Chronic kidney disease (CKD) is closely associated with gut microbiota dysbiosis and impaired intestinal barrier function, yet effective therapeutic strategies targeting the gut-kidney axis remain limited. This study aimed to develop a thiolated chitosan/sodium alginate-based nanoparticle system encapsulating emodin (TCS/ALG/Emodin-NPs), and to evaluate its therapeutic efficacy in CKD through modulation of gut microbiota and intestinal barrier protection. The nanoparticles were synthesized, characterized, and orally administered to CKD mice at varying doses, with irbesartan as a positive control. Our results showed that TCS/ALG/Emodin-NPs significantly improved renal function, reduced renal fibrosis, and restored gut microbiota balance, particularly increasing beneficial bacteria such as Lactobacillus. They also enhanced intestinal tight junction integrity and suppressed systemic inflammation. In a hydrogen peroxide-induced Caco-2 cell model, Emodin-NPs more effectively attenuated oxidative stress and apoptosis compared to free Emodin. The findings suggest that TCS/ALG/Emodin-NPs are a promising strategy for CKD treatment by reshaping gut microbiota and enhancing intestinal function.IMPORTANCEWhile the gut-kidney axis has emerged as a critical target in chronic kidney disease (CKD) management, therapeutic strategies leveraging this pathway remain limited. This study demonstrates that colon-targeted TCS/ALG/Emodin-NPs not only enhance drug bioavailability but also exert dual therapeutic effects by rectifying gut dysbiosis and reinforcing intestinal barrier function-key mechanisms implicated in CKD progression. The superior efficacy of TCS/ALG/Emodin-NPs over free Emodin underscores the transformative potential of nanoparticle delivery systems in overcoming the pharmacokinetic limitations of herbal medicines. This research opens new avenues for the development of microbiota-targeted, anti-inflammatory therapies that can complement existing CKD treatments and potentially slow disease progression in affected patients.

To compare survival differences between hemodialysis (HD) and peritoneal dialysis (PD) in elderly patients (≥ 60 years old) with end-stage renal disease (ESRD), and to analyze the impact of key comorbidities (heart failure, cerebrovascular disease, diabetes) on prognosis and causes of death, to inform dialysis modality selection. This single-center retrospective cohort study enrolled 377 elderly ESRD patients (216 HD, 161 PD) who initiated dialysis between 2012 and 2017, with follow-up until 2024. Survival rates were compared using the Kaplan-Meier method. The Cox proportional hazards model was used to analyze risk factors for all-cause mortality, and the competing risks model was employed to assess risks for specific causes of death. Subgroup analyses were performed for patients with heart failure, cerebrovascular disease, and diabetes. In the overall population, the HD group had a significantly lower risk of all-cause mortality than the PD group (adjusted HR = 0.599, 95

Background:Self-management (SMP) is a novel treatment comprised of multidimensional interventions. Researchers have reported its reliable effects on short-term improvements in surrogate indicators like 24-h urinary protein excretion and systolic blood pressure. However, whether it has any effect on long-term changes in other surrogate indicators and chronic kidney disease (CKD) endpoints remains unclear. Methods:Patients with CKD stages 3-4 were grouped into either a SMP group or a nonself-management (non-SMP) group whether they had complied any of five characterized elements: regular visits, medication adjustment, nutritional intervention, lifestyle modification, education, and behavior guide. We used 1:1 nearest-neighbor propensity score matching (PSM) to balance between-group differences. Cox regression was used to explore the long-term association between SMP and composite outcomes (all-cause mortality, end-stage kidney disease (ESKD), ≥ 50% decline in estimated glomerular filtration rate (eGFR), or doubling of serum creatinine (SCr) from baseline). Linear mixed-effects (LME) model and marginal means comparisons were used to surrogate indicators analysis. Results:The study included 1160 patients with a median follow-up of 27.20 months. Among them, 580 individuals were in the SMP group and 580 were in the non-SMP group. In the non-SMP group, the median follow-up was 24.48 (12.21, 43.39) months with 174 (30.00%) events, whereas the SMP group had a median follow-up of 29.34 (14.75, 42.00) months with 134 (23.10%) composite outcomes. Participation in a SMP program was associated with a 30.9% reduction in CKD progression risk (hazard ratio (HR) of composite outcome: 0.691, 95% CI: 0.549-0.869, and p = 0.002). LME and marginal means comparison indicated that patients with SMP had higher mean difference of eGFR and serum albumin (Alb) than the non-SMP individuals (mean difference of eGFR: 1.791 (0.721, 2.861) mL/min/1.73 m2, p = 0.001; marginal mean difference of eGFR: 2.560 (1.660, 3.470) mL/min/1.73 m2, p < 0.0001; mean difference of Alb: 0.654 (0.202, 1.105) g/L, p = 0.005; and marginal mean difference of Alb: 0.460 (0.166, 0.753) g/L, p = 0.002). Conclusion:SMP programs are associated with a 30.9% reduction in CKD progression risk and improvements in kidney function and nutrition-related surrogate markers, benefiting CKD patients in stages 3-4.

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is characterized by progressive renal fibrosis, yet the key tubular regulatory factors driving this maladaptive repair remain inadequately defined. In this study, we investigated the role of phosphoenolpyruvate carboxykinase 1 (PCK1), the rate-limiting enzyme of gluconeogenesis, in the AKI-to-CKD transition. Analysis of human single-cell RNA sequencing (scRNA-seq) datasets revealed a profound downregulation of PCK1 in injured proximal tubule cells, which correlated with the upregulation of pro-fibrotic markers. In rodent models, we demonstrated that the loss of PCK1 precedes significant collagen deposition and acts as a primary driver of fibrogenesis. Mechanistically, PCK1 deficiency enhanced TGF-β1-induced Smad3 phosphorylation and nuclear translocation, whereas PCK1 overexpression suppressed Smad3 activation as well as the expression of fibrosis-related genes and proteins. Our functional assays supported that PCK1 serves as an endogenous negative regulator and antagonist of Smad3, its depletion releases the restraint on Smad3 phosphorylation and nuclear translocation, leading to the loss of tubular epithelial identity. Significantly, the pharmacological or genetic restoration of PCK1 effectively blunted Smad3 activation and attenuated renal fibrosis in vitro. These findings identify PCK1 as a critical metabolic regulator that maintains tubular homeostasis and suggest that PCK1-targeted modulation of Smad3 signaling may be a promising therapeutic strategy for arresting the progression of chronic kidney disease following acute injury.

Diabetic wounds remain a major health concern due to impaired healing from persistent inflammation, oxidative stress, and compromised neurovascular regeneration. Conventional therapies are often insufficient to modulate the multifaceted pathological microenvironment of diabetic wound, underscoring the urgent need for multifunctional therapeutic strategies. In this study, we developed a polysaccharide-based hydrogel microneedle (MN) system, co-delivering tetramethylpyrazine (TMP) and safflower polysaccharide (SPS) to promote diabetic wound healing through reactive oxygen species (ROS)-responsive release and neurovascular regeneration. SPS was incorporated into a methacrylated dextran (DexMA)-based hydrogel matrix. Meanwhile, the hydrophobic TMP was encapsulated into ROS-responsive micelles formed by amphiphilic poly(propylene sulfide)-hyaluronic acid (PPS-HA), which served as both a redox-sensitive carrier and a hydrophilic polysaccharide component. The resulting D/SPS/T@P-H MN patch demonstrated strong mechanical integrity, dermal penetration capability, and sustained release behavior. In vitro studies showed robust antioxidant, anti-inflammatory, pro-angiogenic, and neuroregenerative activities. In vivo, the MN patch significantly accelerated wound closure in diabetic rat. Transcriptomic analysis further revealed the activation of key genes and signaling pathways involved in immune modulation and neurovascular repair. In summary, this work develops a multifunctional ROS-responsive hydrogel microneedle system that enables ROS-responsive drug delivery and synergistic tissue regeneration, offering a comprehensive materials-based solution for diabetic wound healing.

BackgroundInsulin resistance and dysregulated glucose-lipid metabolism contribute to adverse outcomes in heart failure (HF), yet existing metabolic indicators have limited utility for rapid risk stratification in critically ill patients. The cholesterol, high-density lipoprotein, and glucose (CHG) index may provide a convenient metabolic risk marker in hospitalized HF patients.MethodsThis study adopted a dual-cohort retrospective design. The training cohort included 1,391 patients from the MIMIC-IV database (2008–2019), and the external validation cohort included 296 patients from an independent hospital-based cohort (July 2023 to December 2025). Patients were stratified into quartiles by CHG index. Kaplan–Meier survival analysis, Cox proportional hazards regression models, and restricted cubic spline (RCS) analysis were performed to assess the relationship between CHG index and in-hospital mortality.ResultsIn the training cohort, in-hospital mortality increased from 8.91% in Q1 to 17.87% in Q4 (log-rank test p = 0.0141). In the fully adjusted model, each 1-unit increase in CHG index was associated with a 76.8% increase in in-hospital mortality risk (HR = 1.768, 95% CI 1.337–2.338; p < 0.001). RCS analysis indicated an approximately linear positive association (P for overall < 0.001, P for nonlinearity = 0.139). The external validation cohort showed a similar association, with mortality increasing from 4.05% in Q1 to 16.22% in Q4 and a fully adjusted HR of 2.716 (95% CI 1.483–4.962, p = 0.001).ConclusionThe CHG index was independently associated with in-hospital mortality in patients with HF, with consistent findings in an external cohort. As an integrative biomarker derived from routine laboratory tests, the CHG index may reflect the interplay between metabolic dysregulation and cardiovascular vulnerability, thereby assisting early risk stratification in hospitalized patients with heart failure.

ObjectivesThis study aimed to investigate the efficacy of arteriovenous fistula (AVF) exercise training combined with video-assisted patient education on AVF maturation in adults undergoing maintenance hemodialysis (MHD).MethodsA prospective non-randomized controlled trial was conducted at Guangdong Provincial Hospital of Chinese Medicine from September 2023 to November 2024. A total of 88 eligible patients with newly created forearm AVFs were recruited and divided into an intervention group (n = 43) and a control group (n = 45) according to their willingness to perform novel or traditional exercise training. The control group received standard postoperative care, while the intervention group underwent a structured 8-week program that combined supervised AVF exercise training guided by Chinese Medicine theory with video-assisted feedback education. Primary outcomes included AVF maturation rate, time to maturation, and ultrasonographic parameters (brachial artery blood flow, arterial/venous inner diameter, AVF depth). Secondary outcomes included AVF-related complication rates.ResultsAt 8 weeks, the intervention group demonstrated significantly higher brachial artery flow (P < 0.001), larger brachial artery inner diameter (P < 0.001), and venous diameter (P < 0.001), alongside reduced fistula depth (P < 0.001). The intervention group also demonstrated higher maturation rates (P = 0.030) and shorter median maturation time (P = 0.040) compared to the control group. No significant differences in complication rates were observed.ConclusionAn optimized exercise training program, combined with video-assisted education, enhances fistula maturation parameters and accelerates functional readiness for hemodialysis, suggesting its potential as a complementary strategy to standard AVF care in MHD populations.Clinical trial registrationhttps://www.chictr.org.cn/index.html, identifier ChiCTR2400080010.

BackgroundEarly risk stratification for in-hospital mortality remains challenging in intensive care unit (ICU) patients with heart failure (HF) because of substantial clinical heterogeneity and complex pathophysiological interactions. Explainable machine learning (ML) may offer a practical and transparent approach to prognostic assessment in this high-risk population.MethodsThis retrospective dual-cohort study included 18,526 ICU patients with HF from the MIMIC-IV database (2008–2022) as the development cohort and 314 consecutive ICU patients with HF from an independent hospital-based cohort from August 1, 2023, to May 31, 2026, as the external validation cohort. Candidate predictors available within 24 h of ICU admission were screened using the Boruta algorithm and least absolute shrinkage and selection operator regression. Five ML algorithms were developed in the development cohort and compared using 5-fold nested cross-validation for internal validation. Model interpretability was assessed using Shapley Additive Explanations (SHAP).ResultsNine routinely available predictors were retained for final model development. Among the candidate algorithms, Extreme Gradient Boosting (XGBoost) showed the most balanced overall performance and was selected as the final model. In internal validation using nested cross-validation, the XGBoost model achieved the highest validation area under the receiver operating characteristic curve (AUC), at 0.704 (95% CI 0.682–0.726). In the external validation cohort, the final model achieved an AUC of 0.877 (95% CI 0.820–0.933) and a Brier score of 0.079 (95% CI 0.061–0.099). However, this apparently stronger discrimination should be interpreted cautiously in light of cohort differences and the limited number of external events. SHAP analysis identified blood urea nitrogen, age, and white blood cell count as the most influential predictors.ConclusionAn explainable XGBoost-based model using nine routinely available early clinical variables showed promising performance for predicting in-hospital all-cause mortality in ICU patients with HF. This interpretable tool may support early risk stratification and individualized clinical management in critically ill patients with HF. Further large multicenter external validation is warranted.

Background:Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, and current pharmacotherapies provide limited renal protection. Qitu Qushi Formula (QTQSF), a traditional Chinese medicine prescription, has shown therapeutic potential in DKD, but its underlying mechanisms remain unclear. This study aimed to elucidate whether QTQSF alleviates DKD via gut microbiota-mediated pathways. Methods:Clinical, animal, and cellular studies were integrated to investigate the therapeutic effects of QTQSF. Clinical samples from 30 patients with type 2 DKD received QTQSF treatment for 6 months was used to assess renal function and gut microbiota. To explore microbiota-mediated mechanisms, db/db mice, pseudo-germ-free models, and fecal microbiota transplantation (FMT) were utilized. Multi-omics analyses, including 16S rRNA sequencing, untargeted and targeted metabolomics, and transcriptomics, were conducted to uncover key pathways underlying QTQSF's efficacy. Results:QTQSF significantly improved renal function and remodeled gut microbial composition in DKD patients. In db/db mice, QTQSF reduced albuminuria, fibrosis, and apoptosis, whereas these protective effects were attenuated after gut microbiota depletion. FMT supported that gut microbiota mediated the renoprotective effects of QTQSF. Integrated multi-omics analyses revealed that QTQSF enhanced microbial tryptophan metabolism and increased the gut microbiota-derived metabolite indole-3-propionic acid (IPA). Elevated IPA levels were associated with regulation of the renal Sirt1/FoxO1 pathway, which was further validated in podocytes as a key mechanism underlying the anti-apoptotic effects. Conclusion:QTQSF may ameliorate DKD by enhancing gut microbiota-derived IPA production and regulating the Sirt1/FoxO1 signaling pathway, thereby attenuating renal injury. These findings provide mechanistic insight into the renoprotective effects of QTQSF and highlight a gut microbiota-metabolite-host signaling axis in DKD.

AIM:To provide an early-stage integrative synthesis of shared and scenario-specific ethical risks of Conversational Artificial Intelligence in nursing triage and patient education, and to synthesize governance directions and limitations discussed in the current literature. DESIGN:A systematic integrative review following the Whittemore-Knafl framework and PRISMA guidelines. METHODS:Eight databases were searched. Two researchers independently conducted screening, data extraction, and thematic coding, followed by inductive synthesis. Quality appraisal used design-appropriate tools according to article type. Ethical risks were analysed within and across scenarios. Registered in PROSPERO (CRD420251079144). RESULTS:Nine articles were included (four on nursing triage; five on patient education), comprising two empirical studies, four reviews, two randomized controlled trial protocols, and one debate paper. Both scenarios shared six common ethical challenges: data privacy and security, over-reliance and deskilling, training-data bias and stigma reproduction, lack of empathy and emotional interaction capability, algorithmic black box and insufficient interpretability, and blurred accountability and regulatory gaps. Nursing triage presented additional risks including assessment inaccuracy, contextual misunderstanding, lack of personalization, superficially plausible misguidance and insufficient clinician trust. Patient education revealed four distinct issues: misleading information, digital accessibility gaps, cross-cultural and multilingual adaptation, and fairness and health inequality. Six shared governance directions were synthesized-human oversight and manual review, improvement of legal policies and industry standards, enhanced transparency and interpretability, continuous algorithm optimization and scientific validation, the human-machine balance principle, and capacity building for healthcare professionals. The literature also suggested scenario-specific reinforcements for triage and education. CONCLUSION:Ethical risks of Conversational Artificial Intelligence in nursing show both common and scenario-dependent patterns. Given the limited and heterogeneous evidence base, the identified governance directions should be viewed as preliminary pathways requiring further validation. IMPACT:This review offers evidence-informed ethical insights and scenario-based governance references to support safe, equitable and human-centred application of Conversational Artificial Intelligence in nursing practice. PATIENT OR PUBLIC CONTRIBUTION:Not applicable.

Background:Sarcopenic obesity (SO) combines reduced muscle mass and increased fat, elevating health risks in older adults. The triglyceride-glucose (TyG) index, a marker of insulin resistance, is associated with metabolic dysfunction. However, its role in predicting mortality in SO remains unclear. This study investigates the TyG index as a potential predictor of all-cause mortality in older adults with SO. Methods:This study examined SO trends using data from 30,137 adults with dual-energy X-ray absorptiometry (DXA) and body fat measurements (1999-2018). For mortality analysis, 706 participants from NHANES 1999-2004 were included. Sarcopenia was defined according to the 2014 FNIH criteria. Statistical analyses, including Cox regression, cubic splines, and subgroup analyses, were employed to investigate the association between the TyG index and all-cause mortality in SO, as well as mortality variations among NHANES participants. Results:Older age groups exhibit higher SO prevalence rates, with a notable upward trend in the >70 years group, while younger groups maintain lower rates. Trend analysis indicates no significant change from 1999 to 2006 but suggests a moderate, near-significant increase from 2011 to 2018. There was a U-shaped association between the TyG index and all-cause mortality. After full adjustment, adults in TyG group 1 (less than 3.25) had a 78.1 % higher risk (hazard ratio, 1.781; 95 % CI, 1.406-2.256; p < 0.001), and those in TyG group 5 (6.66 or greater) had a 74.5 % higher risk (hazard ratio, 1.745; 95 % CI, 1.211-2.516; p = 0.003) compared to the reference group (TyG group 3, 4.25 to 5.25). Subgroup analysis by age revealed that, among participants aged 70 and older, the group with the lowest mortality risk transitioned from Group 3 to Group 2. Furthermore, the analysis of varying mortality reveals that Group 5 (HR: 3.088; 95 % CI: 1.462-6.520; p = 0.003) is significantly associated with an increased risk of cardiovascular disease (CVD) mortality compared to Group 3. Similarly, TyG Group 1 demonstrates a significantly higher risk of mortality from other causes (HR: 2.253; 95 % CI: 1.207-4.206; p = 0.011) relative to Group 3. No significant associations are observed for malignant neoplasms, respiratory diseases, or cerebrovascular/Alzheimer's diseases. Conclusion:This national cohort study identified a U-shaped association between the TyG index and all-cause mortality among SO patients, with increased risks observed at both low and high TyG levels. Age-specific analyses further reveal variations in this relationship, underscoring the importance of tailored strategies to enhance metabolic health and reduce mortality risks.

Cardiovascular disease and infections significantly contribute to high mortality and morbidity in patients with chronic kidney disease (CKD). Despite extensive research on cardiovascular complications, infection-related aspects in CKD have received limited attention. This review systematically synthesizes current evidence on the causes and consequences of infections in CKD patients. We focus on immunodeficiency as a primary factor in increased infection susceptibility and examine the clinical outcomes associated with infections in this population. Regarding causes, CKD patients exhibit heightened vulnerability to infections for secondary immunodeficiency related to kidney disease (SIDKD). Regarding its consequences, we review studies on the association between reduced kidney function and adverse outcomes, including hospitalizations, acute kidney injury, cardiovascular events, progression to end-stage kidney disease, infections caused by multidrug-resistant organisms. Infections in CKD patients are associated with increased mortality across different infection types. Infection-related complications are a critical concern in CKD management. We recommend further research to develop effective preventive strategies, including potential interventions involving Chinese medicine, to reduce infection risks in this high-risk population.

The rapid decline of kidney function in middle-aged and elderly people has become an increasingly serious public health problem. Machine learning (ML) technology has substantial potential to disease prediction. The present study use dataset from the Chinese Health and Retirement Longitudinal Study (CHARLS) and utilizes advanced Gradient Boosting algorithms to develop predictive models. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify the key predictors, and multivariate logistic regression was utilized to validate the independent predictive power of the variables. Furthermore, the study integrated SHapley Additive exPlanations (SHAP) to boost the interpretability of the model. The findings show that the Gradient Boosting Model demonstrated robust performance across both the training and test datasets. Specifically, it attained AUC values of 0.8 and 0.765 in the training and test sets, respectively, while achieving accuracy scores of 0.736 and 0.728 in these two datasets. LASSO regression identified key influencing factors, including estimated glomerular filtration rate (eGFR), age, hemoglobin (Hb), glucose, and systolic blood pressure (SBP). Multivariate linear regression further confirmed the independent associations between these variables and rapid kidney function deterioration (P < 0.05). This study developed a risk assessment model for rapid kidney function deterioration that is applicable to middle-aged and elderly populations in China.

BACKGROUND:Bupi Yishen formula (BYF) is a traditional Chinese herbal mixture with proven efficacy in attenuating kidney function deterioration among patients with advanced chronic kidney disease (CKD), and improving renal fibrosis of CKD animal models. Previous studies have shown that BYF rehabilitates metabolic dysregulation under CKD condition, but its exact mechanism remains unclear. PURPOSE:This study aimed to elucidate the therapeutic effect and its potential mechanism on regulating renal energy metabolism in CKD. METHODS:An adenine-induced CKD rat model was treated with two doses of BYF decoction (15 g/kg/day or 30 g/kg/day) and losartan (as the positive control) for 4 weeks. Lipidomic and transcriptomic analyses of kidney samples from CKD rats revealed the BYF-reversed different lipid species and gene expression profiles respectively, thereby identifying potential pharmacological mechanisms. Further in vivo and in vitro experiments, network analyses, and molecular docking was used to confirm the proposed mechanisms affected by BYF. RESULTS:BYF had a profound impact on alleviating renal impairment and profibrotic phenotypes in CKD rats. Lipid profiling of kidneys from CKD rats showed that the dysmetabolism of glycerophospholipids, sphingolipids, and glycerolipids was primarily influenced by BYF. Transcriptome analysis of CKD rats identified renal energy metabolism (including fatty acid oxidation [FAO], glucose metabolism) and mitochondrial oxidative phosphorylation (OXPHOS) as the key dysregulated pathways, which were reversed by BYF. Further experiments confirmed that BYF partially restored defective FAO, dysregulated glucose metabolism, and impaired mitochondrial OXPHOS in the kidneys of CKD rats and TGFβ1-induced human tubule HK-2 cells. Besides, network analyses combined with molecular docking demonstrated a strong binding effect of BYF's core compounds on key targets related to energy metabolism. CONCLUSIONS:These results suggest that BYF protects against CKD by restoring renal energy homeostasis and mitochondrial OXPHOS, offering potential as an alternative therapy for renal fibrosis inherent to CKD.

ETHNOPHARMACOLOGICAL RELEVANCE:Berberine (BBR), a compound widely used in traditional Chinese medicine, has been recognized for its therapeutic effects on chronic kidney disease (CKD), primarily by modulating the gut microbiota. However, further research is needed to fully understand the mechanisms underlying its beneficial effects. AIM OF THE STUDY:This study aims to explore the renoprotective effects of BBR through the modulation of gut microbiota and regulation of short-chain fatty acids (SCFAs). METHODS:In Part I, a CKD mouse model was established using a diet containing 0.2 % adenine for six weeks. Mice were divided into four groups: Normal, Adenine-induced (Ade), and BBR-treated (BBR-L and BBR-H). Renal function was assessed by serum creatinine (SCR) and blood urea nitrogen (BUN). Histological damage was analyzed using staining techniques, and intestinal barrier function was evaluated by measuring Mucin 2 (MUC-2) expression and serum Diamine Oxidase (DAO) and D-lactic acid (D-LA). Gut microbiota composition was analyzed via 16S rRNA sequencing, while SCFA levels were quantified by UHPLC-MRM-MS. Then, the expression of G Protein-Coupled Receptors (GPRs) related to SCFAs in kidney were detected. In Part II, gut microbiota depletion using antibiotics was conducted to examine whether the effects of BBR on kidney injury and intestinal barrier depend on gut microbiota modulation. RESULTS:BBR supplementation significantly reduced SCR and BUN levels in adenine-induced mice (Ade), indicating improved renal function. Histological analysis showed reduced renal tubular and colon tissue damage after BBR treatment. BBR also improved intestinal barrier function by enhancing MUC-2 expression and lowering serum DAO and D-lactic acid levels. 16S rRNA sequencing revealed that BBR increased the abundance of Akkermansia muciniphila. After BBR supplementation, the serum levels of acetate, propionate, and butyrate were elevated in the Ade mice. Additionally, renal GPRs analysis revealed that BBR treatment significantly boosted the expression of GPR41, GPR43, and GPR109a in Ade mice. However, after gut microbiota depletion, BBR lost its therapeutic effects on kidney injury and intestinal barrier function, indicating that its benefits depend on gut microbiota modulation. CONCLUSION:BBR can alleviate CKD progression by modulating gut microbiota, particularly by increasing Akkermansia muciniphila, enhancing SCFA production, improving intestinal barrier function, and activating kidney GPRs. This study highlights the potential of BBR as a prebiotic for CKD treatment and prevention.

BACKGROUND:Abdominal aortic calcification (AAC) is prevalent in chronic kidney disease (CKD) patients and linked to elevated cardiovascular disease (CVD) risk. Obesity, linked to both CKD and CVD, can be better assessed by A Body Shape Index (ABSI), a novel index measuring central obesity and fat distribution. We posit that ABSI may correlate with AAC risk in CKD patients. This research explores the association using 2013-2014 National Health and Nutrition Examination Survey (NHANES) data. MATERIALS AND METHODS:From the 2013-2014 NHANES dataset, we excluded participants lacking data on AAC or ABSI A total of 961 CKD subjects remained. Before analyzing ABSI as a continuous variable, we standardized it, denoting the result as ABSIa. We then plotted restricted cubic splines (RCS). Follow-up univariate and multivariate regression, subgroup, and interaction analyses were conducted to explore the ABSIa-AAC relationship. RESULTS:The analysis revealed a significant positive relationship between ABSIa and AAC in CKD patients (OR = 1.41, 95% CI: 1.23-1.61, p < 0.001). Even after adjustment for multiple confounders, ABSIa remained independently associated with AAC (OR = 1.38, 95%CI: 1.17-1.64, p < 0.001). Subgroup analyses further validated this association across various patient subgroups. CONCLUSIONS:In patients with CKD, this cross-sectional study identified a significant positive association between ABSI and AAC, persisting after adjusting for confounders. This suggests ABSI may be a biomarker for AAC risk assessment and CVD risk stratification in CKD patients.

Background:Early intervention and management of anemia, particularly the commonly used measures of hemoglobin (Hb) and hematocrit (HCT), are important in slowing and preventing the progression of chronic kidney disease (CKD). However, the optimal range for regulating Hb and HCT levels remains uncertain. Objective:The aim of this study was to elucidate the intrinsic relationship between Hb and HCT and the short- and long-term prognosis of CKD, and determine optimal ranges for Hb and HCT. Methods:We retrospectively collected demographic and clinical data over a 6-year follow-up period in Lingnan, China, to show the long-term characteristics of Hb and HCT, and studied the association between Hb, HCT, and the prognosis of patients with CKD stages 3-4. We constructed Cox and group-based trajectory modeling (GBTM) models to examine Hb's and HCT's associations with short- and long-term risk of composite outcomes in patients with CKD stages 3-4. Results:A total of 730 individuals were included, with a median age of 59.30 (48.47, 68.63) years, 306 (41.92%) were women, and median eGFR was 39.24 (26.26, 50.67) mL/min/1.73 m2. A multivariate time-dependent Cox model revealed mean_Hb and mean_HCT as independent protective factors for the composite outcome {hazard ratio (HR) (95% confidence interval [CI]): 0.851 (0.786, 0.921) g/L, p=0.000; 0.578% (0.441%, 0.758%), p=0.000}. Optimized GBTM models categorized Hb and HCT into four groups. Group 1 ("lower and decreasing") (Hb<100 g/L, HCT approximately 30%) served as the reference. Groups 2 ("lower and growing slightly") (Hb 110-120 g/L, HCT approximately 35%), 3 ("higher and growing slightly") (Hb 125-135 g/L, HCT approximately 40%), and 4 ("higher and growing steadily") (Hb 145-160 g/L, HCT approximately 45%) served as independent protective factors for patients with CKD stages 3-4 for the composite outcome (p=0.000; p for trend<0.000). Subgroup analyses showed interactions between mean_Hb and sex (p for interaction=0.034), as well as between Hb trajectory group 2 and CKD stage (p for interaction=0.015). Conclusions:Maintenance of stable and higher Hb levels of 110-130 g/L and HCT levels of 35%-40% in patients with CKD stages 3-4 is both protective and reliable in delaying CKD progression.

Objective:Phase angle (PhA) obtained through bioimpedance analysis has been linked to mortality and malnutrition in dialysis patients. However, it remains unclear whether PhA is associated with renal prognosis in non-dialysis CKD patients. Methods:Two thousand two hundred two CKD patients were enrolled in the SMP-CKD cohort, Guangdong Provincial Hospital of Traditional Chinese Medicine from July 1, 2015 to May 31, 2024. Participants undertook bioimpedance measures, and the correlation between PhA and renal endpoint was analyzed. Analytical approaches include Cox proportional hazards analysis and group-based trajectory modeling. Composite outcome is defined as the first occurrence of >30% decline or <5 mL/min/1.73m2in eGFR, doubled of SCr from the baseline, initiation of continuous dialysis therapy or receipt of a kidney transplant, or all-cause mortality. Results:During a mean follow-up of time 2.5 years, 570(25.9%) participants reached the composite endpoint. In the multivariable Cox regression model, subjects belonging to higher quartiles of phase angle presented with a decreased risk of poor prognosis, showing 29 and 38% risk reductions in Q3 (aHR 0.71, 95%CI 0.55-0.93) and Q4 (aHR 0.62, 0.45-0.85) versus Q1 (both p < 0.05). When modeled in 2 groups according to the turning point of 5.0°, the adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for broad-PhA group was 0.77(0.63, 0.95) compared with narrow-PhA group. The group-based trajectory modelling (GBTM) identified 4 trajectories, and the beneficial association remained consistent, with aHR (95% CIs) for group 2, group 3, group 4 were 0.69 (0.50-0.95), 0.59 (0.39-0.90), 0.47 (0.24-0.93), respectively, compared with group 1. Conclusion:Phase angle could be useful in determining nutritional status of CKD patients, lower phase angle is an independent risk factor for poor prognosis in CKD patients.

BACKGROUND:Previous clinical studies have confirmed that Bupi Yishen formula (BYF) can delay the progression of chronic kidney disease (CKD), and experimental studies have demonstrated that BYF exerts renoprotective effects in CKD models through anti-inflammatory and anti-fibrotic mechanisms. However, the fundamental pathways by which BYF produces these effects remain to be fully elucidated. PURPOSE:This study aims to investigate the potential of BYF to enhance intestinal barrier function through the modulation of gut microbiota and group 3 innate lymphoid cells (ILC3s), and to explore its effects on reducing systemic inflammation and alleviating renal fibrosis in CKD. METHODS:Mice with adenine-induced CKD were treated with oral BYF extract at two doses (15 or 30 g/kg/day). Irbesartan was used as a positive control. We examined the relationship between the renoprotective effects of BYF and changes in gut microbiota, ILC3s, retinoic acid levels, intestinal barrier function, and systemic inflammation. In addition, we conducted an antibiotic-induced gut microbiota depletion experiment to assess the dependence of BYF's effects on microbial presence. RESULTS:Oral BYF treatment reduced serum creatinine, blood urea nitrogen and urine protein levels in mice with adenine-induced CKD and alleviated renal tubular interstitial injury and fibrosis. 16S rRNA sequencing revealed that BYF modulated the gut microbiota composition, significantly enriching Akkermansia muciniphila and Barnesiella intestinihominis while suppressing Flavonifractor plautii and Turicibacter sanguinis. BYF also increased colonic ILC3 numbers, elevated retinoic acid levels, and upregulated interleukin22 (IL-22) expression, thereby improving intestinal barrier integrity and reducing serum levels of lipopolysaccharide (LPS), indoxyl sulfate, IL-1β, interferon gamma (IFN-γ), and tumor necrosis factor-α (TNF-α). However, in gut microbiota-depleted mice, BYF failed to improve kidney injury, fibrosis, ILC3s, retinoic acid, IL-22 expression, or intestinal barrier function. CONCLUSION:BYF may enhance intestinal barrier function by upregulating Akkermansia muciniphila and the ILC3s-IL-22 axis, thereby reducing toxin translocation, suppressing inflammation, alleviating renal fibrosis, and slowing CKD progression. These effects may involve activation of Akkermansia muciniphila-mediated retinoic acid synthesis, which modulates ILC3s-IL-22 signalling in mice with CKD. The breakthrough in our study lies in demonstrating that BYF, through its regulation of gut microbiota and immune cells, significantly impacts the gut-kidney axis to alleviate CKD progression.