e-Cigarette Use and Combustible Cigarette Smoking Initiation Among Youth: Accounting for Time-Varying Exposure and Time-Dependent Confounding.

BACKGROUND: Youth e-cigarette use is associated with the initiation of combustible cigarette smoking, but prior studies have rarely accounted for time-varying measures of e-cigarette exposure or time-dependent confounding of e-cigarette use and smoking initiation. METHODS: Using five waves of the Population Assessment of Tobacco and Health (2013-2019), we estimated marginal structural models with inverse probability of treatment and censoring weights to examine the association between time-varying e-cigarette initiation and subsequent cigarette smoking initiation among e-cigarette- and cigarette-naïve youth (12-17 years) at baseline. Time-dependent confounders used as predictors in inverse probability weights included tobacco-related attitudes or beliefs, mental health symptoms, substance use, and tobacco-marketing exposure. RESULTS: Among 9,584 youth at baseline, those who initiated e-cigarettes were 2.4 times as likely to subsequently initiate cigarette smoking as youth who did not initiate e-cigarettes (risk ratio = 2.4, 95% confidence interval [CI] = 2.1, 2.7), after accounting for time-dependent confounding and selection bias. Among youth who initiated e-cigarettes, more frequent vaping was associated with greater risk of smoking initiation (risk ratio ≥3 days/month = 1.8, 95% CI = 1.4, 2.2; 1-2 days/month = 1.2; 95% CI = 0.93, 1.6 vs. 0 days/month). Weighted marginal structural model estimates were moderately attenuated compared with unweighted estimates adjusted for baseline-only confounders. At the US population level, we estimated over half a million youth initiated cigarette smoking because of prior e-cigarette use over follow-up. CONCLUSIONS: The association between youth vaping and combustible cigarette smoking persisted after accounting for time-dependent confounding. We estimate that e-cigarette use accounts for a considerable share of cigarette initiation among US youth. See video abstract at, http://links.lww.com/EDE/B937.

High prevalence of chronic kidney disease of unknown etiology among workers in the Mesoamerican Nephropathy Occupational Study.

BACKGROUND: Mortality from chronic kidney disease of unknown etiology (CKDu) is extremely high along the Pacific coast of Central America, particularly among sugarcane workers. The Mesoamerican Nephropathy Occupational Study (MANOS) is a prospective cohort study of CKDu among agricultural and non-agricultural workers in El Salvador and Nicaragua. The objective of this manuscript is to describe the MANOS cohort recruitment, baseline data collection, and CKDu prevalence after two rounds. METHODS: Workers with no known diabetes, hypertension, or CKD were recruited from sugarcane, corn, plantain, brickmaking, and road construction industries (n = 569). Investigators administered questionnaires, collected biological samples, and observed workers for three consecutive workdays at the worksite. Serum specimens were analyzed for kidney function parameters, and used to calculate estimated glomerular filtration rate (eGFR). At six months, serum was collected again prior to the work shift. CKD at baseline is defined as eGFR ≤ 60 ml/min/1.73m2 at both timepoints. Age-standardized prevalence was calculated by industry, country, and demographic measures. Kidney function parameters were compared by CKD status. RESULTS: Prevalence of CKD at baseline was 7.4% (n = 42). Age-standardized prevalence was highest in Salvadoran sugarcane (14.1%), followed by Salvadoran corn (11.6%), and Nicaraguan brickmaking (8.1%). Nicaraguan sugarcane had the lowest prevalence, likely due to kidney function screenings prior to employment. CONCLUSION: Despite efforts to enroll participants without CKD, our identification of prevalent CKD among agricultural and non-agricultural workers in the MANOS cohort indicates notable kidney disease in the region, particularly among sugarcane workers.

Biomarkers of kidney injury among children in a high-risk region for chronic kidney disease of uncertain etiology.

BACKGROUND: Mesoamerican Nephropathy (MeN), a form of chronic kidney disease of uncertain etiology, is a leading cause of death in Central America. The disease often presents in young adult male agricultural workers and progresses rapidly. Given the young age at presentation, we hypothesized that children in Central America experience subclinical kidney injury prior to working life. METHODS: We assessed specimens from a cross-sectional study of youth, aged 7-17 years, predominantly residing in a high-risk region of Nicaragua (n = 210). We evaluated urinary concentrations and risk factors for kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40). We evaluated the association between biomarkers and contemporaneous eGFR and compared biomarker concentrations with reference values from healthy children in other countries. RESULTS: Median uNGAL, uIL-18, and uKIM-1 concentrations exceeded healthy reference values. A one-year increase in age was associated with 40% increase in odds of being in the highest quartile of uNGAL (OR 1.4; (95%CI 1.2, 1.5); p < 0.0001). Youth who reported ever experiencing dysuria had 2.5 times the odds of having uNGAL concentrations in the top quartile (OR 2.5; (95%CI 1.4, 4.6); p = 0.003). Girls had significantly higher concentrations of all biomarkers than boys. Nine percent of children demonstrated low eGFR (≤ 100 ml/min/1.73 m2), while 29% showed evidence of hyperfiltration (eGFR ≥ 160 ml/min/1.73 m2), both potentially indicative of renal dysfunction. CONCLUSIONS: Children residing in regions of Nicaragua at high risk for MeN may experience subclinical kidney injury prior to occupational exposures.

Prevalence and Risk Factors for CKD in the General Population of Southwestern Nicaragua.

BACKGROUND: Studies have described Mesoamerican nephropathy among agricultural workers of El Salvador and northwestern Nicaragua. Data on prevalence and risk factors for CKD beyond agricultural workers and in other regions in Nicaragua are sparse. METHODS: We recruited participants from 32 randomly selected communities in the Department of Rivas's ten municipalities in two phases. In phase 1, we screened participants using a field-based capillary creatinine measuring system and collected self-reported information on lifestyle and occupational, exposure, and health histories. Two years later, in phase 2, we enrolled 222 new participants, performing serum creatinine testing in these participants and confirmatory serum creatinine testing in phase 1 participants. RESULTS: We enrolled 1242 of 1397 adults (89%) living in 533 households (median age 41 years; 43% male). We confirmed CKD (eGFR<60 ml/min per 1.73 m2) in 53 of 1227 (4.3%) evaluable participants. In multivariable testing, risk factors for prevalent CKD included age (odds ratio [OR], 1.92; 95% confidence interval [95% CI], 1.89 to 1.96) and self-reported history of hypertension (OR, 1.95; 95% CI, 1.04 to 3.64), diabetes (OR, 2.88; 95% CI, 1.40 to 5.93), or current or past work in the sugarcane industry (OR 2.92; 95% CI, 1.36 to 6.27). CONCLUSIONS: Adjusted CKD prevalence was about 5% with repeat confirmatory testing in southwest Nicaragua, lower than in the northwest region. Risk factors included diabetes, hypertension, and current or prior work in the sugarcane industry but not in other forms of agricultural work. Formal CKD surveillance programs in Nicaragua are needed to assess the overall burden of CKD nationally, with a focus on agricultural workers.

Prevalence and Risk Factors for CKD Among Brickmaking Workers in La Paz Centro, Nicaragua.

RATIONALE & OBJECTIVE: In Central America, there is a high prevalence of chronic kidney disease (CKD) of nontraditional etiology often observed among agricultural workers. Few studies have assessed CKD prevalence among workers in nonagricultural occupations, which was the objective of this investigation. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Male and female workers (n = 224) employed by artisanal brickmaking facilities in La Paz Centro, Nicaragua. PREDICTORS: Age, sex, education, smoking status, body mass index, alcohol consumption, water consumption, first-degree relative(s) with CKD, years worked, hours worked per week, job category, study visit (baseline and follow-up), and self-reported hypertension and diabetes. OUTCOMES: CKD defined as estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m2 at 2 time points 4 months apart and CKD stage. ANALYTICAL APPROACH: A linear mixed-effects model with an unstructured covariance matrix was used to evaluate the association between demographics, occupational risk factors, and eGFR at baseline. The interaction between risk factors and time with change in eGFR was also evaluated. Multivariable logistic regression models were used to evaluate predictors of CKD. RESULTS: The CKD prevalence was 12.1% (n = 27), 100% of cases were male, 30% had stage 5 CKD (eGFR < 15mL/min/1.73m2), and 22% were younger than 35 years. Proportions of participants with eGFRs < 60mL/min/1.73m2 at baseline and follow-up were 13.8% and 15.2%, respectively. Linear regression analysis demonstrated significant predictors of lower kidney function at baseline including oven work, older age, lack of education, and having an immediate family member with CKD. Predictors of CKD identified using logistic regression analysis included oven work and lack of education. LIMITATIONS: Crude job classification measures, loss to follow-up, self-reported exposures. CONCLUSIONS: The prevalence of CKD is high in this population of brick workers, suggesting that the epidemic of CKD affecting Mesoamerica is not limited to agricultural workers. These results are consistent with the hypothesis that occupational heat exposure is a risk factor for kidney disease in this region.

Socioeconomic and Racial/Ethnic Differences in E-Cigarette Uptake Among Cigarette Smokers: Longitudinal Analysis of the Population Assessment of Tobacco and Health (PATH) Study.

INTRODUCTION: Sociodemographic differences in electronic cigarette use among cigarette smokers have not been previously characterized in the US adult population. METHODS: We analyzed longitudinal data from Waves 1 and 2 of the nationally representative Population Assessment of Tobacco and Health (PATH) study. Differences by income (based on federal poverty level (FPL)) and race/ethnicity in e-cigarette uptake at Wave 2 among cigarette smokers who were e-cigarette nonusers at Wave 1 were assessed using binomial and multinomial logistic regression. We differentiated e-cigarette users who quit cigarettes (exclusive users) from those who did not quit cigarettes (dual users). E-cigarette-related attitudes/beliefs were evaluated to understand potential contributions to sociodemographic differences in e-cigarette uptake and use patterns. RESULTS: Among 6592 smokers who were e-cigarette nonusers at Wave 1, 13.5% began using e-cigarettes at Wave 2, of whom 91.3% were dual users. Compared with non-Hispanic Whites, non-Hispanic Black, and Hispanics were less likely to become exclusive e-cigarette users (OR [Blacks] = 0.27, 95% CI = 0.09 to 0.77; OR [Hispanics] = 0.26, 95% CI = 0.09 to 0.70). Low-income smokers were less likely than higher-income smokers to become exclusive e-cigarette users (OR [<100% FPL vs. ≥200% FPL] = 0.48, 95% CI = 0.27 to 0.89). Black, Hispanic, and low-income smokers were more likely to believe e-cigarettes are more harmful than cigarettes and to have positive tobacco-related social norms. CONCLUSIONS: Black, Hispanic, and low-income smokers were less likely than White and higher-income smokers to begin using e-cigarettes in the context of quitting cigarettes. Differences in e-cigarette uptake may be partly explained by perceived harm or social norms of e-cigarettes. IMPLICATIONS: Results of this study show that the exclusive use of e-cigarettes is more prevalent in higher-income and White smokers. Our data suggest that higher-income and White smokers may be more likely to use e-cigarettes as a means to quit combustible cigarettes compared with low-income and racial/ethnic minority smokers. These findings suggest that sociodemographic differences in e-cigarette uptake and use patterns may contribute to widening disparities in cigarette smoking.

Acute Kidney Injury in Sugarcane Workers at Risk for Mesoamerican Nephropathy.

RATIONALE & OBJECTIVE: Mesoamerican nephropathy (MeN), a form of chronic kidney disease (CKD) of unknown cause in Central America, affects young individuals working in physically strenuous occupations. Repeated episodes of work-related kidney injury may lead to CKD in this setting. We aimed to better understand the burden and natural history of acute kidney injury (AKI) in workers at risk for MeN. STUDY DESIGN: Cross-sectional study of active sugarcane workers, followed by prospective follow-up of individuals with AKI. SETTING & PARTICIPANTS: 326 sugarcane workers with normal preharvest serum creatinine (Scr) values and no history of CKD in an MeN hotspot in Nicaragua near the end of the harvest, and prospective follow-up of workers with AKI. PREDICTOR: AKI during the harvest, as defined by Scr level increase ≥ 0.3mg/dL over baseline to a level ≥ 1.3mg/dL. OUTCOMES: Kidney function trajectory and development of CKD over 12 months. ANALYTICAL APPROACH: Linear regression models were used to analyze the association between job category and kidney function. For workers with AKI, the effect of time on Scr level was evaluated using linear mixed effects. RESULTS: 34 of 326 participants were found to have AKI, with a median late-harvest Scr level of 1.64mg/dL in the AKI group. Workers without AKI had a median Scr level of 0.88mg/dL. AKI was more common among cane cutters compared with other field workers. Participants with AKI had variable degrees of kidney function recovery, with median 6- and 12-month Scr values of 1.25 and 1.27mg/dL, respectively (P < 0.001 for each follow-up value compared to late-harvest Scr). When we compared workers' kidney function before the AKI episode to their kidney function at last follow-up, 10 participants with AKI developed de novo estimated glomerular filtration rate < 60mL/min/1.73m2 and 11 had a >30% decrease in estimated glomerular filtration rate. LIMITATIONS: Follow-up limited to 1 year and some loss to follow-up in the prospective component of the study. Broad definition of AKI that includes both acute and subacute kidney injury. CONCLUSIONS: In a group of sugarcane workers with normal preharvest kidney function, newly decreased kidney function developing during the harvest season was common. Of those with kidney injury, nearly half had established CKD 12 months later.

Twelve-Month Outcomes of a Group-Randomized Community Health Advocate-Led Smoking Cessation Intervention in Public Housing.

Background: Lower rates of smoking cessation are a major reason for the higher prevalence of smoking among socioeconomically disadvantaged adults. Because barriers to quitting are both more numerous and severe, socioeconomically disadvantaged smokers may benefit from more intensive intervention. We sought to determine whether a smoking cessation intervention delivered by public housing residents trained as Tobacco Treatment Advocates (TTAs) could increase utilization of cessation resources and increase abstinence. Methods: We conducted a group-randomized trial among Boston public housing residents who were interested in quitting smoking. Participants at control sites received standard cessation materials and a one-time visit from a TTA who provided basic counseling and information about cessation resources. Participants at intervention sites were eligible for multiple visits by a TTA who employed motivational interviewing, cessation counseling, and navigation to encourage smokers to utilize cessation treatment (Smokers' Quitline and clinic-based programs). Utilization and 7-day and 30-day point prevalence abstinence were assessed at 12 months. Self-reported abstinence was biochemically verified. Results: Intervention participants (n = 121) were more likely than control participants (n = 129) to both utilize treatment programs (adjusted odds ratio [aOR]: 2.15; 95% confidence interval [CI]: 0.93-4.91) and 7-day and 30-day point prevalence abstinence (aOR: 2.60 (1.72-3.94); 2.98 (1.56-5.68), respectively). Mediation analysis indicated that the higher level of utilization did not explain the intervention effect. Conclusions: An intervention delivered by peer health advocates was able to increase utilization of treatment programs and smoking abstinence among public housing residents. Future studies of similar types of interventions should identify the key mechanisms responsible for success. Implications: In order to narrow the large and growing socioeconomic disparity in smoking rates, more effective cessation interventions are needed for low-income smokers. Individual culturally-relevant coaching provided in smokers' residences may help overcome the heightened barriers to cessation experienced by this group of smokers. In this study among smokers residing in public housing, an intervention delivered by peer health advocates trained in motivational interviewing, basic smoking cessation skills, and client navigation significantly increased abstinence at 12 months. Future research should address whether these findings are replicable in other settings both within and outside of public housing.

Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea.

Blue-intra-tissue refractive index shaping (Blue-IRIS) is a new approach to laser refractive correction of optical aberrations in the eye, which alters the refractive index of the cornea rather than changing its shape. Before it can be implemented in humans, it is critical to establish whether and to what extent, Blue-IRIS damages the cornea. Here, we contrasted the impact of -1.5 D cylinder refractive corrections inscribed using either Blue-IRIS or femtosecond laser in-situ keratomileusis (femto-LASIK) on corneal cell viability. Blue-IRIS was used to write a -1.5 D cylinder gradient index (GRIN) lens over a 2.5 mm by 2.5 mm area into the mid-stromal region of the cornea in six freshly-enucleated feline eyes. The same correction (-1.5 D cylinder) was inscribed into another four cat eyes using femto-LASIK. Six hours later, all corneas were processed for histology and stained for terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and p-γ-H2AX to label damaged cells. In Blue-IRIS-treated corneas, no tissue was removed and TUNEL-stained cells were confined to the laser focal zone in the stroma. In femto-LASIK, photoablation removed 14 µm of anterior stroma, but in addition, TUNEL-positive cells clustered across the femto-flap, the epithelium at the flap edges and the stroma below the ablation zone. Keratocytes positive for p-γ-H2AX were seen adjacent to all Blue-IRIS focal zones, but were completely absent from femto-LASIK-treated corneas. Unlike femto-LASIK, Blue-IRIS attains refractive correction in the cornea without tissue removal and only causes minimal, localized keratocyte death within the laser focal zones. In addition, Blue-IRIS induced DNA modifications associated with phosphorylation of γ-H2AX in keratocytes adjacent to the laser focal zones. We posit that this p-γ-H2AX response is related to alterations in chromatin structure caused by localized changes in osmolarity, a possible mechanism for the induced refractive index changes.

Biomarkers of Kidney Injury Among Nicaraguan Sugarcane Workers.

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-ß-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.

Characterization of Mesoamerican Nephropathy in a Kidney Failure Hotspot in Nicaragua.

BACKGROUND: Mesoamerican nephropathy (MeN) is a kidney disease of unknown cause that mainly affects working-age men in Central America. Despite being a major cause of morbidity and mortality in this region, its clinical characteristics have not been well defined. STUDY DESIGN: Cross-sectional family-based study. SETTING & PARTICIPANTS: 266 members of 24 families with high chronic kidney disease (CKD) burdens in a MeN hotspot in Northwestern Nicaragua. We compared clinical and biochemical characteristics of affected individuals first with their unaffected relatives and then with NHANES (National Health and Nutrition Examination Survey) participants with CKD in order to reveal identifying features of MeN. PREDICTOR: CKD defined as serum creatinine level ≥ 1.5mg/dL in men and ≥1.4mg/dL in women. OUTCOMES: Clinical and biochemical parameters, including serum sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, and uric acid. RESULTS: Hyperuricemia, in many cases severe, was common among patients with MeN. Uric acid levels in patients with MeN were higher than those in NHANES participants (mean, 9.6 vs 7.4mg/dL for men in each group) despite more frequent use of uric acid-lowering medications in Nicaraguan individuals (71.7% vs 11.2%). In multivariable linear mixed-effects regression analysis, uric acid levels were 2.0mg/dL (95% CI, 1.0-3.0; P<0.001) higher in patients with MeN compared with their NHANES counterparts after adjusting for age, estimated glomerular filtration rate, and uric acid-lowering therapies. In contrast to prior reports, hyponatremia and hypokalemia were not common. LIMITATIONS: CKD defined by single serum creatinine measurement; population likely not representative of full MeN phenotype spectrum across Central America; major differences between MeN and NHANES groups in important characteristics such as age, ancestry, and recruitment method. CONCLUSIONS: Hyperuricemia out of proportion to the degree of decreased kidney function was common among Nicaraguan patients with MeN. Our results suggest that rather than being solely a consequence of CKD, hyperuricemia may play a role in MeN pathogenesis, a hypothesis that deserves further study.

Evaluation of Selection Bias in an Internet-based Study of Pregnancy Planners.

Selection bias is a potential concern in all epidemiologic studies, but it is usually difficult to assess. Recently, concerns have been raised that internet-based prospective cohort studies may be particularly prone to selection bias. Although use of the internet is efficient and facilitates recruitment of subjects that are otherwise difficult to enroll, any compromise in internal validity would be of great concern. Few studies have evaluated selection bias in internet-based prospective cohort studies. Using data from the Danish Medical Birth Registry from 2008 to 2012, we compared six well-known perinatal associations (e.g., smoking and birth weight) in an internet-based preconception cohort (Snart Gravid n = 4,801) with the total population of singleton live births in the registry (n = 239,791). We used log-binomial models to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for each association. We found that most results in both populations were very similar. For example, maternal obesity was associated with an increased risk of delivering a macrosomic infant in Snart Gravid (RR = 1.5; 95% CI: 1.2, 1.7) and the total population (RR = 1.5; 95% CI: 1.45, 1.53), and maternal smoking of >10 cigarettes per day was associated with a higher risk of low birth weight (RR = 2.7; 95% CI: 1.2, 5.9 vs. RR = 2.9; 95% CI: 2.6, 3.1) in Snart Gravid and the total population, respectively. We cannot be certain that our results would apply to other associations or different populations. Nevertheless, our results suggest that recruitment of reproductive aged women via the internet may be no more prone to selection bias than traditional methods of recruitment.

Urine biomarkers of kidney injury among adolescents in Nicaragua, a region affected by an epidemic of chronic kidney disease of unknown aetiology.

BACKGROUND: An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recognized by health authorities as a public health priority in Central America. Previous studies have identified strenuous manual work, agricultural activities and residence at low altitude as potential risk factors; however, the aetiology remains unknown. Because individuals are frequently diagnosed with CKD in early adulthood, we measured biomarkers of kidney injury among adolescents in different regions of Nicaragua to assess whether kidney damage might be initiated during childhood. METHODS: Participants include 200 adolescents aged 12-18 years with no prior work history from four different schools in Nicaragua. The location of the school served as a proxy for environmental exposures and geographic locations were selected to represent a range of factors that have been associated with CKD in adults (e.g. altitude, primary industry and CKD mortality rates). Questionnaires, urine dipsticks and kidney injury biomarkers [interleukin-18, N-acetyl-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and albumin-creatinine ratio] were assessed. Biomarker concentrations were compared by school using linear regression models. RESULTS: Protein (3.5%) and glucose (1%) in urine measured by dipstick were rare and did not differ by school. Urine biomarkers of tubular kidney damage, particularly NGAL and NAG, showed higher concentrations in those schools and regions within Nicaragua that were defined a priori as having increased CKD risk. Painful urination was a frequent self-reported symptom. CONCLUSIONS: Although interpretation of these urine biomarkers is limited because of the lack of population reference values, results suggest the possibility of early kidney damage prior to occupational exposures in these adolescents.

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

BACKGROUND: Northwestern Nicaragua has a high prevalence of chronic kidney disease (CKD) of unknown cause among young adult men. In addition, frequent occurrence of urinary tract infections (UTI) among men and a dysuria syndrome described by sugarcane workers as "chistata" are both reported. This study examines health professionals´ perceptions regarding etiology of these conditions and their treatment approaches, including use of potentially nephrotoxic medications. METHODS: Nineteen in-person semi-structured interviews were conducted in November 2010 among ten physicians and nine pharmacists practicing in the region. RESULTS: Health professionals perceived CKD as a serious and increasing problem in the region, primarily affecting young men working as manual laborers. All interviewees regarded occupational and environmental exposure to sun and heat, and dehydration as critical factors associated with the occurrence of CKD. These factors were also considered to play a role in the occurrence of chistata in the region. Health professionals indicated that reluctance among workers to hydrate might be influenced by perceptions of water contamination. Symptoms often were treated with non-steroidal anti-inflammatory drugs (NSAIDs), diuretics and antibiotics. Physicians acknowledged that the diagnosis of UTI usually was not based on microbial culture and opined that the use of potentially nephrotoxic medications may be contributing to CKD. CONCLUSIONS: Interviews provided evidence suggesting that medications such as diuretics, antibiotics and NSAIDs are widely used and sold over the counter for symptoms that may be related to dehydration and volume depletion. These factors, alone or in combination, may be possible contributors to kidney damage. Acute kidney damage coupled with volume depletion and exposures including medications and infectious agents should be further evaluated as causal factors for CKD in this region.

Ethical considerations for genetic research in low-income countries: perceptions of informed consent, data sharing, and expectations in Nicaragua.

Genetic research presents numerous ethical, legal, and social implications (ELSI), particularly when the research involves collaborations between investigators in high and low-income countries. Some ELSI issues are universal, and others are specific to context and culture. This study investigates perceptions of genetic research in Nicaragua, Central America, where local and U.S. based researchers have collaborated for over a decade. A total of 43 residents from northwestern Nicaragua, a region with high mortality rates attributed to chronic kidney disease of non-traditional causes (CKDnt), were interviewed, including research participants in ongoing studies (n = 36), health professionals (n = 3), labor leaders (n = 2), and family members of research participants (n = 2). Questions focused on informed consent, data-sharing, and post-study expectations. Audio recordings of interviews conducted in Spanish were transcribed and translated into English. English transcripts were coded and analyzed using NVivo 12 software. The lack of familiarity with terms in the consent form presented a barrier to participant comprehension of key elements of the genetic research study, raising concerns about the validity of informed consent. Research participants often viewed their participation as access to health care. Health professionals emphasized the importance of long-term partnerships between foreign-based researchers and local health institutions. Leaders and family members recommended that they be informed of research studies and allowed the opportunity to consent, as they felt the benefits and risks of research also apply to them. Our findings identified genetic research practices to be improved upon in order to be more responsive to the contextual realities of collaborators living in low-resource settings.

Point-of-Care Testing in Chronic Kidney Disease of Non-Traditional Origin: Considerations for Clinical, Epidemiological, and Health Surveillance Research and Practice.

Purpose: As the prevalence of chronic kidney disease of non-traditional origin (CKDnt) rises in low-resource settings, there is a need for reliable point-of-care creatinine testing. The purpose of this analysis was to assess the accuracy of two commonly used point-of-care creatinine devices, the i-STAT handheld (Abbott, Princeton, NJ, USA) and the StatSensor Creatinine (Nova Biomedical, Waltham, MA, USA) in comparison to venipuncture serum creatinine measures. The affordability, sensitivity, specificity, ease of use, and other considerations for each device are also presented. Methods: Three paired data sets were compared. We collected 213 paired i-STAT and venipuncture samples from a community study in Nicaragua in 2015-2016. We also collected 267 paired StatSensor Creatinine and venipuncture samples, including 158 from a community setting in Nicaragua in 2014-2015 and 109 from a Guatemala sugarcane worker cohort in 2017-2018. Pearson correlation coefficients, Bland-Altman plots, and no intercept linear regression models were used to assess agreement between point-of-care devices and blood samples. Results: The i-STAT performed the most accurately, overestimating creatinine by 0.07 mg/dL (95% CI: 0.02, 0.12) with no evidence of proportional bias. The StatSensor Creatinine performed well at low levels of creatinine (Mean (SD): 0.87 (0.19)). Due to proportional bias, the StatSensor Creatinine performed worse in the Nicaragua community setting where creatinine values ranged from 0.31 to 7.04 mg/dL. Discussion: Both devices provide acceptable sensitivity and specificity. Although adequate for routine surveillance, StatSensor Creatinine is less accurate as the values of measured creatinine increase, a consideration when using the point-of-care device for screening individuals at risk for CKDnt. Research, clinical, and screening objectives, cost, ease of use, and background prevalence of disease must all be carefully considered when selecting a point-of-care creatinine device. Conclusion: POC testing can be more accessible in resource-limited settings. The selection of the appropriate device will depend on the use-case.

Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (n = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (n = 78); Nicaraguans performing non-agricultural work (n = 102); and agricultural workers in Spain (n = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (p = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings.