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Trimethylamine-N-oxide (TMAO), a gut microbiota-produced metabolite, is accumulated in chronic kidney disease (CKD) patients. It is well known to contribute to CKD-related cardiovascular complications. However, the effect of TMAO on peritoneal dialysis (PD)-related peritonitis remains largely unknown. Here, we demonstrate that serum concentrations of TMAO were positively correlated with C-reactive protein levels, and the appearance rate of dialysate IL-6 and PAI-1, in PD patients. During the follow-up period of 28.3 ± 8.0 months, patients with higher TMAO levels (≥50 μM) had a higher risk of new-onset peritonitis (HR, 3.60; 95%CI, 1.18-10.99; P=0.025) after adjusting for sex, age, diabetes, PD duration, BUN, rGFR, C-reactive protein, BMI and β2-M. In CKD rat models, TMAO significantly promoted peritoneal dialysate-induced inflammatory cell infiltration, inflammatory cytokines production in the peritoneum. In vitro study revealed that TMAO directly induced primary peritoneal mesothelial cell necrosis, together with increased production of pro-inflammatory cytokines including CCL2, TNF-α, IL-6, and IL-1β. In addition, TMAO significantly increased TNF-α-induced P-selectin production in mesothelial cells, as well as high glucose-induced TNF-α and CCL2 expression in endothelial cells. In conclusion, our data demonstrate that higher levels of TMAO exacerbate peritoneal inflammation and might be a risk factor of incidence of peritonitis in PD patients.

Peritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long‐term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. We showed here that dialysate MMP‐7 levels markedly increased in the patients with PD, and the elevated MMP‐7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP‐7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP‐7 activated mitogen‐activated protein kinases (MAPKs)‐extracellular signal‐regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin‐1 (AQP‐1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP‐7‐mediating AQP‐1 up‐regulation and cellular homeostasis. In summary, all the findings indicate that MMP‐7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP‐7 might be a non‐invasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.

BACKGROUND Hypokalemia (LK) was associated with peritonitis in peritoneal dialysis (PD) patients, while the role of its degree and duration have not been fully established. Here, we conducted a retrospective cohort study to identify the relationships of LK degree and duration with peritonitis in PD patients. METHODS A total of 602 PD patients in our department from Jan 1st, 2009 to Dec 31st, 2019 entered the last analysis. Data were collected from their medical records. Serum potassium (SK) levels, degree of hypokalemia, and duration of hypokalemia were analysed with peritonitis. The time association of hypokalemia and peritonitis was also analysed. RESULTS There were totally 320 (53.7%) and 123 (20.7%) patients who had ever suffered from LK and serious hypokalemia (SLK) in the cohort. Only 6.82% and 0.5% of patients had LK and SLK at baseline, while the incidence increased and kept in 25%-32% and 5.5%-8.2% after PD. Both LK (HR 1.437, 95% CI 1.014-2.038, P = .042) and SLK (HR 2.021, 95% CI 1.429-2.857, P

Background: Serum phosphorus (SP) level is closely associated with overall mortality and cardiovascular events, while the role of SP controlled duration is not fully recognized. Here, we conducted a retrospective cohort study in our department to identify the relationship of SP controlled duration with clinical outcomes in patients undergoing peritoneal dialysis (PD). Methods: PD patients in our center from January 1, 2009, to June 30, 2019, were followed up at 2-month (the first year) or 5-month (the next follow-up period) intervals, and until death, until PD withdrawal, or until June 30, 2019. Data at each follow-up point were collected from their medical records. SP levels, changed degree of SP over baseline, and SP controlled duration were analyzed with overall mortality, PD withdrawal (including death, transferred to hemodialysis, and received renal transplantation), and combined endpoint (including death, acute heart failure, cardiovascular event, and stroke). Results: A total of 530 patients entered the analysis. Of them, 456 (86.0%) had hyperphosphatemia before dialysis, and the SP levels decreased soon after dialysis. The degree of SP change over baseline was the maximum at the 3rd month after dialysis (−31.0%), and lower degree was associated with higher overall mortality (hazard ratio [HR], 1.012; 95% CI, 1.004–1.020; p = 0.003). The median SP controlled duration was 13 (5–28) months, and longer duration was significantly associated with lower overall mortality (HR, 0.968; 95% CI, 0.956–0.981; p < 0.001). After categorization, duration more than 12 months greatly improved overall mortality with a HR of 0.197 (0.082–0.458; p < 0.001 vs. SP never controlled group) and 0.329 (0.150–0.724; p = 0.006 vs. duration Conclusions: In summary, both degree and duration of SP control were tightly associated with overall mortality. We should control SP levels as early, as possible, and as long as we could.

BACKGROUND Peritoneal dialysis-associated peritonitis (PDAP) is one of the major causes of peritoneal dialysis (PD) failure and death. Therefore, it is important to determine how to effectively treat patients with PDAP. MATERIALS AND METHODS We analyzed the pathogen spectrum and bacterial resistance in 203 PDAP cases that were enrolled in this study from January 1, 2015 to December 31, 2017. All patients were infected with peritonitis and had been treated with antibiotics while at our center. Bacterial culture results of PD fluid and pathogen drug resistance were collected and analyzed. A total of 159 cases (78.3%) had a positive bacterial culture of PD fluid. RESULTS A total of 47 pathogens were identified, including 19 (40.4%) Gram-positive cocci strains (the most common was Staphylococcus spp.), 15 (31.9%) Gram-negative bacilli strains (the most common was Escherichia coli, 4 fungal strains, and 9 other strains. The drug sensitivity test showed that Gram-positive cocci were sensitive to vancomycin (94.9%), but had a high resistance to cefazolin (67.7%). Gram-negative bacilli were sensitive to imipenem (96.2%), but had a high resistance to ceftriaxone (60.0%). Voriconazole and itraconazole were sensitive in fungal infections. A total of 162 cases were cured, 37 cases were unresponsive to antibiotic treatment and converted to hemodialysis after Tenckhoff catheter removal, and 4 cases resulted in death. CONCLUSION Gram-positive cocci are still the primary pathogen of PDAP cases in our center, but demonstrate a high resistance to first-generation cephalosporin, which is the suggested treatment per International Society for Peritoneal Dialysis 2016 Peritonitis Recommendations. Therefore, an individualized treatment based on the distribution of pathogens and drug resistance in different centers is more conducive to improve the cure rate of PDAP.

To explore the correlations between AMP-activated protein kinase (AMPK) expression and brain inflammatory response and neurological function factors in rats with chronic renal failure. Chronic renal failure models in rats were established, and the healthy control group (normal group) was set. Chronic renal failure model rats were divided into model group (without any treatment), control group (intraperitoneal injection of normal saline), A-769662 group (intraperitoneal injection of AMPK specific activator), and compound C group (intraperitoneal injection of AMPK specific inhibitor). The results of HE staining showed renal tissue enlargement, and significant pathological changes. Compared with the normal group, AMPK level in peripheral blood and AMPK mRNA and protein expressions in brain tissue were significantly reduced, and AMPK pathway activation was significantly inhibited in other groups. Compared with the model group, rats in the A-769662 group had significantly decreased serum creatinine (Scr) and blood urea nitrogen (BUN) levels and γ-aminobutyric acid (γ-GABA) content, significantly increased brain-derived neurotrophic factor (BDNF) positive expressions and 5-hydroxytryptamine (5-HT) content, and decreased interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule 1 (ICAM-1) expressions (all P

Ultrafiltration failure (UFF) is a major cause of water retention, left heart failure (LHF), and peritoneal dialysis (PD) failure. Automated peritoneal dialysis (APD) might have better ultrafiltration (UF) than continuous ambulatory peritoneal dialysis (CAPD). Here, we have studied whether short-term APD could increase UF and improve LHF. 47 patients were included in this study from December 1, 2015, to January 1, 2017. All patients had been treated with CAPD before they came to our center and were treated with APD in the hospital. 24-hour peritoneal UF volume, 24-hour urine volume, body weight, blood pressure, LHF class, serum creatinine, blood urea nitrogen, albumin, potassium, hemoglobin, and glucose were collected and compared before and after receiving short-time APD. A total of 47 patients (31 men, mean age 46.8 ± 16.2 years, mean duration 26 months (2 - 195 months)) were enrolled in this study. Of the 47 patients, peritoneal dialysis UF was significantly increased when receiving short-term APD compared to CAPD (1,261.9 ± 329.6 mL vs. 706.2 ± 222.3 mL, p < 0.001), and body weights had significantly decreased 3 days after treatment with APD (57.73 ± 10.5 vs. 59.81 ± 10.8, p < 0.001). LHF class was significantly decreased 3 days after receiving APD (1.7 ± 0.8 vs. 2.4 ± 1.0, p < 0.001). Blood pressure was well controlled 3 days after treatment with APD (146.6 ± 14.4 vs. 162.5 ± 23.8 of SBP, p = 0.007, and 85.6 ± 11.1 vs. 95.6 ± 14.7 of DBP, p = 0.001). In conclusion, short-term APD could significantly increase ultrafiltration, rapidly alleviate edema and improve LHF, and might be an effective method to treat UFF and LHF in PD patients. .