annu Rev Pharmacol Toxicol

(2008)

Cited by (88)

Risk factors associated with indicators of dehydration among migrant farmworkers
2024, Environmental Research
Farmworkers are at increased risk of adverse health outcomes related to occupational heat exposure and inadequate access to water, shade, or rest breaks. Presently, there is a dearth of studies examining the prevalence of dehydration and related factors in U.S. farmworkers. Our objectives were to characterize hydration status during typical workdays and to identify risk factors associated with increased dehydration in migrant farmworkers employed in Florida.
Urine samples were collected and analyzed for urine specific gravity (USG) 2–3 times per person per day over five days in May 2021 and 2022. Data collection included demographic characteristics, wet-bulb-globe-temperature (WBGT), and information on working conditions (task type, duration, and crop units harvested), fluid intake, clothing worn, and heat safety behaviors. Multivariable mixed regression models were used to evaluate risk factors associated with change in USG levels (continuous) during a work shift.
A total of 111 farmworkers participated in this study providing 1020 cumulative USG measurements, of which 96.8% of end-of-shift USG samples were above 1.020 indicating potential dehydration. In multivariable models, dehydration assessed using change in USG levels significantly declined with age (β = −0.078; 95%CI: 0.150, −0.006) but showed significant increase with body mass index (β = 0.016; 95%CI: 0.003, 0.028), WGBT (β = 0.054; 95%CI:0.044, 0.064), mean shift duration, and state of primary residence. We did not find significant associations of dehydration with type of clothing worn, intake of employer-provided water, or crop units harvested during a shift in this sample of farmworkers.
Our findings underscore the need for additional research to evaluate adverse outcomes related to dehydration and to better understand recovery patterns from chronic dehydration across workweeks and harvest seasons in migrant farmworkers.
Urinary biomarkers in kidney disease
2024, Clinica Chimica Acta
Chronic kidney disease (CKD) affects many people worldwide and early diagnosis is essential for successful treatment and improved outcome. Unfortunately, current methods are insufficient especially for early disease detection. However, advances in the analytical methods for urinary biomarkers may provide a unique opportunity for diagnosis and management of CKD. This review explores evolving technology and highlights the importance of early marker detection in these patients.
A search strategy was set up using the terms CKD, biomarkers, and urine. The search included 53 studies comprising 37 biomarkers. The value of these biomarkers for CKD are based on their ability to diagnose CKD, monitor progression, assess mortality and nephrotoxicity.
KIM-1 was the best marker for diagnosis as it increased with the development of incident CKD. DKK3 increased in patients with declining eGFR, whereas UMOD decreased in those with declining kidney function. Unfortunately, none fulfilled all criteria to adequately assess mortality and nephrotoxicity.
New developments in the field of urinalysis using smart toilets may open several possibilities for urinary biomarkers. This review explored which biomarkers could be used for CKD disease detection and management.
Recent ambient temperature and fine particulate matter (PM<inf>2.5</inf>) exposure is associated with urinary kidney injury biomarkers in children
2024, Science of the Total Environment
Limited research has examined associations between exposure to ambient temperature, air pollution, and kidney function or injury during the preadolescent period. We examined associations between exposure to ambient temperature and particulate matter with aerodynamic diameter ≤ 2.5 μm (PM_2.5) with preadolescent estimated glomerular filtration rate (eGFR) and urinary kidney injury biomarkers.
Participants included 437 children without cardiovascular or kidney disease enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors birth cohort study in Mexico City. eGFR and urinary kidney injury biomarkers were assessed at 8–12 years. Validated satellite-based spatio-temporal models were used to estimate mean daily temperature and PM_2.5 levels at each participant's residence 7- and 30-days prior to the date of visit. Linear regression and distributed lag nonlinear models (DLNM) were used to examine associations between daily mean temperature and PM_2.5 exposure and kidney outcomes, adjusted for covariates.
In single linear regressions, higher seven-day average PM_2.5 was associated with higher urinary alpha-1-microglobulin and eGFR. In DLNM analyses, higher temperature exposure in the seven days prior to date of visit was associated with a decrease in urinary cystatin C of −0.56 ng/mL (95 % confidence interval (CI): −1.08, −0.04) and in osteopontin of −0.08 ng/mL (95 % CI: −0.15, −0.001). PM_2.5 exposure over the seven days prior to date of visit was associated with an increase in eGFR of 1.77 mL/min/1.73m² (95 % CI: 0.55, 2.99) and urinary cystatin C of 0.19 ng/mL (95 % CI: 0.03, 0.35).
Recent exposure to ambient temperature and PM_2.5 were associated with increased and decreased urinary kidney injury biomarkers that may reflect subclinical glomerular or tubular injury in children. Further research is required to assess environmental exposures and worsening subclinical kidney injury across development.
Exposome and Metabolome Analysis of Sugarcane Workers Reveals Predictors of Kidney Injury
2024, Kidney International Reports
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.
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.
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.
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.
Impact of climate change and heat stress on workers’ health and productivity: A scoping review
2023, Journal of Climate Change and Health
There are indications that heatwaves will be intensified in duration, frequency and magnitude and will pose threats to the livelihoods and health of the global working population. The purpose of this scoping review was to map evidence regarding occupational heat stress risk factors, their impact on workers’ health and productivity, and potential adaptation measures.
Keywords reflecting climate change, heat stress, health, productivity and adaptation strategies were used for searches in PubMed, PubMed Central, Scopus and Web of Science. Manuscripts that focused on heat adaptation, health and productivity outcomes of heat exposure among working populations were considered eligible for this review, while reviews, preprints and papers focused on the general population were excluded.
The evidence suggests that gender, age, pre-shift dehydration, piece-rate payment, poor access to sanitation facilities, use of inappropriate personal protective equipment, physically demanding work, high workload, low job control, and high temperatures are risk factors for heat-related illness, dehydration, kidney diseases and mental distress. Specific working populations including migrants, pregnant women, and children were found to be extremely vulnerable to heat stress. The review identified that frequent intake of fluids, resting under shade or in cooling facilities, changing work hours, and increased electrolyte intake were used as adaptation measures.
Measures targeting adequate hydration, self-pacing, work-rest regimes, provision of shade and appropriate sanitation facilities need to be matched with improved psychosocial work conditions such as optimal work hours, job autonomy and control, and social supports to ensure safe working conditions in changing climates.
Occupational heat exposure alone does not explain chronic kidney disease of uncertain aetiology (CKDu) in Sri Lanka
2022, Journal of Climate Change and Health
Chronic kidney disease of uncertain aetiology (CKDu) is an emerging health concern in tropical farming communities. The role of occupational heat exposure as a potential driver of CKDu remains debated. Our study examines occupational heat exposure and kidney health in three occupational groups in Sri Lanka.
We recruited participants from three occupational groups from three climatic zones; fisherfolk from the dry and intermediate zones (N = 225), paddy farmers from the intermediate zone (N = 180) and tea plantation workers from the wet zone (N = 70). Serum creatinine, cystatin-C, urea and uric acid, estimated glomerular filtration rate and urinary albumin-creatinine ratio were used as diagnostic criteria of impaired renal function.
CKDu susceptibility was at the highest among farmers (13.33 %), with a significant difference compared to the fisherfolk (5.36 %; p = 0.0003). Among the plantation workers, CKDu susceptibility was 5.71 %, and it was not significantly different compared to the farmers (p = 0.087) and the fisherfolk (p = 0.427). Despite higher exposure to heat stress and dehydration, as indicated by the highest simplified wet bulb globe temperature (sWBGT) in the work environments, fisherfolk reported the lowest CKDu susceptibility, while farmers and workers with low to moderate heat exposure showed an increased incidence of abnormal renal function. Further, a multivariable regression analysis identified a significant effect of occupation (p = 0.005), agrochemical exposure (p = 0.001) and age (p = 0.001) on the likelihood of CKDu susceptibility while the sWBGT in the working environments showed no significant effect (p = 0.227).
With the evidence from our findings, heat exposure alone does not appear to be the leading driver of CKDu in Sri Lanka, suggesting that the nephropathy is more likely to be associated with occupational risks such as agrochemical exposures.

View all citing articles on Scopus

: Because 2 authors of this article are editors for AJKD, the peer-review and decision-making processes were handled entirely by an Associate Editor (Morgan Grams, MD, PhD) who served as Acting Editor-in-Chief. Details of the journal’s procedures for potential editor conflicts are given in the Information for Authors & Journal Policies.

View full text

Original InvestigationPathogenesis and Treatment of Kidney DiseaseBiomarkers of Kidney Injury Among Nicaraguan Sugarcane Workers

Background

Study Design

Setting & Participants

Predictors

Outcomes & Measurements

Results

Limitations

Conclusions

Section snippets

Study Design

Description of Study Population

Discussion

Acknowledgements

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Adv Chronic Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Chronic kidney disease in Nicaragua: a qualitative analysis of semi-structured interviews with physicians and pharmacists

BMC Public Health

An epidemic of chronic kidney disease in Central America: an overview

J Epidemiol Community Health

The Central American epidemic of CKD

Clin J Am Soc Nephrol

The epidemic of chronic kidney disease of unknown etiology in Mesoamerica: a call for interdisciplinary research and action

Am J Public Health

Epidemiology of chronic kidney disease in adults of Salvadoran agricultural communities

MEDICC Rev

Risk factors for reduced glomerular filtration rate in a Nicaraguan community affected by Mesoamerican nephropathy

MEDICC Rev

Prevalence of and risk factors for chronic kidney disease in rural Nicaragua

Nephrol Dial Transplant

Chronic kidney disease and associated risk factors in the Bajo Lempa region of El Salvador: Nefrolempa study, 2009

MEDICC Rev

Positive association of renal insufficiency with agriculture employment and unregulated alcohol consumption in Nicaragua

Ren Fail

Changes in kidney function among Nicaraguan sugarcane workers

Int J Occup Environ Health

Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease

Scand J Clin Lab Invest Suppl

Biomarkers of acute kidney injury

Annu Rev Pharmacol Toxicol

Original Investigation
Pathogenesis and Treatment of Kidney Disease
Biomarkers of Kidney Injury Among Nicaraguan Sugarcane Workers