Kidney function in sugarcane cutters in Nicaragua – A longitudinal study of workers at risk of Mesoamerican nephropathy
Introduction
The recognition of Mesoamerican Nephropathy (MeN)-also labelled Chronic Kidney Disease of non-traditional origin (CKDnt) – as an epidemic in Central America, has led to the publication of a number of reports examining risk factors and causal hypotheses (Wesseling et al., 2014, Correa-Rotter et al., 2014). Experimental studies have also been performed (Roncal Jimenez et al., 2014).
To date the findings have shown that the epidemic primarily affects males working in heavy manual labor in hot environments, mainly living in the coastal lowlands. There is generally no history of diabetes or hypertension and no substantial proteinuria. Kidney biopsies have shown a tubulointerstitial pattern with tubular atrophy and interstitial fibrosis, but also global glomerulosclerosis, often with an ischemic component (Wijkstrom et al., 2013, López-Marín et al., 2014).
The main hypothesis to account for the disease is heat stress with repetitive episodes of dehydration (Peraza et al., 2012, Brooks et al., 2012, Wesseling et al., 2014, Correa-Rotter et al., 2014, García-Trabanino et al., 2015). Suggested pathophysiologic mechanisms driven by strenuous work and heat stress include subclinical rhabdomyolysis (Paula Santos et al., 2015), effects of hyperuricemia and hyperuricosuria (Knochel et al., 1974, Johnson, 2015, Roncal-Jimenez et al., 2015, Roncal-Jimenez et al., 2015), hyperosmolality-induced activation of the aldose reductase-fructokinase pathway in the kidney, and vasopressin effects (Roncal Jimenez et al., 2014, Roncal-Jimenez et al., 2015, Roncal-Jimenez et al., 2015). It has also been proposed that the disease is multifactorial, and could include additional factors such as self-medication with nonsteroidal anti-inflammatory drugs, exposure to heavy metals or pesticides/agrochemicals, infections, or genetic factors (Correa-Rotter et al., 2014, Herrera et al., 2014, Laws et al., 2015a, Laws et al., 2015b, Ramírez-Rubio et al., 2015, Wesseling et al., 2014).
Most of the epidemiological studies are cross-sectional population based surveys. Two studies have examined cross-shift changes in biomarkers of hydration and kidney function, over a workday, in Brazil, (Paula Santos et al., 2015), and El Salvador (García-Trabanino et al., 2015), and two studies have performed a follow-up of kidney function among sugarcane cutters over the course of a harvest season, in Brazil (Paula Santos et al., 2015) and in Nicaragua (Laws et al., 2015a, Laws et al., 2015b). While the two studies on cross-shift changes both show a decrease in renal function over a cane cutting shift, the two longitudinal studies were not in agreement, and the question of whether the pre-shift glomerular function changes over a harvest period of several months still remains unclear. The aim of the present study was to assess longitudinal changes of kidney function over a harvest period in sugarcane cutters as well as in a reference group. We examined pre- and post-shift kidney function in sugarcane cutters at the start of harvest, on day 1 and day 6 to assess acclimatization effects, and at mid-harvest two months later. A reference group of non-cane cutters was examined at start and end of the harvest.
Section snippets
Setting and study design
The study was conducted in 2012–2013 in a convenience sample of 29 sugarcane cutters from León and Chinandega municipalities in the northern Nicaraguan Pacific region, and a reference group (N=25, mainly office workers) from the same area. The sugarcane cutters were examined “pre-shift” in the morning between 3 and 5 am and “post-shift” between 4 and 7 pm at their homes on the first day of the harvest in November 2012. The pre-shift examination on the first day (called Cut1) was considered to be
Results
Characteristics of the 29 sugarcane cutters and the 25 referents are shown in Table 1. The mean age of the cane cutters was 25 years. The referents were somewhat older, had slightly higher BMI, smoked slightly less, and used alcohol more often. In the interviews, one participant in each group reported hypertension, but both of them had normal blood pressure at examination and they did not take antihypertensive medications. Six cutters reported ever use of NSAIDS >3 months versus one referent
Discussion
In the present study a group of sugarcane cutters was examined on the first day at start of harvest, after 6 days, and again after 9 weeks. The most remarkable finding was a clear and significant decrease in pre-shift renal function after 9 weeks of work, with a 16% increase in mean serum creatinine, a 40% increase in serum urea N, 10% decrease in estimated GFR and two new cases of reduced eGFR (<60 mL/min).
While the rise in post-shift serum creatinine could reflect dehydration with a loss of
Funding source
This study was funded by DANONE Research. The funding source was not involved in any part of this study, or the decision to submit the manuscript for publication.
Ethics review
All participants signed a written informed consent to participate in the study, which was approved by the IRB at National Autonomous University of Nicaragua, León and the Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico.
Disclosures
The authors disclose no conflicts of interest related to this study. Dr Johnson does have patents and patent applications related to blocking fructose and uric acid metabolism, is on the Scientific Board for Amway and XORT therapeutics, has lectured at Danone symposia, and is a member of Colorado Research Partners that is developing inhibitors for fructose metabolism. Dr. Bobadilla does have patents and patent applications related to Hsp72 as a biomarker of acute kidney injury.
Ackowledgements
We thank Tamara Harra BS, Chris Rivard, PhD, and Rosalba Pérez-Villalva for help in the chemical analyses, and Eva M Andersson, assoc prof, for assistance with programming.
References (30)
- et al.
CKD in Central America: a hot issue
Am. J. Kidney Dis.
(2012) - et al.
Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury
Kidney Int.
(2012) - et al.
CKD of unknown origin in Central America: the case for a Mesoamerican nephropathy
Am. J. Kidney Dis.
(2014) - et al.
Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador – a cross-shift study of workers at risk of Mesoamerican nephropathy
Environ. Res.
(2015) - et al.
Effect of frozen storage on urinary concentration of kidney damage markers
Am. J. Kidney Dis.
(2012) - et al.
Some biomarkers of acute kidney injury are increased in pre-renal acute injury
Kidney Int.
(2012) - et al.
Burnt sugarcance harvesting is associated with acute renal dysfunction
Kidney Int.
(2015) - et al.
Decreased kidney function among agricultural workers in El Salvador
Am. J. Kidney Dis.
(2012) - et al.
Fructokinase activity mediates dehydration-induced renal injury
Kidney Int.
(2014) - et al.
Heat stress nephropathy from exercise-induced uric acid crystalluria: a perspective on Mesoamerican nephropathy
Am. J. Kidney Dis.
(2016)
Resolving the enigma of the Mesoamerican nephropathy: a research workshop summary
Am. J. Kidney Dis.
Clinical and pathological characterization of Mesoamerican nephropathy: a new kidney disease in Central America
Am. J. Kidney Dis.
Hsp72 is an early and sensitive biomarker to detect acute kidney injury
EMBO Mol. Med.
Heat-related symptoms in sugarcane harvesters
Am. J. Ind. Med.
Biological rhythms of biochemical serum parameters in a Brazilian population: a three-year study
Chronobiol. Int.
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