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Article ; Online: Investigating Possible Infectious Causes of Chronic Kidney Disease of Unknown Etiology in a Nicaraguan Mining Community.

Yih, W Katherine / Kulldorff, Martin / Friedman, David J / Leibler, Jessica H / Amador, Juan José / López-Pilarte, Damaris / Galloway, Renee L / Ramírez-Rubio, Oriana / Riefkohl, Alejandro / Brooks, Daniel R

The American journal of tropical medicine and hygiene

2019 Volume 101, Issue 3, Page(s) 676–683

Abstract: A chronic kidney disease of unknown etiology (CKDu) has been killing workers in Central America. Occupational heat stress is thought to play an important role. Leptospirosis and hantavirus have been suggested as additional possible risk factors. In a ... ...

Abstract	A chronic kidney disease of unknown etiology (CKDu) has been killing workers in Central America. Occupational heat stress is thought to play an important role. Leptospirosis and hantavirus have been suggested as additional possible risk factors. In a case-control study in a Nicaraguan mining community, a structured survey was administered to adults, and biological measurements and specimens were taken. Serum was analyzed for antibodies to
MeSH term(s)	Adult ; Aged ; Case-Control Studies ; Creatinine/blood ; Female ; Hantavirus ; Hantavirus Infections/epidemiology ; Humans ; Leptospira ; Leptospirosis/epidemiology ; Male ; Middle Aged ; Mining ; Nicaragua/epidemiology ; Prospective Studies ; Public Health ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/etiology ; Risk Factors ; Young Adult
Chemical Substances	Creatinine (AYI8EX34EU)
Language	English
Publishing date	2019-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.18-0856
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Article ; Online: Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy.

Stallings, Tiffany L / Riefkohl Lisci, Alejandro / McCray, Nathan L / Weiner, Daniel E / Kaufman, James S / Aschengrau, Ann / Ma, Yan / LaValley, Michael P / Ramírez-Rubio, Oriana / Jose Amador, Juan / López-Pilarte, Damaris / Laws, Rebecca L / Winter, Michael / McSorley, V Eloesa / Brooks, Daniel R / Applebaum, Katie M

Scandinavian journal of work, environment & health

2021 Volume 47, Issue 5, Page(s) 377–386

Abstract: Objectives: Nicaraguan sugarcane workers, particularly cane cutters, have an elevated prevalence of chronic kidney disease of unknown origin, also referred to as Mesoamerican nephropathy (MeN). The pathogenesis of MeN may include recurrent heat stress, ... ...

Abstract	Objectives: Nicaraguan sugarcane workers, particularly cane cutters, have an elevated prevalence of chronic kidney disease of unknown origin, also referred to as Mesoamerican nephropathy (MeN). The pathogenesis of MeN may include recurrent heat stress, crystalluria, and muscle injury with subsequent kidney injury. Yet, studies examining the frequency of such events in long-term, longitudinal studies are limited. Methods: Using employment and medical data for male workers at a Nicaraguan sugarcane company, we classified months of active work as either work as a cane cutter or other sugarcane job and determined occurrence of dysuria, heat events and muscle events. Work months and events occurred January 1997 to June 2010. Associations between cane cutting and each outcome were analyzed using logistic regression based on generalized estimating equations for repeated events, controlling for age. Results: Among 242 workers with 7257 active work months, 19.5% of person-months were as a cane cutter. There were 160, 21, and 16 episodes of dysuria, heat events, and muscle events, respectively. Compared with work months in other jobs, cane cutting was associated with an elevated odds of dysuria [odds ratio 2.40 (95% confidence interval 1.56-3.68)]. The number of heat and muscle events by cane cutter and other job were limited. Conclusions: Working as a cane cutter compared with other jobs in the sugarcane industry was associated with increased dysuria, supporting the hypothesis that cane cutters are at increased risk of events suspected of inducing or presaging clinically evident kidney injury.
MeSH term(s)	Dysuria/epidemiology ; Dysuria/etiology ; Heat Stress Disorders ; Heat-Shock Response ; Humans ; Male ; Muscles ; Saccharum
Language	English
Publishing date	2021-05-18
Publishing country	Finland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	191563-0
ISSN	1795-990X ; 0355-3140
ISSN (online)	1795-990X
ISSN	0355-3140
DOI	10.5271/sjweh.3963
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Article ; Online: Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy

Tiffany L Stallings / Alejandro Riefkohl Lisci / Nathan L McCray / Daniel E Weiner / James S Kaufman / Ann Aschengrau / Yan Ma / Michael P LaValley / Oriana Ramírez-Rubio / Juan Jose Amador / Damaris López-Pilarte / Rebecca L Laws / Michael Winter / V Eloesa McSorley / Daniel R Brooks / Katie M Applebaum

Scandinavian Journal of Work, Environment & Health, Vol 47, Iss 5, Pp 377-

2021 Volume 386

Abstract: OBJECTIVES: Nicaraguan sugarcane workers, particularly cane cutters, have an elevated prevalence of chronic kidney disease of unknown origin, also referred to as Mesoamerican nephropathy (MeN). The pathogenesis of MeN may include recurrent heat stress, ... ...

Abstract	OBJECTIVES: Nicaraguan sugarcane workers, particularly cane cutters, have an elevated prevalence of chronic kidney disease of unknown origin, also referred to as Mesoamerican nephropathy (MeN). The pathogenesis of MeN may include recurrent heat stress, crystalluria, and muscle injury with subsequent kidney injury. Yet, studies examining the frequency of such events in long-term, longitudinal studies are limited. METHODS: Using employment and medical data for male workers at a Nicaraguan sugarcane company, we classified months of active work as either work as a cane cutter or other sugarcane job and determined occurrence of dysuria, heat events and muscle events. Work months and events occurred January 1997 to June 2010. Associations between cane cutting and each outcome were analyzed using logistic regression based on generalized estimating equations for repeated events, controlling for age. RESULTS: Among 242 workers with 7257 active work months, 19.5% of person-months were as a cane cutter. There were 160, 21, and 16 episodes of dysuria, heat events, and muscle events, respectively. Compared with work months in other jobs, cane cutting was associated with an elevated odds of dysuria [odds ratio 2.40 (95% confidence interval 1.56–3.68)]. The number of heat and muscle events by cane cutter and other job were limited. CONCLUSIONS: Working as a cane cutter compared with other jobs in the sugarcane industry was associated with increased dysuria, supporting the hypothesis that cane cutters are at increased risk of events suspected of inducing or presaging clinically evident kidney injury.
Keywords	dysuria ; nicaragua ; chronic kidney disease of unknown origin ; ckdu ; crystalluria ; rhabdomyolysis ; heat stress ; muscle injury ; sugarcane worker ; mesoamerican nephropathy ; chronic kidney disease ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Nordic Association of Occupational Safety and Health (NOROSH)
Document type	Article ; Online
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Article ; Online: Biomarkers of Kidney Injury Among Nicaraguan Sugarcane Workers.

Laws, Rebecca L / Brooks, Daniel R / Amador, Juan José / Weiner, Daniel E / Kaufman, James S / Ramírez-Rubio, Oriana / Riefkohl, Alejandro / Scammell, Madeleine K / López-Pilarte, Damaris / Sánchez, José Marcel / Parikh, Chirag R / McClean, Michael D

American journal of kidney diseases : the official journal of the National Kidney Foundation

2016 Volume 67, Issue 2, Page(s) 209–217

Abstract: 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 ... ...

Abstract	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 m(2) 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 m(2), 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.
MeSH term(s)	Adult ; Biomarkers/blood ; Biomarkers/urine ; Cohort Studies ; Dehydration/blood ; Dehydration/epidemiology ; Dehydration/urine ; Farmers ; Female ; Heat-Shock Response/physiology ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Nicaragua/epidemiology ; Occupational Exposure/adverse effects ; Renal Insufficiency, Chronic/blood ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/urine ; Saccharum ; Young Adult
Chemical Substances	Biomarkers
Language	English
Publishing date	2016-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2015.08.022
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Article ; Online: Leptospira seropositivity as a risk factor for Mesoamerican Nephropathy.

Riefkohl, Alejandro / Ramírez-Rubio, Oriana / Laws, Rebecca L / McClean, Michael D / Weiner, Daniel E / Kaufman, James S / Galloway, Renee L / Shadomy, Sean V / Guerra, Marta / Amador, Juan José / Sánchez, José Marcel / López-Pilarte, Damaris / Parikh, Chirag R / Leibler, Jessica H / Brooks, Daniel R

International journal of occupational and environmental health

2017 Volume 23, Issue 1, Page(s) 1–10

Abstract: Background: Leptospirosis is postulated as a possible cause of Mesoamerican Nephropathy (MeN) in Central American workers.: Objectives: Investigate job-specific Leptospira seroprevalence and its association with kidney disease biomarkers.: Methods!# ...

Abstract	Background: Leptospirosis is postulated as a possible cause of Mesoamerican Nephropathy (MeN) in Central American workers. Objectives: Investigate job-specific Leptospira seroprevalence and its association with kidney disease biomarkers. Methods: In 282 sugarcane workers, 47 sugarcane applicants and 160 workers in other industries, we measured anti-leptospiral antibodies, serum creatinine, and urinary injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and N-acetyl-D-glucosaminidase (NAG). Results: Leptospira seroprevalence differed among job categories and was highest among sugarcane cutters (59%). Seropositive sugarcane workers had higher NGAL concentrations (relative mean: 1.28; 95% CI: 0.94-1.75) compared to those who were seronegative, with similar findings among field and non-field workers. Conclusions: Leptospira seroprevalence varied by job category. There was some indication that seropositivity was associated with elevated biomarker levels, but results were inconsistent. Additional studies may help establish whether Leptospira infection plays any role in MeN among Central American workers.
MeSH term(s)	Adult ; Antibodies, Bacterial/blood ; Biomarkers/blood ; Creatinine/blood ; Farmers/statistics & numerical data ; Female ; Humans ; Interleukin-18/blood ; Leptospira/immunology ; Leptospirosis/blood ; Leptospirosis/complications ; Leptospirosis/epidemiology ; Leptospirosis/immunology ; Lipocalin-2/blood ; Male ; Middle Aged ; Nicaragua/epidemiology ; Prospective Studies ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/epidemiology ; Seroepidemiologic Studies ; Young Adult
Chemical Substances	Antibodies, Bacterial ; Biomarkers ; Interleukin-18 ; LCN2 protein, human ; Lipocalin-2 ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2017-02-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1262326-x
ISSN	2049-3967 ; 1077-3525
ISSN (online)	2049-3967
ISSN	1077-3525
DOI	10.1080/10773525.2016.1275462
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Article ; Online: Changes in kidney function among Nicaraguan sugarcane workers.

International journal of occupational and environmental health

2015 Volume 21, Issue 3, Page(s) 241–250

Abstract: Background: There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers.: Objectives: To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the ...

Abstract	Background: There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers. Objectives: To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the potential role of hydration, and measure proteinuria. Methods: We recruited 284 Nicaraguan sugarcane workers performing seven distinct tasks. We measured urine albumin and serum creatinine and estimated glomerular filtration rate (eGFR). Results: eGFR varied by job and decreased during the harvest in seed cutters (-8·6 ml/min/1·73 m(2)), irrigators (-7·4 ml/min/1·73 m(2)), and cane cutters (-5·0 ml/min/1·73 m(2)), as compared to factory workers. The number of years employed at the company was negatively associated with eGFR. Fewer than 5% of workers had albumin-to-creatinine ratio (ACR) >30 mg/g. Conclusions: The decline in kidney function during the harvest and the differences by job category and employment duration provide evidence that one or more risk factors of CKD are occupational.
MeSH term(s)	Adolescent ; Adult ; Albuminuria ; Creatinine/blood ; Farmers ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Diseases/blood ; Kidney Diseases/epidemiology ; Kidney Diseases/physiopathology ; Kidney Diseases/urine ; Male ; Middle Aged ; Nicaragua/epidemiology ; Occupational Diseases/blood ; Occupational Diseases/epidemiology ; Occupational Diseases/physiopathology ; Occupational Diseases/urine ; Proteinuria/blood ; Proteinuria/epidemiology ; Proteinuria/physiopathology ; Proteinuria/urine ; Saccharum ; Young Adult
Chemical Substances	Creatinine (AYI8EX34EU)
Language	English
Publishing date	2015-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1262326-x
ISSN	2049-3967 ; 1077-3525
ISSN (online)	2049-3967
ISSN	1077-3525
DOI	10.1179/2049396714Y.0000000102
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Article: Continuous glucose monitoring system for early detection of graft dysfunction in allogenic islet transplant recipients.

Faradji, R N / Monroy, K / Riefkohl, A / Lozano, L / Gorn, L / Froud, T / Cure, P / Baidal, D / Ponte, G / Messinger, S / Mastrototaro, J / Ricordi, C / Alejandro, R

Transplantation proceedings

2006 Volume 38, Issue 10, Page(s) 3274–3276

Abstract: Background: There are no effective indicators of graft dysfunction in islet transplantation. This study evaluated the role of the Continuous Glucose Monitoring System (CGMS) as an early indicator of graft dysfunction in islet transplant recipients.: ... ...

Abstract	Background: There are no effective indicators of graft dysfunction in islet transplantation. This study evaluated the role of the Continuous Glucose Monitoring System (CGMS) as an early indicator of graft dysfunction in islet transplant recipients. Methods: In 5 islet allograft recipients, we retrospectively determined the date of graft dysfunction: 3 fasting blood glucose levels >7.8 mmol/L (140 mg/dL) and/or 3 postprandial blood glucose levels >10 mmol/L (180 mg/dL) in 1 week. We then determined 2 time points in respect to graft dysfunction, 5 to 9 months before (time point A) and 2 to 3 months before (time point B). For these 2 time points, we assessed the following: HbA1c, C-peptide (CP), C-peptide glucose ratio (CPGR), 90-minute glucose from mixed meal tolerance test, and percentage of capillary blood glucose levels >7.8 mmol/L (%CBG >7.8) in a 15-day interval (1 week before and after CGMS placement). From the CGMS recordings, we calculated the glucose variability and the percentage of time spent in hyperglycemia >7.8 mmol/L (%HGT >7.8) and >10 mmol/L (%HGT >10). Results: No difference was found between time points A and B for the following parameters: HbA1c, CP, CPGR, 90-minute glucose, %CBG >7.8, and %HGT >10. We observed a statistically significant increase from time point A to time point B in glucose variability (1.1 +/- 0.5 mmol/L to 1.6 +/- 0.6 mmol/L; P = .004), and in the %HGT >7.8 (11 +/- 12% to 22 +/- 18%; P = .036). Conclusion: Glucose variability and %HGT >7.8 determined using CGMS are useful as early indicators of graft dysfunction in islet transplant recipients. Further studies with larger sample sizes will help validate these observations.
MeSH term(s)	Adult ; Blood Glucose/metabolism ; C-Peptide/blood ; Female ; Humans ; Immunosuppressive Agents/therapeutic use ; Islets of Langerhans Transplantation/pathology ; Islets of Langerhans Transplantation/physiology ; Male ; Middle Aged ; Monitoring, Ambulatory/methods ; Monitoring, Physiologic/methods ; Postoperative Complications/blood ; Retrospective Studies ; Transplantation, Homologous
Chemical Substances	Blood Glucose ; C-Peptide ; Immunosuppressive Agents
Language	English
Publishing date	2006-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	82046-5
ISSN	1873-2623 ; 0041-1345
ISSN (online)	1873-2623
ISSN	0041-1345
DOI	10.1016/j.transproceed.2006.10.036
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Article ; Online: Investigating Possible Infectious Causes of Chronic Kidney Disease of Unknown Etiology in a Nicaraguan Mining Community.

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Article ; Online: Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy.

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Article ; Online: Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy

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Article ; Online: Biomarkers of Kidney Injury Among Nicaraguan Sugarcane Workers.

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Article ; Online: Leptospira seropositivity as a risk factor for Mesoamerican Nephropathy.

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Article ; Online: Changes in kidney function among Nicaraguan sugarcane workers.

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Article: Continuous glucose monitoring system for early detection of graft dysfunction in allogenic islet transplant recipients.

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