In Central America there is an epidemic of chronic kidney disease (CKD) of non-traditional etiology. Few studies have assessed CKD prevalence among non-agricultural workers. We conducted an observational study of 224 artisanal brick workers in La Paz Centro, Nicaragua. Prevalence was based on serum creatinine measures at two time points four months apart. Predictors examined include: age, sex, education, smoking status, body mass index, alcohol consumption, water consumption, family history of CKD, years worked, hours worked, job category, and time (baseline vs. follow-up). Outcomes included serum creatinine-based estimated glomerular filtration rate (eGFR) and stage of CKD. Results indicate CKD prevalence of 14.3% based on the proportion of participants with eGFR < 60 ml/min/1.73m2 at both time points; 97% of cases were male, 25% were less than 35 years of age, and 28% had stage 5 CKD (eGFR <15 ml/min/1.73m2.) Predictors identified by linear mixed effects models included a job task that entails loading or operating the oven, age, sex, education, smoking status, water intake, and family member with CKD. Limitations of this study include a crude job classification metric, loss to follow-up, small sample size, self-reported questionnaire data, and no quantification of albuminuria. According to NHANES 2011-2014 data, estimates of US prevalence ages 20-39 and 40-59 with eGFR <60 ml/min/1.73m2 were 0.3% and 3.3% respectively, whereas the percentage of participants in the present study (aged 18-61) with eGFR < 60 ml/min/1.73m2 at baseline and follow-up was 15.2% and 17.4%, respectively, suggesting that CKD prevalence is abnormally high in this predominantly young population. High prevalence of CKD including at advanced stages indicates that the epidemic of CKD is affecting non-agricultural workers in Nicaragua. These results support the hypothesis that occupational heat exposure and socioeconomic conditions are risk factors for decreased kidney function in this region.

Interleukin-8 (IL-8) is an angiogenic CXC chemokine that plays an important role in both the development and progression of several human malignancies including prostate cancer (PC). A single nucleotide polymorphism (SNP) at −251 upstream of the transcriptional start site of the IL-8 gene has been shown to influence its production. The effects of IL-8 are mediated by two highly related chemokine receptors, CXCR1 and CXCR2. The present study investigated the influence of the IL-8 and CXCR2 gene variation on susceptibility and clinicopathological characteristics of PC in a group of Brazilian subjects. Methods: Two hundred and one patients and 185 healthy controls were enrolled in a case-control study. Blood was collected for DNA extraction; typing of IL-8 −251 T/A and CXCR2 +1208 C/T genes was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP), followed by agarose gel electrophoresis. Risk association between the genotypes, PC susceptibility and tumor characteristics was estimated by odds ratio (OR) and 95% confidence intervals (95% CI) using logistic regression analysis, after adjusting for age at diagnosis. Results: A significant association was found between the heterozygous CXCR2 +1208 CT genotype and stage of PC. The CXCR2 +1208 CT genotype was significantly less frequent in patients with clinical stage T3-T4 compared to T1-T2 (56.7 versus 80.5%). Our findings suggest that carriers of the CXCR2 +1208 CT genotype had a protective effect for advanced PC (CT versus CC: adjusted OR = 0.25; P = 0.02). No association was observed between the SNP for IL-8 −251 T/A and clinicopathological parameters of PC. Conclusion: These results indicated that the CXCR2 +1208 CT genotype is less frequent in advanced stages of PC, suggesting that this chemokine receptor plays a role in the pathogenesis of this disease.

The molecular diversity of rumen methanogens was investigated using 16S rDNA gene library prepared from the rumen contents of Nili-Ravi buffaloes. Microbial genomic DNA was isolated from four adult male fistulated buffaloes and PCR conditions were set up using specific primers. Amplified product was cloned into a suitable vector, and the inserts of positive clones were sequenced. A total of 142 clones were examined, and the analysis revealed 46 species level (0.01 distance) operational taxonomic units (OTUs). Twenty six OTUs comprising 89 clones (63% of the total clones) were taxonomically assigned to Methanobacterium genus and the majority of them had highest percent identity with Methanobacterium flexile among cultured methanogens. Five OTUs comprising 27 clones (19% of total clones) were taxonomically assigned to Methanomicrobium genus and these clones showed highest sequence identity with Methanomicrobium mobile. Only two OTUs comprising 6 clones (4% of total clones) were assigned to Methanobrevibacter genus. A total of 17 clones belonging to 10 species level OTUs showed highest percent identity (ranging from 85 to 95%) with Methanomassilicoccus luminyensis and were taxonomically classified as Methanomassiliicocaceae. Out of the 142 rDNA clones, 112 clones, which constitute 79% of the total clones representing 42 OTUs, had less than 98.5% sequence identity with any of the cultured strains of methanogens and represent novel species of methanogens. This study has revealed the largest assortment of hydrogenotrophic methanogen phylotypes ever identified from the rumen of Nili-Ravi buffaloes. The study indicates that Methanobacterium is the most dominant methanogen in the rumen of Nili-Ravi buffalo. This is also the first report on the presence of methanogens phylogenetically close to M. luminyensis, an H2 dependent methylotrophic methanogen, in the rumen of buffaloes at such a high level of abundance.

Background: In Central America, an epidemic of chronic kidney disease (CKD) of unknown etiology has been described in young, male agricultural workers. Many potential causes have been hypothesized, one of which is leptospirosis, a bacterial zoonosis that is prevalent in the region and can cause acute kidney injury but has not been clearly associated with CKD. Our aims were to characterize exposure to Leptospira in Nicaraguan sugarcane workers, explore differences by job, and evaluate associations with biomarkers of kidney injury. Methods: Our study population included 282 sugarcane workers representing 7 different job tasks. Blood and urine samples were collected during two rounds of sampling, at the beginning and end of the 6-month harvest. We analyzed biological samples for exposure to Leptospira (using the microscopic agglutination test (MAT)) and biomarkers of kidney injury and function. Results: Among workers, 34% were seropositive, reflecting any prior exposure to Leptospira. Cane cutters had the highest odds of prior exposure (OR=20.5; 95% CI: 6.3-66.5). At late-harvest, linear regression models showed higher levels of urinary interleukin-18 (IL-18) (mean ratio=1.22; 95% CI: 0.88-1.69) and urinary neutrophil gelatinase-associated lipocalin (NGAL) (mean ratio=1.29; 95% CI: 0.95-1.77) among workers with past infection to Leptospira. Among workers with past infection, NGAL increased during the harvest by 10.23 µg/g creatinine (95% CI: -2.44-22.9). Conclusions: There is evidence of high Leptospira seroprevalence among this population, particularly among cane cutters. Workers who had past exposure to Leptospira had higher late-harvest levels of urinary IL-18 and NGAL, novel biomarkers of tubulointerstitial kidney injury. Similarly, NGAL increased during the harvest more among workers who had past infection. This pilot study suggests that leptospirosis infection may be important to consider as a kidney disease susceptibility factor, thus warranting further study.

Background: In Central America, an epidemic of chronic kidney disease (CKD) of unknown etiology has been described in young, male agricultural workers. One potential cause is repeated exposure to heat and strenuous labor, coupled with dehydration and chronic volume depletion. Our aims were to explore differences in self-reported hydration by job category among sugarcane workers and evaluate associations with biomarkers of kidney damage. Methods: Our study population included 284 sugarcane workers representing 7 different job categories. Questionnaires were administered to assess hydration practices, and blood and urine samples were collected at the beginning and end of the 6-month harvest season. We measured biomarkers of kidney damage, including serum creatinine (used to estimate glomerular filtration rate (eGFR)) and urine interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine. Results: Self-reported consumption of water and bolis (an electrolyte and water solution) differed by job category (p<0.0001), with field workers, particularly cane cutters, consuming more than non-field workers. There were no associations of self-reported fluid consumption with eGFR, NGAL, or IL-18, after controlling for job category, sex, age, years worked at the company, and alcohol consumption. When stratified by job category, for every additional bolis packet consumed among cane cutters (n=51), mean change in eGFR during the harvest increased by 5.9 mL/min/1.73 m2 (95% CI: 0.5 to 11.2 mL/min/1.73 m2) and mean change in NGAL decreased by 21.5 µg/g creatinine (95% CI: -36.6 to -6.3 µg/g creatinine). Conclusions: Increased bolis consumption appeared protective for cane cutters, a high risk population, though this was not observed in the population as a whole. These findings suggest that maintaining adequate fluid volume may be important in the pathogenesis of CKD in Nicaragua.

Background An epidemic of Chronic Kidney Disease (CKD) is occurring across Central America, affecting, mainly among younger men. Most studies have focused on occupational factors, but the large number of cases at a young age suggests that initial damage may begin in childhood. The goal of this pilot study was to assess markers of kidney damage among adolescents before they start working. Methods We studied markers of kidney damage in 200 students (age 12-18) with no prior work history from 4 schools in different regions of Nicaragua (Jinotega, Masaya, North Chichigalpa, and South Chichigalpa). Schools represent a range of risk based on regional adult CKD mortality data. Urine was tested by dipstick and analyzed for albumin, NGAL, NAG, and IL-18, all normalized to urine creatinine concentration. Results Dipstick proteinuria (3%) and glucosuria (1%) were rare. Only 8% had an albumin to creatinine ratio (ACR) >30 mg/g. The median IL-18 level was higher than in healthy controls identified from other studies [45 pg/ml (21-115) vs. 15 pg/ml (7-28)]. Boys had lower levels than girls for all markers, particularly NGAL and IL-18. The results by school were consistent with their a priori risk: among boys, the highest mean levels of NAG, NGAL, and IL-18 occurred at the highest risk school while girls at the two highest risk schools had higher levels of NAG. Normalization for urine creatinine did not affect results. Conclusions Non-glomerular kidney damage may be present among children in an area of epidemic CKD. If confirmed, factors in addition to occupational exposure should be studied as possible causes of CKD.

Chronic kidney disease of unknown etiology (CKDu) has emerged as a major public health problem in Central American. In high- and middle-income countries, CKD is primarily caused by diabetes and hypertension and is rare among adults under the age of 60. However, in Central America, diabetes and hypertension appear to play at most a marginal role and the disease affects a much younger demographic. Although data suggest an excess of disease for at least 20 years, the epidemic has received limited attention in the broader medical and public health community. The main objective of this presentation is to describe the epidemiologic characteristics of CKDu in Central America, provide the basis for subsequent presentations on research into possible causes of the disease, and similar CKDu in Southern India. The excess of CKDu in Central America is most apparent in El Salvador and Nicaragua but seems to extend across Central America and is especially concentrated in the lowlands along the Pacific coast. Men seem to be disproportionately affected, with elevated serum creatinine levels often noted in the third or fourth decade of life. Significant proteinuria is uncommon, which supports the growing evidence that the clinical profile is most consistent with tubulointerstitial disease and not glomerular disease. The etiology of CKDu remains unknown but is likely multifactorial, potentially involving a combination of causal and susceptibility factors. To date, causal hypotheses include: volume depletion and occupational exposure to heat; environmental and/or occupational exposure to nephrotoxicants such as heavy metals, pesticides, and aristolochic acid; nephrotoxic medications such as NSAIDs (widely used in the region to treat dysuria); infections such as leptospirosis; and genetic or developmental factors. Consensus has emerged for a multifactorial etiology, with emphasis on recurrent volume depletion and heat-related injury potentially resulting in subclinical acute kidney injury that may progress to CKDu.

Background: In Nicaragua, an excess prevalence of chronic kidney disease (CKD) of unknown etiology has been described in young, male agricultural workers, particularly in sugarcane workers. Many potential causes have been hypothesized, including exposures to extreme heat and heavy metals, but the etiologic agent remains unknown and it is unclear whether the disease results from occupational or nonoccupational factors. Our aims include characterizing the type of kidney damage, evaluating occupational factors, and investigating the role of metals exposure. Methods: Our study population included 284 sugarcane workers representing 7 different job tasks. Blood and urine samples were collected during two rounds of sampling, at the beginning and end of the 6-month harvest season (zafra). We analyzed biological samples for cadmium, uranium, and arsenic (in urine); lead (in blood); and biomarkers of kidney injury and CKD. Results: Estimated glomerular filtration rate (eGFR) was significantly different by sugarcane job and decreased by 6.4 mL/min/1.73 m2 during the zafra in cane cutters as compared to factory workers (p=0.006). Similarly, urine NGAL differed by job, increasing most among cane cutters, by 19.2 mg/g creatinine, as compared to factory workers (p=0.04). Generally, urine albumin was low in all workers. Heavy metals were not associated with markers of kidney function, with the exception of arsenic; workers with the highest urinary arsenic levels had significantly lower eGFR (p=0.01). Conclusions: Biomarkers of kidney injury and CKD were highest among cane cutters and lowest among factory workers, supporting the hypothesis that workers performing the most intensive physical labor in the hottest conditions are at greater risk of developing CKD. The absence of albuminuria suggests a tubulointerstitial, not glomerular, disease. Finally, there is some evidence that high exposure to arsenic is associated with biomarkers of CKD.

1. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA 2. Preventive Medicine and Public Health Department, Universidad Autónoma de Madrid, Madrid, Spain 3. Renal Section, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA 4. Division of Nephrology, Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA 5. Section of Nephrology, Department of Medicine, Yale University, New Haven, CT, USA 6. Program of Applied Translational Research, Department of Medicine, Yale University, New Haven, CT, USA 7. Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA

Kachha ghada phootne mey jyaada takleef hoti hai ... (With the shattering of an un-baked earthen pot the suffering is more... women in Rajasthan) Women use images of earthen pots breaking flowers or fruits falling to symbolize the loss of pregnancy. kachha ghada phoota (UP Rajasthan) phool jhade (Madhya Praciesh) kaacho padi gayo (Rajasthan) garbha-alasyam (Kerala) are some of the terms used to describe miscarriages. In english human embryo death and its exit from the womb if unintended is called miscarriage or if caused purposefully it is called abortion. Spontaneous abortion and induced abortion are terms that doctors use. Miscarriages are not uncommon among women in India. In the west research has estimated that between fifteen to thirty conceptions out of a hundred are miscarried. Most are silent near the time of the expected menstrual period. Early miscarriages are now largely understood as natural selection by a womans body to weed out genetically blighted embryos. But early miscarriages can also result from poverty-linked and gender-tainted factors like under-nutrition infections work stress accidents domestic violence and so on. (excerpt)