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.

Vitamin D deficiency in northern Taiwan: a community-based cohort study.

BACKGROUND: Vitamin D deficiency has become an important public health problem, however few studies have been conducted in subtropical countries, and the predictors of vitamin D deficiency in people with healthy renal function are unclear. The objective of this study was to evaluate the prevalence and factors associated with vitamin D deficiency in northern Taiwan. METHODS: The cross-sectional study was performed between August 2013 and August 2017, and included 3954 participants without chronic kidney disease (CKD) aged ≥30 years in northern Taiwan. Serum 25-hydroxyvitamin D [25(OH)-D] levels, biochemistry, sociodemographic variables (age, sex, education, occupation) and lifestyle habits (tea, coffee consumption and physical activities) were recorded. Associations between vitamin D status and these variables were examined using a regression model. The definition of deficiency was defined as a serum 25(OH)-D level < 20 ng/mL (50 nmol/L). RESULTS: The mean 25(OH)-D concentration was 28.9 ng/mL, and 22.4% of the study population had vitamin D deficiency. There was a significantly higher vitamin D deficiency ratio in the women compared to the men (22.9% vs 9.9%, p < 0.001). Vitamin D deficiency was most prevalent (38.4%) in those aged 30-39 years. Those with a graduate degree had the highest rate of vitamin D deficiency (31.5%). The predictors of vitamin D deficiency included female sex, young age, high education level, living in an urban area and physical inactivity. Tea consumption was negatively associated with vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency is prevalent in subtropical areas such as northern Taiwan in healthy individuals without CKD.

The association between chronic musculoskeletal pain and clinical outcome in chronic kidney disease patients: a prospective cohort study.

BACKGROUND AND OBJECTIVES: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established. METHOD: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients. RESULT: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality (HR, 2.912, 95% CI, 1.004-8.444; p = .049). However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients (4.96 ± 9.4 vs. 4.25 ± 13.3 mg/L, p = .535). CONCLUSION: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.

Factors associated with chronic musculoskeletal pain in patients with chronic kidney disease.

BACKGROUND: Chronic musculoskeletal (MS) pain is common in patients with chronic kidney disease (CKD) undergoing haemodialysis. However, epidemiological data for chronic MS pain and factors associated with chronic MS pain in patients with early- or late-stage CKD who are not undergoing dialysis are limited. METHOD: A cross-sectional study to evaluate the prevalence of chronic MS pain and factors associated with chronic MS pain in patients with early- and late-stage CKD who were not undergoing dialysis, was conducted. In addition, the distribution of pain severity among patients with different stages of CKD was evaluated. RESULTS: Of the 456 CKD patients studied, 53.3% (n = 243/456) had chronic MS pain. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, as well as with the calcium × phosphate product levels. In CKD patients with hyperuricemia, chronic MS pain showed a negative, independent significant association with diabetes mellitus as a co-morbidity (odds ratio: 0.413, p = 0.020). However, in the CKD patients without hyperuricemia as a co-morbidity, chronic MS pain showed an independent significant association with the calcium × phosphate product levels (odds ratio: 1.093, p = 0.027). Furthermore, stage-5 CKD patients seemed to experience more severe chronic MS pain than patients with other stages of CKD. CONCLUSION: Chronic MS pain is common in CKD patients. Chronic MS pain was independently and significantly associated with hyperuricemia as co-morbidity, and with the calcium × phosphate product levels in early- and late-stage CKD patients who were not on dialysis.

Prescription of psychotropic drugs in patients with chronic renal failure on hemodialysis.

OBJECTIVE: Patients on hemodialysis commonly have comorbid depression and require treatment with psychotropic drugs. This study aimed to investigate the prevalence of the use of psychotropic drugs among patients on hemodialysis and to elucidate the factors associated with use of each class of psychotropic medication. METHODS: This cross-sectional study enrolled 195 hemodialysis patients with a mean age of 58.5 years. Patients were assessed using the Mini International Neuropsychiatric Interview, Hospital Anxiety and Depression Scale, Chalder Fatigue Scale and Short-form Health-related Quality of Life. We analyzed the frequency of psychiatric outpatient department visits within six months prior to interview and psychotropic drugs use within one month prior to interview, including antidepressants, antipsychotics, mood stabilizers, benzodiazepines (BZDs) and hypnotics. RESULTS: Of the 195 patients, 47 (24.1%) fulfilled the DSM-IV criteria for major depressive disorder (MDD). Only 6.4% of patients diagnosed with MDD visited the psychiatry outpatient department within six months prior to interview. Of the total patients, the proportions with use of antidepressants, antipsychotics, mood stabilizers, BZDs and hypnotics were 5.6%, 1.0%, 3.1%, 42.6% and 20.0%, respectively. Having MDD was an independent factor associated with taking antidepressants (adjusted OR = 3.98, p = 0.036) and taking hypnotics (adjusted OR = 2.75, p = 0.011). CONCLUSIONS: Depression is generally undetected or not well-managed among hemodialysis patients in the clinical setting. Only a small proportion of depressed patients received antidepressant treatment. BZDs and/or hypnotics might be exorbitantly prescribed. Clinicians should pay more attention to patients' emotional distress and provide appropriate treatment.

Chronic kidney disease stage is a modulator on the association between high-sensitivity C-reactive protein and coronary vasospastic angina.

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1-3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD.

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.

Endocrine-Disrupting Chemicals Exposure and Neurocognitive Function in the General Population: A Community-Based Study.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. METHODS: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. RESULTS: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (ß ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. CONCLUSION: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.

Re-evaluating the predictive roles of metabolic complications and clinical outcome according to eGFR levels--a four-years prospective cohort study in Taiwan.

BACKGROUND: Metabolic complications are associated with clinical outcomes in patients with chronic kidney disease (CKD). These outcomes differ among patients according to the different stages of disease. The prevalence and association of type and number of metabolic complications with renal progression and death in patients having different eGFR levels has high clinical value, but this fact has been rarely evaluated in prospective studies. METHODS: We prospectively followed a cohort of 1157 CKD patients from 2006 to death or until 2010, and evaluated the prevalence of CKD-related complications and their association with renal progression (defined as a decline in eGFR by > 50% from baseline, or end-stage renal disease requiring dialysis) and death in patients with eGFRs above and below 45 mL/min/1.73 m(2) using Cox-proportional hazard models. RESULTS: The estimated rate (per 100 patient-years) of renal progression and death were 11.9 and 4.9, respectively. The eGFR thresholds determined by ROC analysis with a sensitivity of 90% for any metabolic complication were 60.8 mL/min/1.73 m(2) and 74.3 mL/min/1.73 m(2) using the MDRD and CKD Epidemiology Collaboration equations, respectively. CKD-related complications associated with renal progression in patients having eGFR < 45 mL/min/1.73 m(2) were hyperphosphatemia, anemia, microinflammation and hypoalbuminemia. Those CKD-related complications associated with death were hypoalbuminemia and hyperuricemia. Hypoalbuminemia predicted renal progression, and, hypoalbuminemia and microinflammation predicted death in patients with eGFR ≥ 45 mL/min/1.73 m(2). The number of complications (≥ 3) independently predicted both endpoints in patients with eGFR < 45 mL/min/1.73 m(2). CONCLUSIONS: Hypoalbuminemia was a unique and strong predictor of renal progression and all-cause mortality in CKD patients, independent of their demographic characteristics, traditional risk factors, renal function severity, the presence of cardiovascular disease and other metabolic abnormalities. Most other metabolic complications and the number of complications (≥ 3) were associated with the clinical outcomes of patients with eGFR < 45 mL/min/1.73 m(2) rather than in those with higher eGFRs. The findings from the present study offer a novel insight into the association between metabolic complications and patient outcomes and may help to refine risk stratification according to disease stage.

Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients--a prospective cohort study.

BACKGROUND: The mortality rate of elderly hemodialysis (HD) patients is high. Serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) are associated with cardiovascular (CV) disease and mortality in renal patients. The association between such biomarkers and mortality in elderly HD patients has a high clinical value but remains unclear. METHODS: This prospective cohort study investigated the association of serum IS and PCS with all-cause and CV mortality in elderly HD patients. Multivariate Cox regression analysis was used to estimate the risk of all-cause and CV mortality in this prospective cohort. RESULTS: Of 112 patients, 45 deaths (18 CV deaths) were identified after a mean follow-up of 33.2 months. The cumulative and CV survival of patients with lower free PCS was significantly better than high free PCS patients. In multivariate Cox regression analysis, serum free PCS was associated with all-cause and CV mortality after various adjustments, including age, gender and diabetes status (Model 1), albumin (Model 2), Ca × P product and intact parathyroid hormone (Model 3), hemoglobin and high-sensitivity C-reactive protein (Model 4) and hierarchically selected covariates (age, diabetes status and albumin, Model 5). CONCLUSION: Serum free PCS levels may help in predicting risk of all-cause and CV mortality in elderly HD patients beyond traditional and uremia related risk factors.

Association between cold dialysis and cardiovascular survival in hemodialysis patients.

BACKGROUND: Higher cardiovascular mortality has been noted in patients with chronic kidney disease (CKD). CKD patients are also known to have impaired energy expenditure but the role of energy expenditure in cardiovascular disease is not yet known. Furthermore, the association between cold dialysis (CD) and clinical outcomes in hemodialysis patients is unclear. METHODS: This was a single-center retrospective cohort study consisting of two groups: a CD group with dialyzate temperature <35.5 °C and a standard dialysis (SD) group with dialyzate temperature between 35.5 and 37 °C. The end points of the study were overall mortality, cardiac mortality and non-cardiac mortality. The study analyzed the associations between dialyzate temperature and long-term survival in CD and SD groups. Propensity score analysis was used to control for intergroup baseline differences. RESULTS: Baseline characteristics of both groups were similar. Kaplan-Meier analysis showed that CD was significantly associated with a lower risk for overall mortality (P = 0.006) and cardiac mortality (P = 0.023) but not for non-cardiac mortality or infectious mortality. After multivariate Cox regression analysis, adjusting for propensity scores and other possible confounding factors, CD remained a significant beneficial factor for overall mortality (P = 0.030) and cardiac mortality (P = 0.034). CONCLUSION: Our studies show that CD is significantly and independently associated with a lower risk for overall mortality and cardiac mortality.

Global DNA methylation not increased in chronic hemodialysis patients: a case-control study.

Patients with chronic kidney disease have an increased risk of cardiovascular disease and mortality. Since DNA methylation is an important mechanism modulating the gene expression associated with aging, inflammation, and atherosclerosis, the objective of this study was to determine the possible effect of the uremic milieu on global DNA methylation and DNA methyltransferase (DNMT) expression in uremic status by comparing chronic hemodialysis (HD) patients with the normal population. Twenty normal subjects and twenty chronic dialysis patients with similar ages, sex, and body mass indexes (BMIs) were included. We evaluated the clinical characteristics; the levels of homocysteine, total indoxyl sulfate (IS), and total p-cresol sulfate (PCS); and the DNMT messenger RNA expression and global DNA methylation in the peripheral blood leukocytes. The chronic HD patients had significantly higher blood urea nitrogen (BUN), creatinine (Cr), uric acid, Ca, P, intact parathyroid harmone (iPTH), cholesterol, high-sensitivity C-reactive protein (hs-CRP), total indoxyl sulphate (IS) and p-cresol sulphate (PCS), and homocysteine than the normal subjects. The expression of DNMT 1 and 3a did not differ significantly between these two study groups. The chronic HD patients had significantly decreased DNMT 3b expression in the leukocytes. There were no significant correlations between the global DNA methylation and the levels of IS, PCS, and homocysteine. We concluded that chronic HD patients may have lower DNMT 3b expression than normal subjects. However, the status of global DNA methylation may not change significantly in uremic patients when compared with the normal population.

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.

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.

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.

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.

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.

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.