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Although more and more cardiovascular risk factors have been verified in peritoneal dialysis (PD) populations in different countries and regions, it is still difficult for clinicians to accurately and individually predict death in the near future. We aimed to develop and validate machine learning-based models to predict near-term all-cause and cardiovascular death. Machine learning models were developed among 7539 PD patients, which were randomly divided into a training set and an internal test set by five random shuffles of 5-fold cross-validation, to predict the cardiovascular death and all-cause death in 3 months. We chose objectively collected markers such as patient demographics, clinical characteristics, laboratory data, and dialysis-related variables to inform the models and assessed the predictive performance using a range of common performance metrics, such as sensitivity, positive predictive values, the area under the receiver operating curve (AUROC), and the area under the precision recall curve. In the test set, the CVDformer models had a AUROC of 0.8767 (0.8129, 0.9045) and 0.9026 (0.8404, 0.9352) and area under the precision recall curve of 0.9338 (0.8134,0.9453) and 0.9073 (0.8412, 0.9164) in predicting near-term all-cause death and cardiovascular death, respectively. The CVDformer models had high sensitivity and positive predictive values for predicting all-cause and cardiovascular deaths in 3 months in our PD population. Further calibration is warranted in the future. [ABSTRACT FROM AUTHOR]

Aortic aneurysm (AA) is an aortic disease with a high mortality rate, and other than surgery no effective preventive or therapeutic treatment have been developed. The renin–angiotensin system (RAS) is an important endocrine system that regulates vascular health. The ACE2/Ang‐(1–7)/MasR axis can antagonize the adverse effects of the activation of the ACE/Ang II/AT1R axis on vascular dysfunction, atherosclerosis, and the development of aneurysms, thus providing an important therapeutic target for the prevention and treatment of AA. However, products targeting the Ang‐(1–7)/MasR pathway still lack clinical validation. This review will outline the epidemiology of AA, including thoracic, abdominal, and thoracoabdominal AA, as well as current diagnostic and treatment strategies. Due to the highest incidence and most extensive research on abdominal AA (AAA), we will focus on AAA to explain the role of the RAS in its development, the protective function of Ang‐(1–7)/MasR, and the mechanisms involved. We will also describe the roles of agonists and antagonists, suggest improvements in engineering and drug delivery, and provide evidence for Ang‐(1–7)/MasR's clinical potential, discussing risks and solutions for clinical use. This study will enhance our understanding of AA and offer new possibilities and promising targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the potential correlation between baseline red cell distribution width (RDW) to albumin ratio (RAR) levels and treatment failure in peritoneal dialysis‐associated peritonitis (PDAP) patients. Methods: A retrospective single‐center study was conducted on 286 PDAP patients. Logistic regression and generalized estimation equation (GEE) analyses were employed to assess the relationship between RAR and treatment failure. Results: RAR emerged as a robust predictor of treatment failure in PDAP patients. Elevated RAR levels were associated with an increased risk of treatment failure, exhibiting a linear relationship. Even after adjusting for demographic and clinical variables, this association remained statistically significant. ROC analysis revealed that RAR outperformed RDW and albumin individually in predicting PDAP prognosis. Conclusion: This study highlights RAR as a superior prognostic marker for treatment failure in PDAP patients, offering new insights into risk assessment and management strategies for this challenging condition. [ABSTRACT FROM AUTHOR]

Background To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. Methods The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). Results A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19–281], P  = .006}, MACE [HR 1.99 (95% CI 1.16–3.40), P  = .012] and MACE+ [HR 1.77 (95% CI 1.15–2.73), P  = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. Conclusion This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort. [ABSTRACT FROM AUTHOR]

Purpose: Antibiotic administration leads to alterations in pathogenic organisms and antibiotic resistance, posing a significant risk to peritoneal dialysis patients' health. This study aimed to investigate changes in the cause-specific peritonitis, pathogen profiles, antibiotic resistance, and the prognostic factors among patients with peritoneal dialysis-associated peritonitis (PDAP) at our center. Patients and Methods: We included 463 PDAP patients who attended Peking University Shenzhen Hospital between 2002 and 2023. We analyzed the effects of empirical treatment regimens with cefazolin and ceftazidime or gentamicin. Results: From 2002 to 2023, we observed that gram-positive staphylococci emerged as the primary causative agents, while the proportion of gram-negative bacillary, enteric peritonitis, and catheter-associated peritonitis decreased significantly. However, the overall cure rate for PDAP and gram-negative bacillary peritonitis declined significantly from 2014 to 2023. Notably, we observed no increase in antibiotic resistance associated with antibiotic drugs use. In addition, reduced lymphocyte counts due to the prevalence of 2019 coronavirus disease (COVID-19) emerged as an independent risk factor for treatment failure in cases of gram-negative bacillary peritonitis. Conclusion: We did not observe elevated antibiotic resistance in our center when employing empirical dosing strategies involving cefazolin, ceftazidime, or gentamicin. Additionally, we found that a decrease in lymphocyte count due to the COVID-19 epidemic was a significant risk factor for treatment failure in cases of gram-negative bacillary peritonitis at our center. This study provides a foundation for developing clinical treatment strategies for PDAP. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies report that latent tuberculosis infection (LTBI) may lead to an increased risk of cardiovascular disease (CVD) that led us to hypothesize that LTBI may play an important role in major adverse cardiovascular events (MACE) in dialysis patients. Methods: A single‐center retrospective cohort study was conducted. A total of 270 patients undergoing hemodialysis or peritoneal dialysis more than 3 months were included. The interferon enzyme‐linked immunospot (IFN‐γ ELISPOT) assay was used for the diagnosis of LTBI. Primary endpoints were MACE, including all‐cause death and acute coronary syndrome (ACS). The association between LTBI and MACE was examined using multivariate Cox proportional hazards regression after adjusting for covariates and Kaplan–Meier survival analysis. Results: In our study, the patients were classified into LTBI (n = 47) or non‐LTBI (n = 223) groups. Independent risk factors for LTBI in dialysis population were prior tuberculosis (TB) history (odds ratio [OR] 4.817 [1.064–22.306]), tobacco use (OR 2.903 [1.155–7.299]), and older age (OR 1.027 [1.002–1.053]). After a median follow‐up of 39 months, the incidence of active TB was 6.4% versus 0% in dialysis patients with and without LTBI, respectively (p = 0.005). Multivariate Cox analysis showed that LTBI was significantly associated with MACE (hazard ratio [HR] 2.540 [1.490–4.350]) after adjustment for potential confounders. Conclusions: Prior TB history, tobacco use, and the elderly can be used to select cost‐effective LTBI screening target groups in dialysis patients. LTBI is not only closely related to active TB but also an independent risk factor for higher incidence of MACE in dialysis population. [ABSTRACT FROM AUTHOR]

Introduction: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. Methods: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. Results: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. Conclusion: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort. [ABSTRACT FROM AUTHOR]

Renal fibrosis is a main cause of chronic renal failure. Epithelial-to-mesenchymal transition (EMT) markers play a role in renal fibrosis. Transforming growth factor-β1 (TGF-β1) has been shown to initiate and complete the whole EMT process. It is now well accepted that loss of E-cadherin, EMT marker α-SMA, and connective tissue growth factor (CTGF) expression are key events in the EMT process. We found that by stimulating human renal proximal tubular epithelial (HK-2) cells with TGF-β1, the expression of E-cadherin was down regulated and the expression of α-SMA and CTGF were up regulated in a dose dependent manner. In our present study we also found that integrin β4 and peroxisome proliferators-activated receptor-γ (PPAR-γ) play roles in EMT process, with TGF-β1 stimulation increasing integrin β4 expression in HK2 cells. Integrin β4 and PPARγ were detected in tubulointerstitial tissues, immunohistochemistry analysis showed enhanced expression of integrin β4 in early stage, with over-expression at later stage. In contrast, the expression of PPARγ showed little increased in early stage, but was dramatically decreased at later stage. This is consistent with TGF-β1 inducing EMT. Our immune-precipitation studies show that integrin β4 disassociation with PPARγ is present in E-cadherin signaling. It suggests that PPARγ has a role in EMT inhibition.

Chronic renal failure (CRF) mainly results from kidney fibrosis. Epithelial-to-mesenchymal transition (EMT) occurs in stressed tubular epithelial cells and contributes to renal fibrosis. Transforming growth factor-β1 (TGF-β1) has been shown to initiate and complete the whole EMT process. Peroxisome proliferators-activated receptor-γ (PPAR-γ) exerts anti-inflammatory, anti-fibrotic and vaculo-protective effects on different renal diseases. Telmisartan is a member of angiotensin II (Ang II) receptor blocker (ARB) family. Recent studies show that Telmisartan has a partial agonistic effect on PPAR-γ. Therefore, we tested the hypothesis that Telmisartan reverses the progression of induced EMT by TGF-β1 in cultured human renal proximal tubular epithelial (HK-2) cells. Cultured HK-2 cells were treated with TGF-β1 (3 ng/ml), a combination of TGF-β1 and Telmisartan (10-200 umol/L) and a combination of TGF-β1, Telmisartan and GW9662, a PPAR-γ antagonist for 48 hours. EMT was determined by quantitative real-time PCR analysis of E-cadherin (E-cad), Connective Tissue Growth Factor (CTGF) and PPAR-γ transcript expression and immunocytochemical analysis of E-cad, α-Smooth Muscle Actin (α-SMA) and PPAR-γ protein expression. TGF-β1 induced phenotypic EMT in cultured HK-2 cell line via significantly reduced E-cad expression and significantly increased CTGF, α-SMA expression in association with the loss of epithelial morphology. Telmisartan reversed all EMT markers in a dose-dependent manner which was inhibited by PPAR antagonist GW9662. In the present study, it was suggested that Telmisartan attenuated TGF-β1 induced EMT by agonistic activation of PPAR-γ.