To compare the efficacy and safety of predilation-free angioplasty with a scoring paclitaxel-coated balloon catheter versus conventional plain balloon angioplasty for failing arteriovenous access. This prospective multicenter randomized controlled trial enrolled adults with malfunctioning mature arteriovenous fistulas or grafts at nine centers in China between August 21, 2019, and January 4, 2021. Participants were randomly assigned in a 1:1 ratio to predilation-free scoring paclitaxel-coated balloon angioplasty or conventional plain balloon angioplasty. The primary endpoint was 6-month target lesion primary patency. Secondary endpoints included device success, procedural success, clinical success, residual stenosis, 12-month target lesion primary patency, and safety. A total of 219 treated participants were analyzed, including 109 in the scoring paclitaxel-coated balloon group and 110 in the control group. Six-month target lesion primary patency was 78.9

Introduction: The IHOPE study evaluated the efficacy and safety of oral iron polysaccharide complex versus i.v. iron in Chinese patients on hemodialysis (HD). Methods: This randomized, open-label, noninferiority trial enrolled adults (aged 18–75 years) on maintenance HD (MHD) with hemoglobin of 100 to 130 g/l, transferrin saturation (TSAT) of 20% to 50%, or serum ferritin of 100 to 500 μg/l. Patients were randomized 1:1 to receive oral iron polysaccharide complex (150 mg twice daily) or i.v. iron sucrose (100 mg biweekly) for 24 weeks. The primary outcome was TSAT at 12 weeks. Noninferiority margin was set at 7% with significance at 0.05. Results: Among 193 participants (mean age: 55.3 years, 62.2% male), 12-week TSAT was 32.3% (95% CI: 29.39%–35.19%) in the oral group versus 33.4% (95% CI: 30.95%–35.77%) in the i.v. group, demonstrating noninferiority. At 24 weeks, TSAT remained noninferior (29.4% vs. 32.6%), and hemoglobin levels were comparable (114.6 vs. 117.4 g/l; P = 0.166). Adverse events occurred in 51.0% of oral and 47.4% of i.v. group patients, with serious adverse events in 14.6% and 13.4%, respectively. Conclusion: Oral iron polysaccharide complex demonstrated noninferiority to i.v. iron sucrose for maintaining iron status in patients on HD, with comparable safety profiles.

Background Hypoglycemic pharmacotherapy interventions for alleviating the risk of dementia remain controversial, particularly regarding dipeptidyl peptidase 4 (DPP4) inhibitors vs metformin. Our objective was to investigate whether the initiation of DPP4 inhibitors, as opposed to metformin, was linked to a reduced risk of dementia.Methods We included individuals with type 2 diabetes over 40 years old who were new users of DPP4 inhibitors or metformin in the Chinese Renal Disease Data System database between 2009 and 2020. The study employed Kaplan-Meier and Cox regression for survival analysis and the Fine and Gray model for the competing risk of death.Results Following a 1:1 propensity score matching, the analysis included 3626 DPP4 inhibitor new users and an equal number of metformin new users. After adjusting for potential confounders, the utilization of DPP4 inhibitors was associated with a decreased risk of all-cause dementia compared to metformin [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89]. Subgroup analysis revealed that the utilization of DPP4 inhibitors was associated with a reduced incidence of dementia in individuals who initiated drug therapy at the age of 60 years or older (HR 0.69, 95% CI 0.48-0.98), those without baseline macrovascular complications (HR 0.62, 95% CI 0.41-0.96), and those without baseline microvascular complications (HR 0.67, 95% CI 0.47-0.98).Conclusion In this real-world study, we found that DPP4 inhibitors presented an association with a lower risk of dementia in individuals with type 2 diabetes than metformin, particularly in older people and those without diabetes-related comorbidities.

CONTEXT:Thyroid dysfunction is prevalent in chronic kidney disease (CKD) patients and significantly impacts renal outcomes and mortality. OBJECTIVE:This study investigated the associations between thyroid function and clinical outcomes, and also the therapeutic effects of thyroid hormone replacement therapy (THRT) in CKD patients. METHODS:We conducted a retrospective cohort study using data from the China Renal Data System. The primary endpoints were composite renal failure and all-cause mortality. The secondary endpoint was the impact of THRT on renal outcomes. Associations were analyzed using multivariable Cox proportional hazards regression models and Kaplan-Meier survival analyses, with adjustment for relevant clinical and demographic covariates. RESULTS:Among 30 804 CKD patients enrolled, 26 673 (86.6%) had normal thyroid function, 2291 (7.4%) had hypothyroidism, and 1840 (6.0%) had hyperthyroidism. Hypothyroidism independently predicted increased risk of renal failure (adjusted HR = 1.29; 95% CI, 1.15-1.45; P < .001). Both hypothyroidism (adjusted HR = 1.24; 95% CI, 1.11-1.39; P < .001) and hyperthyroidism (adjusted HR = 1.20; 95% CI, 1.07-1.33; P < .01) were associated with increased all-cause mortality. Notably, THRT was associated with significantly reduced risk of renal failure (adjusted HR = 0.65; 95% CI, 0.52-0.82; P < .001) in hypothyroid patients. CONCLUSION:This large-scale cohort study demonstrates that hypothyroidism accelerates CKD progression, while both hypo- and hyperthyroidism increase mortality risk in CKD patients. THRT appears to attenuate the adverse effects of hypothyroidism on renal function. Regular thyroid function monitoring and appropriate THRT should be considered in CKD management.

Introduction: Anemia is common in hemodialysis patients, and iron supplementation is essential for its management. However, the impact of baseline inflammation on the efficacy of oral versus intravenous iron remains unclear. Methods: This post hoc analysis of the IHOPE trial included 193 maintenance hemodialysis patients stratified by median baseline high-sensitivity C-reactive protein (hsCRP). Patients were randomized to receive intravenous iron sucrose (100 mg once biweekly) or oral polysaccharide-iron complex (150 mg twice daily) for 24 weeks. The primary outcome was hemoglobin level at 24 weeks. Secondary outcomes included hsCRP, oxidative stress markers, and iron parameters. Results: At 24 weeks, patients with high baseline hsCRP had lower hemoglobin levels than those with low hsCRP (113.82 ± 12.04 vs. 118.05 ± 13.50 g/L, p = 0.038), despite similar baseline hemoglobin values. Among patients receiving intravenous iron sucrose, those with high hsCRP had significantly lower hemoglobin (112.90 ± 13.19 vs. 121.32 ± 13.46 g/L; p = 0.005) and higher hsCRP and superoxide dismutase levels, suggesting persistent inflammation and oxidative stress. In contrast, hemoglobin levels were similar between high and low hsCRP subgroups in the oral polysaccharide-iron complex group (p = 0.913). Iron parameters and adverse events were comparable across groups. Conclusion: This post hoc analysis suggests baseline inflammation significantly modifies responses to specific iron formulations in hemodialysis patients. Patients with elevated hsCRP showed poorer hemoglobin responses to intravenous iron sucrose, while oral polysaccharide-iron complex maintained consistent efficacy across inflammatory states. These findings warrant prospective studies on inflammation-guided personalization of iron therapy.

Early insulin therapy is capable to achieve glycemic control and restore β-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

IntroductionDiabetic nephropathy (DN), distinguished by detrimental changes in the renal glomeruli, is regarded as the leading cause of death from end-stage renal disease among diabetics. Cellular senescence plays a paramount role, profoundly affecting the onset and progression of chronic kidney disease (CKD) and acute kidney injuries. This study was designed to delve deeply into the pathological mechanisms between glomerulus-associated DN and cellular senescence.MethodsGlomerulus-associated DN datasets and cellular senescence-related genes were acquired from the Gene Expression Omnibus (GEO) and CellAge database respectively. By integrating bioinformatics and machine learning methodologies including the LASSO regression analysis and Random Forest, we screened out four signature genes. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance of the selected genes. Rigorous experimental validations were subsequently conducted in the mouse model to corroborate the identification of three signature genes, namely LOX, FOXD1 and GJA1. Molecular docking with chlorogenic acids (CGA) was further established not only to validate LOX, FOXD1 and GJA1 as diagnostic markers but also reveal their potential therapeutic effects.Results and discussionIn conclusion, our findings pinpointed three diagnostic markers of glomerulus-associated DN on the basis of cellular senescence. These markers could not only predict an increased risk of DN progression but also present promising therapeutic targets, potentially ushering in innovative treatments for DN in the elderly population.

Previously, we reported that serum Semaphorin 5 A (Sema5A) levels were increased in systemic lupus erythematosus (SLE) patients compared with healthy controls (HC), and elevated Sema5A correlated with disease activity and lupus nephritis in SLE patients. In this study, we aimed to further understand the role of Sema5A in promoting Th17 cells differentiation in SLE. Sema5A, interferon gamma (IFN-γ), interleukin 4 (IL-4), interleukin 17 A (IL-17 A) and interleukin 10 (IL-10) were measured by Enzyme Linked Immunosorbent Assay (ELISA). RNA and protein were isolated from peripheral blood mononuclear cells (PBMCs) in SLE patients and HC. Expression of PlexinA1 and PlexinB3 were measured by quantitative RT-PCR (qRT-PCR) and Western Blot. Th cell subsets were detected by flow cytometry. Treatment with recombinant human Sema5A (rhSema5A) and small interfering RNA (siRNA) were employed to examine the in vitro effect of Sema5A in CD4+T cell differentiation in SLE patients. IL-17 A elevated in SLE patients and positively correlated with Sema5A. PlexinA1 was upregulated and mainly expressed in CD4+ T cells of SLE; Sema5A treatment induced the differentiation of Th17 cells, while did not affect the Th1 and Th2 skewing. These effects were associated with an upregulation of the transcription factor RORγt by Th17 cells, but not T-bet or GATA3 in Th1 and Th2 cells, respectively. Knock down PlexinA1 regulates IL-17 A production by CD4+T cells. Functional assays showed that Sema5A-PlexinA1 axis promoted Th17 cells differentiation via PI3K/Akt/mTOR signaling. These findings demonstrated that Sema5A-PlexinA1 axis acts as a key mediator on Th17 differentiation, suggesting that Sema5A might be a novel therapeutic target in SLE.

BackgroundThe ongoing global health crisis of COVID-19, and particularly the challenges posed by recurrent infections of the Omicron variant, have significantly strained healthcare systems worldwide. There is a growing body of evidence indicating an increased susceptibility to Omicron infection in patients suffering from Acute Kidney Injury (AKI). However, the intricate molecular interplay between AKI and Omicron variant of COVID-19 remains largely enigmatic.MethodsThis study employed a comprehensive analysis of human RNA sequencing (RNA-seq) and microarray datasets to identify differentially expressed genes (DEGs) associated with Omicron infection in the context of AKI. We engaged in functional enrichment assessments, an examination of Protein-Protein Interaction (PPI) networks, and advanced network analysis to elucidate the cellular signaling pathways involved, identify critical hub genes, and determine the relevant controlling transcription factors and microRNAs. Additionally, we explored protein-drug interactions to highlight potential pharmacological interventions.ResultsOur investigation revealed significant DEGs and cellular signaling pathways implicated in both Omicron infection and AKI. We identified pivotal hub genes, including EIF2AK2, PLSCR1, GBP1, TNFSF10, C1QB, and BST2, and their associated regulatory transcription factors and microRNAs. Notably, in the murine AKI model, there was a marked reduction in EIF2AK2 expression, in contrast to significant elevations in PLSCR1, C1QB, and BST2. EIF2AK2 exhibited an inverse relationship with the primary AKI mediator, Kim-1, whereas PLSCR1 and C1QB demonstrated strong positive correlations with it. Moreover, we identified potential therapeutic agents such as Suloctidil, Apocarotenal, 3′-Azido-3′-deoxythymidine, among others. Our findings also highlighted a correlation between the identified hub genes and diseases like myocardial ischemia, schizophrenia, and liver cirrhosis. To further validate the credibility of our data, we employed an independent validation dataset to verify the hub genes. Notably, the expression patterns of PLSCR1, GBP1, BST2, and C1QB were consistent with our research findings, reaffirming the reliability of our results.ConclusionOur bioinformatics analysis has provided initial insights into the shared genetic landscape between Omicron COVID-19 infections and AKI, identifying potential therapeutic targets and drugs. This preliminary investigation lays the foundation for further research, with the hope of contributing to the development of innovative treatment strategies for these complex medical conditions.

Background Inflammation is associated with adverse outcomes of chronic kidney disease (CKD) or chronic heart failure (CHF), but few large data exist. We aimed to explore the clinical associations, and prognostic consequences of inflammation-based scores in patients with CKD and CHF.Methods This work was a retrospective cohort study. Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Nutritional Index (PNI) and Prognostic Index (PI), were used to explore its relationship with CKD progression in patients with CKD stage 1-3b and CHF from the China Renal Data System (CRDS). The composite end point of this study was CKD progression which was defined as eGFR reduction of 40% or progression to end stage renal disease (ESRD).Results Of 8491 patients were enrolled. Kaplan-Meier curve showed that compared to the lower inflammation-based scores, the increased scores have a higher rate of CKD progression, whether in GPS, mGPS, PNI or PI (log-rank test, p < 0.001). After considering competing risk events, multivariable Cox hazards analysis revealed that GPS and PNI scores were significantly related to CKD progression [GPS: hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.11-1.76, p = 0.005; PNI: HR 1.54, 95% CI 1.25-1.89, p < 0.001]. PNI showed acceptable prognostic value (C-index = 0.757, 95% CI 0.734-0.78) compared to GPS, mGPS and PI. In subgroup analysis, PNI was consistently related to CKD progression in patients with or without hypertension, DM, MI, VDH and CVD (P for interaction > 0.05).Conclusions Inflammation-based scores, especially PNI may be a useful clinical biomarker for CKD progression in CKD with CHF patients.

Background: To investigate the feasibility, methods and effects of interventional ultrasound in nitinol stent implantation to treat early restenosis after percutaneous transluminal angioplasty (PTA) in autogenous arteriovenous fistula (AVF).Methods: From April 2018 to December 2021, 69 patients with early restenosis of AVF received ultrasound-guided nitinol stent implantation (UNSI) and were followed-up. Imaging features of the stent and procedure by ultrasound were observed. The technical success rate, clinical success rate and incidence of complications were recorded and counted. Target lesion primary patency (TLPP), access circuit primary patency (ACPP) and access circuit secondary patency (ACSP) were estimated.Results: Ultrasonography can show the structure of the stent and guide the stenting process clearly. Both the technical and clinical success rates were 100%. Thirty-one patients had in-stent restenosis (ISR), which was treated by plain balloon (PB) PTA or drug coated balloon (DCB) PTA. The TLPP at 3, 6, 12 and 24 months were 100.0%, 94.2%, 63.4% and 39.6%, respectively. The ACPP at 3, 6, 12 and 24 months were 98.6%, 91.6%, 60.2% and 35.2%, respectively. The ACSP at 3, 6, 12 and 24 months were 98.6%, 98.6%, 95.6% and 93.8%, respectively. The TLPP of ISR after DCB PTA at 3, 6 and 12 months were 100.0%, 100.0% and 93.6%, respectively.Conclusions: This pilot study indicates ultrasonography can accurately guide nitinol stent implantation in AVF and this technique is a feasible and minimally invasive treatment for early restenosis after PTA with good short- and medium-term patency. DCB PTA may be used to deal with the ISR and is a way to prolong the patency of nitinol stent.

>Dear Editor,Heart failure (HF) is a common multi-faceted and lifethreatening syndrome,of which up to 23%occur acute kidney injury (AKI)[1].HF-related AKI is largely overlooked or delayed in identification[2].Approximately 85%of AKI cases that occurred during cardiac hospitalization in China were either ignored or identified too late [3].Currently,there are no specific guidelines for the management of HF-related AKI.Hence,it is essential to identify patients at the risk of developing AKI and intervene promptly,to reduce social and economic burden.

Background. Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from large and high-quality studies are limited. This study aimed to determine the incidence, risk factors and outcomes of postoperative AKI among patients undergoing surgery in China. Methods. This was a large, multicentre, retrospective study performed in 16 tertiary medical centres in China. Adult patients (>= 18 years of age) who underwent surgical procedures from 1 January 2013 to 31 December 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders. Results. Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%), urologic (8.7%) and general (4.2%) surgeries. A total of 89.2% of postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included older age, male sex, lower baseline kidney function, pre-surgery hospital stay <= 3 days or >7 days, hypertension, diabetes mellitus and use of proton pump inhibitors or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer lengths of hospital stay (12 versus 19 days) and were more likely to require intensive care unit care (13.1% versus 45.0%) and renal replacement therapy (0.4% versus 7.7%). Conclusions. Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.

ABSTRACT Background Electrolyte abnormalities are common symptoms of chronic kidney disease (CKD), but previous studies have mainly focussed on serum potassium and sodium levels. Chloride is an important biomarker for the prognosis of various diseases. However, the relationship between serum chloride levels and atrial fibrillation (AF) in CKD patients is unclear. Objective In this study, we sought to determine the association between serum chloride homeostasis and AF in CKD patients. Methods In this retrospective cohort study, we included patients who met the diagnostic criteria for CKD in China between 2000 and 2021. Competing risk regression for AF was performed. The associations of the baseline serum chloride concentration with heart failure (HF) and stroke incidence were also calculated by competing risk regression. The association of baseline serum chloride levels with all-cause death was determined by a Cox regression model. Results The study cohort comprised 20 550 participants. During a median follow-up of 350 days (interquartile range, 123–730 days), 211 of the 20 550 CKD patients developed AF. After multivariable adjustment, every decrease in the standard deviation of serum chloride (5.02 mmol/l) was associated with a high risk for AF [sub-hazard ratio (sHR) 0.78, 95% confidence interval (CI) 0.65–0.94, P = .008]. These results were also consistent with those of the stratified and sensitivity analyses. According to the fully adjusted models, the serum chloride concentration was also associated with a high risk for incident HF (sHR 0.85, 95% CI 0.80–0.91, P < .001), a high risk for incident stroke (sHR 0.87, 95% CI 0.81–0.94, P < .001), and a high risk for all-cause death [hazard ratio (HR) 0.82, 95% CI 0.73–0.91, P < .001]. Conclusion In this CKD population, serum chloride levels were independently and inversely associated with the incidence of AF. Lower serum chloride levels were also associated with an increased risk of incident HF, stroke, and all-cause death.

Purpose The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. Materials and methods This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. Results No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p < .05). Finally, adverse events were more frequent in warfarin-treated patients. Conclusions This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome.