ABSTRACT Uremic cardiomyopathy (UCM) is a severe complication of uraemia that lacks effective treatments. The role of immune dysfunction in haemodialysis patients with UCM remains unclear. Peripheral blood mononuclear cells (PBMCs) are major components of the immune system; however, they do not directly contact cardiomyocytes. In general, extracellular vesicles (EVs) function as intercellular communication mediators. Therefore, in this study, we first investigated the role of PBMC‐derived EVs (PBMC‐EVs) in UCM and identified EV‐miR‐744‐5p as a key molecule involved in PBMC–cardiomyocyte communication. Mechanistically, indoxyl sulphate (IS) downregulated miR‐744‐5p expression in PBMC‐EVs, leading to IGF2R upregulation in cardiomyocytes, thereby exacerbating myocardial injury via induction of hypertrophy, apoptosis and inflammatory pathway activation in the cardiomyocytes. We also explored the potential of natural products to treat UCM by modifying PBMC‐EVs and found that the traditional Chinese medicine monomer salvianolic acid B (Sal B) could bind to YY1, enhancing miR‐744‐5p expression in PBMC‐EVs and thus mitigating myocardial injury in UCM. Taken together, these findings indicate the critical role of PBMC‐EVs in UCM and suggest the cardioprotective effects of Sal B via PBMC‐EV modification. They also provide novel insights into immune mechanisms underlying UCM, particularly indicating that targeting PBMC‐EVs may be a promising UCM treatment strategy.

Cardiovascular disease is the leading cause of mortality in patients with hemodialysis. Coronary artery calcification represents a major pathological substrate and an independent risk factor for adverse cardiovascular outcomes. Although endothelial-smooth muscle cell crosstalk is critical in vascular calcification and extracellular vesicles (EVs) are key intercellular mediators, their role in coronary artery calcification remains unexplored. Additionally, the mechanisms linking α-1,6-fucosyltransferase (FUT8) upregulation in calcified vascular smooth muscle cells to endothelial EV signaling are unknown. High phosphorus and high calcium conditions were applied to coronary artery endothelial cells to induce EV secretion. The EVs were isolated and characterized, and their uptake by coronary artery smooth muscle cells was examined. Molecular analyses assessed the effects of EV-derived miR-122b-3p on FOXP1 repression, FUT8 expression, integrin αV (ITGAV) core fucosylation, and autophagy suppression. Endothelial EVs were highly enriched with miR-122b-3p under calcifying conditions and were internalized by smooth muscle cells, leading to FOXP1 repression, FUT8 upregulation, enhanced ITGAV core fucosylation, autophagy suppression, and accelerated coronary artery calcification. In uremic rats, EVs overexpressing miR-122b-3p aggravated coronary artery calcification by modulating the FOXP1/ FUT8/ITGAV signaling pathway. Preliminary analysis of serum EVs from healthy controls and patients with CKD/uremia further showed increased serum EV miR-122b-3p levels and associations with renal dysfunction and mineral metabolism-related parameters, supporting the potential clinical relevance of this EV-miRNA axis. This study identifies a novel extracellular vesicle-dependent intercellular communication mechanism linking FUT8-mediated core fucosylation to autophagy dysfunction in coronary artery calcification.

Uremic cardiomyopathy (UCM) is the leading cause of hemodialysis patient mortality. Indoxyl sulfate (IS), a key uremic toxin, activates multiple signaling pathways, causing cardiac hypertrophy and apoptosis. We previously demonstrated that core fucosylation (CF), a post-translational modification, is crucial in activating these pathways. Additionally exosome-mediated cardiac microvascular endothelial cell (CMEC)-cardiomyocyte (CM) crosstalk is important for UCM progression. However, the characteristics and roles of CF modification in IS-induced CMEC-derived exosomes (IS-Exos) that cause CM injury remain unexplored. Our studies have revealed that hemodialysis patients had significantly higher serum IS and α1,6-fucosyltransferase (FUT8), which were positively correlated with the severity of cardiac injury. Using a microfluidic chip model of IS-induced cardiac injury, we visualized exosome transfer from CMECs to CMs, which caused mitochondrial impairment, hypertrophy and apoptosis in CMs, with elevated CF levels playing critical roles. To investigate this further, we performed FUT8 knockout in IS-mice treated with IS-Exos and transfected FUT8 siRNA into CMs exposed to IS-Exos. We found that the inhibition of FUT8 leads to a reduction in ARG2 expression, which consequently diminishes reactive oxygen species (ROS) and ameliorates cardiac hypertrophy and apoptosis. Mechanistically, miR-27a-5p was markedly downregulated in IS-Exos. CD44 on IS-Exos interacts with EGFR in CMs, enhancing cardiac injury. Supplementation with miR-27a-5p in vivo and in vitro specifically targets USF2, leading to a downregulation of FUT8 expression. This cascade leads to a diminished expression of ARG2, alleviation of ROS, and the reversal of cardiac hypertrophy and apoptosis. Our findings offer new insights, suggesting that targeting CF modification may represent a promising therapeutic strategy for alleviating UCM in the future.

Peritoneal catheter thinning is a rare complication that often occurs in patients undergoing peritoneal dialysis, finally leading to catheter rupture. Once it occurs near the proximal portion of the exit site, catheter removal and simultaneous insertion of a new catheter are often required. Here, we report a case of PD catheter rupture due to catheter thinning 6 years ago, and catheter thinning of a new catheter reoccurred 6 years later. In this recurrence, we successfully addressed the issue through tunnel reconstruction without removing the catheter. After cutting the catheter proximally 1 cm away from the thinning site, we connected a new catheter to the original catheter using a bidirectional connector. A new tunnel was re-constructed on the same side with subsequent excellent catheter function. Tunnel reconstruction may be a simple and safe therapeutic alternative for PD patients with worn or ruptured PD catheters.

BACKGROUND:The fluid status and rate of blood flow through the arteriovenous fistula (AVF) are two important factors affecting hemodynamic in hemodialysis patients; however, their effects on pulmonary hypertension have rarely been studied. Hence, we aimed to evaluate the effects of these factors in hemodialysis patients with pulmonary hypertension. METHODS:This single-center cross-sectional survey included 219 maintenance hemodialysis patients (139 [63.5%] male). The prevalence of pulmonary hypertension was 13.6% (30 of 219). Pulmonary artery pressure was measured by echocardiography, fluid status was measured objectively using bioimpedance spectroscopy, and blood flow rate in the AVF (Qa) was determined using Doppler ultrasound. RESULTS:The overall mean overhydration before hemodialysis was 1.5 L (range, 0.6-2.8 L). The mean overhydration in patients with and without pulmonary hypertension was 3.6 L (range, 2.3-4.6 L) and 1.4 L (range, 0.6-2.4 L), respectively (p < 0.001). The overall mean Qa was 780 mL/min (range, 570-1,015.5 mL/min). The mean Qa of patients with and without pulmonary hypertension was 672 mL/min (range, 505.7-982.2 mL/min) and 790 mL/min (range, 591-1,026 mL/min), respectively (p = 0.27). Overhydration (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.08-1.97; p = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP; OR, 1.36; 95% CI, 1.09-1.71; p = 0.007), and left atrial diameter (OR, 1.14; 95% CI, 1.01-1.28; p = 0.03) were risk factors. CONCLUSION:Pulmonary hypertension is strongly associated with overhydration, NT-proBNP, and left atrial diameter in hemodialysis patients.

BACKGROUND:Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis (AAV) experience different manifestations at the initial onset and relapse. However, such cases of different initial and relapse manifestations have not been reported in myeloperoxidase (MPO)-AAV patients.CASE SUMMARY:A 52-year-old woman was admitted to our hospital because of headache. Laboratory findings indicated nephrotic range proteinuria and microscopic hematuria, serum creatinine of 243 μmol/L, anti-MPO antibody titer of > 400 RU/mL, and positive perinuclearantineutrophil cytoplasmic antibody. Renal biopsy showed pauci-immune crescentic glomerulonephritis. The cerebrospinal fluid examination and brain magnetic resonance imaging did not show any abnormality. Therefore, MPO-AAV was diagnosed. Corticosteroids, plasmapheresis, and cyclophosphamide as induction therapy and mycophenolate mofetil (MMF) as maintenance therapy were administered. The patient's headache disappeared; serum creatinine returned to normal; complete remission of microscopic hematuria and proteinuria was observed. Anti-MPO antibody titer reached normal limits after immunosuppressive treatment. Twenty-five months after stopping the immunosuppressive treatment, the patient relapsed with arthralgia, without neurological or renal involvement. The patient's arthralgia improved after treatment with prednisone and MMF.CONCLUSION:We have reported a rare case of MPO-AAV who initially presented with headache and kidney involvement. However, relapse presented with only arthralgia, which was completely different from the initial manifestations. This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission, when clinical manifestations at relapse are different from those at onset. Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.

Abstract Background National holidays are associated with high mortality in some diseases, but little is known about patients undergoing peritoneal dialysis (PD). The research aimed to investigate the impact of national holidays on the health outcomes of PD patients. Methods Over ten years, all episodes of unplanned hospitalization, death, and peritonitis in PD patients were collected in our center. Seven national holidays in China were chosen, and non-holiday days were selected as the control period. The effect of national holidays was observed by comparing the hospitalization, death, and peritonitis rates between holiday and non-holiday groups. Results There were 297 events in all holiday periods and 1247 in non-holiday periods. There is no significant difference in hospitalization rate between holiday and non-holiday groups (32.4% ± 6.4% vs. 29.2% ± 3.4%, p = 0.175). So is the death rate [6.3% (4.8–12.3%) vs.5.0% (4.2–8.9%), p = 0.324] and peritonitis rate [0.19 (0.13–0.53) vs. 0.22 (0.18–0.27), p = 0.445] between the two groups. Significant differences were observed in the distribution of peritonitis causes between the two groups (p = 0.017). The rate of secondary to other infections in the holiday group was significantly higher than in the non-holiday group (25.0 vs. 10.3%, p = 0.015). Conclusion Our study suggested no national holiday effect on health outcomes of PD patients based on ten-year data in our center.

BACKGROUND:Residual kidney function (RKF) impacts patients' survival rate and quality of life when undergoing peritoneal dialysis (PD). This meta-analysis was conducted to systematically identify risk and protective factors associated with RKF decline and loss.METHODS:We searched three English and one Chinese databases from inception to January 31, 2023, for cohort and cross-sectional studies exploring factors associated with RKF decline or loss. The random effects model was employed to aggregate risk estimates and 95% confidence intervals (CIs) from multivariate analysis. Sensitivity and subgroup analyses were performed to explore the heterogeneity among the studies.RESULTS:Twenty-seven studies comprising 13549 individuals and 14 factors were included in the meta-analysis. Based on the meta-analysis results, risk factors involving male gender (hazard ratio (HR) 1.689, 95%CI 1.385-2.061), greater body mass index (BMI) (odds ratio (OR) 1.081, 95% confidence interval (CI) 1.029-1.135), higher systolic blood pressure (SBP) (HR 1.014, 95%CI 1.005-1.024), diabetes mellitus (DM) (HRRKF loss 1.873, 95%CI 1.475-2.378), DM (ORRKF decline 1.906, 95%CI 1.262-2.879), peritonitis (relative ratio (RR) 2.291, 95%CI 1.633-3.213), proteinuria (OR 1.223, 95%CI 1.117-1.338), and elevated serum phosphorus (RR 2.655, 95%CI 1.679-4.201) significantly contributed to the risk of RKF decline and loss in PD patients. Conversely, older age (HR 0.968, 95%CI 0.956-0.981), higher serum albumin (OR 0.834, 95%CI 0.720-0.966), weekly Kt/V urea (HR 0.414, 95%CI 0.248-0.690), baseline urine volume (UV) (HR 0.791, 95%CI 0.639-0.979), baseline RKF (HR 0.795, 95%CI 0.739-0.857) exhibited protective effects. However, diuretics use, automatic peritoneal dialysis (APD) modality and baseline RKF did not significantly impact RKF decline.CONCLUSIONS:Patients with male gender, greater BMI, higher SBP, DM, peritonitis, proteinuria, and elevated serum phosphorus might have a higher risk of RKF decline and loss. In contrast, older age, higher serum albumin, weekly Kt/V urea, baseline UV, and baseline RKF might protect against RKF deterioration.

Renal ischemia-reperfusion injury (IRI) is a common reason of acute kidney injury (AKI). AKI can progress to chronic kidney disease (CKD) in some survivors. Inflammation is considered the first-line response to early-stage IRI. We previously reported that core fucosylation (CF), specifically catalyzed by α-1,6 fucosyltransferase (FUT8), exacerbates renal fibrosis. However, the FUT8 characteristics, role, and mechanism in inflammation and fibrosis transition remain unclear. Considering renal tubular cells are the trigger cells that initiate the fibrosis in the AKI-to-CKD transition in IRI, we targeted CF by generating a renal tubular epithelial cell (TEC)-specific FUT8 knockout mouse and measured FUT8-driven and downstream signaling pathway expression and AKI-to-CKD transition. During the IRI extension phase, specific FUT8 deletion in the TECs ameliorated the IRI-induced renal interstitial inflammation and fibrosis mainly via the TLR3 CF-NF-κB signaling pathway. The results firstly indicated the role of FUT8 in the transition of inflammation and fibrosis. Therefore, the loss of FUT8 in TECs may be a novel potential strategy for treating AKI-CKD transition.

•Encapsulating peritoneal sclerosis, a rare but potentially catastrophic complication with high mortality in PD patients, appears to occur in long-term PD patients.•A continuous annular calcification of the intestinal wall (like a "ring") is rare in previous EPS cases.•Hemoperitoneum, ultrafiltration failure, and elevated inflammation markers may show the early inflammatory nature of the disease.•Many patients were diagnosed with EPS after discontinuing PD, it is vital to start EPS screening (abdominal CT scan) regularly.

Background & Aims Complete blood count (CBC)-derived inflammatory markers are predictive biomarkers for the prognosis of many diseases. However, there was no study on patients with peritoneal dialysis-associated peritonitis (PDAP). We aimed to investigate the value of these markers in predicting treatment failure of acute peritonitis in chronic PD patients. Methods The records of 138 peritonitis episodes were reviewed and divided into treatment success or failure groups in a single center for 10 years. CBC-derived markers and other routine data were recorded before peritonitis treatment was initiated. Univariate and multivariate regression analyses and the receiver operating characteristic (ROC) curve about the predictors of treatment outcomes were performed. Results Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and derived NLR were significantly higher in the failure group. Univariate logistic regression results showed that NLR and PLR were risk factors of treatment outcomes. The backward stepwise multivariate logistic regression results demonstrated that NLR [adjusted odds ratio (aOR), 1.376; 95% confidence intervals (CI), 1.105-1.713; p = .004], PLR (aOR, 1.010; 95%CI, 1.004-1.017; p = .002) were risk factors, but hemoglobin-to-lymphocyte ratio (HLR) (aOR, 0.977; 95%CI, 0.963-0.991; p = .001), and SII (aOR, 0.999; 95%CI, 0.998-1.000; p = .040) were protective factors. A combination of age, PD vintage, Gram-positive peritonitis, staphylococcus aureus, culture-negative, NLR, PLR, HLR, and SII would improve prognostic performance. The area under this ROC curve was 0.85, higher than other factors. Conclusions NLR, PLR, HLR, and SII were associated with PDAP outcomes. Age, PD vintage, NLR, and PLR were significant risk factors in PDAP patients.

Abstract Background α‐1,6 Fucosyltransferase (FUT8) appears to play an essential role in the pathogenesis of renal fibrosis. However, it remained unknown whether FUT8 also contributed to renal fibrosis in immunoglobulin A nephropathy (IgAN). In the present study, we explored the association of serum FUT8 activity with renal tubulointerstitial injury in IgAN patients. Methods Serum FUT8 activity was measured in 135 IgAN patients and 68 healthy controls from January 2016 to December 2018. The relationships of serum FUT8 activity with clinical and pathological features were analyzed. Results Relative to healthy controls, IgAN patients had significantly higher serum FUT8 activity and upregulation of renal FUT8 protein (p < .05). Among IgAN patients, there was a positive correlation of serum FUT8 activity with renal FUT8 protein expression (p < .05). Multivariable logistic regression analyses showed that serum FUT8 activity was significantly associated with serum creatinine and eGFR (p < .05). Based on a cut‐off value determined from ROC curve analysis, we divided IgAN patients into a low serum FUT8 activity group (≤12.2 pmol/h/mL, n = 40) and a high serum FUT8 activity group (>12.2 pmol/h/ml, n = 95). The high serum FUT8 activity group had a higher Oxford T score, increased inflammatory cell infiltration, more severe fibrosis and poor renal function (p < .05). Conclusion Serum FUT8 activity was positive association with renal tubulointerstitial injury in IgAN patients.

Perforation of bowel is a rare but recognized complication of peritoneal dialysis (PD) catheter placement [1] that may be difficult to avoid even for the experienced doctor, especially when using percutaneous needle-guidewire PD catheter insertion. Its incidence varied from 0.7% to 2.6% [1] although catheter insertion techniques have improved nowadays. In addition to operation procedures, there are also other causes of bowel perforation such as diseases of the bowel, abdominal wall adhesions [2], and other unknown reasons. From a physical perspective, the bowel would be easily injured during percutaneous needle-guidewire catheter insertion if there is a solid fulcrum beneath the bowel, such as a peritoneal loose body (PLB). The PLB is generally a solid mass with smooth surface and gray or white color, the origin of which is thought to be torsed, infarcted, and detached epiploic appendages that slowly turn into fibrotic masses, which can move freely in the cavity [3]. The PLB is rare and – as far as we know – not reported previously in PD patients. Here, we present a case with bowel perforation which we believe was caused by a peritoneal loose body, which served as a supporting point under the sigmoid during percutaneous PD catheter insertion.

Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01-1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01-1.48 and 1.27, 1.01-1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.