Long-term impacts of endocrine-disrupting chemicals exposure on kidney function: A community-based cohort study.

This study explores the extended renal effects of endocrine-disrupting chemicals (EDCs) exposure, a linkage already established with adverse health outcomes, notably chronic kidney disease. To delve deeper, the Chang Gung Community Research Center conducted a longitudinal study with 887 participants. Among them, 120 individuals were scrutinized based on EDC scores, analyzing 17 urinary EDCs and renal function. Findings revealed elevated mono-(2-ethylhexyl) phthalate (MEHP) and bisphenol A levels in higher EDC exposure cases. MEHP notably correlated with increased urinary albumin-to-creatinine ratio (UACR), predicting a > 15% decline in estimated glomerular filtration rate. Higher MEHP levels also hinted at declining renal function. UACR escalation linked significantly with specific EDCs: MEHP, methylparaben, nonylphenol, and 4-tert-octylphenol. This research underscores enduring renal hazards tied to environmental EDC exposure, particularly MEHP, emphasizing the urgent call for robust preventive public health strategies.

Performance of urinary C-C motif chemokine ligand 14 for the prediction of persistent acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Urinary C-C motif chemokine ligand 14 (CCL14) has been described as an effective marker for delayed recovery of acute kidney injury (AKI), yet its efficacy has been found to vary between different trials. The goal of this research was to assess the predictive performance of urinary CCL14 as a marker for persistent AKI. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to April 2023 for studies of adults (> 18 years) that reported the diagnostic performance of urinary CCL14. The sensitivity, specificity, number of events, true positive, and false positive results were extracted and evaluated. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. RESULTS: We included six studies with 952 patients in this meta-analysis. The occurrence of persistent AKI among these patients was 39.6% (377/952). The pooled sensitivity and specificity results of urinary CCL14 in predicting persistent AKI were 0.81 (95% CI 0.72-0.87) and 0.71 (95% CI 0.53-0.84), respectively. The pooled positive likelihood ratio (LR) was 2.75 (95% CI 1.63-4.66), and the negative LR was 0.27 (95% CI 0.18-0.41). The HSROC with pooled diagnostic accuracy was 0.84. CONCLUSION: Our results suggest that urinary CCL14 can be used as an effective marker for predicting persistent AKI.

Discovering a trans-omics biomarker signature that predisposes high risk diabetic patients to diabetic kidney disease.

Diabetic kidney disease is the leading cause of end-stage kidney disease worldwide; however, the integration of high-dimensional trans-omics data to predict this diabetic complication is rare. We develop artificial intelligence (AI)-assisted models using machine learning algorithms to identify a biomarker signature that predisposes high risk patients with diabetes mellitus (DM) to diabetic kidney disease based on clinical information, untargeted metabolomics, targeted lipidomics and genome-wide single nucleotide polymorphism (SNP) datasets. This involves 618 individuals who are split into training and testing cohorts of 557 and 61 subjects, respectively. Three models are developed. In model 1, the top 20 features selected by AI give an accuracy rate of 0.83 and an area under curve (AUC) of 0.89 when differentiating DM and non-DM individuals. In model 2, among DM patients, a biomarker signature of 10 AI-selected features gives an accuracy rate of 0.70 and an AUC of 0.76 when identifying subjects at high risk of renal impairment. In model 3, among non-DM patients, a biomarker signature of 25 AI-selected features gives an accuracy rate of 0.82 and an AUC of 0.76 when pinpointing subjects at high risk of chronic kidney disease. In addition, the performance of the three models is rigorously verified using an independent validation cohort. Intriguingly, analysis of the protein-protein interaction network of the genes containing the identified SNPs (RPTOR, CLPTM1L, ALDH1L1, LY6D, PCDH9, B3GNTL1, CDS1, ADCYAP and FAM53A) reveals that, at the molecular level, there seems to be interconnected factors that have an effect on the progression of renal impairment among DM patients. In conclusion, our findings reveal the potential of employing machine learning algorithms to augment traditional methods and our findings suggest what molecular mechanisms may underlie the complex interaction between DM and chronic kidney disease. Moreover, the development of our AI-assisted models will improve precision when diagnosing renal impairment in predisposed patients, both DM and non-DM. Finally, a large prospective cohort study is needed to validate the clinical utility and mechanistic implications of these biomarker signatures.

Serum Cystatin C Levels Could Predict Rapid Kidney Function Decline in A Community-Based Population.

BACKGROUND: Several biomarkers have been correlated with the prevalence and severity of chronic kidney disease (CKD); however, the association between biomarkers and rapid kidney function decline (RKFD) is unknown. This study aimed to evaluate the predictive performance of biomarkers to determine who is likely to develop RKFD in a healthy population. METHODS: A community-based cohort of 2608 people residing in northern Taiwan were enrolled, and their renal function was followed annually from January 2014 to December 2019. The outcomes of interest were RKFD, defined as a 15% decrease in the estimated glomerular filtration rate (eGFR) within the first 4 years, and a decrease in eGFR without improvement in the fifth year. Clinical variables and potential predictors of RKFD, namely adiponectin, leptin, tumor necrosis factor-alpha, and cystatin C, were measured and analyzed. RESULTS: The incidence of RKFD was 17.0% (105/619). After matching for age and sex at a 1:1 ratio, a total of 200 subjects were included for analysis. The levels of cystatin C and total vitamin D were significantly negatively correlated with eGFR. eGFR was negatively correlated with the levels of cystatin C and total vitamin D. Among the biomarkers, cystatin C showed the best predictive performance for RKFD (area under the receiver operating characteristic curve: 0.789). Lower serum cystatin C was associated with a higher rate of RKFD in healthy subjects. A generalized additive model showed that 0.82 mg/L was an adequate cut-off value of cystatin C to predict RKFD. Multivariable logistic regression analysis further indicated that low cystatin C and eGFR were independent predictors of the possibility of RKFD. CONCLUSIONS: Serum cystatin C level could predict the possibility of RKFD. We suggest that a low cystatin C level should be considered as a risk factor for RKFD in healthy subjects.

Oral Absorbent AST-120 Is Associated with Compositional and Functional Adaptations of Gut Microbiota and Modification of Serum Short and Medium-Chain Fatty Acids in Advanced CKD Patients.

Background: Animal studies have demonstrated that an oral absorbent AST-120 modulates gut environment. However, this phenomenon remains unclear in humans. This study aimed to assess the effects of AST-120 on the gut microbiota, related functional capability and metabolomic profiling in advanced chronic kidney diseases (CKD) patients. Methods: Eight advanced CKD patients with AST-120 (CKD+AST), 24 CKD patients (CKD), and 24 non-CKD controls were enrolled. We analyzed 16S rRNA pyrosequencing of feces and serum metabolomics profiling. Results: The CKD+AST group exhibited dispersed microbial community structure (ß-diversity, p < 0.001) compared to other groups. The relative abundances of at least 16 genera were significantly different amongst the three groups. Increases of fatty acids-producing bacteria (Clostridium_sensu_stricto_1, Ruminococcus_2, Eubacterium_nodatum and Phascolarctobacterium) associated with elevated serum acetic acid and octanoic acid levels were found in CKD+AST group. Analysis of microbial gene function indicated that pathway modules relevant to metabolisms of lipids, amino acids and carbohydrates were differentially enriched between CKD+AST and CKD groups. Specifically, enrichments of gene markers of the biosynthesis of fatty acids were noted in the CKD+AST group. Conclusion: Advanced CKD patients exhibited significant gut dysbiosis. AST-120 can partially restore the gut microbiota and intervenes in a possible signature of short- and medium-chain fatty acids metabolism.

Micronutrients and Renal Outcomes: A Prospective Cohort Study.

Background: Micronutrients are essential in maintaining normal human physiology. Data regarding the association between micronutrients and renal outcomes in chronic kidney disease (CKD) are lacking. Methods: This prospective observational cohort study enrolled 261 patients with CKD stages 1−5 and 30 subjects with normal renal function. Baseline serum zinc (Zn), selenium (Se), chromium, manganese, and copper, and laboratory tests were performed at enrolment. The primary endpoint was the presence of end-stage renal disease (ESRD) requiring long-term renal replacement therapy. Results: The median follow-up periods of renal and non-renal survivals were 67.78 and 29.03 months, respectively. Multiple linear regression showed that Zn and Se (ß ± SE: 24.298 ± 8.616, p = 0.005; 60.316 ± 21.875, p = 0.006, respectively) levels were positively correlated with renal function. Time to ESRD was significantly longer for those with Zn levels ≥1287.24 ng/g and Se levels ≥189.28 ng/g (both p < 0.001). Cox regression analysis identified a higher Zn level as an independently negative predictor of ESRD after adjusting for renal function (hazard ratio, 0.450, p = 0.019). Conclusion: Serum Se and Zn concentrations are positively associated with renal function and better renal outcomes. A higher Zn concentration could independently predict better renal survival.

Adequacy of Hemodialysis Serves as an Independent Predictor of Humoral Response to ChAdOx1 Prime-Boost Vaccination in Hemodialysis Patients.

Background: Immune response assessed by the quantification of neutralizing antibodies (nAbs) and predictors associated with immunogenicity after the prime-boost ChAdOx1 (Oxford−AstraZeneca) COVID-19 vaccine in hemodialysis (HD) patients remains unclear. Methods: This prospective study enrolled 174 HD patients and 67 healthy subjects to evaluate antibodies against the spike protein 1 and receptor-binding domain of severe acute respiratory syndrome coronavirus type 2 after prime-booster vaccination, by using enzyme-linked immunosorbent assay and applied spline-based generalized additive model regression analysis to predict 50% neutralization titer (NT50). The correlation between HD parameters and NT50 was analyzed. Results: NT50 was lower in HD patients compared with healthy controls after the prime-boost dose (p < 0.001). The geometric mean titer ratios were higher in first-dose seronegative than in the seropositive subgroup in HD patients and healthy controls (6.96 vs. 2.36, p = 0.002, and 9.28 vs. 1.26, p = 0.011, respectively). After two doses of ChAdOx1, one-way ANOVA showed that Ca × P was positively associated with NT50 (p trend = 0.043) and multiple linear regression showed the similar results (p = 0.021). Kt/V (a quantification of dialysis adequacy) (OR = 20.295, p = 0.005) could independently predict seroconversion (NT50 ≥ 35.13 IU/mL). Conclusion: Adequacy of hemodialysis could independently predict seroconversion in HD subjects vaccinated with prime-boost doses of ChAdOx1.

Relationships Between Metabolic Body Composition Status and Rapid Kidney Function Decline in a Community-Based Population: A Prospective Observational Study.

Obesity and metabolic syndrome are strong risk factors for incident chronic kidney disease (CKD). However, the predictive accuracy of metabolic body composition status (MBCS), which combines the status of obesity and metabolic syndrome, for rapid kidney function decline (RKFD) is unclear. The aim of this study was to investigate the relationship between MBCS and RKFD in a healthy population in a prospective community-based cohort study. In the current study, we followed changes in renal function in 731 people residing in northern Taiwan for 5 years. The participants were divided into four groups according to their MBCS, including metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight (MUOW). We evaluated traditional risk factors for CKD and metabolic profiles. The primary outcome was RKFD, which was defined as a 15% decline in estimated glomerular filtration rate (eGFR) within the first 4 years, and a reduction in eGFR which did not improve in the 5th year. During the study period, a total of 731 participants were enrolled. The incidence of RKFD was 17.1% (125/731). Multiple Cox logistic regression hazard analysis revealed that age, cerebrovascular accident, eGFR, urine albumin-to-creatinine ratio, use of painkillers, depressive mood, MUNW and MUOW were independent predictors of RKFD. After adjusting for age, sex, eGFR and total cholesterol, the participants with MUNW and MUOW had higher hazard ratios (HRs) for RKFD [HR: 2.19, 95% confidence interval (CI): 1.22-3.95 for MUNW; HR: 1.86, 95% CI: 1.21-2.87 for MUOW] than those with MHNW. Similar results were also observed in subgroup analysis of those aged above 65 years. On the basis of the results of this study, we conclude that MBCS was independently associated with RKFD, especially in the older adults. On the basis of our results, we suggest that MUNW and MUOW should be considered as risk factors for RKFD.

Neutralization Assessments Reveal High Cardiothoracic Ratio and Old Age as Independent Predictors of Low Neutralizing Antibody Titers in Hemodialysis Patients Receiving a Single Dose of COVID-19 Vaccine.

BACKGROUND: Data are lacking regarding predictors of quantification of neutralizing antibodies (nAbs) based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 50% neutralization titer (NT50) after a single dose of COVID-19 vaccine in hemodialysis (HD) patients. METHODS: This prospective single-center study enrolled 200 HD patients and 82 healthy subjects to estimate antibodies against the SARS-CoV-2 viral spike protein 1 and receptor-binding domain after a first dose of a COVID-19 vaccine (ChAdOx1 or mRNA-1273), measured by enzyme-linked immunosorbent assay and applied spline-based generalized additive model regression analysis to predict NT50 converted to international units. RESULTS: After the first dose of ChAdOx1, multiple linear regression showed that age (p = 0.011) and cardiothoracic ratio (p = 0.002) were negatively associated with NT50. Older age (OR = 0.958, p = 0.052) and higher cardiothoracic ratio (OR < 0.001, p = 0.037) could predict negative humoral response (NT50 < 35.13 IU/mL). NT50 was lower in HD patients compared with healthy controls receiving ChAdOx1 (10.68 vs. 43.01 IU/m, p < 0.001) or mRNA-1273 (36.39 vs. 262.2 IU/mL, p < 0.001). ChAdOx1 elicited lower GMTs than mRNA-1273 in the HD cohort (10.68 vs. 36.39 IU/mL, p < 0.001) and in healthy controls (43.01 vs. 262.22 IU/mL, p < 0.001). CONCLUSION: High cardiothoracic ratio and old age could independently predict a decline in nAb titers in an HD cohort vaccinated with a single dose of ChAdOx1.

Circulating Fibroblast Growth Factor-23 Levels Can Predict Rapid Kidney Function Decline in a Healthy Population: A Community-Based Study.

BACKGROUND: Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. METHODS: A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD-a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. RESULTS: The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. CONCLUSIONS: Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population.

The association between low protein diet and body composition, muscle function, inflammation, and amino acid-based metabolic profile in chronic kidney disease stage 3-5 patients.

BACKGROUND: Chronic kidney disease (CKD) is a global burden in the world. Low protein diet (LPD) recommendation is suggested in CKD patients to avoid or defer dialysis initiation and slow down CKD progression. However, nutritional imbalance and protein energy wasting represent key worries. The amino acid-based metabolic profile may provide a sensitive biomarker to evaluate CKD patients' nutrition status with LPD recommendations. METHODS: We conducted a cross-sectional study in CKD stage 3-5 patients who had received LPD recommendation to evaluate the association between LPD and traditional markers (including plasma levels of albumin, pre-albumin, transferrin, total iron-binding capacity), inflammation markers (including peripheral leukocyte count and plasma levels of high-sensitivity C-reactive protein), body composition, muscle strength, and physical function, and novel nutrition markers (including amino acid-based metabolic profile) in CKD stage 3-5 patients. RESULTS: In our study CKD stage 3-5 patients with the total number of 73, the mean age was around 71 ± 10 years old. The mean daily protein intake (DPI) was around 0.9 ± 0.3 g/kg/day and 25 (34%) patients met the recommended goal of DPI <0.8 g/kg/day. The mean daily calorie intake (DCI) was around 23 ± 6 kcal/kg/day, with only 11 (15%) patients met the recommend DCI with 30-35 kcal/kg/day. Compared to CKD patients with non-LPD, patients with LPD had significantly lower hemoglobin and albumin levels, shorter 6-min walking distance (6MWD), and lower leucine levels. Multivariable analysis found that lower hemoglobin and leucine levels, and shorter 6MWD were negatively and independently associated with LPD (all p < 0.05). Then ROC curve analysis found that the optimal cut-off value of leucine plasma levels was 95.5 µM with 60% sensitivity and 71% specificity to predict those CKD patients with LPD with the area under the curve of 0.646 (95% CI: 0.512-0.780). CONCLUSION: LPD attainment was noted in 34% patients and most of CKD stage 3-5 patients (around 85%) had inadequate daily calorie intake although receiving standard dietary counseling routinely. A low protein diet and inadequate daily calorie intake in CKD patients were associated with shorter 6MWD, and lower hemoglobin and leucine levels. Plasma leucine levels lower than 95.5 µM may be a herald for muscle wasting and malnutrition in these CKD stage 3-5 patients with inadequate calorie intake.

Dynamic Echocardiographic Assessments Reveal Septal E/e' Ratio as Independent Predictor of Intradialytic Hypotension in Maintenance for Hemodialysis Patients with Preserved Ejection Fraction.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent and grave complication of hemodialysis (HD). However, the dynamic hemodynamic changes and cardiac performances during each dialytic session have been rarely explored in patients having IDH. METHODS: Seventy-six HD patients (IDH = 40, controls = 36) were enrolled. Echocardiography examinations were performed in all patients at the pre-HD, during-HD and post-HD phases of a single HD session. A two-way analysis of variance was applied to compare differences of echocardiographic parameters between IDH and controls over time. The risk association was estimated by using a logistic regression analysis. RESULTS: The IDH patients had a higher ejection fraction during HD followed by a greater reduction at the post-HD phase than the controls. Significant decreases in septal ratios of transmitral flow velocity to annular velocity (E/e') over times were detected between IDH patients and controls after adjusting for gender, age and ultrafiltration (p = 0.016). A lower septal E/e' ratio was independently associated with IDH (OR = 0.040; 95% CI = 0.003-0.606; p = 0.02). In contrast, significant systolic and diastolic dysfunctions over time were found in diabetic IDH compared to non-diabetic counterparts. CONCLUSION: The septal E/e' ratio was a significant predictor for IDH.

The prognostic value of peripheral total and differential leukocyte count in renal progression: A community-based study.

BACKGROUND: Systemic inflammation is related to chronic kidney disease (CKD) patients. Elevated peripheral leukocyte count may be a herald of increased systemic inflammation and subclinical disease. Inflammation plays an important role in renal progression. The pattern of total and differential leukocyte count in CKD is not well understood. Besides, the association between total and differential leukocyte count and renal progression is still uncertain. METHODS: We conducted a community-based cohort study with a follow-up period of two years to evaluate the total and differential leukocyte counts and renal progression association. RESULTS: In our study population from the community with a total number of 2128, we found 15.7% (335/2128) CKD patients with a mean estimated glomerular filtration rate (eGFR) around 96 ± 26 ml/min/1.73 m2. The peripheral total leukocyte count and also differential leukocyte count were significantly negatively correlated with eGFR. A total of 56 patients (3%) experienced a rapid progression of the kidney with the definition of eGFR reduction changes of 30% or greater within two years. Univariate analysis indicated that rapid renal progression was significantly associated with male gender, co-morbidity of diabetes mellitus (DM), higher uric acid levels, higher peripheral neutrophil, monocyte, and eosinophil counts. However, only the peripheral neutrophil count was positively and independently associated with rapid renal progression after multivariate analysis. The ROC curve analysis found that the optimal cutoff value of peripheral neutrophil count for rapid progression was 2760/ mm3, with an area under the curve of 0.813. CONCLUSION: Hyperinflammation with higher peripheral total and differential leukocyte count was noted in CKD patients. The peripheral neutrophil count was the only independent factor significantly associated with rapid renal progression. The optimal cutoff point of the peripheral neutrophil count with 2760/mm3 is useful for determining the high-risk population for rapid renal progression with a satisfying sensitivity and specificity.

Effective Preventive Strategies to Prevent Secondary Transmission of COVID-19 in Hemodialysis Unit: The First Month of Community Outbreak in Taiwan.

BACKGROUND: Dialyzed patients are vulnerable to coronavirus infection disease 2019 (COVID-19). The incidence and outcome of COVID-19 in hemodialysis (HD) patients in Taiwan remain unclear. A series of preventive measures were executed to combat COVID-19 transmission among HD patients. METHODS: We carried out a series of forward-looking and practical preventive strategies of COVID-19 control in our HD center. Incidences of COVID-19 of our HD unit were compared with those of national and local estimates from a community outbreak from 15 May to 30 June 2021. Prognostic factors associated with mortality were analyzed. RESULTS: The national incidence of COVID-19 was 0.062%; being highest in Taipei City (0.173%), followed by New Taipei City (0.161%) and Keelung (0.083%). The overall incidence in Keelung HD patients was 0.666%. One patient of our HD center contracted COVID-19 from the household; however, we have contained secondary transmission in our HD center by implementing strict preventive measures. The mortality rate of HD patients in Keelung was 66.6%. The median Ct value of HD patients was 17.53 (11.75-27.90) upon diagnosis. The deceased patients had a higher cardiac/thoracic ratio than alive (0.61 vs. 0.55, p = 0.036). CONCLUSIONS: Taking aggressive and proactive infection preventive measures impedes the secondary transmission of COVID-19 in HD facilities. COVID-19-associated mortality was high in HD patients, being the high cardiac-thoracic ratio, an important prognostic factor for clinical outcome of infected HD patients.

Renal function trajectories in hepatitis C infection: differences between renal healthy and chronic kidney disease individuals.

Associations between hepatitis C virus (HCV) and chronic kidney disease (CKD) have been reported; however, differences of renal progression between general and CKD population remain to be elucidated in prospective studies. A total of 1179 participants, who have tested for anti-HCV antibody, were enrolled and prospectively followed for 3 years. The risks associated with HCV infection, in terms of incidence of CKD, annual estimated glomerular filtration rate (eGFR) changes and 50% decline of eGFR at 3-year from baseline, were compared between normal renal function subjects and CKD patients. Overall, 111 of 233 (47.6%) CKD patients and 167 of 946 (17.7%) non-CKD subjects had HCV infection. The crude incidence rates of CKD were 226.9 per 1000 person-years and 14.8 per 1000 person-years in in HCV and non-HCV infected patients, respectively. The adjusted hazard ratio of HCV infection for incident CKD was 7.9 (95% CI 5-12.7). The HCV-infected normal renal function subjects were independently associated with increased risks of eGFR decline in the 1-year, 2-year and 3-year, respectively. The risk associations remained significant in 50% decline of eGFR at 3 years models and in different subgroup analyses. The increases of risks of eGFR decline were also notorious among overall HCV-infected CKD patients. However, the risk associations were less prominent in subgroup analyses (elderly, women and diabetic patients). The findings highlighted the importance of viral diagnosis with not only prognostic but also public health implications for preserving kidney function.

Xenoestrogen exposure and kidney function in the general population: Results of a community-based study by laboratory tests and questionnaire-based interviewing.

BACKGROUND: Chronic kidney disease (CKD) is a growing concern worldwide. Exposure to xenoestrogens (XEs), such as phthalates, parabens, and phenols, lead to CKD. However, kidney function and its complex relationship with XEs, lifestyle, and dietary habits are not well understood. METHODS: In the present cross-sectional community-based cohort study, we enrolled 887 subjects for a questionnaire-based interview and laboratory tests. XE exposure concerning lifestyle/dietary habits were evaluated using questionnaires. Urinary levels of 17XE metabolites were measured in 60 subjects with high exposure risk scores and 60 subjects with low exposure risk scores. RESULTS: Univariate and multivariate linear regression showed that a high exposure score (ß ± SE: 4.226 ± 1.830, P = 0.021) was independently negatively associated with eGFR in 887 subjects. Univariate and multivariate linear regression to urinary XEs and urine albumin creatinine excretion ratio (UACR) in 120 subjects indicated that ethylparaben (EP) (ß: 1.934, 95% CI: 0.135-3.733, P = 0.035) was significantly associated with increased UACR. Multivariate regression analyses of the CKD subgroup (n = 38), after adjusting for age, showed that higher levels of mono-(2-ethylhexyl) phthalate (MEHP), EP, nonylphenol (NP), and benzophenone-3 (BP-3) were significantly associated with lower estimated glomerular filtration rate (eGFR). Higher urinary levels of MEHP (OR: 3.037, 95% CI: 1.274-7.241) were more likely associated with high exposure scores (>5 points), after adjusting for diabetes, gender, eGFR, age, Na, Ca, albumin, vitamin D, systolic blood pressure (SBP), white blood cell count, total bilirubin, aspartate transaminase, and heart rate. MEHP (ß ± SE: 0.033 ± 0.009, P < 0.001) was also significantly positively associated with total exposure scores after applying multivariate linear regression analyses. CONCLUSION: XE exposure scores obtained from the questionnaires were negatively associated with kidney function. Urinary metabolites of XEs, including EP, NP, BP-3, and MEHP, are potential risk factors for microalbuminuria and decline in kidney function. MEHP seemed to have the strongest correlation with high exposure scores and decline in kidney function.

Incidence and Clinical Impacts of COVID-19 Infection in Patients with Hemodialysis: Systematic Review and Meta-Analysis of 396,062 Hemodialysis Patients.

Hemodialysis (HD) patients are highly susceptible to COVID-19 infection. However, comprehensive assessments of current evidence regarding COVID-19 in HD patients remain incomplete. We systematically searched PUBMED and EMBASE for articles published on incidence or mortality of COVID-19 infection in HD patients until September 2020. Two independent researchers extracted data and study-level risk of bias across studies. We conducted meta-analysis of proportions for incidence and mortality rate. Study heterogeneity and publication bias were assessed. A total of 29 articles with 3261 confirmed COVID-19 cases from a pool of 396,062 HD patients were identified. Incidence of COVID-19 in these HD patients was 7.7% (95% CI: 5.0-10.9%; study heterogeneity: I2 = 99.7%, p < 0.001; risk of publication bias, Egger's test, p < 0.001). Overall mortality rate was 22.4% (95% CI: 17.9-27.1%; study heterogeneity: I2 = 87.1%, p < 0.001; risk of publication bias, Egger's test: p = 0.197) in HD patients with COVID-19. Reported estimates were higher in non-Asian than Asian countries. Quality of study may affect the reported incidence but not the mortality among studies. Both incidence and mortality of COVID-19 infection were higher in HD patients. Available data may underestimate the real incidence of infection. International collaboration and standardized reporting of epidemiological data should be needed for further studies.

Compositional and Functional Adaptations of Intestinal Microbiota and Related Metabolites in CKD Patients Receiving Dietary Protein Restriction.

The relationship between change of gut microbiota and host serum metabolomics associated with low protein diet (LPD) has been unraveled incompletely in CKD patients. Fecal 16S rRNA gene sequencing and serum metabolomics profiling were performed. We reported significant changes in the ß-diversity of gut microbiota in CKD patients having LPD (CKD-LPD, n = 16). We identified 19 genera and 12 species with significant differences in their relative abundance among CKD-LPD patients compared to patients receiving normal protein diet (CKD-NPD, n = 27) or non-CKD controls (n = 34), respectively. CKD-LPD had a significant decrease in the abundance of many butyrate-producing bacteria (family Lachnospiraceae and Bacteroidaceae) associated with enrichment of functional module of butanoate metabolism, leading to concomitant reduction in serum levels of SCFA (acetic, heptanoic and nonanoic acid). A secondary bile acid, glyco λ-muricholic acid, was significantly increased in CKD-LPD patients. Serum levels of indoxyl sulfate and p-cresyl sulfate did not differ among groups. The relationship between abundances of microbes and metabolites remained significant in subset of resampling subjects of comparable characteristics. Enrichment of bacterial gene markers related to D-alanine, ketone bodies and glutathione metabolism was noted in CKD-LPD patients. Our analyses reveal signatures and functions of gut microbiota to adapt dietary protein restriction in renal patients.

Vitamin D deficiency, cardiothoracic ratio, and long-term mortality in hemodialysis patients.

Hemodialysis patients are a special group of patients with higher mortality rates. Hemodialysis patients with vitamin D deficiency {plasma levels of 25-hydroxyvitamin D [25(OH)D] below 20 ng/mL} are associated with even higher mortality rates. The prognostic importance of vitamin D deficiency in hemodialysis patients with different cardiothoracic ratios (CTRs) is still unclear. This prospective study was performed in a single hemodialysis center, and 186 patients were included. This study analyzed the prognostic importance of vitamin D deficiency in hemodialysis patients with different CTRs. Vitamin D deficiency patients had a significantly higher prevalence of stroke and diabetic mellitus than those without vitamin D deficiency. In addition, the CTR was higher in patients with vitamin D deficiency than in those without vitamin D deficiency. After multivariate logistic regression, we found that CTR was the solitary factor that was independently significantly associated with vitamin D deficiency [odds ratio: 1.07, 95% confidence internal (CI): 1.01-1.13, p = 0.02]. Additionally, vitamin D deficiency was associated with all-cause mortality in patients with higher CTR after adjustment in hierarchical regression models. In conclusion, we reported that vitamin D deficiency was independently significantly associated with a higher CTR. We additionally revealed that vitamin D deficiency was an independent predicator for all-cause mortality in higher CTR hemodialysis patients.

Gut Microbiota as Diagnostic Tools for Mirroring Disease Progression and Circulating Nephrotoxin Levels in Chronic Kidney Disease: Discovery and Validation Study.

The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remains unclear in large human cohort. Significant compositional and functional differences in the intestinal microbiota (by 16S rRNA gene sequencing) were noted among 30 controls and 92 (31 mild, 30 moderate and 31 advanced) patients at different chronic kidney disease (CKD) stages (discovery cohort). A core CKD-associated microbiota consisted of 7 genera (Escherichia_Shigella, Dialister, Lachnospiraceae_ND3007_group, Pseudobutyrivibrio, Roseburia, Paraprevotella and Ruminiclostridium) and 2 species (Collinsella stercoris and Bacteroides eggerthii) were identified to be highly correlated with the stages of CKD. Paraprevotella, Pseudobutyrivibrio and Collinsella stercoris were superior in discriminating CKD from the controls than the use of urine protein/creatinine ratio, even at early-stage of disease. The performance was further confirmed in a validation cohort comprising 22 controls and 76 peritoneal dialysis patients. Bacterial genera highly correlated with indoxyl sulfate and p-cresyl sulfate levels were identified. Prediction of the functional capabilities of microbial communities showed that microbial genes related to the metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) were differentially enriched among the control and different CKD stages. Collectively, our results provide solid human evidence of the impact of gut-metabolite-kidney axis on the severity of chronic kidney disease and highlight a usefulness of specific gut microorganisms as possible disease differentiate marker of this global health burden.