Associations between prenatal exposure to cadmium and lead with neural tube defect risks are modified by single-nucleotide polymorphisms of fetal MTHFR and SOD2: a case-control study.

BACKGROUND: Prenatal exposure to heavy metals is implicated in the etiology of birth defects. We investigated whether concentrations of cadmium (Cd) and lead (Pb) in umbilical cord tissue are associated with risk for neural tube defects (NTDs) and whether selected genetic variants of the fetus modify their associations. METHODS: This study included 166 cases of NTD fetuses/newborns and 166 newborns without congenital malformations. Umbilical cord tissue was collected at birth or elective pregnancy termination. Cd and Pb concentrations were assessed by inductively coupled plasma-mass spectrometry, and 20 single-nucleotide polymorphisms (SNPs) in 9 genes were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the risk for NTDs in association with metal concentrations or genotype using logistic regression. Multiplicative-scale interactions between the metals and genotypes on NTD risk were assessed with logistic regression, and additive-scale interactions were estimated with a non-linear mixed effects model. RESULTS: Higher concentrations of Cd were observed in the NTD group than in the control group, but no difference was found for Pb. Concentrations of Cd above the median level showed a risk effect, while the association between Pb and NTD risk was not significant in univariate analyses. The association of Cd was attenuated after adjusting for periconceptional folic acid supplementation. Fetuses with the AG and GG genotypes of rs4880 in SOD2 (superoxide dismutase 2) tended to have a lower risk, but fetuses with the CT and TT genotypes of rs1801133 in MTHFR (5,10-methylenetetrahydrofolatereductase) have a higher risk for NTDs when compared to their respective wild-type. rs4880 and Cd exhibited a multiplicative-scale interaction on NTD risk: the association between higher Cd and the risk for NTDs was increased by over fourfold in fetuses carrying the G allele [OR 4.43 (1.30-15.07)] compared to fetuses with the wild-type genotype. rs1801133 and Cd exposure showed an additive interaction, with a significant relative excess risk of interaction [RERI 0.64 (0.02-1.25)]. CONCLUSIONS: Prenatal exposure to Cd may be a risk factor for NTDs, and the risk effect may be enhanced in fetuses who carry the G allele of rs4880 in SOD2 and T allele of rs1801133 in MTHFR.

Estimation of Prevalence of Kidney Disease Treated With Dialysis in China: A Study of Insurance Claims Data.

RATIONALE & OBJECTIVE: The national prevalence of dialysis in China has not been well studied. We aimed to estimate the prevalence of kidney disease treated with dialysis and predict the trend using claims data in order to provide evidence for developing prevention strategies. STUDY DESIGN: Cross-sectional study of insurance claims. SETTING & PARTICIPANTS: Medical claims data from January 1, 2013, to December 31, 2017, were extracted from a large claims database by using a 2-stage sampling design to obtain a national sample covered by the urban basic medical insurance, the most predominant insurance program in China. EXPOSURE: Patients receiving maintenance dialysis, including hemodialysis (HD) and peritoneal dialysis (PD), were identified according to medical billing data and International Classification of Diseases, Tenth Revision (ICD-10) codes. OUTCOMES: The age- and sex-standardized population prevalence of kidney disease treated with dialysis was estimated by year and treatment modality. ANALYTICAL APPROACH: Crude and age- and sex-standardized prevalence of kidney disease treated with dialysis were calculated stratified by year and treatment modality. The gray Verhulst model was used to predict dialysis prevalence from 2018 to 2025. RESULTS: The age-and sex-standardized prevalence of dialysis patients increased from 255.11 per million population (pmp) in 2013 to 419.39 pmp in 2017. The age- and sex-standardized prevalence of HD and PD in 2017 were 384.41 pmp and 34.98 pmp, respectively, and the total number of dialysis patients in China was estimated to be 581,273. The prevalence of dialysis was predicted to rise above 2017 levels, with a predicted prevalence of 534.60 pmp in 2020 and 629.67 pmp in 2025, corresponding to 744,817 and 874,373 patients, respectively. LIMITATIONS: Claims data have potential errors in classification of patients, and population selection bias may have limited inferences to the entire Chinese population. CONCLUSIONS: The prevalence of kidney disease treated with dialysis has risen between 2013 and 2017 in China and is predicted to increase further through 2025. These findings highlight the importance of prevention and control strategies to reduce the escalating burden of kidney failure.

Prenatal exposure to organochlorine pesticides is associated with increased risk for neural tube defects.

Neural tube defects (NTDs) are among the most common and disabling fetal congenital defects. Organochlorine pesticides (OCPs) are ubiquitous in the environment. In this study, 119 women who had NTD-affected pregnancies (cases) and 119 women who delivered healthy neonates (controls) were recruited in a rural area of Northern China. We used concentrations of OCPs in umbilical cord tissue as markers of prenatal exposure to investigate the association between in utero exposure to OCPs and NTD risk. Concentrations of 20 OCPs were quantified by gas chromatography-mass spectrometry, and 16 of the 20 OCPs were included in the analyses. Odds ratios and 95% confidence intervals (95% CIs) for the associations between levels of individual OCPs and NTD risk were estimated separately with logistic regression adjusting for potential confounders. The combined effects of exposure to the 16 OCPs as a mixture were analyzed with Bayesian kernel machine regression (BKMR). Logistic regression showed that the risk for NTDs increased 5.44-fold (95% CI, 2.21-13.41) for ß-hexachlorocyclohexane, 2.51-fold (95% CI, 1.07-5.86) for endosulfan I, 3.78-fold (95% CI, 1.60-8.89) for endosulfan II, 3.42-fold (95% CI, 1.44-8.12) for ο,ρ'-dichlorodiphenyldichloroethane, and 2.89-fold (95% CI, 1.22-6.86) for ρ,ρ'-dichlorodiphenyltrichloroethane when the concentration of each of these OCPs was above its median (exposed) compared to below its median (non-exposed). Other OCPs were not associated with NTD risk in multivariate models. In BKMR, NTD risk increased almost linearly with concentrations of the 16 OCPs as a mixture, which suggests joint effects on NTD risk. Exposure to α-hexachlorocyclohexane, ß-hexachlorocyclohexane, endosulfan II, ο,ρ'-dichlorodiphenyldichloroethane, and ρ,ρ'-dichlorodiphenyldichloroethane was associated with an increased risk for NTDs when levels of the remaining 15 OCPs were taken into account. Taken together, these findings show that prenatal exposure to OCPs is associated with increased risk for NTDs.

Long-Term Exposure to Ambient PM2.5, Sunlight, and Obesity: A Nationwide Study in China.

Background: Accumulated researches revealed that both fine particulate matter (PM2.5) and sunlight exposure may be a risk factor for obesity, while researches regarding the potential effect modification by sunlight exposure on the relationship between PM2.5 and obesity are limited. We aim to investigate whether the effect of PM2.5 on obesity is affected by sunlight exposure among the general population in China. Methods: A sample of 47,204 adults in China was included. Obesity and abdominal obesity were assessed based on body mass index, waist circumference and waist-to-hip ratio, respectively. The five-year exposure to PM2.5 and sunlight were accessed using the multi-source satellite products and a geochemical transport model. The relationship between PM2.5, sunshine duration, and the obesity or abdominal obesity risk was evaluated using the general additive model. Results: The proportion of obesity and abdominal obesity was 12.6% and 26.8%, respectively. Levels of long-term PM2.5 ranged from 13.2 to 72.1 µg/m3 with the mean of 46.6 µg/m3. Each 10 µg/m3 rise in PM2.5 was related to a higher obesity risk [OR 1.12 (95% CI 1.09-1.14)] and abdominal obesity [OR 1.10 (95% CI 1.07-1.13)]. The association between PM2.5 and obesity varied according to sunshine duration, with the highest ORs of 1.56 (95% CI 1.28-1.91) for obesity and 1.66 (95% CI 1.34-2.07) for abdominal obesity in the bottom quartile of sunlight exposure (3.21-5.34 hours/day). Conclusion: Long-term PM2.5 effect on obesity risk among the general Chinese population are influenced by sunlight exposure. More attention might be paid to reduce the adverse impacts of exposure to air pollution under short sunshine duration conditions.

Executive summary for China Kidney Disease Network (CK-NET) 2016 Annual Data Report.

Chronic kidney disease (CKD) has been recognized as a public health problem globally. The spectrum of CKD in China has been evolving toward that of developed countries, which will have enormous impacts on the health care system. However, there has been no well-established national surveillance system for kidney diseases. Furthermore, China still faces several challenges of kidney care, including limited capacity and efficiency, suboptimal awareness, and huge heterogeneity in diagnosis and treatment. The China Kidney Disease Network has published 2 reports regarding the burden of CKD and end-stage kidney disease in China and intends to become a comprehensive surveillance system for kidney diseases based on multisource data. With the expansion of research group and data sources, the content of the China Kidney Disease Network 2016 Annual Data Report was further enriched. Section I addresses the epidemiologic characteristics of patients with CKD based on a national inpatient database, Hospital Quality Monitoring System, covering more than 52% of China's tertiary hospitals in China in 2016. Section II focuses on the burden of patients receiving dialysis, mainly based on the nationwide claims database, China Health Insurance Research Association database, which collects data from approximately 2% of the insured population from the municipalities/provincial capital cities and approximately 5% from the prefecture-level cities. An independent chapter regarding dialysis in 3 provincial dialysis quality control centers has been added. The China Kidney Disease Network 2016 Annual Data Report symbolizes a successful team effort in the era of big data, with support from the specialists and partners of the collaborative network, which is of substantial value for understanding the burden of kidney diseases in China and developing prevention and control strategies.

Anemia and Kidney Function Decline among the Middle-Aged and Elderly in China: A Population-Based National Longitudinal Study.

Chronic kidney disease (CKD) is a public health burden, and anemia is common among patients with CKD. However, less is known regarding the longitudinal association between anemia and deterioration of kidney function among the general population. The China Health and Retirement Longitudinal Study is a nationally representative survey for households with members aged ≥ 45 years. Participants without creatinine and demographic data in 2011 and 2015 were excluded. Anemia was defined according to definitions of the World Health Organization. Rapid decline in kidney function was defined as a ≥16.9% (quartile 3) decline in estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI equation during 2011-2015. Multivariate logistic regression and restricted cubic splines were used to explore their relationship. Altogether, 7210 eligible participants were included in the analysis, with a mean age of 58.6 ± 8.8 years. Rapid decline in kidney function occurred among 1802 (25.0%) participants. Those with kidney function decline were more likely to be older, male, and have anemia, lower eGFRs, hypertension, and cardiovascular disease (P < 0.05). Anemia, or hemoglobin, was independently associated with rapid decline in kidney function after adjusting for potential confounding factors (OR = 1.64, 95% CI, 1.32-2.04; OR = 0.90, 95% CI, 0.87-0.94, respectively). Restricted cubic splines showed a nonlinear relationship between hemoglobin and rapid decline in kidney function, especially for men with anemia (P < 0.05). In conclusion, anemia is an independent risk factor for progression of kidney function among the middle-aged and elderly population. Attentive management and intervention strategies targeting anemia could be effective to reduce the risk of kidney failure and improve the prognosis of the general population.

Essential trace elements in umbilical cord tissue and risk for neural tube defects.

Deficient or excessive quantities of essential trace elements (ETEs)1 in the fetal environment can compromise developmental processes. We investigated whether concentrations of zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), molybdenum (Mo), and nickel (Ni) in umbilical cord tissue are associated with risk for neural tube defects (NTDs). Umbilical cord tissues from 166 cases of NTD cases and 166 matched controls were collected and element concentrations were measured using inductively coupled plasma-mass spectrometry. Associations between ETE concentrations and the risk for NTDs were estimated using multivariate logistic regression while adjusting for potential confounders. Bayesian kernel machine regression (BKMR) was used to examine the joint effects of these ETEs. We found that median concentrations of Ni were higher but those of Mo and Co were lower in the NTD group than in the control group. Co was the only element that was associated with NTD risk after adjusting for confounders (OR 0.31, 95 % CI 0.12-0.79 for the second and OR 0.37, 95 % CI 0.15-0.91 for the top tertile relative to the lowest tertile). The association between Co and NTD risk was confirmed with the BKMR model. In addition, a joint effect of the six ETE mixture on NTD risk was observed: the risk decreased with the levels of the mixture from 25th percentile through 75th percentile. In conclusion, higher levels of Co were associated with lower risk for NTDs, and NTD risk decreased with the levels of the six ETEs as a co-exposure mixture, suggesting a protective effect.

The association between reduced kidney function and hearing loss: a cross-sectional study.

BACKGROUND: The relationship between kidney function and hearing loss has long been recognized, but evidence of this association mostly comes from small observational studies or other populations. The aim of this study is to explore the association between reduced kidney function and hearing loss in a large population-based study among the middle-aged and elderly Chinese. METHODS: Data collected from the Chinese Health and Retirement Longitudinal Study (CHARLS) in 2015 were used for analysis. A cross-sectional study was conducted among 12,508 participants aged 45 years and older. Hearing loss, the outcome of this study, was defined according to interviewees' responses to three survey questions related to hearing in the CHARLS. Estimated glomerular filtration rate (eGFR) was employed to assess kidney function, and participants were classified into three categories based on eGFR: ≥90, 60-89 and < 60 mL/min/1.73 m2. Multivariable logistic regression was employed to adjust for potential confounders, including demographics, health-related behaviors, and cardiovascular risk factors. RESULTS: The overall prevalence of self-reported hearing loss in the study population was 23.6%. Compared with participants with eGFR ≥90 mL/min/1.73 m2, participants with eGFR of 60-89 mL/min/1.73 m2 (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.00-1.23) and eGFR < 60 mL/min/1.73 m2 (OR: 1.25, 95% CI: 1.04-1.49) showed increased risk of hearing loss after adjusting for potential confounders. CONCLUSIONS: Reduced kidney function is independently associated with hearing loss. Testing for hearing should be included in the integrated management of patients with chronic kidney disease.

Executive summary for the 2015 Annual Data Report of the China Kidney Disease Network (CK-NET).

Chronic kidney disease (CKD) has received increased attention as a leading public health problem worldwide. Globally surveillance systems for kidney disease are still lacking, especially in developing countries like China, which constitutes an obstacle to develop effective preventive strategies. China Kidney Disease Network (CK-NET) was initiated in 2014 and further developed in accordance with the national strategy of prompting Big Data application in China. One major output of CK-NET is to generate an Annual Data Report (ADR) providing resourceful information regarding kidney disease in China. Entering the second cycle of ADR, we have expanded the scope and depth of our research based on the previous ADR. There are 2 sections in the current ADR, generated from data from 2015 from various sources. Section I is based on a dataset of national hospitalized patients and describes the characteristics regarding hospitalized patients with CKD. Section II focuses on patients receiving renal replacement therapy based on 2 nationwide claims databases. There is also a chapter that focuses on patients on the waiting list for renal transplantation based on the China Organ Transplant Response System. Certain findings, including the effect of metabolic disease on the spectrum of CKD, the underdiagnoses of CKD and acute kidney injury among hospitalized patients, and the less-optimal treatment of complications among dialysis patients, will inspire the following research as well as changes in health policy. By integrating and mining national patient-level administrative or claim databases, we are able to provide a comprehensive description of the burden of CKD and end stage kidney disease in China, which could be used by multiple stakeholders with interests in kidney disease.