Clinical characteristics and antibiotic treatment of peritoneal dialysis-associated peritonitis caused by Pseudomonas species: a review of 15 years' experience from southern China.

Pseudomonas can lead to peritoneal dialysis-associated peritonitis, which is characterized by a poor prognosis, such as a substantial failure rate and a high death rate. This study aimed to provide an overview of Pseudomonas peritonitis's clinical features, the regimens of antibiotic, antibiotic resistance, and outcomes in peritoneal dialysis (PD) patients. This study observed patients with Pseudomonas peritonitis in two large PD centers in South China from January 2008 to December 2022. The demographics, symptomatology, antibiotics regimens, resistance to common antibiotics, and clinical outcomes of all included patients were reviewed. A total of 3,459 PD patients were included, among them 57 cases of peritonitis caused by Pseudomonas, including 48 cases (84.2%) of Pseudomonas aeruginosa. The incidence rate of Pseudomonas peritonitis was 0.0041 episode per patient-year. Of them, 28.1% (16 cases) of the patients were accompanied by exit site infection (ESI), and all had abdominal pain and turbid ascites at the time of onset. The most commonly used antibiotic combination was ceftazidime combined with amikacin. Approximately 89% of Pseudomonas species were sensitive to ceftazidime, and 88% were sensitive to amikacin. The overall primary response rate was 28.1% (16 patients), and the complete cure rate was 40.4% (23 patients). There was no significant difference in the complete cure rate of peritonitis using three and other antibiotic treatment regimens (44.8% vs 46.4%; P = 0.9). The successful treatment group had higher baseline albumin level (35.9 ± 6.2; P = 0.008) and residual urine volume (650.7 ± 375.5; P = 0.04). Although the incidence of peritonitis caused by Pseudomonas was low, the symptoms were serious, and prognosis was very poor. Pseudomonas was still highly susceptible to first-line antibiotics currently in use against Gram-negative bacteria. Patients with successful treatment had higher albumin levels and higher urine output. IMPORTANCE: Although the incidence of peritoneal dialysis-associated peritonitis caused by Pseudomonas is very low, it seriously affects the technique survival of peritoneal dialysis patients. However, there are few studies and reports on Pseudomonas peritonitis in the Chinese mainland area. Therefore, the purpose of this study is to describe the clinical characteristics, the regimens of antibiotic, drug resistance, and outcome of peritoneal dialysis patients in southern China in the past 15 years and summarize the clinical experience in the treatment of Pseudomonas peritonitis.

Left ventricular strain and myocardial work in short-term peritoneal dialysis patients.

BACKGROUND: Initiation of dialysis encompasses new cardiovascular challenges on patients with end-stage renal disease (ESRD). This study used two-dimensional speckle-tracking echocardiography (2D-STE) to investigate the change of left ventricular (LV) myocardial function undergoing peritoneal dialysis (PD) within 1-3 months. METHODS: A total of 56 patients with ESRD and 27 healthy controls were enrolled in this prospective study. Mean duration of PD was 44.41 ± 16.44 days. We evaluated LV myocardial function of patients with ESRD in baseline and within 1-3 months after PD by 2D-STE with global longitudinal strains (GLS) and myocardial work (MW). Based on the level of serum phosphate before PD, patients were divided into two groups: the group with normal serum phosphate or hyperphosphatemia. RESULTS: Compared with healthy controls, patients with ESRD had impaired GLS (p < .001) and increased global work index (GWI) (p = .034), global constructive work (GCW) (p < .001), global wasted work (GWW) (p < .001), and lower global work efficiency (GWE) (p = .002). After PD therapy, GWI (p = .001), GCW (p < .001), and GWW (p = .023) decreased and closed to healthy subjects (p > .05) and no significant improvement was observed in GLS (p = .387). GLS of basal segments worsened in the hyperphosphatemia group (p = .005) and GWW reduced remarkably in the group with normal serum phosphate after PD treatment (p = .008). The change of left ventricular internal diameter in diastole (LVIDd) was the only parameter influenced GWI in post-dialysis patients (ß = 0.324, p = .013). CONCLUSIONS: Short-term PD treatment improved LV MW in ESRD patients. They benefited more when receiving treatment before the increase of serum phosphorus.

The centre-calculated cutoff value is better for identifying fast peritoneal solute transfer of patients on peritoneal dialysis than the traditional value: a retrospective cohort study.

Background: The mean 4-h dialysate to plasma ratio of creatinine (4-h D/Pcr) is a vital cutoff value for recognizing the fast peritoneal solute transfer rate (PSTR) in patients on peritoneal dialysis (PD); however, it shows a noticeable centre effect. We aimed to investigate our centre-calculated cutoff value (CCV) of 4-h D/Pcr and compare it with the traditional cutoff value (TCV) (0.65). Methods: In this study, we enrolled incident PD patients at our centre from 2008 to 2019, and divided them into fast or non-fast PSTR groups according to baseline 4-h D/Pcr-based CCV or TCV. We compared the efficiency of the fast PSTR recognized by two cutoff values in predicting mortality, ultrafiltration (UF) insufficiency and technical survival. Results: In total, 1905 patients were enrolled, with a mean 4-h D/Pcr of 0.71 ± 0.11. Compared with TCV (0.65), CCV (0.71) showed superiority in predicting mortality of PD patients [hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.02-1.59 vs HR 1.24, 95% CI 0.97-1.59]. The odds ratio (OR) of the fast PSTR in centre classification was slightly higher than traditional classification in predicting UF insufficiency (OR 1.67, 95% CI 1.25-2.24 vs OR 1.60, 95% CI 1.15-2.22). Additionally, the restricted cubic splines 4-h D/Pcr has an S-shaped association with mortality and UF insufficiency, and the inflection points of 4-h D/Pcr were 0.71 (equal to CCV). Conclusions: The CCV of 4-h D/Pcr for identifying fast PSTR was 0.71. It was superior to TCV in predicting mortality and UF insufficiency.

Current status of exercise and its impact on quality of life in patients undergoing peritoneal dialysis in the post-COVID-19 period.

OBJECTIVES: The aims of this study were to investigate the current status and the influence factors of exercise, and to explore the impact of exercise on the quality of life (QoL) in peritoneal dialysis (PD) patients in the post-COVID-19 period. MATERIALS AND METHODS: Those PD patients who were followed up between September 2020 and August 2021 were enrolled. The collected data included demographic information, clinical data, exercise data, and QoL. RESULTS: In total, 339 PD patients were included in this cross-sectional study. The mean age was 44.0 ± 13.0 years, with a median PD duration of 6.7 (1.7 - 41.9) months. The primary renal disease was glomerulonephritis (68.4%). 277 (81.7%) PD patients performed exercise, with median exercise time 5.0 (3.5 - 7.8) hours per week. The main type of exercise was slow walking. Pain (odds ratio (OR) = 0.311, p = 0.002) and lower hemoglobin level (OR = 1.016, p = 0.033) were independent risk factors for exercise. Moreover, male sex (B = 2.803, p < 0.001) was an independent protective factor, while advanced age (B = -0.097, p < 0.001), higher body mass index (B = -0.154, p < 0.001), and pain (B = -0.643, p = 0.023) were independent risk factors for exercise intensity. After adjustment for other confounders, exercise (B = 5.787, p = 0.037) was an independent protective factor for total score of QoL in PD patients. CONCLUSION: In the current study, 81.7% of PD patients performed exercise in the post-COVID-19 period. Pain and anemia were independent risk factors for exercise in PD patients. Advanced age, female sex, higher body mass index, and pain were independently associated with lower exercise capacity in PD patients. PD patients undergoing exercise had better QoL.

Triglyceride glucose-body mass index and cardiovascular mortality in patients undergoing peritoneal dialysis: a retrospective cohort study.

BACKGROUND: Recent studies have shown that triglyceride glucose-body mass index (TyG-BMI) is associated with the risk of ischemic stroke and coronary artery disease. However, little attention has been given to the association between TyG-BMI and cardiovascular disease (CVD) mortality in patients undergoing peritoneal dialysis (PD). Therefore, this study aimed to explore the relationship between TyG-BMI and CVD mortality in southern Chinese patients undergoing PD. METHODS: Incident patients receiving PD from January 1, 2006, to December 31, 2018, with baseline serum triglyceride, glucose, and body mass index (BMI) information, were recruited for this single-center retrospective cohort study. TyG-BMI was calculated based on fasting plasma glucose, triglyceride, and BMI values. The association between TyG-BMI, CVD and all-cause mortality was evaluated using a multivariate-adjusted Cox proportional hazard regression model. RESULTS: Of 2,335 patients, the mean age was 46.1 ± 14.8 years; 1,382 (59.2%) were male, and 564 (24.2%) had diabetes. The median TyG-BMI was 183.7 (165.5-209.2). Multivariate linear regression showed that advanced age, male sex, history of CVD, higher levels of albumin and low-density lipoprotein cholesterol, and higher urine output were correlated with a higher TyG-BMI (P < 0.05). During a median follow-up period of 46.6 (22.4-78.0) months, 615 patients died, of whom 297 (48.2%) died as a result of CVD. After adjusting for demographics and comorbidities, TyG-BMI was significantly associated with an increased risk of CVD mortality (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.05-2.17) and all-cause mortality (HR 1.36, 95% CI 1.05-1.75). After full adjustment, the 28% risk of CVD mortality (HR 1.28, 95% CI 1.13-1.45) and 19% risk of all-cause mortality were elevated (HR 1.19, 95% CI 1.09-1.31) when TyG-BMI increased by 1 stand deviation (SD) (34.2). CONCLUSIONS: A higher baseline TyG-BMI was independently associated with an increased risk of CVD and all-cause mortality in patients receiving PD.

Remnant cholesterol predicts cardiovascular mortality beyond low-density lipoprotein cholesterol in patients with peritoneal dialysis.

BACKGROUND: Patients undergoing peritoneal dialysis (PD) are prone to dyslipidemia. However, studies concerning remnant cholesterol (RC) in such patients are limited. OBJECTIVE: We aimed to investigate the association between RC and cardiovascular (CV) mortality in patients on PD. METHODS: Patients who initiated PD at our center (2006-2018) were retrospectively enrolled. Adjusted Cox models were used to evaluate the independent association between baseline RC levels and CV mortality. We classified patients into 4 concordant/discordant categories according to their baseline lipid profiles. Cox models were then used to determine the association between different low-density lipoprotein cholesterol (LDL-C) and RC levels and CV mortality risk. RESULTS: The study enrolled 2333 individuals, with a mean RC of 33.4 mg/dL. RC levels were positively associated with CV mortality risk independent of LDL-C in patients on PD (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1. 00-1.10). In the concordant/discordant categories, patients with high LDL-C and RC levels had a higher CV mortality risk (HR: 1.52; 95% CI: 1.01-2.28) than those with low LDL-C and RC levels in the entire cohort. Moreover, in older patients, a higher RC level increased CV mortality risk regardless of the LDL-C level (HR: 2.41, 95% CI: 1.22-4.74; HR: 2.15, 95% CI: 1.12-4.14). CONCLUSIONS: RC levels are elevated in patients on PD and can predict CV mortality beyond LDL-C levels. RC levels should be considered alongside LDL-C levels when assessing prognostic lipid levels in these patients. More attention should be given to RC than to LDL-C in older patients undergoing PD.

FNDC5 inhibits autophagy of bone marrow mesenchymal stem cells and promotes their survival after transplantation by downregulating Sp1.

Regenerative therapy based on mesenchymal stem cells (MSCs) has great promise to achieve functional recovery in cerebral infarction patients. However, the survival rate of transplanted MSCs is extremely low because of destructive autophagy caused by the harsh ischemic microenvironment in cerebral infarct tissue. The mechanism by which fibronectin type III domain protein 5 (FNDC5) regulates autophagy of transplanted bone marrow-MSCs (BMSCs) following ischemic injury needs to be elucidated. In this study, we confirmed that FNDC5 promotes the survival of transplanted BMSCs in a rat cerebral infarction model. Furthermore, bioinformatic analysis and verification experiments revealed the transcription factor, Sp1, to be a key mediator of autophagy regulation by FNDC5. FNDC5 significantly inhibited BMSC autophagy by down-regulating Sp1 and the autophagy-related Sp1-target gene, ULK2. Transplanted BMSCs overexpressing FNDC5 (BMSCs-OE-FNDC5) promoted neurovascular proliferation and alleviated ischemic brain injury in cerebral infarct model rats. However, the increased survival and enhanced neuroprotective effect of transplanted BMSCs-OE-FNDC5 were reversed by simultaneous overexpression of Sp1. Our data indicate a role for FNDC5 in BMSC survival and reveal a novel mechanism of transcription regulation through Sp1 for the autophagy-related gene ULK2. Modulation of FNDC5 may promote survival capacity and improve the therapeutic effect of BMSCs in various tissues following ischemia.

The feasibility of incremental peritoneal dialysis for older patients on peritoneal dialysis.

Background: This study was performed to investigate the feasibility of incremental peritoneal dialysis (iPD) in older patients. Methods: In this retrospective cohort study, we enrolled peritoneal dialysis (PD) patients with age ≥ 60 years old at our center from 2008 to 2017. The patients were divided into two groups based on the daily PD exchanges: iPD group (≤3 × 2 L exchanges), and full dose group (≥4 × 2 L exchanges). Kaplan-Meier curves and multivariate Cox regression models were applied to evaluate the risks of anuria and mortalities between groups. Results: A total of 238 patients (186 in full dose group and 52 in iPD group) were enrolled. The mean age was 67.8 ± 5.7 years, and 45.8% were females. The baseline glomerular filtration rate was 4.15 ± 2.39 mL/min/1.73 m2 . Multivariate Cox regression models showed that patients in the iPD group patients had significantly decreased risk of anuria (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.81; p = 0.008), and all-cause mortality (HR, 0.59; 95% CI, 0.36-0.98; p = 0.04). Additionally, the incidence of peritonitis was significantly lower in the iPD group than that in the full dose group (0.115 vs. 0.197 episodes per person-year, p = 0.03) during the 36 months of PD commencement. Conclusion: Older patients with iPD were independently associated with better preservation of residual kidney function and survival outcomes. Moreover, iPD regimens are also associated with reduced incidence of peritonitis. The iPD strategy might offer a feasible option for older patients.

Mesenteric elasticity assessed by shear wave elastography and its relationship with peritoneal function in peritoneal dialysis patients.

Background: We evaluated the mesenteric elasticity in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using shear wave elastography (SWE) and investigated its relationships with peritoneal function. Methods: Patients were recruited in our peritoneal dialysis (PD) centre between 15 July 2019 and 31 December 2021 and followed up to 31 March 2022. Twelve chronic kidney disease (CKD) patients and nineteen healthy people were included as controls. Correlation, linear regression and Cox regression analyses were applied. Results: Of the 218 PD patients, 104 (47.8%) were male. Their mean age was 48.0 ± 13.2 years and the median PD duration was 59.0 months [interquartile range (IQR) 17.0-105]. The median mesenteric SWE value was 8.15 kPa (IQR 5.20-16.1). The mesenteric SWE values of patients with a PD duration of <3 months [5.20 kPa (IQR 3.10-7.60)] were not significantly different from those of CKD patients [4.35 kPa (IQR 2.63-5.20), P = .17] and healthy controls [3.60 kPa (IQR 2.90-5.10), P = .13] but were lower than those of patients with a PD duration of 3 months-5 years [6.40 kPa (IQR 4.10-10.5), P < .001], 5-10 years [11.9 kPa (IQR 7.40-18.2), P < .001] and >10 years [19.3 kPa (IQR 11.7-27.3), P < .001]. Longer PD duration (ß = 0.58, P < .001), high effluent interleukin-6 (ß = 0.61, P = .001) and low effluent cancer antigen 125 (ß = -0.34, P = .03) were independently associated with low mesenteric elasticity. The mesenteric SWE value was independently correlated with the dialysate:plasma creatinine ratio (ß = 0.39, P = .01) and negatively correlated with the total daily fluid volume removed (ß = -0.17, P = .03). High mesenteric SWE values were an independent risk factor for death-censored technique failure [adjusted hazard ratio 4.14 (95% confidence interval 1.25-13.7), P = .02). Conclusions: SWE could be used to non-invasively characterize peritoneal textural changes, which were closely associated with changes in peritoneal function.

Temporal regulation of notch activation improves arteriovenous fistula maturation.

BACKGROUND: Arteriovenous fistula (AVF) maturation is a process involving remodeling of venous arm of the AVFs. It is a challenge to balance adaptive AVF remodeling and neointima formation. In this study we temporally controlled Notch activation to promote AVF maturation while avoiding neointima formation. METHODS: Temporal Notch activation was controlled by regulating the expression of Notch transcription factor, RBP-Jκ, or dnMAML1 (dominant negative MAML2) in vascular smooth muscle cells (VSMCs). AVF mouse model was created and VSMC phenotype dynamic changes during AVF remodeling were determined. RESULTS: Activated Notch was found in the nuclei of neointimal VSMCs in AVFs from uremic mice. We found that the VSMCs near the anastomosis became dedifferentiated and activated after AVF creation. These dedifferentiated VSMCs regained smooth muscle contractile markers later during AVF remodeling. However, global or VSMC-specific KO of RBP-Jκ at early stage (before or 1 week after AVF surgery) blocked VSMC differentiation and neointima formation in AVFs. These un-matured AVFs showed less intact endothelium and increased infiltration of inflammatory cells. Consequently, the VSMC fate in the neointima was completely shut down, leading to an un-arterialized AVF. In contrast, KO of RBP-Jκ at late stage (3 weeks after AVF surgery), it could not block neointima formation and vascular stenosis. Inhibition of Notch activation at week 1 or 2, could maintain VSMC contractile markers expression and facilitate AVF maturation. CONCLUSIONS: This work uncovers the molecular and cellular events in each segment of AVF remodeling and found that neither sustained increasing nor blocking of Notch signaling improves AVF maturation. It highlights a novel strategy to improve AVF patency: temporally controlled Notch activation can achieve a balance between adaptive AVF remodeling and neointima formation to improve AVF maturation. TRANSLATIONAL PERSPECTIVE: Adaptive vascular remodeling is required for AVF maturation. The balance of wall thickening of the vein and neointima formation in AVF determines the fate of AVF function. Sustained activation of Notch signaling in VSMCs promotes neointima formation, while deficiency of Notch signaling at early stage during AVF remodeling prevents VSMC accumulation and differentiation from forming a functional AVFs. These responses also delay EC regeneration and impair EC barrier function with increased inflammation leading to failed vascular remodeling of AVFs. Thus, a strategy to temporal regulate Notch activation will improve AVF maturation.

Downregulation of the endothelial histone demethylase JMJD3 is associated with neointimal hyperplasia of arteriovenous fistulas in kidney failure.

Jumonji domain-containing protein-3 (JMJD3), a histone H3 lysine 27 (H3K27) demethylase, promotes endothelial regeneration, but its function in neointimal hyperplasia (NIH) of arteriovenous fistulas (AVFs) has not been explored. In this study, we examined the contribution of endothelial JMJD3 to NIH of AVFs and the mechanisms underlying JMJD3 expression during kidney failure. We found that endothelial JMJD3 expression was negatively associated with NIH of AVFs in patients with kidney failure. JMJD3 expression in endothelial cells (ECs) was also downregulated in the vasculature of chronic kidney disease (CKD) mice. In addition, specific knockout of endothelial JMJD3 delayed EC regeneration, enhanced endothelial mesenchymal transition, impaired endothelial barrier function as determined by increased Evans blue staining and inflammatory cell infiltration, and accelerated neointima formation in AVFs created by venous end to arterial side anastomosis in CKD mice. Mechanistically, JMJD3 expression was downregulated via binding of transforming growth factor beta 1-mediated Hes family transcription factor Hes1 to its gene promoter. Knockdown of JMJD3 enhanced H3K27 methylation, thereby inhibiting transcriptional activity at promoters of EC markers and reducing migration and proliferation of ECs. Furthermore, knockdown of endothelial JMJD3 decreased endothelial nitric oxide synthase expression and nitric oxide production, leading to the proliferation of vascular smooth muscle cells. In conclusion, we demonstrate that decreased expression of endothelial JMJD3 impairs EC regeneration and function and accelerates neointima formation in AVFs. We propose increasing the expression of endothelial JMJD3 could represent a new strategy for preventing endothelial dysfunction, attenuating NIH, and improving AVF patency in patients with kidney disease.

Changes of antibiotic resistance over time among Escherichia coli peritonitis in Southern China.

Escherichia coli (E. coli) is the main cause of Gram-negative bacterial peritonitis among peritoneal dialysis patients. According to the 2016 update of the International Society for Peritoneal Dialysis Peritonitis Recommendations, drug susceptibilities of specific organisms should be regularly monitored. The aim of this study was to examine the evolution of antimicrobial resistance of E. coli peritonitis from 2006 to 2018. Two hundred and fifty-three episodes of E. coli peritonitis were enrolled in our study, corresponding to a rate of 0.024 episodes per patient-year. According to drug sensitivity test results, isolates were most sensitive to carbapenems, followed by cefmetazole, piperacillin/tazobactam, cefotetan and amikacin, with an overall rate of more than 90% in both cohorts. Cefazolin and ciprofloxacin resistance increased significantly from 2006-2011 to 2012-2018. Conversely, cefepime and ceftazidime resistance decreased significantly. The extended-spectrum ß-lactamase (ESBL) rate fluctuated from 34.7% in 2006-2011 to 46.8% in 2012-2018. Compared with the ESBL-negative strains, ESBL-producing E. coli were more likely be resistant to ampicillin, ampicillin/sulbactam, cephalosporins, quinolones, aminoglycosides, furadantin and sulfamethoxazole and accounted for over 50% of the drug resistance. In the correlation analysis, E. coli displayed significantly increased resistance to cefazolin and ciprofloxacin, a finding correlated with ESBL production (r = 0.883 and 0.276 respectively, p < 0.001 and p = 0.003). In conclusion, the rate of E. coli peritonitis declined stably in recent years, but the resistance to antimicrobial was high.

Association between urinary VEGFA and renal pathology of IgA nephropathy patients.

BACKGROUND: Renal biopsy remains the golden standard for diagnosing and monitoring IgA nephropathy (IgAN). Vascular endothelial growth factor A (VEGFA) was crucial for the survival of glomerular cells. Our aim was to screen the expression pattern of urinary, circulating and renal VEGFA in IgAN patients to reveal their relationship with renal pathology and outcomes. METHODS: Baseline VEGFA levels were determined with ELISA, real-time PCR and immunohistochemistry. Associations between VEGFA expression and clinical-pathological parameters, and renal outcomes were evaluated. RESULTS: Compared with healthy controls, urinary VEGFA level was obviously elevated in IgAN patients (76.19 ± 63.67 pg/mg Cr vs 146.67 ± 232.71 pg/mg Cr, p = 0.0291) and not correlated with serum VEGFA level. Baseline urinary VEGFA was significantly associated with gender and tubular atrophy/interstitial fibrosis by stepwise multivariate regression analysis. Urinary VEGFA was higher in male patients accompanied with higher serum creatinine, larger proportion of hypertension and recurrent hematuria than in female patients. In the kidney of IgAN patients, VEGFA were robustly expressed in the parietal epithelial cells, podocytes, mesangial cells and tubular epithelial cells. After a follow-up duration of 38.53 ± 27.14 months, IgAN patients with higher urinary VEGFA level were found to have a poorer renal outcome of renal replacement therapy (HR = 1.027, p = 0.037) or composite outcome (HR = 1.023, p = 0.039) after adjusting for confounders. CONCLUSIONS: Increased urinary VEGFA might reflect certain renal pathology and, although not fully specific, still could be served as a valuable noninvasive indicator in predicting renal progression of IgAN.

PDGFRA in vascular adventitial MSCs promotes neointima formation in arteriovenous fistula in chronic kidney disease.

Chronic kidney disease (CKD) induces the failure of arteriovenous fistulas (AVFs) and promotes the differentiation of vascular adventitial GLI1-positive mesenchymal stem cells (GMCs). However, the roles of GMCs in forming neointima in AVFs remain unknown. GMCs isolated from CKD mice showed increased potential capacity of differentiation into myofibroblast-like cells. Increased activation of expression of PDGFRA and hedgehog (HH) signaling were detected in adventitial cells of AVFs from patients with end-stage kidney disease and CKD mice. PDGFRA was translocated and accumulated in early endosome when sonic hedgehog was overexpressed. In endosome, PDGFRA-mediated activation of TGFB1/SMAD signaling promoted the differentiation of GMCs into myofibroblasts, extracellular matrix deposition, and vascular fibrosis. These responses resulted in neointima formation and AVF failure. KO of Pdgfra or inhibition of HH signaling in GMCs suppressed the differentiation of GMCs into myofibroblasts. In vivo, specific KO of Pdgfra inhibited GMC activation and vascular fibrosis, resulting in suppression of neointima formation and improvement of AVF patency despite CKD. Our findings could yield strategies for maintaining AVF functions.

Bioimpedance Guided Fluid Management in Peritoneal Dialysis: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Bioelectrical impedance analysis (BIA) devices can help assess volume overload in patients receiving maintenance peritoneal dialysis. However, the effects of BIA on the short-term hard end points of peritoneal dialysis lack consistency. This study aimed to test whether BIA-guided fluid management could improve short-term outcomes in patients on peritoneal dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A single-center, open-labeled, randomized, controlled trial was conducted. Patients on prevalent peritoneal dialysis with volume overload were recruited from July 1, 2013 to March 30, 2014 and followed for 1 year in the initial protocol. All participants with volume overload were 1:1 randomized to the BIA-guided arm (BIA and traditional clinical methods) and control arm (only traditional clinical methods). The primary end point was all-cause mortality and secondary end points were cardiovascular disease mortality and technique survival. RESULTS: A total of 240 patients (mean age, 49 years; men, 51%; diabetic, 21%, 120 per group) were enrolled. After 1-year follow-up, 11(5%) patients died (three in BIA versus eight in control) and 21 patients were permanently transferred to hemodialysis (eight in BIA versus 13 in control). The rate of extracellular water/total body water decline in the BIA group was significantly higher than that in the control group. The 1-year patient survival rates were 96% and 92% in BIA and control groups, respectively. No significant statistical differences were found between patients randomized to the BIA-guided or control arm in terms of patient survival, cardiovascular disease mortality, and technique survival (P>0.05). CONCLUSIONS: Although BIA-guided fluid management improved the fluid overload status better than the traditional clinical method, no significant effect was found on 1-year patient survival and technique survival in patients on peritoneal dialysis.

Decreased Jagged1 expression in vascular smooth muscle cells delays endothelial regeneration in arteriovenous graft.

AIMS: It is well-established that endothelial dysfunction promotes activation of vascular smooth muscle cell (VSMC). Whether decreased accumulation of VSMCs affects endothelial regeneration and functions in arteriovenous graft (AVG) remodelling has not been studied. We sought to identify mechanisms by which the Notch ligand, Jagged1, in VSMCs regulates endothelial cell (EC) functions in AVGs. METHODS AND RESULTS: AVGs were created in transgenic mice bearing VSMC-specific knockout (KO) or overexpression of Jagged1. VSMC migration, EC regeneration, and its barrier functions as well as AVG remodelling were evaluated. Jagged1 expression was induced in VSMCs of neointima in the AVGs. Jagged1 KO in VSMCs inhibited the accumulation of extracellular matrix as well as VSMC migration. Fewer α-SMA-positive VSMCs were found in AVGs created in VSMC-specific Jagged1 KO mice (VSMCJagged1 KO mice) vs. in WT mice. Decreased VSMCs in AVGs were associated with deterioration of EC functions. In AVGs created in transgenic mice bearing Jagged1 KO in VSMCs exhibited delayed EC regeneration and impaired EC barrier function. Barrier dysfunction of ECs increased inflammatory cell infiltration and dysregulation of AVG remodelling and arterialization. The increased expression of IL-1ß in macrophages was associated with expression of adhesion markers in ECs in AVGs created in VSMCJagged1 KO mice. In contrast, AVGs created in mice with overexpression of Jagged1 in VSMCs exhibited improved EC regeneration plus decreased macrophage infiltration. This led to AVG remodelling and arterialization. In co-cultures of ECs and VSMCs, Jagged1 deficiency in VSMCs suppressed N-cadherin and integrin ß3 expression in ECs. Inhibition of integrin ß3 activation delayed EC spreading and migration. Notably, Jagged1 overexpression in VSMCs or treatment with recombinant Jagged1 stimulated the expression of N-cadherin and integrin ß3 in ECs. Jagged1-induced responses were blocked by inhibition of Notch signalling. CONCLUSIONS: Jagged1 expression in VSMCs maintains EC barrier functions and blocks infiltration of macrophages. These responses promote remodelling and arterialization of AVGs.

Type D personality, medication adherence and peritonitis in continuous ambulatory peritoneal dialysis patients.

The present study attempted to investigate the association among Type D, medication adherence and peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. Type D personality was assessed by the Chinese 14-item Type D Personality Scale (DS14) in CAPD patients. Patients' medication adherence was assessed by the Medication Adherence Report Scale, retrospectively. Of the 385 CAPD patients who were investigated, 137 (35.6%) patients had a Type D personality. The medication adherence was significantly poorer in the Type Ds compared with that of the non-Type Ds (21.5 ± 2.8 vs. 22.5 ± 2.5 score, p = 0.002). Using multiple linear regression analysis, we found that Type D personality was independently associated with medication adherence (ß = 0.56, p < 0.05). Furthermore, the overall peritonitis-free survival rate of non-Type Ds was significantly higher than that of Type Ds (X2 = 4.41, p = 0.025). Using Cox regression, Type D personality (HR 1.67; 95% confidence interval [CI] 1.07-2.59; p = 0.022) and adherence to bag exchange procedure (HR 1.54; 95% CI 1.11-2.14; p = 0.009) predicted the development of the first peritonitis, even after adjustment for confounders. The current study is the first to identify a strong association among Type D, medication adherence and peritonitis in CAPD patients.

Peritonitis Affects the Relationship Between Low-Density Lipoprotein Cholesterol and Cardiovascular Events in Peritoneal Dialysis Patients.

BACKGROUND: In peritoneal dialysis (PD), the relationship among low-density lipoprotein cholesterol (LDL-C), peritonitis, and cardiovascular (CV) disease has not been clarified. This study was performed to explore their associations in a large PD cohort. METHODS: This retrospective cohort study included incident patients who received PD catheter insertion in our centre. The primary outcome was the first CV event (nonfatal myocardial infarction, CV death, non-haemorrhagic stroke, or any arterial revascularization procedure). Secondary outcomes were the occurrence of peritonitis, CV mortality, and all-cause mortality. RESULTS: This study included 1294 patients, whose mean age was 48.1 years. After adjustment for confounders in negative binomial regression models, lower LDL-C quartiles were independently associated with a higher risk of peritonitis, compared with the highest quartile. The multivariate competing risk model showed no significant association between baseline LDL-C and the first CV event in the overall population. However, stratified analysis showed that each 1 mmol/L increase in LDL-C was independently associated with a 21% (subdistribution hazard ratio: 1.21, 95% confidence interval: 1.06-1.39) increased risk of the first CV event among peritonitis-free patients, and with a 20% (subdistribution hazard ratio: 0.80, 95% confidence interval: 0.65-0.99) decreased risk among patients with peritonitis. Moderating-effect analysis showed that the presence of peritonitis significantly influenced the relationships between LDL-C and CV events (P < 0.001). Similar results were also observed in the relationship between LDL-C and mortality. CONCLUSIONS: PD patients with lower baseline LDL-C had a higher risk of peritonitis. The effect of LDL-C on CV events and mortality was different by the presence of peritonitis events.

Long-Term Clinical Outcomes of Lupus Nephritis Patients Undergoing Peritoneal Dialysis: A Matched, Case-Control Study.

The long-term clinical outcomes of peritoneal dialysis (PD) for patients with lupus nephritis (LN) have not been well researched. In the present study, we investigated the long-term prognosis of a Chinese PD cohort. This was a retrospective case-control study that included LN patients receiving PD treatment for more than 90 days from January 2006 to December 2012. Non-diabetic control patients were selected using a ratio of 1:2 for age- and gender-matching. The primary outcome was all-cause mortality. Secondary outcomes included technique failure and hospitalization rate. All patients were followed up to 31 December 2017. A total of 28 LN patients on PD (89.3% female, mean age 42.2±15.8 years) and 56 controls were included. After a median follow-up period of 53.1 months, 11 LN patients died. The cumulative 1-, 3-, and 5-year patient survival rates were 92.4%, 84.7%, and 67.6% in LN patients, and 100%, 93.5%, and 82.9% in the control group, respectively (p = 0.035). After adjusting for confounders, LN was not significantly associated with mortality (hazard ratio [HR]: 1.39, 95% confidence interval [CI]: 0.45 - 4.26); However, LN was still an independent risk factor of technique failure (HR: 2.87, 95% CI: 1.08 - 7.66). Meanwhile, the LN group had significantly higher hospitalization and infection rates. In conclusion, LN patients undergoing PD had poor patient survival and technique survival, and higher hospitalization and infection rates.

Gender impact on baseline peritoneal transport properties in incident peritoneal dialysis patients.

OBJECTIVE: To explore the impact of gender on baseline peritoneal transportation properties and ultrafiltration (UF) ability. METHOD: Patients who started peritoneal dialysis (PD) in our PD center were retrospectively analyzed. Peritoneal transportation characteristics and other UF-associated factors were compared between male and female patients. Stepwise linear regression analysis and propensity score (PS) analysis were used to identify the predictors of peritoneal equilibration test (PET) UF. RESULTS: A total of 1052 patients (424 women and 628 men) were included. Compared with male PD patients, females were older (48.4 ± 15.3 vs 46.0 ± 14.6 years), with less total body water (27.6 ± 2.5 vs 36.9 ± 3.8 L), lower body mass index (21.2 ± 3.4 vs 22.0 ± 2.9 kg/m2), lower albumin levels (37.4 ± 5.2 vs 38.0 ± 5.4 g/L), worse renal function [residual glomerular filtration rate: 2.6 (1.2, 3.9) vs 3.2 (1.8, 5.5) mL/min/1.73 m2], lower dialysate-to-plasma ratio of creatinine at 4-h PET (D/PCr; 0.68 ± 0.11 vs 0.72 ± 0.12), higher 4-h effluent glucose level/0-h effluent glucose level of PET (D4/D0; 0.41 ± 0.08 vs 0.38 ± 0.08), better UF ability [PET UF: 320 (200, 400) vs 260 (150, 360) mL], and higher Kt/V (2.66 ± 0.60 vs 2.23 ± 0.66) (all P < 0.05) when starting PD. Stepwise linear regression analysis showed that D4/D0, residual urine output, D/PCr, and gender are independently associated with PET UF. By propensity score analysis, female patients still showed significantly more PET UF than male counterparts even with balanced D/PCr, D4/D0, and residual urine. CONCLUSION: Among the new PD patients, females showed much higher D4/D0, lower D/PCr, and more PET UF than males, with better PET UF being independent of slower solute transportation.