Analysis of factors influencing vascular calcification in peritoneal dialysis patients and their impact on long-term prognosis.

BACKGROUND: This study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis. METHODS: This retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results. RESULTS: A total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P < 0.001) and longer dialysis time (P = 0.004). Multivariable logistic regression analysis indicated that risk factors for vascular calcification in PD patients included dialysis time, diabetes, hypertension, and SOST. Kaplan-Meier survival analysis showed that the AAC group had a significantly higher mortality rate than the non-AAC group (χ2 = 35.993, P < 0.001). Multivariable Cox regression analysis revealed that dialysis time, diabetes and AAC were risk factors for all-cause mortality in peritoneal dialysis patients. CONCLUSION: Longer dialysis time, comorbid diabetes, comorbid hypertension, and SOST are risk factors for vascular calcification in PD patients. Additionally, AAC, longer dialysis time, and comorbid diabetes are associated with increased risk of all-cause mortality in peritoneal dialysis patients.

Sterile inflammation of peritoneal membrane caused by peritoneal dialysis: focus on the communication between immune cells and peritoneal stroma.

Peritoneal dialysis is a widely used method for treating kidney failure. However, over time, the peritoneal structure and function can deteriorate, leading to the failure of this therapy. This deterioration is primarily caused by infectious and sterile inflammation. Sterile inflammation, which is inflammation without infection, is particularly concerning as it can be subtle and often goes unnoticed. The onset of sterile inflammation involves various pathological processes. Peritoneal cells detect signals that promote inflammation and release substances that attract immune cells from the bloodstream. These immune cells contribute to the initiation and escalation of the inflammatory response. The existing literature extensively covers the involvement of different cell types in the sterile inflammation, including mesothelial cells, fibroblasts, endothelial cells, and adipocytes, as well as immune cells such as macrophages, lymphocytes, and mast cells. These cells work together to promote the occurrence and progression of sterile inflammation, although the exact mechanisms are not fully understood. This review aims to provide a comprehensive overview of the signals from both stromal cells and components of immune system, as well as the reciprocal interactions between cellular components, during the initiation of sterile inflammation. By understanding the cellular and molecular mechanisms underlying sterile inflammation, we may potentially develop therapeutic interventions to counteract peritoneal membrane damage and restore normal function.

Higher N-terminal pro-brain natriuretic peptide level at onset of peritoneal dialysis-related peritonitis is a risk factor for technique failure.

BACKGROUND: Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP. METHODS: A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure. RESULTS: Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure. CONCLUSIONS: This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.

LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis.

Peritoneal dialysis (PD), hemodialysis and kidney transplantation are the three therapies to treat uremia. However, PD is discontinued for peritoneal membrane fibrosis (PMF) and loss of peritoneal transport function (PTF) due to damage from high concentrations of glucose in PD fluids (PDFs). The mechanism behind PMF is unclear, and there are no available biomarkers for the evaluation of PMF and PTF. Using microarray screening, we found that a new long noncoding RNA (lncRNA), RPL29P2, was upregulated in the PM (peritoneal membrane) of long-term PD patients, and its expression level was correlated with PMF severity and the PTF loss. In vitro and rat model assays suggested that lncRNA RPL29P2 targets miR-1184 and induces the expression of collagen type I alpha 1 chain (COL1A1). Silencing RPL29P2 in the PD rat model might suppress the HG-induced phenotypic transition of Human peritoneal mesothelial cells (HPMCs), alleviate HG-induced fibrosis and prevent the loss of PTF. Overall, our findings revealed that lncRNA RPL29P2, which targets miR-1184 and collagen, may represent a useful marker and therapeutic target of PMF in PD patients.

Inhibition of STAT3 by S3I-201 suppress peritoneal fibroblast phenotype conversion and alleviate peritoneal fibrosis.

Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis.

Bone mineral density and related clinical and laboratory factors in peritoneal dialysis patients: Implications for bone health management.

BACKGROUND: End-stage renal disease (ESRD) patients often experience accelerated bone turnover, leading to osteoporosis and osteopenia. This study aimed to determine the prevalence of osteoporosis in Peritoneal Dialysis (PD) patients using bone mineral density (BMD) measurements obtained through dual-energy X-ray absorptiometry (DEXA) scan and to explore any possible associations with clinical and biochemical factors. METHODS: In this cross-sectional study, we enrolled 76 peritoneal dialysis patients from the dialysis center at An-Najah National University Hospital in Nablus, Palestine. We used the DEXA scan to measure BMD at the lumbar spine and hip, with values expressed as T-scores. We conducted a multivariate analysis to explore the relationship between BMD and clinical and biochemical parameters. RESULTS: Over half (52.6%) of the PD patients had osteoporosis, with a higher prevalence observed among patients with lower BMI (p<0.001). Higher alkaline phosphatase levels were found among osteoporotic patients compared to non-osteoporotic patients (p = 0.045). Vitamin D deficiency was also prevalent in this population, affecting 86.6% of patients. No significant correlation was found between 25 vitamin D levels and BMD. No significant correlation was found between Parathyroid hormone (PTH) levels and BMD. CONCLUSION: A notable proportion of PD patients experience reduced BMD. Our study found no correlation between vitamin D levels and BMD, but it highlighted the significant vitamin D deficiency in this population. Furthermore, our analysis indicated a positive correlation between BMI and BMD, especially in the femoral neck area. This underscores the significance of addressing bone health in PD patients to mitigate the risk of fractures and improve their overall well-being.

Peritoneal dialysis related peritonitis: insights from a long-term analysis of an Italian center.

BACKGROUND: Peritonitis is a common and severe complication of peritoneal dialysis (PD). For comparative analysis standardized definitions as well as measurements and outcomes are crucial. However, most PD-related peritonitis studies have been using heterogenous definitions and variable methods to measure outcomes. The ISPD 2022 guidelines have revised and clarified numerous definitions and proposed new peritonitis categories and outcomes. METHODS: Between 1st January 2009 and 31st May 2023, 267 patients who started PD at our institution were included in the study. All PD-related peritonitis episodes that occurred in our unit during the study period were collected. The new definitions and outcomes of ISPD 2022 recommendations were employed. RESULTS: The overall peritonitis rate was 0.25 episode/patient year. Patient cumulative probability of remaining peritonitis-free at one year was 84.2%. The medical cure and refractory peritonitis rates were equal to 70.3 and 22.4%, respectively. Culture-negative peritonitis accounted for 25.6% of all specimens. The rates of peritonitis associated death, hemodialysis transfer, catheter removal and hospitalization were 6.8%, 18.3%, 18.7% and 64.4%, respectively. Relapsing, repeat, recurrent and enteric peritonitis accounted for 7.8%, 6.8%, 4.1% and 2.7% of all episodes, respectively. Catheter insertion, catheter related and pre-PD peritonitis were 4.2, 2.1 and 0.5%. CONCLUSIONS: The implementation of PD-related peritonitis reports using standardized definitions and outcome measurements is of paramount importance to enhance clinical practice and to allow comparative studies.

Peritoneal dialysis in an end-stage renal disease patient with massive ascites and primary liver cancer.

End-stage renal disease (ESRD) coexisted with cirrhosis, ascites, and primary liver cancer represents an extraordinarily rare clinical condition that typically occurs in very late-stage decompensated cirrhosis and is associated with an extremely poor prognosis. We present a case of a 68-year-old male patient with ESRD who experienced various decompensated complications of liver cirrhosis, particularly massive ascites and hepatic space-occupying lesions. Peritoneal dialysis (PD) catheter insertion and continuous ambulatory peritoneal dialysis (CAPD) treatment were successfully performed. During meticulous follow-up, the patient survived for one year but ultimately succumbed to complications related to liver cancer. PD can serve as an efficacious therapeutic approach for such late-stage patients afflicted together with severe cirrhosis, massive ascites and primary liver cancer.

Caffeic acid phenethyl ester restores mitochondrial homeostasis against peritoneal fibrosis induced by peritoneal dialysis through the AMPK/SIRT1 pathway.

Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective interventions for peritoneal fibrosis. In the present study, we explored whether adding caffeic acid phenethyl ester (CAPE) to peritoneal dialysis fluid (PDF) improved peritoneal fibrosis caused by PD and explored the molecular mechanism. We established a peritoneal fibrosis model in Sprague-Dawley rats through intraperitoneal injection of PDF and lipopolysaccharide (LPS). Rats in the PD group showed increased peritoneal thickness, submesothelial collagen deposition, and the expression of TGFß1 and α-SMA. Adding CAPE to PDF significantly inhibited PD-induced submesothelial thickening, reduced TGFß1 and α-SMA expression, alleviated peritoneal fibrosis, and improved the peritoneal ultrafiltration function. In vitro, peritoneal mesothelial cells (PMCs) treated with PDF showed inhibition of the AMPK/SIRT1 pathway, mitochondrial membrane potential depolarization, overproduction of mitochondrial reactive oxygen species (ROS), decreased ATP synthesis, and induction of mesothelial-mesenchymal transition (MMT). CAPE activated the AMPK/SIRT1 pathway, thereby inhibiting mitochondrial membrane potential depolarization, reducing mitochondrial ROS generation, and maintaining ATP synthesis. However, the beneficial effects of CAPE were counteracted by an AMPK inhibitor and siSIRT1. Our results suggest that CAPE maintains mitochondrial homeostasis by upregulating the AMPK/SIRT1 pathway, which alleviates oxidative stress and MMT, thereby mitigating the damage to the peritoneal structure and function caused by PD. These findings suggest that adding CAPE to PDF may prevent and treat peritoneal fibrosis.

The efficacy of fluconazole for anti-fungal prophylaxis in peritoneal dialysis patients: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: The efficacy of fluconazole as a prophylactic strategy in patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) with prior antibiotic exposure is controversial in the current literature. This study aimed to compare a strategy of fluconazole prophylaxis versus no-prophylaxis for patients in PD on antibiotics for previous episodes of peritonitis. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) comparing fluconazole prophylaxis with no prophylaxis for PD-related peritonitis. The search was conducted on PubMed, EMBASE, and Cochrane Central in January 23, 2023. The outcome of interest was the occurrence of fungal peritonitis (FP). RESULTS: We included six studies (1 RCT, 5 observational) with 4515 occurrences of peritonitis, of which 1098 (24.8%) received fluconazole prophylaxis in variable doses, whereas 3417 (75.6%) did not receive prophylaxis during peritonitis episodes. Overall, fluconazole prophylaxis was associated with a lower incidence of FP (OR 0.22; 95% CI 0.12-0.41; p<0.001; I2=0%). Subgroup analysis of studies that administered daily doses of fluconazole also demonstrated a reduced incidence of FP in patients who received antifungal prophylaxis (OR 0.31; CI 0.14-0.69; p=0.004; I2=0%). CONCLUSIONS: In this meta-analysis of 4515 episodes of PD-related peritonitis, prophylaxis with fluconazole significantly reduced episodes of FP as compared with no antifungal prophylaxis.

Exploring the Role of Cell-Free Nucleic Acids and Peritoneal Dialysis: A Narrative Review.

INTRODUCTION: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation. CONCLUSIONS: This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.

The role of macrophage-derived Exosomes in reversing peritoneal fibrosis: Insights from Astragaloside IV.

BACKGROUND: Peritoneal dialysis (PD) is a successful renal replacement therapy for end-stage renal disease. Long-term PD causes mesothelial-mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs), leading to peritoneal fibrosis (PF), which reduces the efficiency of PD. Macrophages are thought to play a role in the onset and perpetuation of peritoneal injury. However, the mechanisms by which macrophages-PMCs communication regulates peritoneal fibrosis are not fully understood resulting in a lack of disease-modifying drugs. Astragaloside IV (AS-IV) possessed anti-fibrotic effect towards PF in PD whereas the mechanistic effect of AS-IV in PD is unknown. METHODS: The primary macrophages were extracted and treated with LPS or AS-IV, then co-cultured with primary PMCs in transwell plates. The macrophage-derived exosomes were extracted and purified by differential centrifugation, then co-cultured with primary PMCs. Small RNA-seq was used to detect differential miRNAs in exosomes, and then KEGG analysis and q-PCR were performed for validation. In vivo PD rat models were established by inducing with high-glucose peritoneal dialysis fluid and different concentrations of AS-IV and exosomes were intraperitoneal injection. Through qRT-PCR, western blotting, and luciferase reporting, candidate proteins and pathways were validated in vivo and in vitro. The functions of the validated pathways were further investigated using the mimic or inhibition strategy. PF and inflammatory situations were assessed. RESULTS: We found AS-IV reversed the MMT of PMCs caused by LPS-stimulated macrophages and the improving effect was mediated by macrophage-derived exosomes in vitro. We also demonstrated that AS-IV significantly reduced the MMT of PMCs in vitro or PF in a rat PD model via regulating exosome-contained miR-204-5p which targets Foxc1/ß-catenin signaling pathway. CONCLUSION: AS-IV attenuates macrophage-derived exosomes induced fibrosis in PD through the miR-204-5p/Foxc1 pathway.

Prognosis and factors related to severe secondary hyperparathyroidism in long-term peritoneal dialysis patients.

Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.

[Cuff Shaving in Recurrent Exit-Site Infections in a Patient on Peritoneal Dialysis].

In patients on peritoneal dialysis, the cutaneous emergency (exit-site) represents a potential access route to the peritoneum; consequently, it can become a site for microbial infections. These infections, initially localized to the exit-site, may spread to the peritoneum causing peritonitis, which is the most common cause of drop-out from peritoneal dialysis and transition to hemodialysis. Peritoneal catheters have dacron caps which have the function of counteracting the traction of the catheter itself and at the same time acting as a barrier for microorganisms, preventing the spread towards the peritoneum. Despite this, the same dacron cap can represent a sort of nest for microorganisms to colonize and, with the formation of a biofilm that facilitates their proliferation, make the same organisms impervious to antibiotic therapy and even resistance to them. The most effective tool for monitoring the health status of the exit-site is represented by the objective examination. This examination, through the use of well-defined scales, helps to provide a pathological score of the exit, facilitating the implementation of necessary precautions. In the presence of recurrent exit-site infections, from both Gram positive and Gram negative bacteria, minimally invasive surgical therapy is a valid approach to break this vicious circle. It helps avoid subjecting the patient to the removal of the peritoneal catheter, temporary transition to hemodialysis with the insertion of a central venous catheter, and subsequent repositioning of another peritoneal catheter. We propose the case of a recurrent Staphylococcus Aureus infection resolved after cuff shaving of the exit-site.

Surgical Treatment of Medically Refractory Encapsulating Peritoneal Sclerosis in a Patient After Kidney Transplant.

Encapsulating peritoneal sclerosis is a rare but highly morbid disease process in patients with end-stage kidney disease on peritoneal dialysis. Surgical management has been described in patients with encapsulation of bowel causing obstruction. Here, we describe a case of surgical management in a patient following kidney transplant with medically refractory ascites and lower extremity edema.

The urogenital microbiome in chronic kidney disease patients on peritoneal dialysis.

INTRODUCTION AND OBJECTIVES: Diabetes, dyslipidemia, older age, gender, urinary tract infections, and recent antibiotic intake have been associated with a decrease in the urobiome richness and other fluctuations in this microbiome. Gut and blood microbiome have been reported to be altered in patients with chronic kidney disease (CKD), and specifically in peritoneal dialysis (PD) patients. Still, there are currently no studies describing the urogenital microbiome in CKD-PD patients. In this study we characterized the urobiome profile in 46 PD patients and analyzed its clinical and inflammatory parameters. MATERIALS AND METHODS: Mid-stream urine, fecal and blood samples were collected from 46 patients undergoing PD at Centro Hospitalar Universitário de São João (CHUSJ) in Porto, Portugal. Exclusion criteria were age under 18 years old, inability to give informed consent, history of infection in the last three months, and antibiotic intake in the last three months. The microbiome communities were analyzed by amplification and sequencing of the V3-V4 region of the bacterial 16S rRNA gene. Correlations with the patients' clinical data and inflammatory profile were performed. RESULTS: CKD-PD patients presented a unique urobiome profile dominated by Bacillota, Actinomycetota and Pseudomonadota and characterized by a lower Shannon diversity than fecal and blood microbiome. The taxonomic profiles of urogenital samples were organized in multiple subtypes dominated by populations of Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, being similar to other non-PD-CKD patients. Gender, sCD14, residual diuresis and history of peritonitis were significantly associated to variations in the urobiome. Although not reaching statistical significance, diabetes and the time on PD also showed association with particular taxonomic groups. Depletion of Gardnerella, Staphylococcus, Corynebacterium, Lactobacillus or Dermabacter populations correlated with CKD-PD patients with history of diabetes, history of peritonitis and altered levels of sCD14. CONCLUSIONS: Our results highlight urogenital microbiome as a potential partner and/or marker in the overall health state of CKD-PD patients.

Correlation Between the 8-hydroxy-2'-deoxyguanosine Level in the Peritoneal Solution of Patients Undergoing Peritoneal Dialysis and the Peritoneal Equilibration Test, Kt/V, Ferritin, and Albumin Levels.

INTRODUCTION: Peritoneal dialysis (PD) is an effective treatment  modality for advanced kidney failure, offering patients a significant  degree of independence. However, the long-term use of PD is  limited due to the degeneration of the peritoneal membrane,  resulting in reduced dialysis adequacy. Evaluating the peritoneal  membrane condition in patients with advanced kidney failure  who are undergoing PD is challenging with existing methods.  Therefore, this study aimed to investigate the correlation between  8-hydroxy-2'-deoxyguanosine (8OHDG) levels in the peritoneal  solution of patients undergoing PD and various factors, such  as peritoneal equilibration test (PET), dialysis adequacy (Kt/V),  underlying diseases, serum ferritin, and albumin levels. 8OHDG  is a sensitive marker of oxidative stress caused by DNA damage. METHODS: A total of 56 patients were included in this cross-sectional  study. Five milliliters of PD fluid were collected from the patients,  and 8-OHdG levels were measured using ELISA method. Then, they  were compared with PET, Kt/V, albumin, and ferritin markers in  the patients' files, and the results were analyzed by statistical tests. RESULTS: The study examined the correlation between 8OHDG  and other markers. It was found that this index had significant  associations with PET and underlying HTN (P < .05), whereas no  significant associations were identified with the other markers. CONCLUSION: The results of the present study demonstrate that  the level of 8OHDG, as one of the oxidative stress markers, could  be used to evaluate the function of the peritoneum in patients  undergoing PD. DOI: 10.52547/ijkd.7654.

Risk factors of different mortality periods in older patients with end-stage renal disease undergoing urgent-start peritoneal dialysis: a retrospective observational study.

BACKGROUND: The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. METHODS: We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. RESULTS: Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III-IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200-5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021-1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III-IV cardiac function (HR = 1.945, 95% CI: 1.149-3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845-0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429-0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025-4.554, p = 0.043) increased the mortality risk after six months of USPD. CONCLUSION: Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III-IV cardiac function, WBC count, potassium, and calcium levels.

Peritoneal Inflammation in PD-Related Peritonitis Induces Systemic Eryptosis: In Vitro and In Vivo Assessments.

Erythrocytes (RBCs) have a highly specialized and organized membrane structure and undergo programmed cell death, known as eryptosis. Our preliminary data show a significant increase in the eryptosis during peritoneal dialysis (PD)-associated peritonitis. The objectives of the present study were assessment of the incrementation of eryptosis in PD patients with peritonitis, evaluation of the relationship between systemic eryptosis in peritonitis and specific peritonitis biomarkers in PD effluent (PDE), and confirmation of the induction of eryptosis by peritonitis in a vitro setting. We enrolled 22 PD patients with peritonitis and 17 healthy subjects (control group, CTR). For the in vivo study, eryptosis was measured in freshly isolated RBCs. For the in vitro study, healthy RBCs were exposed to the plasma of 22 PD patients with peritonitis and the plasma of the CTR group for 2, 4, and 24 h. Eryptosis was evaluated by flow cytometric analyses in vivo and in vitro. PDE samples were collected for biomarkers analysis.The percentage of eryptotic RBCs was significantly higher in PD patients with peritonitis than in CTR (PD patients with peritonitis: 7.7; IQR 4.3-14.2, versus CTR: 0.8; IQR 0.7-1.3; p < 0.001). We confirmed these in vivo results by in vitro experiments: healthy RBCs incubated with plasma from PD patients with peritonitis demonstrated a significant increase in eryptosis compared to healthy RBCs exposed to plasma from the control group at all times. Furthermore, significant positive correlations were observed between eryptosis level and all analyzed peritoneal biomarkers of peritonitis. We investigated a potential connection between systemic eryptosis and peritoneal biomarkers of peritonitis. Up-regulation of inflammatory markers could explain the increased rate of systemic eryptosis during PD-related peritonitis.

MiR-132-3p suppresses peritoneal fibrosis induced by peritoneal dialysis via targeting TGF-ß1/Smad2/3 signaling pathway.

BACKGROUND: Peritoneal fibrosis (PF) is the main complication of peritoneal dialysis (PD) and the most common cause of cessation from PD. There is still no effective therapeutic approach to reserve PF. We aimed to investigate the role of miR-132-3p and underlying potential mechanisms in PF. METHODS: A total of 18 Sprague-Dawley (SD) rats were divided randomly into three groups (n = 6): (i)Control group (ii)PF group (iii)PF+Losartan group; Rats in the PF group and PF+Losartan group received daily intraperitoneal injections of 3 mg/kg chlorhexidine for 14 days, and rats in the PF+Losartan group simultaneously received daily intraperitoneal injections of 2 mg/kg losartan for 14 days. The control group was injected with saline in the same volume. Met-5A cells were treated for 24h with TGF-ß1 dissolved in recombinant buffered saline at a concentration of 10 ng/ml, meanwhile, PBS solution as a negative control. The human peritoneal solution was collected for the detection of miR-132-3p. RESULTS: In vivo, SD rats were infused with chlorhexidine to establish PF model, and we found that miR-132-3p significantly decreased and the expressions of transforming growth factor-ß1 (TGF-ß1), and Smad2/3 were up-regulated in PF. In vitro, miR-132-3p mimics suppressed TGF-ß1/Smad2/3 activity, whereas miR-132-3p inhibition activated the pathway. In human peritoneal solution, we found that the expression of miR-132-3p decreased in a time-dependent model and its effect became more pronounced with longer PD duration. CONCLUSION: MiR-132-3p ameliorated PF by suppressing TGF-ß1/Smad2/3 activity, suggesting that miR-132-3p represented a potential therapeutic approach for PF.