Comparative efficacy and choice of lipid-lowering drugs for cardiovascular and kidney outcomes in patients with chronic kidney disease: A systematic review and network meta-analysis.

BACKGROUND: The effect of exact classes of lipid-lowering drugs (LLDs) on preventing major adverse cardiovascular events (MACEs) and poor renal outcomes is not well characterized in the chronic kidney disease (CKD) population. METHODS: We performed a frequentist random-effects network meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effect of the LLDs in non-dialysis CKD patients. The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for relevant trials published before March 31, 2024. The primary outcome was the incidence of MACEs. The secondary outcomes comprised all-cause mortality, end-stage kidney disease, changes in estimated glomerular filtration rate (eGFR) and proteinuria, and safety. RESULTS: Forty-nine eligible RCTs with 77,826 participants with non-dialysis CKD were included. With moderate confidence in the evidence, rosuvastatin and atorvastatin showed statistically significantly more efficacy in reducing the risk of MACE, with a pooled risk ratio of 0.55 (95% CI 0.33-0.91) for rosuvastatin and 0.67 (0.49-0.90) for atorvastatin, respectively, compared with the control group. For the change in the eGFR, atorvastatin (mean difference [MD], 1.40; 95% CI, 0.61 to 2.18), rosuvastatin (MD, 1.73; 95% CI, 0.63 to 2.83), and statin plus ezetimibe (MD, 2.35; 95% CI, 0.44 to 4.26) showed statistically significant increases in the mean eGFR. CONCLUSION: In patients with non-dialysis CKD, there is sufficient evidence to show that rosuvastatin and atorvastatin were statistically significantly more effective and preferable in reducing the risk of MACE and increasing the mean eGFR compared with the control group.

The ability of peripheral neurophysiological biomarkers to predict future psychological conditions among geriatric populations.

OBJECTIVE: Though the association between peripheral neurophysiological biomarkers and psychological conditions is widely discussed, there is still limited evidence about the ability of peripheral biomarkers to predict psychological outcomes, especially among geriatric populations. METHODS: The study is designed as a prospective cohort study. We collected information from participants aged over 55 years. The participants were evaluated at the start of the study (T0) and 6-9 months later (T1). Information about demographic profiles, peripheral neurophysiological biomarker recordings (including heart rate variability, finger temperature, skin conductance, and electromyogram), and psychological measurements (including Brief Symptom Rating Scale-5, Chinese Happiness Inventory, and Short Portable Mental Status Questionnaire) were collected at T0. At T1, participants reported self-rated questionnaires for psychological outcomes (Patient Health Questionnaire-15, health anxiety questionnaire, Beck Depression Inventory-II, and Beck Anxiety Inventory) and were evaluated with Mini-Mental State Examination by the staff. The association between the peripheral biomarkers and psychological outcomes was evaluated via multiple regression models. RESULTS: A total of 385 participants were included in the study and the average age was 74.49 ± 7.34 years. Both stepwise multiple linear and logistic models showed a significant association between decreased skin conductance and increased/presence of depression at T1. The receiver operating characteristic (ROC) curve analysis of skin conductance for depression was fair (area under curve = 0.812). CONCLUSIONS: The ability of skin conductance to predict depression among geriatric populations may facilitate the detection of geriatric depression and future research on the pathophysiology.

Climate Change Projections for Stroke Incidence in Taiwan: Impact of 2 °C and 4 °C Global Warming Level.

OBJECTIVES: This study aimed to establish the exposure-lag-response effect between daily maximum temperature and stroke-related emergency department visits and to project heat-induced stroke impacts under global warming levels (GWL) of 2 °C and 4 °C. METHODS: Stroke-related emergency department visits in Taiwan from 2001 to 2020 were identified using the National Health Insurance Research Database (NHIRD). The study population consisted of 1,100,074 initial stroke cases matched with 2,200,148 non-stroke controls. We employed Distributed Lag Nonlinear Models (DLNM) in a case-crossover study to investigate the association between temperature and stroke. Generalized Estimating Equations (GEE) models with a Poisson function were used to correlate high-temperature exposure with annual stroke incidence rates. Projections were made under two global warming scenarios, GWL 2.0 °C and 4.0 °C, using Coupled General Circulation Model (GCMs). Baseline data from 1995 to 2014 were transformed for spatial distribution at the township level. Geographic Information System (GIS) spatial analysis was performed using Quantum GIS 3.2.0 software. RESULTS: DLNM exposure-lag-response effect revealed that daily maximum temperature exceeding 34 °C significantly increased the risk of stroke-related emergency department visits, particularly for ischemic stroke. Under the 2 °C GWL scenario, the frequency of days with temperatures surpassing 34 °C is projected to rise substantially by the median year of 2042, with a further increase to 92.6 ± 18.0 days/year by 2065 under the 4 °C GWL scenario. Ischemic stroke showed the highest increase in temperature-related incidence rates, notably rising from 7.80% under the GWL 2 °C to 36.06% under the GWL 4 °C. Specifically, the annual temperature-related incidence rate for ischemic stroke is expected to increase significantly by 2065. Regions such as Taichung, Hsinchu, Yilan, and Taitung demonstrated pronounced changes in heat-related ischemic stroke incidence under the GWL 4 °C. CONCLUSIONS: The findings emphasize the importance of addressing temperature-related stroke risks, particularly in regions projected to experience significant temperature increases. Effective mitigation strategies are crucial to reduce the impact of rising temperatures on stroke incidence and safeguard public health.

Prospective Impacts of Social Participation Activities on Cognitive and Psychopathological Statuses in Community-Dwelling Older Adults.

OBJECTIVES: This study investigated the impact of social activities on cognitive functioning and psychopathological symptoms. METHODS: Participants aged 55 or older were enrolled through communities. Initial measures assessed demographic data, neuropsychological functioning, psychopathological state, and happiness. Social activities were evaluated using a modified 12-item tool, with 3-4 activities as the cutoff. Follow-up after 6-9 months included Mini-Mental State Examination (MMSE), Beck Depression Inventory - II (BDI-II), Beck Anxiety Inventory (BAI), Health Assessment Questionnaire (HAQ), and Patient Health Questionnaire-15 (PHQ-15) measurements. Predictive models for psychiatric and cognitive statuses were built using multiple linear regression, adjusting for baseline conditions. RESULTS: Initially, 516 older individuals enrolled, with 403 undergoing follow-up. During follow-up, the low participation group reported lower MMSE scores, higher BAI scores, and increased PHQ-15 risk. Negative correlations between social activity numbers and PHQ-15 results were found. Engagement in social clubs correlated positively with higher MMSE scores, while regular interactions with one's adult child(ren) were linked to decreased BAI scores. CONCLUSIONS: The quantity of social activities was associated with lower somatic distress. Social club engagement positively influenced cognition, and regular interactions with one's adult child(ren) mitigated anxiety among older individuals. CLINICAL IMPLICATIONS: Enough types of social activities, participating in social clubs, and adequate interactions with children protected against psychopathologies.

Development of a tool measuring various aspects of social detachment: The social detachment questionnaire for older population.

BACKGROUND: Social detachment includes the subjective aspect "loneliness" and the objective aspect "social isolation," but tools to assess both dimensions are limited. This study aims to develop a questionnaire, the Social Detachment Questionnaire for Older Population (SDQO), that considers multiple dimensions of social detachment simultaneously. METHODS: The study collected 600 valid samples from individuals aged 55 and above to examine the psychometric properties of the developed SDQO. Item analysis was conducted to assess the performance of each item, and exploratory factor analysis (EFA) was employed to analyze its initial structure and eliminate less ideal items. Subsequently, confirmatory factor analysis (CFA) was used to examine the model fit of the suggested structure by EFA, using different subsamples. Internal consistency, concurrent validity, and other analyses were also performed. RESULTS: The original 27-item SDQO was reduced to 17 items after removing 4 questions in item analysis and 6 questions in EFA. The Cronbach's alpha for the 17-item version of SDQO was 0.80. Both EFA and CFA supported its 6-factor structure, with factors identified as community activities, loneliness, personal resources, leisure activities, friendship, and family resources. SDQO also demonstrated expected performance in concurrent validity. CONCLUSION: The 17-item version of SDQO exhibited good reliability and validity, measuring various aspects of social detachment behavior, feelings, and resources. It holds value for future research applications.

DNA methylation in peripheral blood is associated with renal aging and renal function decline: a national community study.

BACKGROUND: Older patients are at risk for acute kidney injury and chronic kidney disease. Age-related increases in DNA methylation at CpG islands have been linked to aging-related diseases like cancer and cardiovascular disease, but the exact causal relationship between methylation in renal aging and other kidney diseases remains unclear. This study aimed to elucidate the methylation status of peripheral blood mononuclear cells (PBMCs) in the Asian population. Using human whole blood DNA methylation analysis from the Taiwan Biobank, we included participants with both whole blood genome-wide methylation data and follow-up data on serum creatinine. We investigated hyper- and hypomethylated genes in comparison of participants with higher and lower estimated glomerular filtration (eGFR) decline rate in overall cohort as well as in comparison of old and young participants in subgroup of participants with higher eGFR decline rate. Common genes and signaling pathways in both comparative analyses were identified. RESULTS: Among 1587 participants in the analysis, 187 participants had higher eGFR decline rate. According to the comparison of methylation in participants with different eGFR declines and at different ages, respectively, we identified common hypermethylated genes, including DNMT3A and GGACT, as well as hypomethylated genes such as ARL6IP5, CYB5D1, BCL6, RPRD2, ZNF451, and MIAT in both participants with higher eGFR decline and those of older age. We observed associations between the methylation status of signaling pathways and aging as well as renal function decline. These pathways notably included autophagy, p38 mitogen-activated protein kinases, and sirtuins, which were associated with autophagy process and cytokine production. CONCLUSIONS: Through methylation analysis of PBMCs, we identified genes and signaling pathways which could play crucial roles in the interplay of renal aging and renal function decline. These findings contribute to the development of novel biomarkers for identifying at-risk groups and even for therapeutic agent discovery.

A multi-trait GWAS identifies novel genes influencing albuminuria.

BACKGROUND: Albuminuria is common and associated with increased risks of end-stage kidney disease and cardiovascular diseases, yet its underlying mechanism remains obscure. Previous genome-wide association studies (GWAS) for albuminuria did not consider gene pleiotropy and primarily focused on European ancestry populations. This study adopted a multi-trait analysis of GWAS (MTAG) approach to jointly analyze two vital kidney traits, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) to identify and prioritize the genes associated with UACR. METHODS: Data from the Taiwan Biobank from 2012 to 2023 were analyzed. GWAS of UACR and eGFR were performed separately and the summary statistics from these GWAS were jointly analyzed using MTAG. The polygenic risk scores (PRS) of UACR were constructed for validation. The UACR-associated loci were further fine-mapped and prioritized based on their deleteriousness, eQTL associations, and relatedness to Mendelian kidney diseases. RESULTS: MTAG analysis of the UACR revealed 15 genetic loci, including 12 novel loci. The PRS for UACR was significantly associated with urinary albumin level (P < 0.001) and microalbuminuria (P = 0.001 ∼ 0.045). A list of priority genes was generated. Twelve genes with high priority included the albumin endocytic receptor gene LRP2 and ciliary genes  IFT172. CONCLUSIONS: The findings of this multi-trait GWAS suggest that primary cilia play a role in sensing mechanical stimuli, leading to albumin endocytosis. The priority list of genes warrants further translational investigation to reduce albuminuria.

Percutaneous Coronary Intervention With a Drug-Eluting Stent Versus Coronary Artery Bypass Grafting in Patients Receiving Dialysis: A National Study From Taiwan.

Rationale & Objective: We aimed to study the comparative effectiveness of percutaneous coronary intervention with drug-eluting stent and coronary artery bypass grafting in patients receiving dialysis. Study Design: This was a retrospective observational cohort study. Setting & Participants: This population-based study identified patients receiving dialysis hospitalized for coronary revascularization between January 1, 2009 and December 31, 2015, in the Taiwan National Health Insurance Research Database. Exposures: Patients received percutaneous coronary intervention with drug-eluting stent versus coronary artery bypass grafting. Outcomes: The study outcomes were all-cause mortality, in-hospital mortality, and repeat revascularization. Analytical Approach: Propensity scores were used to match patients. Cox proportional hazards models and logistic regression models were constructed to examine associations between revascularization strategies and mortality. Interval Cox models were fitted to estimate time-varying hazards during different periods. Results: A total of 1,840 propensity score-matched patients receiving dialysis were analyzed. Coronary artery bypass grafting was associated with higher in-hospital mortality (coronary artery bypass grafting vs percutaneous coronary intervention with drug-eluting stent; crude mortality rate 12.5% vs 3.3%; adjusted OR, 5.22; 95% CI, 3.42-7.97; P < 0.001) and longer hospitalization duration (median [IQR], 20 [14-30] days vs 3 [2-8] days; P < 0.001). After discharge, repeat revascularization, acute coronary syndrome, and repeat hospitalization all occurred more frequently in the percutaneous coronary intervention with drug-eluting stent group. Importantly, with a median follow-up of 2.8 years, coronary artery bypass grafting was significantly associated with a higher risk of all-cause overall mortality (adjusted HR, 1.19; 95% CI, 1.05-1.35; P = 0.006) in the multivariable Cox proportional hazard model. Sensitivity and subgroup analyses yielded consistent results. Limitations: This was an observational study with mainly Asian ethnicity. Conclusions: Percutaneous coronary intervention with drug-eluting stent may be associated with better survival than coronary artery bypass grafting in patients receiving dialysis. Future studies are warranted to confirm this finding.

Although coronary artery bypass grafting offers better long-term survival in the general population than percutaneous coronary intervention with drug-eluting stent, patients receiving dialysis may be too frail to tolerate the increased perioperative mortality risk of coronary artery bypass grafting. In this retrospective study in a national cohort of patients receiving dialysis from Taiwan, percutaneous coronary intervention with drug-eluting stent is associated with lower in-hospital mortality and better long-term survival when compared with coronary artery bypass grafting. Subsequent acute coronary syndrome, repeat revascularization, and rehospitalization were noted more frequently in the percutaneous coronary intervention with drug-eluting stent group. These findings may suggest percutaneous coronary intervention with drug-eluting stent as a safe revascularization strategy for patients receiving dialysis.

Clinical implications of frailty in peritoneal dialysis patients - A prospective observational study.

BACKGROUND: Frailty is an age-related condition that predicts adverse outcomes. The study was aimed to investigate the clinical implications of frailty evolution in patients undergoing peritoneal dialysis (PD). METHOD: In this prospective study, all new-onset (<6 months) and prevalent (≧6 months) PD patients completed frailty assessment at entry and 6 months by a semiautomated frailty index of 80 risk factors (FI80) which also contained the 5 components of Fried frailty phenotype. A score ≧13/80 (FI80 > 0.16) or ≧3/5 (frailty phenotype) was designated to define frailty. RESULT: 337 PD patients were recruited (new-onset 23.4%, prevalent 76.6%). Two hundred (59.3%) and 163 (48.4%) patients were frail by FI80 and frailty phenotype, respectively. Predictors for frailty were old age, dialysis, diabetes mellitus, gout and sleep disorder. New-onset patients aged <55 years displayed the best evolution of frailty over 6 months (stable or improved, n = 29/47, 61.7% by FI80, p = 0.0293), compared with other groups. Survival analysis found that frail patients exhibited the worse outcomes (overall death and hospitalization). Poisson regression showed frailty was associated with increased utilizations of outpatient and ER services; however multivariate Cox models identified only diabetes, gout and low body mass index (<19 kg/m2), but not frailty, predicted overall death and hospitalizations. CONCLUSION: Frailty is a common medical condition in PD patients, and the status of which can be stabilized or improved in new-onset, young patients at least over the short term. Compared with frailty, certain comorbidities (diabetes and gout) and undernutrition appeared to be more robust in the prediction of adverse outcomes.

A competing risk predictive model for kidney failure in patients with advanced chronic kidney disease.

BACKGROUND/PURPOSE: Predictive modeling aids in identifying patients at high risk of adverse events. Using routinely collected data, we report a competing risk prediction model for kidney failure. METHODS: A total of 5138 patients with CKD stages 3b-5 were included and randomized into the development and validation cohorts at a ratio of 7:3. The outcome was end-stage kidney disease, defined as the initiation of dialysis or kidney transplantation. All patients were followed-up until December 31, 2020. A Fine and Gray model was applied to estimate the sub-hazard ratio of kidney failure, with death as a competing event. RESULTS: In the development cohort, the mean age was 67.6 ± 13.9 years and 60 % were male. The mean index eGFR and median urinary protein-creatinine ratio (UPCR) were 26.5 ± 12.8 mL/min/1.73 m2 and 1051 mg/g, respectively. The median follow-up duration was 1051 days. The proportion of patients with kidney failure and death was 25.4 % and 14.1 %, respectively. Four models were applied, including eGFR, age, sex, UPCR, systolic and diastolic blood pressure, serum albumin, phosphate, uric acid, haemoglobin, and potassium levels had the best goodness of fit. All models had good discrimination with time-to-event c statistics of 0.89-0.95 in the development cohort and 0.86-0.95 in the validation cohort. The prediction models showed excellent and fairly good calibration at 2 and 5-year risk, respectively. CONCLUSION: Using real-world data, our competing risk model can accurately predict progression to kidney failure over 2 years in patients with advanced CKD.

Muscle strength in ostensibly healthy non-diabetic subjects.

BACKGROUND/PURPOSE: Sarcopenia and decreased muscle strength (dynapenia) are emerging health issues. However, the study exploring muscle strength changes of both upper and lower limbs at the same time among all age groups is rare. This study aims to investigate the muscle strength and to establish a muscle strength norm of an ostensibly healthy non-diabetic Asian population. METHODS: From 2018 June to 2020 March, subjects (aged from 20 to <80 years old) undergoing health checkup in Good Liver Medical Examination Center and National Taiwan University Hospital Geriatrics and Gerontology Department were enrolled. A battery of muscle power examinations including handgrip strength (HGS), five times sit-to-stand test (5TSTS), and one-leg standing test (OLST) were performed. RESULTS: A total of 183 participants was enrolled, consisting of 92 females and 91 males. The finding shows the strongest HGS, best 5TSTS, and the longest OLST of both genders appeared in the 20-29-year-old group. Age, gender, and palm length are significantly related to HGS, whereas age is the only factor affecting 5TSTS and OLST. It revealed a progressive decline during ageing process, especially after age 60. Finally, Z-score and T-score norms of these were established. CONCLUSION: These data will be useful as normal controls for muscle strength of specific disease groups. The application of the cutoffs from these data and their comparisons with the recommended cutoffs from various guidelines worth further exploration.

Effect of Lipid-Lowering Drugs on Renal and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Dyslipidemia: A Retrospective Cohort Study.

The effects of lipid-lowering drugs (LLDs) on cardiovascular and renal outcomes in patients with advanced chronic kidney disease (CKD) and dyslipidemia are not completely understood. We conducted a retrospective cohort study to evaluate the effect of LLDs on end-stage kidney disease (ESKD), major adverse cardiovascular events (MACEs), and mortality in adult patients with CKD stage 3b, 4, or 5, and dyslipidemia. Participants were recruited between January 1, 2008, and December 31, 2018, and classified as LLD or non-LLD users; the final follow-up date was December 31, 2020. The primary outcome was time to ESKD or death due to renal failure. Sub-distribution hazard regression models adjusted for multivariables, including time-varying lipid profile covariates, were used for the analysis. Among the 6,740 participants, 4,280 patients with CKD and dyslipidemia, including 872 using LLDs and 3,408 not using LLDs, completed the primary analysis. The multivariable analyses showed that LLD users had a significantly lower risk of time to the composite renal outcome (adjusted hazard ratio [aHR], 0.76, 95% confidence interval [CI], 0.65-0.89), and MACE incidence (aHR, 0.75, 95% CI, 0.62-0.93) than did non-LLD users. After adjusting for time-varying covariates of the lipid profile, there was a significant difference in the composite renal outcome (aHR, 0.78, 95% CI, 0.65-0.93) and MACEs (aHR, 0.77, 95% CI, 0.60-0.98). Among adult patients with advanced CKD and dyslipidemia, LLD users had a significantly lower risk of composite renal outcomes and MACEs than non-LLD users. In addition to reducing lipid profile, the use of LLD is associated with renal and cardiovascular protective effects.

Prediction of adverse health outcomes using an electronic frailty index among nonfrail and prefrail community elders.

BACKGROUND: Early recognition of older people at risk of undesirable clinical outcomes is vital in preventing future disabling conditions. Here, we report the prognostic performance of an electronic frailty index (eFI) in comparison with traditional tools among nonfrail and prefrail community-dwelling older adults. The study is to investigate the predictive utility of a deficit-accumulation eFI in community elders without overt frailty. METHODS: Participants aged 65-80 years with a Clinical Frailty Scale of 1-3 points were recruited and followed for 2 years. The eFI score and Fried's frailty scale were determined by using a semiautomated platform of self-reported questionnaires and objective measurements which yielded cumulative deficits and physical phenotypes from 80 items of risk variables. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the severity of frailty in relation to adverse outcomes of falls, emergency room (ER) visits and hospitalizations during 2 years' follow-up. RESULTS: A total of 427 older adults were evaluated and dichotomized by the median FI score. Two hundred and sixty (60.9%) and 167 (39.1%) elders were stratified into the low- (eFI ≤ 0.075) and the high-risk (eFI > 0.075) groups, respectively. During the follow-up, 77 (47.0%) individuals developed adverse events in the high-risk group, compared with 79 (30.5%) in the low-risk group (x2, p = 0.0006). In multivariable models adjusted for age and sex, the increased risk of all three events combined in the high- vs. low-risk group remained significant (adjusted hazard ratio (aHR) = 3.08, 95% confidence interval (CI): 1.87-5.07). For individual adverse event, the aHRs were 2.20 (CI: 1.44-3.36) for falls; 1.67 (CI: 1.03-2.70) for ER visits; and 2.84 (CI: 1.73-4.67) for hospitalizations. Compared with the traditional tools, the eFI stratification (high- vs. low-risk) showed better predictive performance than either CFS rating (managing well vs. fit to very fit; not discriminative in hospitalizations) or Fried's scale (prefrail to frail vs. nonfrail; not discriminative in ER visits). CONCLUSION: The eFI system is a useful frailty tool which effectively predicts the risk of adverse healthcare outcomes in nonfrail and/or prefrail older adults over a period of 2 years.

Predialysis trajectories of estimated GFR and concurrent trends of Chronic Kidney Disease-relevant biomarkers.

Background: The glomerular filtration rate (GFR) decline varies in patients with advanced chronic kidney disease (CKD), and the concurrent changes in CKD-related biomarkers are unclear. Objectives: This study aimed to examine the changes in CKD-related biomarkers along with the kidney function decline in various GFR trajectory groups. Design: This study was a longitudinal cohort study originated from the pre-end-stage renal disease (pre-ESRD) care program in a single tertiary center between 2006 and 2019. Methods: We adopted a group-based trajectory model to categorize CKD patients into three trajectories according to estimated glomerular filtration rate (eGFR) changes. A repeated-measures linear mixed model was used to estimate the concurrent biomarker trends in a 2-year period before dialysis and to examine the differences among trajectory groups. A total of 15 biomarkers were analyzed, including urine protein, serum uric acid, albumin, lipid, electrolytes, and hematologic markers. Results: Using longitudinal data from 2 years before dialysis initiation, 1758 CKD patients were included. We identified three distinct eGFR trajectories: persistently low eGFR levels, progressive loss of eGFR, and accelerated loss of eGFR. Eight of the 15 biomarkers showed distinct patterns among the trajectory groups. Compared with the group with persistently low eGFR values, the other two groups were associated with a more rapid increase in the blood urea nitrogen (BUN) level and urine protein-creatinine ratio (UPCR), especially in the year before dialysis initiation, and a more rapid decline in hemoglobin and platelet counts. A rapid eGFR decline was associated with lower levels of albumin and potassium, and higher levels of mean corpuscular hemoglobin concentration (MCHC) and white blood cell (WBC). The albumin level in the group with an accelerated loss of eGFR was below the normal range. Conclusion: Using longitudinal data, we delineated the changes in CKD biomarkers with disease progression. The results provide information to clinicians and clues to elucidate the mechanism of CKD progression.

Unsupervised clustering identifies sub-phenotypes and reveals novel outcome predictors in patients with dialysis-requiring sepsis-associated acute kidney injury.

INTRODUCTION: Heterogeneity exists in sepsis-associated acute kidney injury (SA-AKI). This study aimed to perform unsupervised consensus clustering in critically ill patients with dialysis-requiring SA-AKI. PATIENTS AND METHODS: This prospective observational cohort study included all septic patients, defined by the Sepsis-3 criteria, with dialysis-requiring SA-AKI in surgical intensive care units in Taiwan between 2009 and 2018. We employed unsupervised consensus clustering based on 23 clinical variables upon initializing renal replacement therapy. Multivariate-adjusted Cox regression models and Fine-Gray sub-distribution hazard models were built to test associations between cluster memberships with mortality and being free of dialysis at 90 days after hospital discharge, respectively. RESULTS: Consensus clustering among 999 enrolled patients identified three sub-phenotypes characterized with distinct clinical manifestations upon renal replacement therapy initiation (n = 352, 396 and 251 in cluster 1, 2 and 3, respectively). They were followed for a median of 48 (interquartile range 9.5-128.5) days. Phenotypic cluster 1, featured by younger age, lower Charlson Comorbidity Index, higher baseline estimated glomerular filtration rate but with higher severity of acute illness was associated with an increased risk of death (adjusted hazard ratio of 3.05 [95% CI, 2.35-3.97]) and less probability to become free of dialysis (adjusted sub-distribution hazard ratio of 0.55 [95% CI, 0.38-0.8]) than cluster 3. By examining distinct features of the sub-phenotypes, we discovered that pre-dialysis hyperlactatemia ≥3.3 mmol/L was an independent outcome predictor. A clinical model developed to determine high-risk sub-phenotype 1 in this cohort (C-static 0.99) can identify a sub-phenotype with high in-hospital mortality risk (adjusted hazard ratio of 1.48 [95% CI, 1.25-1.74]) in another independent multi-centre SA-AKI cohort. CONCLUSIONS: Our data-driven approach suggests sub-phenotypes with clinical relevance in dialysis-requiring SA-AKI and serves an outcome predictor. This strategy represents further development toward precision medicine in the definition of high-risk sub-phenotype in patients with SA-AKI.Key messagesUnsupervised consensus clustering can identify sub-phenotypes of patients with SA-AKI and provide a risk prediction.Examining the features of patient heterogeneity contributes to the discovery of serum lactate levels ≥ 3.3 mmol/L upon initializing RRT as an independent outcome predictor.This data-driven approach can be useful for prognostication and lead to a better understanding of therapeutic strategies in heterogeneous clinical syndromes.

Effect of isotemporal substitution of sedentary behavior with different intensities of physical activity on the muscle function of older adults in the context of a medical center.

BACKGROUND: Engaging in physical activity and reducing sedentary time in daily life may enable older individuals to maintain muscle mass. This study aimed to investigate the effects of replacing sedentary behavior with light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on the muscle function of older adults at a medical center in Taiwan. METHODS: We recruited 141 older adults (51.1% men; 81.1 ± 6.9 years old) and asked them to wear a triaxial accelerometer on the waist to measure their sedentary behavior and physical activity. Functional performance was assessed based on handgrip strength, Timed Up and Go (TUG) test, gait speed, and five-times-sit-to-stand test (5XSST). Isotemporal substitution analysis was performed to examine the effect of substituting 60 min of sedentary time with 60 min of LPA, MVPA, and combined LPA and MVPA in different proportions. RESULTS: Reallocating 60 min of sedentary behavior per day to LPA was associated with better handgrip strength (Beta [B] = 1.587, 95% confidence interval [CI] = 0.706, 2.468), TUG test findings (B = -1.415, 95% CI = -2.186, -0.643), and gait speed (B = 0.042, 95% CI = 0.007, 0.078). Reallocating 60 min of sedentary behavior per day to MVPA was associated with better gait speed (B = 0.105, 95% CI = 0.018, 0.193) and 5XSST findings (B = -0.060, 95% CI = -0.117, -0.003). In addition, each 5-min increment in MVPA in the total physical activity replacing 60 min of sedentary behavior per day resulted in greater gait speed. Replacing 60 min of sedentary behavior with 30-min of LPA and 30-min of MVPA per day significantly decreased the 5XSST test time. CONCLUSION: Our study indicates that introducing LPA and a combination of LPA and MVPA to specifically replace sedentary behavior may help maintain muscle function in older adults.

Serum Urate and Risk of Chronic Kidney Disease: A Mendelian Randomization Study Using Taiwan Biobank.

OBJECTIVE: To evaluate the association between serum urate and risk of incident chronic kidney disease (CKD) and to assess whether serum urate plays a causal role in CKD. PATIENTS AND METHODS: We conducted a prospective cohort study and Mendelian randomization analysis that analyzed longitudinal data from the Taiwan Biobank between January 1, 2012, and December 31, 2021. RESULTS: A total of 34,831 individuals met the inclusion criteria, of which 4697 (13.5%) had hyperuricemia. After a median (interquartile range) follow-up of 4.1 (3.1-4.9) years, 429 participants developed CKD. After adjustment for age, sex, and comorbid conditions, each mg/dL increase in serum urate was associated with a 15% higher risk of incident CKD (HR, 1.15; 95% CI, 1.08 to 1.24; P<.001). The genetic risk score and seven Mendelian randomization methods revealed no significant association between serum urate levels and the risk of incident CKD (HR, 1.03; 95% CI, 0.72 to 1.46; P=0.89; all P>.05 for 7 Mendelian randomization methods). CONCLUSION: This prospective, population-based cohort study showed that elevated serum urate is a significant risk factor for incident CKD; however, Mendelian randomization analyses failed to provide evidence that serum urate had a causal effect on CKD in the East Asian population.

Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis.

BACKGROUND: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). METHOD: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. RESULT: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. CONCLUSION: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Can peripheral biomarkers reflect the psychological condition in geriatric populations? The influence of cardiovascular comorbidities.

BACKGROUND: Although previous studies indicated the association between peripheral biomarkers and psychological conditions, a higher prevalence of cardiovascular diseases (CVD) among geriatric populations may hinder the applicability of the biomarkers. The objective of this study was to assess the adequacy of the application of biomarkers to evaluate psychological conditions among geriatric populations. METHOD: We collected information on the demographics and history of CVD in all participants. All participants completed the Brief Symptom Rating Scale (BSRS-5) and the Chinese Happiness Inventory (CHI), which are the measurement of negative and positive psychological conditions, respectively. Four indicators of the peripheral biomarkers, including the standard deviation of normal to normal RR intervals (SDNN), finger temperature, skin conductance, and electromyogram were collected for each participant during a 5-min resting state. Multiple linear regression models were conducted to evaluate the association between the biomarkers and the psychological measurements (BSRS-5, CHI) with and without the inclusion of the participants with CVD. RESULTS: A total of 233 participants without CVD (non-CVD group) and 283 participants with CVD (CVD group) were included. The CVD group was older and with higher body mass index compared to the non-CVD group. In the multiple linear regression model with all participants, only BSRS-5 scores had a positive association with electromyogram. After the exclusion of the CVD group, the association between the BSRS-5 scores and electromyogram was more relevant, while CHI scores became positively associated with SDNN. CONCLUSIONS: A single measurement of the peripheral biomarker may be insufficient to depict psychological conditions among geriatric populations.

A Randomized Trial of Postoperative Handgrip Exercises for Fistula Maturation in Patients With Newly Created Wrist Radiocephalic Arteriovenous Fistulas.

Introduction: We aimed to substantiate the benefit of postoperative handgrip exercises (HGEs) in enhancing the maturation of an arteriovenous wrist fistula. Methods: We randomly assigned 119 patients aged 20 to 80 years who had wrist arteriovenous fistulas (AVFs) to undergo either a basic HGE program (group A), an advanced program (group B), or an advanced-plus upper arm banding program (group C). Outcomes were assessed by ultrasonographic evaluation of the diameter and flow at each follow-up. The attending nephrologist decided the clinical use of the fistula. Results: We identified no significant differences among the HGE groups in the mean diameter and blood flow 14, 30, 60, and 90 days after the creation of the wrist AVF (P = 0.55, 0.88, 0.21, and 0.19 for the diameter; 0.94, 0.81, 0.49, and 0.56 for the flow, respectively). The intent-to-treat analysis also found no difference in the clinical use of fistulas for hemodialysis (HD) (P = 0.997). Conclusion: In patients with a newly created wrist AVF, advancing frequency, with or without adding intensity using an upper arm tourniquet, of postoperative HGEs did not enhance the growth of the fistula or increase the rate of clinical use over 3 months. (ClinicalTrials.gov ID: NCT03077815).