Vascular calcification (VC), a common complication of chronic kidney disease (CKD), substantially contributes to cardiovascular morbidity. Although distinct forms of programmed cell death have been implicated in VC, the role of PANoptosis remains unclear. This study investigated the involvement of PANoptosis in CKD-associated VC and explored its regulatory mechanisms. Transcriptomic analysis of the GSE146638 dataset combined with machine learning algorithms was used to identify key PANoptosis-related genes associated with VC. CKD-associated VC was established in adenine/high-phosphate-fed mice and 5/6-nephrectomized rats fed a high-phosphate diet. In vitro, vascular smooth muscle cells (VSMCs) transfected with cartilage oligomeric matrix protein (COMP) small interfering RNA (siRNA) were subsequently stimulated with β-glycerophosphate (β-GP), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) to induce calcification-associated PANoptosis. Protein interactions and downstream signaling pathways were explored using co-immunoprecipitation (Co-IP). CKD-associated VC was characterized by concurrent activation of apoptosis, pyroptosis, and necroptosis in VSMCs, indicating PANoptosis activation in vivo and in vitro. Through an integrative bioinformatics strategy, COMP was identified as a hub gene exhibiting markedly reduced expression in calcified vessels. COMP deficiency aggravated VSMC calcification and enhanced PANoptotic signaling. Mechanistically, COMP directly interacted with angiotensin II type 1 receptor (AT1R) and restrained β-arrestin-2-dependent signaling, thereby limiting PANoptosome assembly. Conversely, COMP depletion promoted PANoptosis and calcification, whereas β-arrestin-2 inhibition largely reversed these effects. Collectively, these findings demonstrate that PANoptosis contributes to CKD-associated VC. COMP protects against VC by restraining AT1R-dependent β-arrestin-2 signaling, thereby suppressing PANoptosis, identifying the COMP-AT1R-β-arrestin-2 axis as a potential therapeutic target for cardiovascular complications in CKD.

INTRODUCTION:Cardio-renal syndrome type 4 (CRS4) is defined as heart failure driven by chronic kidney disease (CKD). Cardiovascular mortality is the leading cause of death in patients with advanced CKD with current medical treatments exhibiting limited efficacy. Short leukocyte telomere lengths in such patients are correlated with increased mortality, particularly cardiovascular mortality. Here, we examined telomere shortening in mouse and human cardiomyocyte models of CRS4 and its potential protective role by overexpression of telomerase reverse transcriptase. METHODS:We engineered an adeno-associated virus 9 (AAV9) gene therapy JV101, which overexpressed catalytically inactive and nuclear localized human telomerase reverse transcriptase (modhTERT) under cardiac troponin T promoter control. Both in vivo and in vitro models were utilized to conduct a comprehensive evaluation of the therapeutic effects of modhTERT on CRS4. RESULTS:Overexpression of modhTERT recapped myocardial telomeres and reversed cardiac dysfunction, hypertrophy and fibrosis, and mitochondrial dysfunction in two CRS4 mouse models: 5/6 nephrectomy and Angiotensin II - high salt - uninephrectomy. The reversal of cardiac dysfunction by modhTERT was both long-term and persistent. In contrast, beta-blocker administration merely delayed the progression of heart failure in these models, without achieving functional reversal. Surprisingly, JV101 ameliorated kidney function as measured by blood urea nitrogen levels in CKD murine models. Experiments in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) demonstrated that modhTERT bound to myocardial telomeric ends. Transcriptomic analysis of isolated mouse cardiomyocytes revealed that modhTERT reversed differentially repressed genes that were highly enriched in mitochondrial metabolism. Coculture of hiPSC-CMs with serum from hemodialysis patients or indoxyl sulfate toxin induced myocardial contractile dysfunction. Overexpression of modhTERT also blocked further telomere shortening and reversed contractile dysfunction in hiPSC-CMs. CONCLUSIONS:Our results provide proof-of-concept evidence for treating CRS4 by telomere recapping gene therapy.

IntroductionCardiovascular disease is the leading cause of death in maintenance hemodialysis (MHD) patients. This cross-sectional study investigated the associations between bioelectrical impedance analysis (BIA) parameters, physical function, and cardiac function in MHD patients, with the aim of identifying predictors of cardiac dysfunction.MethodsThe study included 130 MHD patients from Shanghai Ninth People’s Hospital on December 2022. BIA measurements were executed using the Body Composition Monitor. Physical function was assessed by handgrip strength and natural gait speed. Cardiac systolic and diastolic functions were evaluated by echocardiography. Univariate and multivariable logistic regression analyses were performed to identify determinants of cardiac dysfunction.ResultsMean age of all participants was 62.39 ± 13.91 years old while 78 (60%) were male. Univariate and multivariable logistic regression analyses were performed to identify determinants of cardiac dysfunction. Multivariable analysis revealed that NT-proBNP (odds ratio [OR], 1.098; 95% CI, 1.011-1.193; P = 0.027) and natural gait speed (OR, 0.002; 95% CI, 0.001-0.528; P = 0.033) were independent determinants of impaired systolic function. Their combination had a high predictive value (area under the curve [AUC] = 0.854; P < 0.001). Total body water (OR, 1.104; 95% CI, 1.010-1.206; P = 0.029) and NT-proBNP (OR, 1.078; 95% CI, 1.010-1.151; P = 0.025) were significant determinants of impaired diastolic function, with the combined prediction (AUC = 0.746; P < 0.001) outperforming either marker alone.DiscussionBIA and physical function parameters improved risk stratification beyond conventional biomarkers, providing practical tools for screening cardiac risk in MHD patients.

Forkhead box P1 (Foxp1) plays a key role in endothelial preservation and the suppression of inflammatory responses. However, its exact function in valvular calcification (VC) of chronic kidney disease (CKD) remains unclear. Our previous work showed that parathyroid hormone (PTH) contributes to CKD-related VC by driving valvular endothelial-to-mesenchymal transition (EndMT). Whether Foxp1 inhibits PTH-induced EndMT remains determined. This study investigates whether Foxp1 reduces VC by restraining EndMT and delineates the underlying mechanisms. The Foxp1-KI mice were crossed with the Cdh5-Cre (ERT2) mice to generate endothelial-specific Foxp1 knock-in mice (named Foxp1EC-OE). Here, it was found that Foxp1EC-OE mice exhibited reduced valvular calcification compared with CKD mice. Foxp1 overexpression suppressed valvular EndMT and inhibited Notch signaling by binding the Jagged-1 promoter and repressing its transcription. This led to decreased TGF-β1 secretion, thereby attenuating osteogenic transition of valvular interstitial cells. Additionally, Foxp1 restored endothelial integrity and reduced high mobility group box 1 protein (HMGB1)-driven macrophage infiltration. These findings identify Foxp1 as a key regulator of VC via Notch-mediated EndMT inhibition, revealing regulatory nodes in the Jagged-1/Notch pathway that may be amenable to future pharmacological targeting for CKD-related VC.

Acute kidney injury (AKI) is a severe clinical syndrome with limited therapeutic options, and its underlying molecular mechanisms remain incompletely understood. Nephroblastoma overexpressed (NOV), a matricellular protein, has been implicated in renal pathophysiology; however, its role in AKI remains unclear. Using a murine renal ischemia-reperfusion (I/R) model and HK-2 cells subjected to hypoxia/reoxygenation (H/R), we found that NOV was rapidly induced in renal tubular epithelial cells (RTECs) during the early phase of AKI. RTEC-specific NOV knockdown significantly alleviated renal dysfunction and tubular injury after I/R. Transcriptomic analysis implicated ferroptosis as a major pathway regulated by NOV. Consistently, NOV knockdown attenuated lipid peroxidation, iron accumulation, and ferroptosis-associated injury both in vivo and in vitro. NOV overexpression increased ferroptotic susceptibility under H/R, and ferrostatin-1 attenuated these effects. Mechanistically, NOV interacted with transferrin receptor (TFRC) and promoted ferroptosis by stabilizing TFRC through reduced K48-linked ubiquitination. NEDD4L was identified as a candidate E3 ligase mediating TFRC ubiquitination, and NOV disrupted NEDD4L-associated K48-linked ubiquitination of TFRC. Collectively, these findings identify the NOV-TFRC axis as a regulator of ferroptotic tubular injury and suggest NOV as a potential therapeutic target in I/R-AKI.

Intestinal injury is an important complication of burn sepsis with limited therapeutic choices. Phellodendrine is a promising compound for gastrointestinal inflammatory diseases and is extracted from the traditional Chinese medicine phellodendron bark. The study aimed to explore the role of phellodendrine against oxidative stress and autophagy in burn sepsis-induced intestinal injury. A mouse model of burn sepsis model was established by intraperitoneally injecting 10 mg/kg lipopolysaccharide (LPS) to mice burned by boiled water. Phellodendrine (30 mg/kg) was injected into mice in the drug group after scalding and before LPS injection. Hematoxylin and eosin staining was performed to observe histopathological changes in murine small intestines. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay was performed to evaluate intestinal cell apoptosis. Immunofluorescence staining was performed to measure the expression and distribution of autophagy markers, light chain 3II (LC3II) and p62 in intestinal tissues. Oxidative stress indicators were detected using corresponding commercial kits. Protein levels of apoptotic markers, autophagy markers, and factors involved in adenosine monophosphate-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) pathway in intestines were quantified by western blotting. Phellodendrine attenuated bun sepsis-induced intestinal pathological changes. Meanwhile, aggravated cell apoptosis, reduction of antioxidant enzymes, and downregulation of autophagy markers in intestinal tissues of burn sepsis group were all improved by phellodendrine. In addition, phellodendrine activated the phosphorylation (p) of AMPK and inhibited p-mTOR signaling in intestines of burn septic mice. In conclusion, phellodendrine suppresses oxidative stress and activates autophagy in burn sepsis-induced intestinal injury by activating AMPK and inhibiting mTOR signaling.

OBJECTIVES:Maintenance hemodialysis (MHD) patients often impairs physical function, leading to reduced quality of life and increased mortality. Phase angle (PhA), derived by bioelectrical impedance analysis, has been proposed as a predictor of sarcopenia, holds promise as a potential indicator of physical function. The aim of this study was to identify the association between PhA and physical function in MHD patients. METHODS:This was a multicenter, cross-sectional study included MHD patients from seven dialysis centers from 2020 to 2021. Physical function was measured by handgrip strength (HGS), Short Physical Performance Battery (SPPB), 4-meter gait speed, and timed up and go test (TUGT). Nutritional status was assessed by malnutrition inflammation score (MIS). Body composition, including PhA at 50kHz, was measured by bioelectrical impedance analysis. Sarcopenia was diagnosed according to the 2019 update version of the Asian Working Group for Sarcopenia. Multivariable linear regression models were performed to determine the association between PhA and physical function. RESULTS:A total of 864 patients (61% male, median age 63 years) were analyzed. The median PhA was 4.5 (interquartile range: 3.9-5.2)°. PhA was negatively associated with age, MIS, Charlson comorbidity index, extracellular water/total body water, visceral fat area, and TUGT, and positively associated with hemoglobin, serum albumin, body mass index, height, weight, skeletal muscle mass index (SMI), SPPB, 4-meter gait speed, and HGS. These associations were consistent across PhA values of whole body and five body segments-right arm, left arm, trunk, right leg, and left leg. Multivariable linear regression analyses indicated that PhA was independently associated with higher SPPB scores (β = 0.33, P < 0.001), faster gait speed (β = 0.29, P < 0.001), greater HGS (β = 0.28, P < 0.001) and shorter TUGT time (β = -0.20, P < 0.001) after fully adjusted for age, sex, spKt/V, dialysis vintage, Charlson comorbidity index, MIS and skeletal muscle index. Subgroup analyses confirmed the robust association of PhA with physical function across different patient characteristics including sarcopenia, malnutrition, age, sex, and diabetes. CONCLUSIONS:Higher PhA was independently associated with better physical function in MHD patients. Our study suggested that PhA may serve as a non-invasive, reliable clinical indicator for assessing functional status in this population.

Osteoporosis and sarcopenia frequently occur in patients with end-stage renal disease undergoing hemodialysis (HD), and depression is also a common mental health issue in this population. Despite the prevalence of these conditions, the interrelationships among them remain poorly understood in HD patients. In this multicenter cross-sectional study, 858 HD patients from 7 dialysis centers were recruited. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Skeletal muscle mass index (SMI) was calculated from body composition data obtained through multifrequency bioimpedance analysis (BIA), while handgrip strength (HGS) was measured with a dynamometer. Gait speed was evaluated with a 4-meter walk test, and depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Among the 858 participants (524 men, 334 women), 39.2

Ischemia reperfusion-induced acute kidney injury (IRI-AKI) is a prevalent clinical complication among hospitalized patients with high morbidity and mortality. Mitochondria, as crucial organelles for maintaining cellular homeostasis, play a pivotal role in IRI-AKI pathogenesis. Currently, no effective and definitive therapeutic targets have been established for IRI-AKI treatment. Previous sequencing data analysis revealed significant upregulation of Arfgef3 following renal ischemia-reperfusion injury, suggesting its potential as a therapeutic target. This study demonstrates that Arfgef3 expression is markedly elevated after ischemia reperfusion injury. Furthermore, Arfgef3 knockout (KO) significantly ameliorated renal injury induced by ischemia-reperfusion in mice. In addition, Arfgef3 knockout effectively attenuates renal inflammation (IL6, MCP1, TNF-α), oxidative stress and apoptosis levels. In addition, Arfgef3 knockout substantially improves ischemia reperfusion-induced mitochondrial abnormalities including mitochondrial biogenesis markers and ATP production capacity. In conclusion, Arfgef3 participates in IRI-AKI pathogenesis by regulating mitochondrial function. Arfgef3 knockout confers renal protection through improving mitochondrial dysfunction, thereby reducing inflammatory response, oxidative stress and apoptosis. These findings provide novel insights into IRI-AKI mechanisms and highlight Arfgef3 as a potential therapeutic target.

There was an increasing uptake of hemodialysis and patient life expectancy due to improved treatment efficiency. However, the quality of life (QOL) of chronic kidney disease (CKD) patients is not parallelly improved, leading to a shift in focus towards promoting the QOL. Among the common complications of CKD such as anaemia and mineral bone disorder, uremic syndrome has been found as the main contributor to poor QOL. We present the case of an 80-year-old man with hemodialysis, who presented with poor appetite and weakness following recovering from COVID-19. Biochemical, echocardiographic, body composition, psychological, nutritional, and QOL assessments suggested multi-organ dysfunction attributable to uremic syndrome. Renal rehabilitation involving the combination of clinic- and home-based exercise and nutritional interventions effectively improved his symptoms while elevating spKt/V. Our case report not only demonstrated exercise and nutritional rehabilitation as an effective approach to managing uremic syndrome in hemodialysis patients, but also provided insight into the effects of improved nutritional status on spKt/V.

Acute kidney injury (AKI), associated with a major health burden globally, is frequently caused by nephrotoxic agents, specifically cisplatin. Prohibitin (PHB) 2, a highly conserved mitochondrial protein localized at the inner mitochondrial membrane, is key to maintaining mitochondrial respiration, cristae morphogenesis, and regulating cell death. Despite being extensively assessed in chronic kidney disease models, the role of PHB2 in AKI, particularly cisplatin-induced AKI, warrants further exploration. Here, we investigated the protective effects of PHB2 in cisplatin-induced AKI in in vitro and in vivo models. The results demonstrated that cisplatin upregulated PHB2 expression both in vitro and in vivo. Mechanistically, PHB2 deficiency exacerbated cisplatin-induced cell apoptosis and mitochondrial dysfunction, indicated by increased caspase-3 activity and reactive oxygen species (ROS) production, as well as mitochondrial membrane potential loss, in vitro. Our Western blot analysis results further validated PHB2’s involvement in autophagy processes within renal tubular cells. Nevertheless, PHB2 overexpression mitigated these detrimental effects, suggesting the protective role of PHB2 in cisplatin-induced AKI. In vivo, adeno-associated virus–mediated PHB2 overexpression reduced cisplatin-induced renal tubular injury and enhanced mitochondrial ultrastructure, supporting its potential therapeutic benefits. Taken together, our findings underscore the protective role of PHB2 in cisplatin-induced AKI, highlighting its potential as a therapeutic target for mitigating renal injury. Future studies elucidating the mechanisms underlying the protective effects of PHB2 and exploring its clinical implications in AKI management are warranted.

Background The purpose of this study was to explore the separate and combined associations of obstructive sleep apnea (OSA) risk and sleep duration with ideal cardiovascular health metrics in hemodialysis (HD) patients. Methods 470 HD participants (average: 59.48 ± 12.89 y, 281 men) were included in this study. Sleep duration was measured as self-reported average sleep time during the previous month. The OSA risk was assessed using the STOP-BANG questionnaire. Participants were divided into three groups based on the number of ideal cardiovascular health (CVH) metrics: 0–2,3–4, and 5–7. Ordinal logistic regression was conducted to model the associations of CVH metrics with sleep duration, OSA risk, and their combined effects by adjusting for specific covariates. Results After adjusting for covariates, short sleep duration (< 7 h) (OR = 0.53; 95% CI [ 0.30, 0.92]) and OSA risk (OR = 0.58; 95% CI [0.32, 0.83]) were negatively associated with better CVH (ideal vs. intermediate; intermediate vs. poor), respectively. For HD patients with both short sleep duration and OSA risk, the odds of ideal CVH metrics were reduced by 72% (odds ratio 0.28 [95% CI 0.13, 0.60]). Conclusions Short sleep duration and OSA risk are separately and jointly associated with poor CVH in hemodialysis patients. Suitable interventions for sleep may minimize the risk of developing cardiovascular disease.

Introduction: Depression is a common psychiatric problem in maintenance hemodialysis (MHD) patients. Recent studies have begun to explore the relationship between body composition and depression. Phase angle (PhA), a core parameter for assessing body composition, has been observed to be associated with frailty and cognitive dysfunction. The aim of this study was to investigate the association between PhA and depression in MHD patients. Methods: This multicenter, cross-sectional study included 843 MHD patients from seven dialysis centers in Shanghai, China. Depressive symptoms were evaluated using the Patient Health Questionnaire (PHQ-9), with a score of >= 10 indicating depression. PhA was measured by bioelectrical impedance analysis. Nutritional status was assessed by malnutrition inflammation score (MIS). Multivariable logistic regression models were used to investigate the association between PhA and depression. Restricted cubic spline (RCS) analysis was utilized to examine the association. Receiver operating characteristic curve was used to identify the cut-off value of PhA for depression. Results: A total of 15.2% of patients (62.8% male, median age 66 years) had depression. Median PhA level (interquartile range) of depressed patients was 4.4 degrees (3.9-4.9 degrees) for males and 3.9 degrees (3.2-4.7 degrees) for females. There was a significant decrease in the prevalence of depression with increasing quartiles of PhA levels. In multivariable logistic regression analyses, after adjusting for age, sex, education level, spKt/V, dialysis vintage, Charlson comorbidity index, hemoglobin, and serum albumin, lower PhA levels (lowest quartile group) were significantly associated with depressive symptoms (adjusted odds ratio, 2.19; 95% confidence interval, 1.07 to 4.48), compared to higher PhA levels (highest quartile group). RCS analysis showed a relatively inverse linear association between PhA and depression. The optimal cut-off value of PhA for depression was 4.9 degrees for males and 3.5 degrees for females. Subgroup analyses validated the findings across patient characteristics, including age, sex, diabetes, education, and malnutrition. Conclusion: Our findings indicated an inverse association between PhA and depressive symptoms in Chinese MHD patients, suggesting that PhA could serve as a valuable indicator for assessing the risk of depression in this population. Further studies are needed to explore the potential of PhA as a prognostic tool and its implications for intervention strategies.

OBJECTIVE:To determine the prevalence of cognitive impairment (CI) among middle-aged to older patients receiving maintenance haemodialysis (MHD) and to investigate the potential association between CI and physical performance. METHODS:This cross-sectional observational study enrolled participants aged 55-85 years who received MHD. Cognitive status was assessed using the Mini Mental State Examination (MMSE). Physical performance was measured by hand grip strength, the Timed Up and Go Test (TUGT) and the 4-m walking speed. Sociodemographic, clinical and laboratory parameters were recorded for each patient. RESULTS:The study included 592 patients (363 males); and of these, 126 (21.3%) were diagnosed with CI. Compared with patients with normal cognitive function, those with CI were significantly older and had significantly longer dialysis duration, lower educational level, higher Malnutrition Inflammation Score, higher depression and higher Charlson Comorbidity Index score. After adjustment for covariates, multiple regression analysis suggested that grip strength (odds ratio [OR] = 0.959, 95% confidence interval [CI] = 0.924, 0.996) and 4-m walking speed (OR = 0.161, 95% CI = 0.070, 0.368) were protective factors. TUGT (OR = 1.037, 95%CI = 1.003, 1.071) was a risk factor. CONCLUSION:Physical performance was correlated with CI and might be a significant indicator for the early identification of CI in middle-aged to older MHD patients.

Ischemia/reperfusion (I/R) injury has been demonstrated to exert a significant role in acute myocardial infarction (AMI), which constitutes a crucial cause of AMI. Ferroptosis represents a novel form of cell death that is intimately linked to myocardial ischemia-reperfusion (MIR) injury. Urolithin A (UA), an intestinal metabolite of ellagitannins, has not been fully elucidated for its role in MIR injury. In the present study, we analyzed the effects of UA on ischemia-reperfusion-induced oxidative stress and ferroptosis both in vitro and in vivo, and explored the potential mechanisms of UA action. The results indicated that UA was capable of protecting the heart from ischemia-reperfusion injury and enhancing cardiac function both in vitro and in vivo. In addition, UA also attenuated oxidative stress, mitochondrial damage, and ferroptosis during MIR. Mechanistically, UA not only augmented the Nrf2 expression but also promoted Nrf2 entry into the nucleus and activated the downstream antioxidant defense system. Moreover, after the inhibition of Nrf2, the myocardial protective function of UA was lost, and its function of attenuating oxidative stress and ferroptosis was suppressed. In conclusion, we found that UA protected the heart from ischemia-reperfusion injury by attenuating oxidative stress and ferroptosis through the Nrf2 signaling pathway, suggesting that UA might be a potential therapeutic agent for the treatment of AMI.

Abstract Physical performance in hemodialysis patients declines and serves as a cardiovascular disease (CVD) incidence and mortality predictor. However, lower extremity function's role remains unclear. This study aimed to quantify the association between lower extremity function and CVD risk in hemodialysis patients. This was a multicenter cross‐sectional study enrolling 868 participants (532 males, 336 females) from seven hemodialysis centers in Shanghai, China. Patients were divided into three groups per lower extremity function, evaluated by short physical performance battery (SPPB) scores: 0–6, 7–9, and 10–12. Upper extremity function was quantified through grip strength assessment. CVD risk was assessed using the Framingham Risk Score. Approximately 35% of hemodialysis patients had impaired lower extremity function (SPPB score < 10). Participants with high SPPB scores had stronger handgrip and lower Framingham CVD risk scores than those with low and moderate SPPB scores (p < 0.05). After adjusting clinical confounders, SPPB was independently associated with CVD risk, as a categorized variable (odds ratio: 0.577, 95% confidence interval [CI]: 0.388–0.857, p = 0.006) and as a continuous variable (odds ratio: 0.858, 95% CI: 0.772–0.953, p = 0.004). An SPPB score < 10 predicted an increased CVD risk (area under curve: 0.649, 95% CI: 0.599–0.699, p < 0.001). Causality between physical performance and CVD risk was not considered. Some upper limb results may not be generalizable to peritoneal dialysis and kidney transplant patients. Lower extremity function was significantly associated with CVD risk in hemodialysis patients. Further studies are needed to explore the long‐term relationship between lower extremity function and CVD risk.

BackgroundProtein energy wasting (PEW) is common in patients on hemodialysis, and its development may involve gut microbial dysbiosis. However, the exact relationship between the composition of different flora and the development of PEW remains unclear.MethodsThis is an observational longitudinal study on 115 patients undergoing hemodialysis who were followed up for 1 year. All the patients were evaluated at baseline, and different microbiota compositions were determined. After a 1 year follow-up period, the correlations between clinical parameter variations and the relative abundance of different gut flora were assessed using Spearman correlation. Moreover, the associations of the abundance of different gut microbiota with decrease in lean tissue mass and the development of PEW were analyzed using ROC curve and logistical regression analyses.ResultsWe found that the relative abundances of Actinobacteria and Bifidobacteriaceae were significantly lower in patients with PEW than in those who did not develop PEW (p < 0.05). The abundance of Actinobacteria and Bifidobacteriaceae correlated positively with variations in serum albumin levels (r = 0.213, p = 0.035 and r = 0.214, p = 0.034, respectively), lean tissue mass (r = 0.296, p = 0.007 and r = 0.238, p = 0.002, respectively), and lean tissue index (r = 0.377, p < 0.001 and r = 0.419, p < 0.001, respectively). The area under the ROC curve or AUC values of Actinobacteria and Bifidobacteriaceae for the prediction of lean tissue mass decrease ranged from 0.676 to 0.708 (p < 0.05). Thus, decrease in the abundance of Actinobacteria and Bifidobacteriaceae may be associated with decrease in lean tissue mass and the occurrence of PEW.ConclusionThe present findings imply Actinobacteria and Bifidobacteriaceae may be potential markers for predicting skeletal muscle mass decrease and PEW development in patients on hemodialysis.