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Chronic kidney disease (CKD) is a multifactorial disorder with an important genetic component, and several studies have demonstrated potential associations with allelic variants. In addition, CKD patients are also characterized by high levels of genomic damage. Nevertheless, no studies have established relationships between DNA damage, or genomic instability present in CKD patients, and gene polymorphisms. To fill in this gap, the potential role of polymorphisms in genes involved in base excision repair (OGG1, rs1052133; MUTYH, rs3219489; XRCC1, rs25487), nucleotide excision repair (ERCC2/XPD, rs1799793, rs171140, rs13181; ERCC4, rs3136166); phase II metabolism (GSTP1, rs749174; GST01, rs2164624; GSTO2, rs156697), and antioxidant enzymes (SOD1, rs17880135, rs1041740, rs202446; SOD2, rs4880; CAT, rs1001179; GPX1, rs17080528; GPX3, rs870406: GPX4, rs713041) were inquired. In addition, some genes involved in CKD (AGT, rs5050; GL01, rs386572987; SHROOM3, rs17319721) were also evaluated. The genomic damage, the genomic instability, and oxidative damage were evaluated by using the micronucleus and the comet assay in 589 donors (415 CKD patients and 174 controls). Our results showed significant associations between genomic damage and genes directly involved in DNA repair pathways (XRCC1, and ERCC2), and with genes encoding for antioxidant enzymes (SOD1 and GPX1). GSTO2, as a gene involved in phase II metabolism, and MUTYH showed also an association with genomic instability. Interestingly, the three genes associated with CKD (AGT, GLO1, and SHROOM3) showed associations with both the high levels of oxidatively damaged DNA and genomic instability. These results support our view that genomic instability can be considered a biomarker of the CKD status.

Background: Exposure to trihalomethanes (THMs) in drinking water has consistently been associated with an increased risk of bladder cancer, but evidence on other cancers including the breast is very limited. Objectives: We assessed long-term exposure to THMs to evaluate the association with female breast cancer (BC) risk. Methods: A multi case-control study was conducted in Spain from 2008 to 2013. We included 1003 incident BC cases (women 20-85 years old) recruited from 14 hospitals and 1458 population controls. Subjects were interviewed to ascertain residential histories and major recognized risk factors for BC. Mean residential levels of chloroform, brominated THMs (Br-THMs) and the sum of both as total THM (TTHMs) during the adult-lifetime were calculated. Results: Mean adult-lifetime residential levels ranged from 0.8 to 145.7 mu g/L for TTHM (median= 30.8), from 0.2 to 62.4 mu g/L for chloroform (median = 19.7) and from 0.3 to 126.0 mu g/L for Br-THMs (median= 9.7). Adult-lifetime residential chloroform was associated with BC (adjusted OR = 1.47; 95% CI = 1.05, 2.06 for the highest (> 24 mu g/L) vs. lowest (< 8 mu g/L) quartile; p-trend = 0.024). No association was detected for residential Br-THMs (OR= 0.91; 95% CI = 0.68, 1.23 for> 31 mu g/L vs.< 6 mu g/L) or TTHMs (OR = 1.14; 95% CI = 0.83, 1.57 for> 48 mu g/L vs.< 22 mu g/L). Conclusions: At common levels in Europe, long-term residential total THMs were not related to female breast cancer. A moderate association with chloroform was suggested at the highest exposure category. This large epidemiological study with extensive exposure assessment overcomes several limitations of previous studies but further studies are needed to confirm these results.

End-stage renal disease (ESRD) patients present high levels of phosphorus and calcium products in serum, which contribute to the development of vascular calcification and cardiovascular disease, and to low iron stores and carnitine deficiency. For these reasons, ESRD patients are generally supplemented with different medicines. Some of the most common treatments include the use of Carnicor, Venofer, and Sevelamer drugs. Carnicor is used as a source of L-carnitine, acting as antioxidant and neuroprotector. Venofer is used to reduce the deficit of iron. Sevelamer is used to treat hyperphosphatemia. To determine the potential harmful genotoxic effects of these drugs, a group of 214 patients included in a hemodialysis program with different intakes of Carnicor, Venofer, and Sevelamer were evaluated. The levels of basal and oxidative DNA damage, as well as chromosomal damage, were measured in all individuals using the comet and the micronucleus assays, respectively. Our results indicate that Carnicor administration was associated with low but significant increases in the frequency of basal DNA damage and micronuclei. Environ. Mol. Mutagen. 59:302-311, 2018. (c) 2018 Wiley Periodicals, Inc.

Epidemiological studies provide evidence that environmental exposures may affect health through complex mixtures. Formal investigation of the effect of exposure mixtures is usually achieved by modelling interactions, which relies on strong assumptions relating to the identity and the number of the exposures involved in such interactions, and on the order and parametric form of these interactions. These hypotheses become difficult to formulate and justify in an exposome context, where influential exposures are numerous and heterogeneous. To capture both the complexity of the exposome and its possibly pleiotropic effects, models handling multivariate predictors and responses, such as partial least squares (PLS) algorithms, can prove useful. As an illustrative example, we applied PLS models to data from a study investigating the inflammatory response (blood concentration of 13 immune markers) to the exposure to four disinfection by-products (one brominated and three chlorinated compounds), while swimming in a pool. To accommodate the multiple observations per participant (n=60; before and after the swim), we adopted a multilevel extension of PLS algorithms, including sparse PLS models shrinking loadings coefficients of unimportant predictors (exposures) and/or responses (protein levels). Despite the strong correlation among co-occurring exposures, our approach identified a subset of exposures (n=3/4) affecting the exhaled levels of 8 (out of 13) immune markers. PLS algorithms can easily scale to high-dimensional exposures and responses, and prove useful for exposome research to identify sparse sets of exposures jointly affecting a set of (selected) biological markers. Our descriptive work may guide these extensions for higher dimensional data.

WOS: 000398117600023, PubMed ID: 28025382, Background. From an individual participant data (IPD) meta-analysis from four randomized controlled trials comparing haemodialysis (HD) with post-dilution online-haemodiafiltration (ol-HDF), previously it appeared that HDF decreases all-cause mortality by 14% (95% confidence interval 25; 1) and fatal cardiovascular disease (CVD) by 23% (39; 3). Significant differences were not found for fatal infections and sudden death. So far, it is unclear, however, whether the reduced mortality risk of HDF is only due to a decrease in CVD events and if so, which CVD in particular is prevented, if compared with HD. Methods. The IPD base was used for the present study. Hazard ratios and 95% confidence intervals for cause-specific mortality overall and in thirds of the convection volume were calculated using the Cox proportional hazard regression models. Annualized mortality and numbers needed to treat (NNT) were calculated as well. Results. Besides 554 patients dying from CVD, fatal infections and sudden death, 215 participants died from 'other causes', such as withdrawal from treatment and malignancies. In this group, the mortality risk was comparable between HD and ol-HDF patients, both overall and in thirds of the convection volume. Subdivision of CVD mortality in fatal cardiac, non-cardiac and unclassified CVD showed that ol-HDF was only associated with a lower risk of cardiac casualties [0.64 (0.61; 0.90)]. Annual mortality rates also suggest that the reduction in CVD death is mainly due to a decrease in cardiac fatalities, including both ischaemic heart disease and congestion. Overall, 32 and 75 patients, respectively, need to be treated by high-volume HDF (HV-HDF) to prevent one all-cause and one CVD death, respectively, per year. Conclusion. The beneficial effect of ol-HDF on all-cause and CVD mortality appears to be mainly due to a reduction in fatal cardiac events, including ischaemic heart disease as well as congestion. In HV-HDF, the NNT to prevent one CVD death is 75 per year., EuDial working group; European Nephrology and Dialysis Institute; Catalan Society of Nephrology; Fresenius Medical Care; Dutch Kidney Foundation [C02.2019]; Fresenius Medical Care, Netherlands; Gambro Lundia AB, Sweden; Dr E.E. Twiss Fund; International Society of Nephrology/Baxter Extramural Grant Program; Netherlands Organization for Health Research and DevelopmentNetherlands Organization for Health Research and Development [170882802]; national grant from the Health Ministry (Programme Hospitalier de Recherche Clinique, PHRC); Gambro through the Catalan Society of Nephrology; Roche Netherlands, The HDF Pooling project was designed, conducted and analysed independently of the financial contributors of the individual studies as listed below. Study data were collected and retained by the investigators and were not available for the financial contributors of the individual studies. S.A.E.P. and the meetings of the representatives of the combined authors of the four studies were financially supported by the EuDial working group. EuDial is an official working group of the European Renal Association-European Dialysis Transplant Association (ERA-EDTA, http://era-edta.org/eudial/European_Dialysis_Working_Group.html). No industry funding was received for any part of or activity related to the present analysis.; The Turkish HDF study was supported by European Nephrology and Dialysis Institute with an unrestricted grant. The study was performed in Fresenius Medical Care haemodialysis clinics in Turkey. ESHOL was supported by The Catalan Society of Nephrology and by grants from Fresenius Medical Care and Gambro through the Catalan Society of Nephrology. The CONTRAST study was supported by a grant from the Dutch Kidney Foundation (Nierstichting Nederland Grant C02.2019), and unrestricted grants from Fresenius Medical Care, Netherlands, and Gambro Lundia AB, Sweden. Additional support was received from the Dr E.E. Twiss Fund, Roche Netherlands, the International Society of Nephrology/Baxter Extramural Grant Program, and the Netherlands Organization for Health Research and Development (ZONMw Grant 170882802). The French HDF study was supported by a national grant from the Health Ministry (Programme Hospitalier de Recherche Clinique, PHRC) as a means to improve care and outcome of elderly chronic disease patients.

Chronic kidney disease (CKD) patients are characterized by elevated levels of genomic damage. This damage increases when kidney function decreases being maximum in hemodialysis patients. As kidney transplantation improves renal function, and it is related with better survival, the aim of our study was to evaluate potential changes in DNA damage levels after kidney transplantation, and comparing living donor recipients with cadaveric donor recipients. The alkaline comet assay was used to determine DNA breaks and oxidative damaged DNA; and the micronucleus assay was used to determine chromosomal breakage and/or aneuploidy. Fifty CKD patients were followed up after 6 and 12 months of their kidney transplantation. All patients increased their genomic damage levels after 6 and 12 months of renal transplantation, compared with those observed before transplantation, despite of the improvement of their metabolic functions. Donor advanced age correlated positively with higher DNA damage. Genomic damage was lower in living donor transplants with respect to cadaveric donor transplants. Our conclusion is that DNA damage increased in kidney transplantation patients, whereas their renal function improved. Higher levels of DNA damage were found in cadaveric donor transplants when compared to living donor transplants. (C) 2017 Wiley Periodicals, Inc.

This study describes the relationship between physical activity and intake of trihalomethanes (THMs), namely chloroform (CHCl3), bromodichloromethane (CHCl2Br), dibromochloromethane (CHClBr2) and bromoform (CHBr3), in individuals exposed in two indoor swimming pools which used different disinfection agents, chlorine (Cl-SP) and bromine (Br-SP). CHCl3 and CHBr3 were the dominant compounds in air and water of the Cl-SP and Br-SP, respectively. Physical exercise was assessed from distance swum and energy expenditure. The changes in exhaled breath concentrations of these compounds were measured from the differences after and before physical activity. A clear dependence between distance swum or energy expenditure and exhaled breath THM concentrations was observed. The statistically significant relationships involved higher THM concentrations at higher distances swum. However, air concentration was the major factor determining the CHCl3 and CHCl2Br intake in swimmers whereas distance swum was the main factor for CHBr3 intake. These two causes of THM incorporation into swimmers concurrently intensify the concentrations of these compounds into exhaled breath and pointed to inhalation as primary mechanism for THM uptake. Furthermore, the rates of THM incorporation were proportionally higher as higher was the degree of bromination of the THM species. This trend suggested that air-water partition mechanisms in the pulmonary system determined higher retention of the THM compounds with lower Henry's Law volatility constants than those of higher constant values. Inhalation is therefore the primary mechanisms for THM exposure of swimmers in indoor buildings.

Background: Exposure to hard water has been suggested as a risk factor for eczema in childhood, based on limited evidence from two ecologic and two cross-sectional studies. Objectives: We evaluate this hypothesis for the first time in early infancy using prospective data from a mother-child cohort study. Methods: We used data from the INMA cohorts in Gipuzkoa, Sabadell and Valencia, Spain (N = 1638). Current and ever eczema, bathing frequency and duration and covariables were collected by questionnaires at 14 months (14 m) and 4 years (4 y). Calcium carbonate (CaCO3) level in municipal water was assigned to home addresses at birth, 14 m and 4 y. We calculated Odds Ratio (OR) of eczema related to CaCO3 at home, bath exposure and a combination of both. Results: Prevalence of eczema ever was 18.4% at 14 m and 33.4% at 4 y. Mean CaCO3 ranged from 51.6 to 272.8 mg/L among areas. No association was detected between water hardness at home and current or ever eczema. Adjusted OR was 0.79 (95%CI=0.45, 1.39) at 14 m and 0.93 (0.56, 1.52) at 4 y among children in the highest vs. lowest tertiles of CaCO3. Bath exposure alone or in combination with water hardness did not increase the OR of eczema at 14 m or 4 y either. Conclusions: We did not find an association between eczema and water hardness at home or bathing exposure during the first four years of life. This first cohort study in a critical age period with improved exposure assessment does not confirm the association suggested among children by previous studies. (C) 2015 Elsevier Inc. All rights reserved.

It is assumed that hemodialysis treatment can diminish the levels of genetic damage in circulating lymphocytes by cleaning the blood of uremic toxins that cause oxidative stress. However, the hemodialysis process by itself may also induce genomic damage by producing reactive oxygen species (ROS). We conducted a follow-up study in a group of 70 hemodialysis patients followed for a mean time of 15 months. We investigated the effect of exposure time in hemodialysis on the levels of genetic damage in peripheral blood lymphocytes using the micronucleus assay. In addition, genetic damage after in vitro irradiation with 0.5 Gy was also analyzed to evaluate changes in radiosensitivity. Our results showed that, at the end of the study, there was a decrease in both the basal levels of genetic damage (9.9 +/- 1.0 vs. 7.6 +/- 0.7) and radiosensitivity values (38.5 +/- 3.0 vs. 27.6 +/- 2.4). We conclude that hemodialysis procedures may act as an ameliorating factor reducing the genetic damage present in chronic kidney disease patients. Environ. Mol. Mutagen. 55:363-368, 2014. (c) 2014 Wiley Periodicals, Inc.

Objective: To identify and describe studies on social inequalities in child and adolescent health conducted in Spain with special emphasis on social determinants. Methods: In July 2012, we conducted a systematic review in the PubMed, MEDES, SCOPUS and COCHRANE databases. We included studies on social inequalities in child and adolescent health in Spain published between 2000 and 2012. A total of 2147 abstracts were reviewed by two researchers and 80 manuscripts were fully reviewed by three researchers. Risk of bias was assessed. Seventy-two articles were finally included. Results: A total of 83% of the studies were cross-sectional and the most frequently studied age group consisted of 13-15-year-olds. More than 20 individual or group determinants were identified. The most frequently analyzed determinants were the most advantaged educational level and occupation of the mother or the father. In 38% of the studies analyzing education and occupation, there was no definition of the determinant. Social inequalities were detected in dental health with all determinants and in all age groups (9% of studies with a high risk of bias). Social inequalities were also detected in obesity, physical activity and mental health with some determinants. Specific data were missing for younger children. No social inequalities were found in the use of health services, excluding dental care. Few studies analyzed immigration and 42% of them had a high risk of bias. Conclusion: Wide diversity was found in the measurement of social determinants, with a lack of studies in preschoolers and of studies with longitudinal designs. The results of this study confirm social inequalities in some aspects of health. (C) 2013 SESPAS. Published by Elsevier Espana, S.L. All rights reserved.

We evaluated the relationship between indoor and outdoor swimming pool attendance and respiratory symptoms and infections during the first year of life. A population-based mother-child cohort study was conducted in four Spanish areas (INMA project). Study subjects were recruited at pregnancy, followed to delivery and 14 months after birth. Information on swimming pool attendance and health manifestations during the first year of life was collected at 14 months: low respiratory tract infection (LRTI), persistent cough, wheezing, atopic eczema and otitis. Odds ratios and 95 % confidence interval (OR 95 %CI) were calculated by logistic regression adjusting for confounders. Among the 2,205 babies included, 37 % reported having LRTI, 37 % wheezing, 16 % persistent cough, 22 % atopic eczema, 33 % otitis and 50 % attended swimming pools during the first year of life. Around 40 % went to outdoor pools in summer with a median cumulative duration of 7.5 h/year, and 20 % attended indoor pools with a median cumulative duration of 18 h/year. Pool attendance differed by area, season of birth and sociodemographic characteristics, and was not associated with LRTI, wheezing, persistent cough, atopic eczema or otitis. Adjusted OR of wheezing and LRTI were, respectively, 1.06 (95 %CI, 0.88-1.28) and 1.09 (0.90-1.31) for babies attending vs. babies not attending pools. Stratification by type of swimming pool, cumulative duration or parental atopy did not modify the results.

Increased asthma risk has been associated with pool attendance in children but evidence is inconsistent and inconclusive. A survey was conducted of 3,223 9-12-yr-old children in Sabadell (Spain) to evaluate association between swimming pool attendance and prevalence of asthma and allergic conditions and symptoms. Parents completed a questionnaire on lifetime frequency of pool attendance and symptoms in the last 12 months (wheezing, asthma medication, rhinitis and allergic rhinitis), ever having asthma and eczema, and potential confounders. Indicators of indoor and outdoor swimming pool attendance early in life, cumulatively and currently were calculated. Swimming pool attendance before the age of 2 yrs was associated with slightly lower prevalence of current asthma (OR 0.79, 95% CI 0.43-1.46), rhinitis (OR 0.86, 95% CI 0.68-1.08) and allergic rhinitis symptoms (OR 0.72, 95% CI 0.54-0.96) compared to those who started attending swimming pools after 4 yrs of age. An increased prevalence of eczema was associated with duration of lifetime pool attendance (OR 1.71, 95%CI 1.38-2.12 for >5 yrs versus 0 yrs). Swimming pool attendance in Spanish children was associated with slightly less upper and lower respiratory tract symptoms and with more eczema. Longitudinal studies are required to confirm these findings and avoid potential reverse causation.

Background: Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in the water and related that to mutagenicity. Objectives: We performed a comprehensive identification of DBPs and disinfectant species in waters from public swimming pools in Barcelona, Catalonia, Spain, that disinfect with either chlorine or bromine and we determined the mutagenicity of the waters to compare with the analytical results. Methods: We used gas chromatography/mass spectrometry (GC/MS) to measure trihalomethanes in water, GC with electron capture detection for air, low- and high-resolution GC/MS to comprehensively identify DBPs, photometry to measure disinfectant species (free chlorine, monochloroamine, dichloramine, and trichloramine) in the waters, and an ion chromatography method to measure trichloramine in air. We assessed mutagenicity with the Salmonella mutagenicity assay. Results: We identified > 100 DBPs, including many nitrogen-containing DBPs that were likely formed from nitrogen-containing precursors from human inputs, such as urine, sweat, and skin cells. Many DBPs were new and have not been reported previously in either swimming pool or drinking waters. Bromoform levels were greater in brominated than in chlorinated pool waters, but we also identified many brominated DBPs in the chlorinated waters. The pool waters were mutagenic at levels similar to that of drinking water (~ 1,200 revertants/L-equivalents in strain TA100-S9 mix). Conclusions: This study identified many new DBPs not identified previously in swimming pool or drinking water and found that swimming pool waters are as mutagenic as typical drinking waters.

The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies and recurrent thrombosis, affecting the venous system more frequently than the arterial one. Renal involvement is only observed in approximately 20-25% of cases, main renal artery thrombosis has been exceptionally described. We report a 39-year-old woman with previous history of recurrent thrombosis diagnosed as primary antiphospholipid syndrome, who presented malignant hypertension in the context of a renal artery thrombosis. She had a high IgG anticardiolipin antibody titre and positive lupus anticoagulant. An isotopic renogram demonstrated asymmetrical activity (60% right vs 40% left kidney). Renal arteriography demonstrated preoclusive thrombosis in the left renal artery. Blood pressure was well controlled by the use of ACE-inhibitor and alpha blockers.

Pregnancy can be regarded as a secondary hyper-coagulability state. The development of thrombin-anti-thrombin complexes (TATC), D dimer and anti-thrombin III (AT III) was analysed in the present work on 33 pregnant women. A significant increase of the TATC records was found between the first and third trimesters and between the second and third trimesters (p = 0.005 and p = 0.02, respectively). The AT III values were within the normal range. The values of the D dimer increased progressively during pregnancy, but only the figures achieved in the third trimester were statistically significant with respect to the control group (p = 0.14). The increase of TATC and D dimer during pregnancy are considered as hypercoagulability.