Dialysis enrollment patterns in Guatemala: Evidence of the chronic kidney disease of non-traditional causes epidemic in Mesoamerica

BACKGROUND: In western Nicaragua and El Salvador, chronic kidney disease (CKD) is highly prevalent and generally affects young, male, agricultural (usually sugar cane) workers without the established CKD risk factors. It is yet unknown if the prevalence of this CKD of Non-Traditional causes (CKDnT) extends to the northernmost Central American country, Guatemala. Therefore, we sought to compare dialysis enrollment rates by region, municipality, sex, daily temperature, and agricultural production in Guatemala and assess if there is a similar CKDnT distribution pattern as in Nicaragua and El Salvador. METHODS: The National Center for Chronic Kidney Disease Treatment (Unidad Nacional de Atención al Enfermo Renal Crónico) is the largest provider of dialysis in Guatemala. We used population, Human Development Index, literacy, and agricultural databases to assess the geographic, economic, and educational correlations with the National Center for Chronic Kidney Disease Treatment’s hemodialysis and peritoneal dialysis enrollment database. Enrollment rates (per 100 000) inhabitants were compared by region and mapped for comparison to regional agricultural and daytime temperature data. The distribution of men and women enrolled in dialysis were compared by region using Fisher’s exact tests. Spearman’s rank correlation coefficients were calculated. RESULTS: Dialysis enrollment is higher in the Southwest compared to the rest of the country where enrollees are more likely (p < 0.01) to be male (57.8%) compared to the rest of the country (49.3%). Dialysis enrollment positively correlates with Human Development Index and literacy rates. These correlations are weaker in the agricultural regions (predominantly sugar cane) of Southwest Guatemala. CONCLUSIONS: In Guatemala, CKDnT incidence may have a similar geographic distribution as Nicaragua and El Salvador (higher in the high temperature and sugar cane growing regions). Therefore, it is likely that the CKNnT epidemic extends throughout the Mesoamerican region

Prevalencia de enfermedad renal crónica de causa no tradicional (ERCnT) en pacientes en hemodiálisis de la costa sur de Guatemala

La enfermedad renal crónica (ERC) de causa no tradicional (ERCnT) se presenta frecuentemente en la costa sur de América Central y regiones de Sri Lanka. Poco se sabe de esta patología pero, afecta poblaciones jóvenes, trabajadores de la agroindustria que se exponen al golpe de calor, viven debajo de 200 m.snm, tienden a tener poca proteinuria y no se asocian a factores tradicionales de ERC, además se reconocen otros factores como, deshidratación frecuente, rabdomiolisis, uso de AINES, contexto de pobreza, bajo peso al nacer y malnutrición. Se estableció la prevalencia de pacientes con ERCnT y los factores asociados a través de un estudio descriptivo de corte transversal en donde se entrevistaron 242 pacientes que reciben tratamiento de hemodiálisis en diferentes unidades de la costa sur (Escuintla, Mazatenango y Retalhuleu). Los pacientes fueron clasificados en diabéticos, hipertensos, obesos o si ninguno de esos factores. Se analizó la relación entre pacientes con factores no tradicionales de ERC: ocupación, demográficos, hábitos, altitud y tiempo en llegar a su clínica de diálisis, usando un análisis multivariado de regresión logística. Se encontró que 171 (71%) pacientes no presentaron factores tradicionales de ERC. Aunque la ocupación de agricultor es la más común, únicamente alcanzó significancia estadística la edad &lt;50 años y el tiempo &gt;30 min que tardan en desplazarse a la clínica de diálisis. El uso de AINES y consumo de bebidas carbonatadas fue descrito como frecuente. La prevalencia de ERCNT en pacientes que reciben hemodiálisis en la costa sur de Guatemala es alta. Es el mismo fenómeno reportado en El Salvador y Nicaragua. Queda entonces demostrado que la ERCnT también se presenta en la costa sur de Guatemala

A New Approach for Heparin Standardization: Combination of Scanning UV Spectroscopy, Nuclear Magnetic Resonance and Principal Component Analysis

The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA), was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities

Zinc Coordination Is Required for and Regulates Transcription Activation by Epstein-Barr Nuclear Antigen 1

Epstein-Barr Nuclear Antigen 1 (EBNA1) is essential for Epstein-Barr virus to immortalize naïve B-cells. Upon binding a cluster of 20 cognate binding-sites termed the family of repeats, EBNA1 transactivates promoters for EBV genes that are required for immortalization. A small domain, termed UR1, that is 25 amino-acids in length, has been identified previously as essential for EBNA1 to activate transcription. In this study, we have elucidated how UR1 contributes to EBNA1's ability to transactivate. We show that zinc is necessary for EBNA1 to activate transcription, and that UR1 coordinates zinc through a pair of essential cysteines contained within it. UR1 dimerizes upon coordinating zinc, indicating that EBNA1 contains a second dimerization interface in its amino-terminus. There is a strong correlation between UR1-mediated dimerization and EBNA1's ability to transactivate cooperatively. Point mutants of EBNA1 that disrupt zinc coordination also prevent self-association, and do not activate transcription cooperatively. Further, we demonstrate that UR1 acts as a molecular sensor that regulates the ability of EBNA1 to activate transcription in response to changes in redox and oxygen partial pressure (pO2). Mild oxidative stress mimicking such environmental changes decreases EBNA1-dependent transcription in a lymphoblastoid cell-line. Coincident with a reduction in EBNA1-dependent transcription, reductions are observed in EBNA2 and LMP1 protein levels. Although these changes do not affect LCL survival, treated cells accumulate in G0/G1. These findings are discussed in the context of EBV latency in body compartments that differ strikingly in their pO2 and redox potential

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Prevalence of obesity, tobacco use, and alcohol consumption by socioeconomic status among six communities in Nicaragua Prevalencia de la obesidad, el tabaquismo y el consumo de alcohol según la condición socioeconómica en seis comunidades de Nicaragua

OBJECTIVE: To describe the prevalence of noncommunicable disease (NCD) risk factors (overweight/obesity, tobacco smoking, and alcohol consumption) and identify correlations between these and sociodemographic characteristics in western and central Nicaragua. METHODS: This was a cross-sectional study of 1 355 participants from six communities in Nicaragua conducted in September 2007-July 2009. Demographic and NCD risk-related health behavior information was collected from each individual, and their body mass index (BMI), blood pressure, diabetes status, and renal function were assessed. Data were analyzed using descriptive statistics, bivariate analyses, and (non-stratified and stratified) logistic regression models. RESULTS: Of the 1 355 study participants, 22.0% were obese and 55.1% were overweight/obese. Female sex, higher income, and increasing age were significantly associated with obesity. Among men, lifelong urban living correlated with obesity (Odds Ratio [OR] = 4.39, 1.18-16.31). Of the total participants, 31.3% reported ever smoking tobacco and 47.7% reported ever drinking alcohol. Both tobacco smoking and alcohol consumption were strikingly more common among men (OR = 13.0, 8.8-19.3 and 15.6, 10.7-22.6, respectively) and lifelong urban residents (OR = 2.42, 1.31-4.47 and 4.10, 2.33-7.21, respectively). CONCLUSIONS: There was a high prevalence of obesity/overweight across all income levels. Women were much more likely to be obese, but men had higher rates of tobacco and alcohol use. The rising prevalence of NCD risk factors among even the poorest subjects suggests that an epidemiologic transition in underway in western and central Nicaragua whereby NCD prevalence is shifting to all segments of society. Raising awareness that health clinics can be used for chronic conditions needs to be priority.<br>OBJETIVO: Describir la prevalencia de los factores de riesgo (sobrepeso/obesidad, tabaquismo y consumo de alcohol) de las enfermedades no transmisibles (ENT), y determinar las correlaciones entre estos y las características sociodemográficas en las zonas occidental y central de Nicaragua. MÉTODOS: De septiembre del 2007 a julio del 2009, se llevó a cabo este estudio transversal en 1 355 participantes de seis comunidades de Nicaragua. Para cada persona, se recopiló información demográfica y sobre la conducta en materia de salud relacionada con el riesgo de ENT, y se evaluaron el índice de masa corporal (IMC), la presión arterial, la presencia o no de diabetes y la función renal. Se analizaron los datos mediante estadísticas descriptivas, análisis de dos variables, y modelos de regresión logística (análisis no estratificado y estratificado). RESULTADOS: De los 1 355 participantes en el estudio, 22,0% eran obesos y 55,1% presentaban sobrepeso u obesidad. El sexo femenino, los ingresos más altos y la edad más avanzada se asociaron significativamente con la obesidad. En los varones, la residencia de por vida en un entorno urbano se correlacionó con la obesidad (razón de posibilidades [OR] = 4,39, 1,18-16,31). Del total de participantes, 31,3% habían fumado tabaco y 47,7% habían consumido alcohol alguna vez. Tanto el tabaquismo como el consumo de alcohol fueron considerablemente más frecuentes en los varones (OR = 13,0, 8,8-19,3 y 15,6, 10,7-22,6, respectivamente) y en los que residían de por vida en un entorno urbano (OR = 2,42, 1,31-4,47 y 4,10, 2,33-7,21, respectivamente). CONCLUSIONES: Se observó una alta prevalencia de obesidad/sobrepeso en todos los niveles de ingresos. Las mujeres tenían muchas más probabilidades de ser obesas, pero los varones mostraban mayores tasas de tabaquismo y consumo del alcohol. La creciente prevalencia de los factores de riesgo de las ENT, incluso en las personas más pobres, sugiere que se está produciendo una transición epidemiológica en las zonas occidental y central de Nicaragua mediante la cual la prevalencia de las ENT se está desplazando a todos los segmentos de la sociedad. La concientización de que los dispensarios pueden utilizarse para atender a las afecciones crónicas debe ser prioritaria

Prevalence of chronic kidney disease of non-traditional causes in patients on hemodialysis in southwest Guatemala

ABSTRACT Objective To document the prevalence of patients on hemodialysis in southwestern Guatemala who have chronic kidney disease (CKD) of non-traditional causes (CKDnt). Methods This cross-sectional descriptive study interviewed patients on hemodialysis at the Instituto Guatemalteco de Seguridad Social on their health and occupational history. Laboratory serum, urine and vital sign data at the initiation of hemodialysis were obtained from chart reviews. Patients were classified according to whether they had hypertension or obesity or neither. The proportion of patients with and without these traditional CKD risk factors was recorded and the association between demographic and occupational factors and a lack of traditional CKD risk factors analyzed using multivariate logistic regression. Results Of 242 total patients (including 171 non-diabetics) enrolled in hemodialysis in southwestern Guatemala, 45 (18.6% of total patients and 26.3% of non-diabetics) lacked traditional CKD risk factors. While agricultural work history was common, only travel time greater than 30 minutes and age less than 50 years old were significantly associated with CKD in the absence of traditional risk factors. Individuals without such risk factors lived throughout southwestern Guatemala’s five departments. Conclusions The prevalence of CKDnT appears to be much lower in this sample of patients receiving hemodialysis in Southwestern Guatemala than in hospitalized patients in El Salvador. It has yet to be determined whether the prevalence is higher in the general population and in patients on peritoneal dialysis