Preventing kidney injury among sugarcane workers: promising evidence from enhanced workplace interventions.

OBJECTIVES: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin. METHODS: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest schedule and improved access to hydration and shade were given before the 2018-2019 harvest (harvest 2). Actual work conditions during harvest 2 were then observed. Serum creatinine (SCr) was measured before and at end-harvest, and cross-harvest changes in estimated glomerular filtration rate (eGFR) and incident kidney injury (IKI, ie, SCr increase by ≥0.30 mg/dL or ≥1.5 times the baseline value) were compared between harvest 1 and harvest 2 for three jobs with different physical workloads using regression modelling. Workers who left during harvest were contacted at home, to address the healthy worker selection effect. RESULTS: In burned cane cutters, mean cross-harvest eGFR decreased 6 mL/min/1.73 m2 (95% CI 2 to 9 mL/min/1.73 m2) less and IKI was 70% (95% CI 90% to 50%) lower in harvest 2 as compared with harvest 1 data. No such improvements were seen among seed cutters groups with less successful intervention implementation. CONCLUSION: Kidney injury risk was again elevated in workers with strenuous jobs. The results support further efforts to prevent kidney injury among sugarcane workers, and other heat-stressed workers, by improving access to water, rest and shade. The distinction between design and implementation of such interventions should be recognised.

Insufficient mixing of thawed serum samples leading to erroneous results - experience from a field study and use of a correction procedure.

Incorrect analysis results that are close to expected might not be recognized in scientific studies or routine patient care. In two field studies we obtained unexpected results in a large number of samples. The present study aimed to identify the source of error in the samples from these studies and to validate a method to obtain correct results. Pre-analytical procedures were scrutinized, giving no indications of inappropriate pre-analytical sample handling in the field or during transport in a tropical climate. Using a new set of samples from volunteers in simulation experiments, we observed the known concentration gradient of analytes sampled in gel as well as plain tubes after freezer storage and thawing. Experiments demonstrated that mixing of samples by vortexing alone was not sufficient to disrupt the gradient formed by freezing and thawing, which appeared to cause the problem encountered when we in field studies analyzed and biobanked large sample sets by robot pipetting. A correction procedure was introduced, in which the obtained value of an analyte was multiplied by a correction factor calculated for each sample using the expected sodium level (140 mmol/L) divided by the measured sodium value. When it was validated on results from the simulation experiments, we repeatedly found that the correction lead to results very close to true values for analytes of different size and charge. Usefulness of the procedure was demonstrated when applied to a large set of field study results.

Workload and cross-harvest kidney injury in a Nicaraguan sugarcane worker cohort.

OBJECTIVES: To examine the association between workload and kidney injury in a fieldworker cohort with different levels of physically demanding work over a sugarcane harvest, and to assess whether the existing heat prevention efforts at a leading occupational safety and health programme are sufficient to mitigate kidney injury. METHODS: Biological and questionnaire data were collected before (n=545) and at the end (n=427) of harvest among field support staff (low workload), drip irrigation workers (moderate), seed cutters (high) and burned sugarcane cutters (very high). Dropouts were contacted (87%) and reported the reason for leaving work. Cross-harvest incident kidney injury (IKI) was defined as serum creatinine increase ≥0.30 mg/dL or ≥1.5 times the baseline value, or among dropouts reporting kidney injury leading to leaving work. RESULTS: Mean cross-harvest estimated glomerular filtration rate change was significantly associated with workload, increasing from 0 mL/min/1.73 m2 in the low-moderate category to -5 mL/min/1.73 m2 in the high and -9 mL/min/1.73 m2 in the very high workload group. A similar pattern occurred with IKI, where low-moderate workload had 2% compared with 27% in the very high workload category. A healthy worker selection effect was detected, with 32% of dropouts reporting kidney injury. Fever and C reactive protein elevation were associated with kidney injury. CONCLUSIONS: Workers considered to have the highest workload had more cross-harvest kidney damage than workers with less workload. Work practices preventing heat stress should be strengthened and their role in preventing kidney damage examined further. Future occupational studies on chronic kidney disease of unknown aetiology should account for a healthy worker effect by pursuing those lost to follow-up.

Intervention to diminish dehydration and kidney damage among sugarcane workers.

Objective The aim of this study was to assess the potential to reduce kidney function damage during the implementation of a water, rest, shade (WRS) and efficiency intervention program among sugarcane workers. Methods A WRS intervention program adapted from the US Occupational Safety and Health Administration (OSHA) coupled with an efficiency program began two months into the 5-month harvest. One of the two groups of workers studied was provided with portable water reservoirs, mobile shaded tents, and scheduled rest periods. Health data (anthropometric and questionnaires), blood, and urine were collected at baseline and at three subsequent times over the course of the harvest. Daily wet bulb globe temperatures (WBGT) were recorded. Results Across a working day there were changes in biomarkers indicating dehydration (urine osmolality) and serum albumin and reduced estimated glomerular filtration rate (eGFR). Cross-shift eGFR decrease was present in both groups; -10.5 mL/min/1.73m2 [95% confidence interval (95% CI) -11.8- -9.1], but smaller for the intervention group after receiving the program. Decreased eGFR over the 5-month harvest was seen in both groups: in the one receiving the intervention -3.4 mL/min/1.73m 2(95% CI -5.5- -1.3) and in the other -5.3 (95% CI -7.9- -2.7). The decrease appeared to halt after the introduction of the intervention in the group receiving the program. Conclusion A WRS and efficiency intervention program was successfully introduced for workers in sugarcane fields and appears to reduce the impact of heat stress on acute and over-harvest biomarkers of kidney function. Further research is needed to determine whether biomarker changes predict reduced risk of chronic kidney disease in this type of work.

Low-level internalization of cystatin E/M affects legumain activity and migration of melanoma cells.

The ratio between proteases and their inhibitors is unbalanced in cancer. The cysteine protease inhibitor cystatin C is internalized by some cancer cells, which affects cellular properties. Here we aimed to investigate if uptake of cystatin C and the related inhibitor cystatin E/M occur in melanoma cell lines and to evaluate to what extent the uptake affects the legumain activity that is typically increased in melanoma. First we studied the basic expression, secretion, and intracellular content of all type 2 cystatins as well as expression and activity of their possible target enzymes legumain and cathepsin B in MDA-MB-435S, A375, and C8161 melanoma cells. Legumain activity was measureable in all cell lines, and of the potential legumain inhibitors, cystatin C, E/M, and F, cystatin C was the one mainly produced. All cells internalized cystatin C added to culture media, leading to increased intracellular cystatin C levels by 120-200%. Cystatin E/M was internalized as well but at a modest rate. The effects on intracellular legumain activity were nevertheless pronounced, probably because the cells lacked this inhibitor, and its affinity for legumain is 100-fold higher than that of cystatin C. Likewise, the low-degree uptake resulted in reduced migration and invasion of A375 cells in Matrigel to an extent comparable with the W106F variant of cystatin C with optimal uptake properties and resulting in much higher intracellular levels. Thus, cystatin E/M appears to be a good candidate to efficiently down-regulate the increased legumain activity, possibly important for the malignant phenotype of melanoma cells.