Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer.

A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2TS, MRC1; MS4A4A; CD36; CCL13; CCL18; CCL23; SLC38A6; FGL2; FN1; MAF) and M1 (M1TS, CCR7; IL2RA; CXCL11; CCL19; CXCL10; PLA1A; PTX3) macrophages, and cytolytic T-lymphocytes (CTLTS, GZMA; GZMB; GZMH; GZMM; PRF1). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2TS expression was associated with histological types and later stages. Low M2TS expression was associated with significantly better 5-year OS and DFI. We validated M2TS in prospectively collected peritoneal fluid of a GC patient cohort (n = 28). Single-cell RNA sequencing was used for signature expression in CD68+CD163+ cells and the log-rank test compared OS. GC patients with high M2TS in CD68+CD163+ cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2TS was significantly and independently associated with survival. As an independent predictor of poor survival, M2TS may be prognostic in primary tumors and peritoneal fluid of GC patients.

Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-ß- and PDGF-B-Mediated Fibrotic Processes.

Among patients on peritoneal dialysis (PD), 50-80% will develop peritoneal fibrosis, and 0.5-4.4% will develop life-threatening encapsulating peritoneal sclerosis (EPS). Here, we investigated the role of extracellular vesicles (EVs) on the TGF-ß- and PDGF-B-driven processes of peritoneal fibrosis. EVs were isolated from the peritoneal dialysis effluent (PDE) of children receiving continuous ambulatory PD. The impact of PDE-EVs on the epithelial-mesenchymal transition (EMT) and collagen production of the peritoneal mesothelial cells and fibroblasts were investigated in vitro and in vivo in the chlorhexidine digluconate (CG)-induced mice model of peritoneal fibrosis. PDE-EVs showed spherical morphology in the 100 nm size range, and their spectral features, CD63, and annexin positivity were characteristic of EVs. PDE-EVs penetrated into the peritoneal mesothelial cells and fibroblasts and reduced their PDE- or PDGF-B-induced proliferation. Furthermore, PDE-EVs inhibited the PDE- or TGF-ß-induced EMT and collagen production of the investigated cell types. PDE-EVs contributed to the mesothelial layer integrity and decreased the submesothelial thickening of CG-treated mice. We demonstrated that PDE-EVs significantly inhibit the PDGF-B- or TGF-ß-induced fibrotic processes in vitro and in vivo, suggesting that EVs may contribute to new therapeutic strategies to treat peritoneal fibrosis and other fibroproliferative diseases.

Differential expression and clinical significance of IGF2BP3 in peritoneal dialysate of patients with varying duration of peritoneal dialysis.

This study aims to investigate the differential expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the peritoneal dialysate among patients with different durations of peritoneal dialysis and its association with the angiogenic marker vascular* endothelial growth factor (VEGF), the fibronectin (FN), and various clinical indicators. A cohort of 122 peritoneal dialysis patients was categorized into short-term (≤1 year, n = 33), mid-term (>1 and ≤5 years, n = 55), and long-term (>5 years, n = 34) groups based on dialysis duration. We utilized enzyme-linked immunosorbent assay (ELISA) and western blot assays to quantify the levels of IGF2BP3, VEGF, and FN in the dialysate. Our findings showed a progressive increase in IGF2BP3 levels with the duration of PD, with the long-term group exhibiting significantly higher levels than both the short-term and mid-term groups (p < 0.001). A positive correlation between IGF2BP3 and VEGF (r = 0.386, p = 0.013), as well as between IGF2BP3 and FN (r = 0.340, p = 0.030), was observed. IGF2BP3 levels also correlated positively with serum creatinine, calcium, and phosphorus levels. In vitro analysis further confirmed that IGF2BP3 expression is enhanced in human peritoneal mesothelial cells under high-glucose conditions (p < 0.05). The study highlights the potential of IGF2BP3 in PD effluent as a biomarker for monitoring PF progression, with its expression significantly correlated with the duration of PD (Pearson r = 0.897, p < 0.001). In conclusion, our results underscore a correlation between elevated IGF2BP3 levels and PD duration, suggesting the clinical significance of IGF2BP3 as a biomarker for PF progression.

Neoadjuvant chemotherapy does not improve survival for patients with high volume colorectal peritoneal metastases undergoing cytoreductive surgery.

BACKGROUND: Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. METHODS: A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). RESULTS: A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). CONCLUSION: Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery.

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.

The role of cytoreductive surgery and HIPEC for the treatment of primary and secondary peritoneal malignancies-experience from a tertiary care center in Germany.

PURPOSE: Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM. METHODS: A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins. RESULTS: Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69 years. CONCLUSION: Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.

Role of endothelial hyaluronan in peritoneal membrane transport and disease conditions during peritoneal dialysis.

Peritoneal membrane dysfunction in peritoneal dialysis (PD) is primarily attributed to angiogenesis; however, the integrity of vascular endothelial cells can affect peritoneal permeability. Hyaluronan, a component of the endothelial glycocalyx, is reportedly involved in preventing proteinuria in the normal glomerulus. One hypothesis suggests that development of encapsulating peritoneal sclerosis (EPS) is triggered by protein leakage due to vascular endothelial injury. We therefore investigated the effect of hyaluronan in the glycocalyx on peritoneal permeability and disease conditions. After hyaluronidase-mediated degradation of hyaluronan on the endothelial cells of mice, macromolecules, including albumin and ß2 microglobulin, leaked into the dialysate. However, peritoneal transport of small solute molecules was not affected. Pathologically, hyaluronan expression was diminished; however, expression of vascular endothelial cadherin and heparan sulfate, a core protein of the glycocalyx, was preserved. Hyaluronan expression on endothelial cells was studied using 254 human peritoneal membrane samples. Hyaluronan expression decreased in patients undergoing long-term PD treatment and EPS patients treated with conventional solutions. Furthermore, the extent of hyaluronan loss correlated with the severity of vasculopathy. Hyaluronan on endothelial cells is involved in the peritoneal transport of macromolecules. Treatment strategies that preserve hyaluronan in the glycocalyx could prevent the leakage of macromolecules and subsequent related complications.

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge.

Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

68 Ga-FAPI-04 PET/CT for the Evaluation of Cholangiocarcinoma : Comparison With 18 F-FDG PET/CT and Abdominal 68 Ga-FAPI-04 PET/MR.

PURPOSE: In this study, we evaluated and compared the diagnostic performances of 68 Ga-FAPI-04 PET/CT and 18 F-FDG PET/CT for primary and metastatic cholangiocarcinoma (CCA) lesions. We also investigated the performance of PET/MR for visualizing and characterizing CCA and liver metastasis lesions. PATIENTS AND METHODS: Forty-four patients with suspected CCA were recruited and underwent 68 Ga-FAPI-04 and 18 F-FDG PET/CT within 1 week, including 30 patients who underwent simultaneous abdominal 68 Ga-FAPI-04 PET/MR scanning. The findings were confirmed by histopathology or radiographic follow-up. RESULTS: Compared with 18 F-FDG PET/CT, 68 Ga-FAPI-04 PET/CT showed higher sensitivity (94.3% vs 88.6%) and the same accuracy (86.4% vs 86.4%) in evaluating primary tumors. However, its specificity was lower (55.6% vs 77.8%). 68 Ga-FAPI-04 PET was superior to 18 F-FDG PET in both patient-based and lesion-based evaluations except for metastatic lesions in the liver and bone. For intrahepatic CCA, 68 Ga-FAPI-04 PET/CT and 18 F-FDG PET/CT (100% vs 100%) had similar detection rates, with similar uptake levels between tracers ( P > 0.05). However, for extrahepatic CCA, 68 Ga-FAPI-04 PET/CT had a higher detection rate (89.5% vs 78.9%), and 68 Ga-FAPI-04 had a higher uptake ( P < 0.05). PET/MR was more effective than PET/CT in terms of lesion conspicuity and diagnostic confidence for primary tumors and liver metastases. In addition, multisequence MRI identified more liver metastases than 68 Ga-FAPI-04 PET/CT and 18 F-FDG PET/CT. CONCLUSIONS: Compared with 18 F-FDG PET/CT, 68 Ga-FAPI-04 PET/CT showed a higher sensitivity in detecting primary CCA tumors, involved lymph nodes, and peritoneal metastases. Compared with 68 Ga-FAPI-04 PET/CT, PET/MR detected primary and liver metastatic lesions more accurately. For extrahepatic CCA, the combination of 68 Ga-FAPI-04 PET/CT and abdominal PET/MRI may replace 18 F-FDG PET/CT.

Inferior vena cava reconstruction with non-fascial autologous peritoneum: Retrospective study and literature review.

BACKGROUND: Inferior vena cava (IVC) resection is essential for complete (R0) excision of some malignancies. However, the optimal material for IVC reconstruction remains unclear. Our objective is to demonstrate the efficacy, safety, and advantages of using Non-Fascial Autologous Peritoneum (NFAP) for IVC reconstruction. To conduct a literature review of surgical strategies for tumors involving the IVC. METHODS: We reviewed all IVC reconstructions performed at our institution between 2015 and 2023. Preoperative, operative, postoperative, and follow-up data were collected and analyzed. RESULTS: A total of 33 consecutive IVC reconstructions were identified: seven direct sutures, eight venous homografts (VH), and 18 NFAP. With regard to NFAP, eight tubular (mean length, 12.5 cm) and 10 patch (mean length, 7.9 cm) IVC reconstructions were performed. Resection was R0 in 89% of the cases. Two patients had Clavien-Dindo grade I complications, 2 grade II, 2 grade III and 2 grade V complications. The only graft-related complication was a case of early partial thrombosis, which was conservatively treated. At a mean follow-up of 25.9 months, graft patency was 100%. There were seven recurrences and six deaths. Mean overall survival (OS) was 23.4 months and mean disease-free survival (DFS) was 14.4 months. According to our results, no statistically significant differences were found between NFAP and VH. CONCLUSIONS: NFAP is a safe and effective alternative for partial or complete IVC reconstruction and has many advantages over other techniques, including its lack of cost, wide and ready availability, extreme handiness, and versatility. Further comparative studies are required to determine the optimal technique for IVC reconstruction.

Peritoneal Tumor DNA as a Prognostic Biomarker in Gastric Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Gastric cancers commonly spread to the peritoneum. Its presence significantly alters patient prognosis and treatment-intent; however, current methods of peritoneal staging are inaccurate. Peritoneal tumor DNA (ptDNA) is tumor-derived DNA detectable in peritoneal lavage fluid. ptDNA positivity may indicate peritoneal micrometastasis and may be more sensitive than cytology in staging the peritoneum. In this meta-analysis, we evaluated the prognostic potential of ptDNA in gastric cancer. METHODS: PubMed, Embase, Scopus, and Web of Science databases were searched using PRISMA guidelines. Studies published between January 1, 1990, and April 30, 2023, containing quantitative data relating to ptDNA in gastric cancer were meta-analyzed. RESULTS: Six studies were analyzed. Of the total 757 patients with gastric adenocarcinoma, 318 (42.0%) were stage I, 311 (41.0%) were stage II/III, 116 (15.3%) were stage IV, and 22 (2.9%) were undetermined. Overall, ptDNA detected cytology-positive cases with a sensitivity and specificity of 85.2% (95% CI, 66.5 to 100.0) and 91.5% (95% CI, 86.5 to 96.6), respectively. Additionally, ptDNA was detected in 54 (8.5%) of 634 cytology-negative patients. The presence of ptDNA negatively correlated with pathological stage I (relative risk [RR], 0.29 [95% CI, 0.13 to 0.66]) and positively correlated with pathological stage IV (RR, 8.61 [95% CI, 1.86 to 39.89]) disease. Importantly, ptDNA positivity predicted an increased risk of peritoneal-specific metastasis (RR, 13.81 [95% CI, 8.11 to 23.53]) and reduced 3-year progression-free (RR, 5.37 [95% CI, 1.39 to 20.74]) and overall (hazard ratio, 4.13 [95% CI, 1.51 to 11.32]) survival. CONCLUSION: ptDNA carries valuable prognostic information and can detect peritoneal micrometastases in patients with gastric cancer. Its clinical utility in peritoneal staging for gastric cancer deserves further investigation.

Human tissue-resident peritoneal macrophages reveal resistance towards oxidative cell stress induced by non-invasive physical plasma.

In the context of multimodal treatments for abdominal cancer, including procedures such as cytoreductive surgery and intraperitoneal chemotherapy, recurrence rates remain high, and long-term survival benefits are uncertain due to post-operative complications. Notably, treatment-limiting side effects often arise from an uncontrolled activation of the immune system, particularly peritoneally localized macrophages, leading to massive cytokine secretion and phenotype changes. Exploring alternatives, an increasing number of studies investigated the potential of plasma-activated liquids (PAL) for adjuvant peritoneal cancer treatment, aiming to mitigate side effects, preserve healthy tissue, and reduce cytotoxicity towards non-cancer cells. To assess the non-toxicity of PAL, we isolated primary human macrophages from the peritoneum and subjected them to PAL exposure. Employing an extensive methodological spectrum, including flow cytometry, Raman microspectroscopy, and DigiWest protein analysis, we observed a pronounced resistance of macrophages towards PAL. This resistance was characterized by an upregulation of proliferation and anti-oxidative pathways, countering PAL-derived oxidative stress-induced cell death. The observed cellular effects of PAL treatment on human tissue-resident peritoneal macrophages unveil a potential avenue for PAL-derived immunomodulatory effects within the human peritoneal cavity. Our findings contribute to understanding the intricate interplay between PAL and macrophages, shedding light on the promising prospects for PAL in the adjuvant treatment of peritoneal cancer.

[Diffuse Hepatoid Adenocarcinoma in the Peritoneal Cavity:Report of One Case].

Hepatoid adenocarcinoma is a rare and unique type of adenocarcinoma,resembling hepatocellular carcinoma in histopathology.Most cases occur in the stomach,lacking specific clinical and imaging manifestations,which leads to high rates of missed diagnosis and misdiagnosis.Hepatoid adenocarcinoma in the peritoneal cavity is even rarer.This article reports a case of hepatoid adenocarcinoma with the manifestation of diffuse peritoneal thickening,aiming to provide reference for clinical diagnosis and treatment.

[Long-Term Suppression with First-Line Chemotherapy(FOLFIRI plus BV)for Peritoneal Metastasis].

A 72-year-old man underwent right hemicolectomy for transverse colon cancer(pT4aN1aM0, Stage ⅢB), after which he received adjuvant chemotherapy(capecitabine plus oxaliplatin[CAPOX])for 6 months. Three years after the first surgery, FDG-PET/CT revealed a tumor in the abdomen. He underwent a tumorectomy and adjuvant chemotherapy(CAPOX plus bevacizumab[BV])performed for 6 months. Two years after a tumorectomy, the CEA level rose again. He was diagnosed peritoneal metastasis again. A central venous(CV)port was implanted for access to the right internal jugular vein, and he received systemic chemotherapy(fluorouracil, Leucovorin, and irinotecan[FOLFIRI]plus BV)as an outpatient. One year after this recurrence, no peritoneal dissemination was detected by CT. Thereafter, total 49 courses of FOLFIRI plus BV were introduced, but chemotherapy was discontinued due to CV port-related infection. Three months later, low back pain appeared and became a diagnosis of spondylodiscitis. He had surgery, but follow-up CT performed 8 years after the first surgery detected multiple liver metastasis. It was considered necessary to take infection control measures during long-term chemotherapy.

Tuberculous peritonitis diagnosed following laparoscopic examination for suspected advanced ovarian cancer.

Laparoscopy for intra-abdominal exploration and tissue sampling is useful in advanced ovarian cancers, in which it is presumed to be difficult to achieve complete tumour reduction in the initial surgery. This is a report of a case of suspected advanced ovarian cancer in a patient, who underwent laparoscopic screening and was later pathologically diagnosed with tuberculous peritonitis. A woman in her 50s visited her local doctor with constipation. Since imaging showed massive ascites she was referred for further evaluation. We initially suspected advanced ovarian cancer due to the presence of massive ascites and multiple peritoneal nodules. However, histopathological examination indicated that the nodules were tubercles, and the patient was subsequently diagnosed with tuberculous peritonitis. It is important to be aware that tuberculosis peritonitis can be misdiagnosed or mistaken for advanced ovarian cancer. Preoperative diagnosis of tuberculous peritonitis is often difficult. Tuberculous peritonitis should be considered if intraoperative findings show diffuse nodular disseminated lesions.

Comparison of clinical and ultrasound examinations in assessing the parametria in patients with deep infiltrating endometriosis: a multicentre prospective study.

RESEARCH QUESTION: How do clinical rectovaginal examination and transvaginal ultrasound examination perform in the diagnosis of parametrial infiltration in patients with endometriosis? DESIGN: This was a multicentre prospective observational study. Patients with suspected deep endometriosis at clinical examination and/or at ultrasound evaluation and scheduled for surgery were included. Following multicentre multidisciplinary meetings, consensus was obtained on terms and methodology to define the parametrium at pelvic anatomy, ultrasound and surgery. Sensitivity, specificity, accuracy, and positive and negative likelihood ratios were calculated for clinical and ultrasound examinations with respect to surgery. RESULTS: In total, 195 women were selected for the present study and 164 were included in the analysis. Ultrasound examination had good to high specificity (>80%) for all parameters, except the left lateral parametrium (78.8%). The sensitivity of ultrasound examination was good to high for fixity of the right and left ovaries, uterosacral ligaments, retrocervix and rectovaginal space; and low for the anterior and lateral parametria, vagina, bladder and bowel. Clinical examination had good to high specificity for fixity of the left ovary, anterior parametrium, right uterosacral ligament, retrocervix and vagina; and low specificity for fixity of the right ovary, lateral parametrium, left uterosacral ligament and rectovaginal space. The sensitivity of clinical examination was good for the uterosacral ligaments and rectovaginal space, and low for the remaining parameters. CONCLUSION: Ultrasound examination provided good specificity for all the parameters, but sensitivity was low for the anterior and lateral parametria. Clinical examination provided good specificity for the anterior and posterior parametria, but sensitivity was low for the anterior and lateral parametria. Further prospective studies are needed to validate this methodology and confirm the results.

Peritoneal Protein Loss With Time in Peritoneal Dialysis.

Longitudinal evolution of peritoneal protein loss (PPL), a reflection of hydrostatic pressure-driven leak of plasma proteins through the large-pore pathway, is not clear. Time on PD causes loss of mesothelial cells, vasculopathy, and increased thickness of the submesothelial fibrous layer. Are these structural changes associated with progressive increase of PPL, in a parallel with the rise in the D/P creatinine? The aim of the present study was to identify longitudinal changes of PPL over time. This single-center, longitudinal study included 52 peritoneal dialysis (PD) patients with a median follow-up of 26.5 months, evaluated at two different time points with a minimum interval of 6 months. Repeated measures analysis was performed using paired sample t-test or the nonparametric Wilcoxon signed-rank test, depending on the distribution. After a median interval of 15.5 months, lower levels of residual renal function and urine volume, lower Kt/V, and creatinine clearance were found. D/P creatinine and PPL were stable, but a decrease in ultrafiltration was present. Systemic inflammation, nutrition, and volume overload showed no significant change with time on PD. Analysis of a subpopulation with over 48 months between initial and subsequential assessment (n = 11) showed again no difference in inflammation, nutritional and hydration parameters from baseline, but importantly PPL decreased after more than 4 years on PD (mean difference 1.2 g/24, p = 0.033). D/P creatinine and dip of sodium remained unchanged. The absence of deleterious effects of time on PD is reassuring, pointing to the benefit of updated PD prescription, including the standard use of more biocompatible solutions towards membrane preservation and adjusted prescription avoiding overhydration and inflammation while maintaining nutritional status. After controlling for confounders, PPL may act as a biomarker of acquired venous vasculopathy, even if small pore fluid transport rates and free water transport are preserved.