Clinical markers to predict progression from acute to chronic kidney disease in Mesoamerican nephropathy

Fischer, R.; Vangala, Chandan; Mandayam, Sreedhar; Chavarria, Denis; Gárcía-Trabanino, Ramón; Garcia, Felix; Garcia, Linda L.; Murray, Kristy O.

doi:10.1016/j.kint.2018.08.020

Cited by 37 publications

(52 citation statements)

References 49 publications

(54 reference statements)

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“…We found urinary nitrites to be uncommon (0.4%) and all 70 urine cultures to be negative, indicating that dipstick leukocyte esterase in our current study was not a marker of a urinary tract infection in men, which suggests a different source of kidney pathology than infection. This finding appears to be supported by other research: all twelve urine cultures conducted in a study by Fischer et al were negative, and all CKD patients were negative for nitrites 31 . Sterile pyuria can be attributed to a number of different causes, including sexually-transmitted infections, viral or fungal infections, parasitic diseases, and interstitial nephritis from medications or other causes of cystitis 32,33 .…”

Section: Discussionsupporting

confidence: 80%

Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane Workers

et al. 2020

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BackgroundAn epidemic of CKD in Central America predominantly affects males working in certain industries, including sugarcane. Urinary tract infections are commonly diagnosed among men in Nicaragua, who often receive antibiotics and nonsteroidal anti-inflammatory drugs for urinary symptoms.MethodsWe followed 251 male Nicaraguan sugarcane workers in seven job tasks over one harvest and measured urine dipstick parameters, kidney injury biomarkers, and eGFR. We administered a questionnaire about urinary symptoms, health-related behaviors, and medication history. We cultured urine in a subset of workers.ResultsThe study population was composed of factory workers (23%), cane cutters (20%), irrigators (20%), drivers (16%), agrichemical applicators (12%), seeders/reseeders (6%), and seed cutters (4%). The mean age of participants was 33.9 years, and mean employment duration was 10.1 years. Cane cutters reported higher proportions of urinary-related symptoms compared with agrichemical applicators, irrigators, and seeders/reseeders. Seed cutters were more likely to take antibiotics (22%), whereas drivers and seeders/reseeders were more likely to take pain medications (27% and 27%, respectively). Proteinuria was uncommon, whereas dipstick leukocyte esterase was relatively common, especially among cane cutters, seed cutters, and seeders/reseeders (33%, 22%, and 21% at late harvest, respectively). Dipstick leukocyte esterase at late harvest was associated with a 12.9 ml/min per 1.73 m2 (95% CI, −18.7 to −7.0) lower mean eGFR and 2.8 times (95% CI, 1.8 to 4.3) higher mean neutrophil gelatinase-associated lipocalin. In general, workers who reported urinary-related symptoms had higher mean kidney injury biomarker levels at late harvest. None of the workers had positive urine cultures, including those reporting urinary symptoms and/or with positive leukocyte esterase results. Amoxicillin, ibuprofen, and acetaminophen were the most commonly used medications.ConclusionsJob task is associated with urinary symptoms and dipstick leukocyte esterase. Urinary tract infection is misdiagnosed based on leukocyte esterase, which may be an important predictor of kidney outcomes.

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Section: Discussionsupporting

confidence: 80%

Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane Workers

et al. 2020

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“…A recent prevalent case-control study in a mining area of Nicaragua observed a high rate of Leptospira seropositivity (26%) among study participants but did not find a positive association with CKDnt; Hantavirus seropositivity was not associated either (33). The observed acute early phase of the disease points to a systemic inflammatory process, which was hypothesized to be due to an exogenous infectious or toxic cause (69). However, sugarcane workers attending the company hospital with acute kidney disease did not have raised titers of leptospirosis or Hantavirus, and probing for pathogen genomes using advanced molecular methods in blood, urine and kidney tissue in a subset (n=10) did not reveal any DNA or RNA patterns suggesting involvement of any known or novel pathogen (70).…”

Section: Infectious Agentsmentioning

confidence: 86%

“…One study examined 34 workers with cross-harvest incident kidney injury 6 and 12 months later; 10 (34.5%) progressed to eGFR <60 ml/ min/1.73m 2 and 11 (38%) to a decline of eGFR >30% of baseline (54). After proposing that CKDnt starts with an acute adverse kidney event (32), sugarcane workers with acute kidney injury episodes were captured at the company hospital in Nicaragua and then followed up for progress to CKD (69). Acute kidney injury occurred more frequently among male workers and in cutters and other fieldworkers.…”

Section: Towards Understanding the Natural History Of Ckdntmentioning

confidence: 99%

Chronic kidney disease of non-traditional origin in Mesoamerica: a disease primarily driven by occupational heat stress

Wesseling

Glaser²,

Rodríguez-Guzmán

et al. 2020

Revista Panamericana De Salud Pública

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The death toll of the epidemic of chronic kidney disease of nontraditional origin (CKDnt) in Mesoamerica runs into the tens of thousands, affecting mostly young men. There is no consensus on the etiology. Anecdotal evidence from the 1990s pointed to work in sugarcane; pesticides and heat stress were suspected. Subsequent population-based surveys supported an occupational origin with overall high male-female ratios in high-risk lowlands, but small sex differences within occupational categories, and low prevalence in non-workers. CKDnt was reported in sugarcane and other high-intensity agriculture, and in non-agricultural occupations with heavy manual labor in hot environments, but not among subsistence farmers. Recent studies with stronger designs have shown cross-shift changes in kidney function and hydration biomarkers and cross-harvest kidney function declines related to heat and workload. The implementation of a water-rest-shade intervention midharvest in El Salvador appeared to halt declining kidney function among cane cutters. In Nicaragua a water-rest-shade program appeared sufficient to prevent kidney damage among cane workers with low-moderate workload but not among cutters with heaviest workload. Studies on pesticides and infectious risk factors have been largely negative. Non-occupational risk factors do not explain the observed epidemiologic patterns. In conclusion, work is the main driver of the CKDnt epidemic in Mesoamerica, with occupational heat stress being the single uniting factor shown to lead to kidney dysfunction in affected populations. Sugarcane cutters with extreme heat stress could be viewed as a sentinel occupational population. Occupational heat stress prevention is critical, even more so in view of climate change.

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“…As part of a large, ongoing investigation into the etiology of MeN, we established active surveillance for impaired renal function in a region of northwestern Nicaragua with excess kidney-related morbidity and mortality [1,6]. While previously characterized as an insidious chronic disease, we now understand that an early phase often presents as acute kidney injury (AKI) with neutrophilic leukocytosis, leukocyturia, and anemia, often with mild flu-like illness [12,13]. Early renal pathology reflects acute tubulointerstitial nephritis with inflammatory infiltrate concentrated at the corticomedullary junction [14].…”

Section: Introductionmentioning

confidence: 99%

“…These observations suggest that the acute renal event is triggered by an exogenous, pro-inflammatory agent. While most patients recover renal function following AKI, approximately 10% are diagnosed with CKDu within the first year [13]. It is yet unknown if the AKI epidemic reflects incident kidney disease (e.g.…”

Section: Introductionmentioning

confidence: 99%

Evidence of nickel and other trace elements and their relationship to clinical findings in acute Mesoamerican Nephropathy: A case-control analysis

et al. 2020

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Background Although there are several hypothesized etiologies of Mesoamerican Nephropathy (MeN), evidence has not yet pointed to the underlying cause. Exposure to various trace elements can cause the clinical features observed in MeN. Methods and findings We measured 15 trace elements, including heavy metals, in renal case-patients (n = 18) and healthy controls (n = 36) in a MeN high-risk region of Nicaragua. Toenails clippings from study participants were analyzed using inductively coupled plasma mass spectrometry. A case-control analysis was performed, and concentrations were also analyzed over participant characteristics and clinical parameters. Nickel (Ni) concentrations were significantly higher in toenails from cases (1.554 mg/kg [0.176–42.647]) than controls (0.208 mg/kg [0.055–51.235]; p<0.001). Ni concentrations correlated positively with serum creatinine levels (p = 0.001) and negatively with eGFR (p = 0.001). Greater Ni exposure was also associated with higher leukocyte (p = 0.001) and neutrophil (p = 0.003) counts, fewer lymphocytes (p = 0.003), and lower hemoglobin (p = 0.004) and hematocrit (p = 0.011). Conclusions Low-dose, chronic environmental exposure to Ni is a possible health risk in this setting. Ni intoxication and resulting systemic and renal effects could explain the clinical signs observed during early MeN. This study provides compelling evidence for a role of Ni in the acute renal impairment observed in this MeN high-risk population. Additional work to assess exposure levels in a larger and heterogeneous population, identify environmental sources of Ni and exposure pathways, and evaluate the link between Ni and MeN pathogenesis are urgently needed.

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Clinical markers to predict progression from acute to chronic kidney disease in Mesoamerican nephropathy

Cited by 37 publications

References 49 publications

Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane Workers

Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane Workers

Chronic kidney disease of non-traditional origin in Mesoamerica: a disease primarily driven by occupational heat stress

Evidence of nickel and other trace elements and their relationship to clinical findings in acute Mesoamerican Nephropathy: A case-control analysis

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