Neutrophil Gelatinase-Associated Lipocalin in Peritoneal Dialysis-Related Peritonitis: Correlation with White Blood Cells over Time and a Possible Role as the Outcome Predictor.

INTRODUCTION: The present study aimed to monitor peritoneal neutrophil gelatinase-associated lipocalin (pNGAL) during peritonitis episodes and to enhance its diagnostic value by evaluating pNGAL at scheduled times in parallel with white blood cell (WBC) count. In addition, we investigated possible correlations between pNGAL and the etiology of peritonitis, evaluating it as a possible marker of the clinical outcome. METHODS: Twenty-two patients with peritoneal dialysis (PD)-related peritonitis were enrolled. Peritonitis was divided into Gram-positive, Gram-negative, polymicrobial, and sterile. WBC count and neutrophil gelatinase-associated lipocalin (NGAL) in PD effluent were measured at different times (days 0, 1, 5, 10, 15, and/or 20 and 10 days after antibiotic therapy discontinuation). NGAL was measured by standard quantitative laboratory-based immunoassay and by colorimetric NGAL dipstick (NGALds) (dipstick test). RESULTS: We found strong correlations between peritoneal WBC, laboratory-based NGAL, and NGALds values, both overall and separated at each time point. On day 1, we observed no significant difference in WBC, both NGALds (p = 0.3, 0.9, and 0.2) between Gram-positive, Gram-negative, polymicrobial, and sterile peritonitis. No significant difference has been found between de novo versus relapsing peritonitis for all markers (p > 0.05). We observed a parallel decrease of WBC and both NGAL in patients with favorable outcomes. WBC count and both pNGAL resulted higher in patients with negative outcomes (defined as relapsing peritonitis, peritonitis-associated catheter removal, peritonitis-associated hemodialysis transfer, peritonitis-associated death) at day 10 (p = 0.04, p = 0.03, and p = 0.05, respectively) and day 15 (p = 0.01, p = 0.04, and tendency for p = 0.005). There was a tendency toward higher levels of WBC and NGAL in patients with a negative outcome at day 5. No significant difference in all parameters was proven at day 1 (p = 0.3, p = 0.9, p = 0.2) between groups. CONCLUSION: This study confirms pNGAL as a valid and reliable biomarker for the diagnosis of PD-peritonitis and its monitoring. Its trend is parallel to WBC count during peritonitis episodes, in particular, patients with unfavorable outcomes.

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.

Peritoneal Vicenza "Short" Catheter Outcomes and Comparison with International Society for Peritoneal Dialysis Guidelines.

INTRODUCTION: A well-functioning peritoneal catheter is key to success of peritoneal dialysis (PD). The Vicenza "short" catheter is a modified Tenckhoff catheter with a shorter intraperitoneal segment. The aim of this study was to evaluate the incidence of catheter-related complications and catheter survival rate using the Vicenza "short" catheter, according to the goals suggested by the International Society for Peritoneal Dialysis (ISPD) guidelines. Second, we compared insertion techniques used in our center. METHODS: This is a retrospective cohort, single-center study analyzing incident PD patients undergoing Vicenza "short" peritoneal catheter placement between January 1, 2015, and December 31, 2019. As clinical outcomes, we evaluated catheter patency at 12 months, exit-site/tunnel infection and peritonitis within 30 days of catheter insertion, visceral injury, or significant hemorrhage during the procedure, in accordance with ISPD guidelines. RESULTS: The percentage of patency at 12 months for all catheter insertion methods was 88.91%, and the percentage for laparoscopic placement was 93.75%. The exit-site/tunnel infection and peritonitis occurring within 30 days of catheter insertion were, respectively, 0.75% and 2.2%; the visceral injury leading to intervention was 0.75%. We did not have any case of significant hemorrhage. All results were in line with ISPD guidelines. CONCLUSION: We conclude that the Vicenza "short" catheter is a suitable device for peritoneal access. The implantation procedure is safe and easy to perform, and both nephrologists and surgeons can do it. A confident use and a proper implantation of the Vicenza "short" catheter help achieve the clinical ISPD goals for the PD access procedure in terms of catheter survival and complication rates.

Intraperitoneal Pressure in Polycystic and Non-Polycystic Kidney Disease Patients, Treated by Peritoneal Dialysis.

INTRODUCTION: Intraperitoneal volume (IPV) should be individualized and aimed to maintain an intraperitoneal pressure (IPP) lower than 17 cm H2O. IPP is very variable, given its relation with body size. However, it is not yet fully understood which anthropometric variable mostly affects IPP and the relation between IPP and organomegaly in polycystic kidney disease (PKD) patients is not known. OBJECTIVES: The aim of the present study was to analyse the relation between antropometric variables and IPP in a large cohort of peritoneal dialysis (PD) patients and to identify if a relation between nephromegaly and IPP exists in PKD patients. METHODS: IPP was measured in PD patients and data was retrospectively collected. In PKD patients, total kidney volumes were measured in CT scans, and normalized with height (hTKV). RESULTS: Seventy-seven patients were included in the study, 18% affected by PKD. Mean IPP was 14.9 ± 2.9 cm H2O and it showed significant positive correlation with body mass index (BMI; ρ = 0.42, p < 0.001). No correlation was found between IPP and absolute IPV; conversely, IPP has a significant inverse correlation with IPV normalized with BMI and body surface area (ρ -0.38, p = 0.001 and ρ -0.25, p = 0.02, -respectively). Patients with IPP >17 cm H2O have significant larger BMI and lower IPV/BMI compared to those with IPP <17 cm H2O (29 ± 3.6 vs. 26 ± 4 kg/m2, p < 0.05 and 97 ± 15.5 vs. 109 ± 22 mL/kg/m2, p < 0.05). PKD patients have a wide variability in hTKV (range 645-3,787 mL/m2) and it showed a significant correlation with IPP/IPV (ρ = 0.6, p < 0.05). CONCLUSIONS: Patients with larger BMI have greater IPP, irrespectively to IPV. In PKD patients, hTKV correlate with IPP/IPV ratio. However, given the wide range of distribution of hTKV, increased IPP cannot be presumed because of pre-existing polycystic kidney, but need to be quantified.

Lipopolysaccharide Evaluation in Peritoneal Dialysis Patients with Peritonitis.

BACKGROUND: Lipopolysaccharide (LPS), also known as endotoxin, is cell wall component of Gram-negative (GN) bacteria, which may contribute to the progression of a local infection to sepsis. Previous studies demonstrate that LBP is detectable in peritoneal effluents of peritoneal dialysis (PD) patients and it is significantly elevated in PD patients with peritonitis caused by both GN and Gram-positive (GP) bacteria. AIM: The aim of this study was to evaluate LPS levels in PD patients; in particular, we investigated different LPS levels in the context of GP and GN peritonitis. MATERIAL AND METHODS: We enrolled 49PD (61% Continuous Ambulatory PD and 39% Automated PD) patients: 37 with peritonitis and 12 without. Quantitative determination of LPS was performed by Enzyme-linked Immunosorbent Assay Kitin peritoneal and plasma samples. RESULTS: Quantitative analysis of peritoneal and plasma LPS showed significantly higher levels in PD patients with peritonitis compared to patients without (p = 0.001). Furthermore, we divided patients with peritonitis in 2 groups on the basis of Gram staining (GP 27; GN 12). Peritoneal and plasma LPS levels showed significantly lower levels in PD patients with GP peritonitis than in patients with GN (p = 0.001). The median level of LPS showed no significant differences between patients without peritonitis and with GP peritonitis (p = 0.195). On the contrary, LPS levels showed significantly higher levels in PD patients with GN peritonitis compared to patients without peritonitis (p = 0.001). A significant positive correlation was observed between peritoneal white blood cells count (pWBC) and peritoneal LPS (Spearman's rho = 0,412, p = 0.013). However, no statistically significant correlation was observed between plasma LPS and WBC count. CONCLUSION: We observed LPS presence in all PD patients. In particular, our results demonstrated that LPS is significantly elevated in PD patients with GN peritonitis. Furthermore, pWBC and LPS levels increased proportionally in PD patients with peritonitis. Peritoneal and plasma LPS levels could be a useful marker for diagnosis and management of GN peritonitis in PD patients.

Eryptosis Is Altered in Peritoneal Dialysis Patients.

BACKGROUND: Red blood cells (RBCs) undergo programmed cell death known as eryptosis. Triggers of eryptosis include increased cytosolic Ca(2+) concentration, oxidative stress, osmotic shock, energy depletion and several uremic toxins. Little is known about the pathogenesis of eryptosis in peritoneal dialysis (PD) patients; furthermore, its relevance in worsening clinical conditions in these patients is still not completely defined. OBJECTIVES: We investigated eryptosis levels in PD patients and its association with inflammatory and clinical parameters. MATERIAL AND METHODS: A total of 46 PD patients and 17 healthy subjects (CTR) were enrolled. All eryptosis measurements were made in freshly isolated RBCs using the flow cytometer. RESULTS: Eryptosis was significantly higher in PD patients than that in CTR (p < 0.001). Eryptosis levels did not differ significantly between PD patients with and without diabetes, with and without hypertension, and with and without cardiovascular disease. Eryptosis showed no significant differences between patients treated with continuous ambulatory PD/automated PD, with Kt/Vurea value ≤1.7 and >1.7, with a negative or positive history of peritonitis. On the contrary, eryptosis showed significantly lower levels in PD patients with weekly creatinine clearance ≥45 L/week/1.73 m2 (2.8%, 1.7-4.9 vs. 5.6%, 5.0-13.5; p= 0.049). Eryptosis showed significantly lower levels in PD patients with residual diuresis (n = 23) than that in patients without (3.7%, 2.6-5.6 vs. 5%, 3.1-16; p = 0.03). In these 23 patients, significant negative correlations between percentage of eryptosis and residual glomerular filtration rate (rGFR; Spearman's rho = -0.51, p = 0.01) and diuresis volume (Spearman's rho = -0.43, p = 0.05) were found. CONCLUSIONS: The present study demonstrated higher eryptosis levels in PD patients compared to corresponding levels in CTR. Furthermore, important PD comorbidity and main PD parameters do not influence eryptosis. Importantly, our data have reported an increase in eryptosis levels with progressive residual diuresis and rGFR loss, probably due to decreased uremic toxins clearance.

Remote Monitoring of Automated Peritoneal Dialysis Improves Personalization of Dialytic Prescription and Patient's Independence.

BACKGROUND: Remote monitoring (RM) supports a healthcare model that enhances patients' self-management. We evaluated the utility of RM in patients undergoing automated peritoneal dialysis (APD). METHODS: We observed 37 -RM-APD patients, 16 incidents, and 21 prevalents switched from traditional APD (T-APD). We observed the number of changes for APD prescription, the frequency of visits, and PD adequacy parameters during 1 year of RM utilization in APD. RESULTS: The APD prescriptions were modified more frequently in RM-APD vs. T-APD in incident (p = 0.002) and prevalent patients (p = 0.045). Visits were significant less in -RM-APD than in T-APD for incident patient (p = 0.008). No significant difference was found between prevalent populations. PD adequacy was similar in both groups. CONCLUSIONS: Our results demonstrate that RM allows an efficient use of healthcare resources, helping to improve personalization of APD prescription and to intervene early with "trouble shooting", thereby reducing the frequency of in-person visits for emergency problems.

Brief Review and a Clinical Case of Hemolytic Uremic Syndrome Associated with Interferon ß Treatment.

The hemolytic uremic syndrome (HUS) is one of the thrombotic microangiopathies and it consists of the triad of nonimmune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The atypical form of HUS (aHUS) is related to causative mutations in complement genes. Some conditions act as a trigger for aHUS in individuals that have a genetic background predisposing to complement activation. Interferon ß is a recombinant-protein therapy approved to treat multiple sclerosis (MS), and can be a causative agent in the occurrence of HUS through anti-angiogenic activity. In this paper, we briefly review aHUS clinical and genetic characteristics. Furthermore, we present a case of a 48-year-old woman, diagnosed with MS and treated with INFß-1b from 2008. In December 2015, she presented with asthenia and loss of muscular strength in the legs and she quickly developed aHUS. Our case suggests that INFß is a possible triggering factor for HUS.

[Peritoneal Dialysis Network in North-East Italy: Survey About the Peritoneal Catheter Exit-Site Infection Management and Comparison with ISPD Guidelines].

Introduction. The Triveneto Peritoneal Dialysis (PD) Network aims to bring together doctors and nurses who deal with PD in a collaborative network in which to exchange mutual knowledge and optimize the use of this method of replacing renal function. A topic of particular interest was the management of peritoneal catheter exit-site infection, given the recent publication of the new guidelines of the International Society of Peritoneal Dialysis (ISPD). Materials and methods. The survey concerned the criteria for carrying out nasal swab and exit-site, management of exuberant granulation tissue "Proud Flesh", treatment of exit-site infection (ESI), use of silver dressings, the role of subcutaneous tunnel ultrasound and cuff shaving. Results. All PD centers in the North-East Italy area have joined the survey with at least one operator per centre. There was a wide variability between the indications for performing the exit-site swab. In the presence of ESI, the prevalent approach is that of oral systemic empiric therapy associated (20.0%) or less (28.9%) with topical therapy, and then adapting it in a targeted manner to the culture examination. Discussion. From the discussion of the survey emerged the importance of the ESI as an outcome indicator, which allows us to verify whether our clinical practice is in line with the reference standards. It is essential to know and base our activity on what is indicated in national and international guidelines and to document the events that occur in the patient population of each dialysis unit.

Scheduling of Remote Monitoring for Peritoneal Dialysis Patients.

Peritoneal dialysis (PD) is performed as a home-based treatment and in this context, telemedicine has been proven helpful for improving clinicians' surveillance and maintaining PD patients in their home setting. The new e-health devices make remote patient monitoring (RPM) for automated peritoneal dialysis (APD) treatment possible, evaluating the data at the end of every treatment and adapting the prescription at distance if necessary. This paper aims to share a method for improving clinical surveillance and enabling PD patients to receive their treatment at home. In the present case series, we delineate the clinical protocol of the Vicenza PD Center regarding patient characteristics, timing, and the purpose of the APD-RPM. We present the Vicenza PD Center's experience, illustrating its application through three case reports as exemplars. Telemedicine helps to carefully allocate healthcare resources while removing the barriers to accessing care. However, there is a risk of data overload, as some data might not be analyzed because of an increased workload for healthcare professionals. A proactive physician's attitude towards the e-health system has to be supported by clinical instructions and legislative rules. International and national guidelines may suggest which patients should be candidates for RPM, which parameters should be monitored, and with what timing. According to our experience, we suggest that the care team should define a workflow that helps in formulating a correct approach to RPM, adequately utilizing resources. The workflow has to consider the different needs of patients, in order to assure frequent remote control for incident or unstable patients, while prevalent and stable patients can perform their home treatment more independently, helped by periodic and deferred clinical supervision.

Ongoing Peritoneal Dialysis Training at Home Allows for the Improvement of Patients' Empowerment: A Single Center Experience.

INTRODUCTION: Peritoneal dialysis (PD), as a home treatment, ensures better patient autonomy and lower intrusiveness compared to hemodialysis. However, choosing PD comes with an increased burden of responsibility that the patient may not always be able to bear, due to advanced age and deteriorating health condition. Various approaches have been explored to address this issue and mitigate its primary complications. In this study, we aim to present the ongoing PD training at-home program implemented by the Vicenza PD Center, and evaluate its impact on patients' prognoses. MATERIAL AND METHODS: We enrolled 210 patients who underwent PD at Vicenza Hospital between 1 January 2019 and 1 January 2022 for a minimum of 90 days. Each patient was observed retrospectively for one year. We categorized the patients into three groups based on their level of autonomy regarding their PD management: completely independent patients; patients able to perform some parts of the PD method on their own, while the remaining aspects were carried out by a caregiver; and patients who required complete assistance from a caregiver, like in the assisted PD program (asPD). RESULTS: A total of 70% of the PD population were autonomous regarding their PD therapy, 14% had an intermediate degree of autonomy, and 16% were entirely dependent on caregivers. The PD nurses performed a median of four home visits per patient per year, with a tendency to make more visits to patients with a lower degree of autonomy. All the groups achieved similar clinical outcomes. At the end of the year of observation, only 6% of the patients witnessed a decline in their autonomy level, whereas 7% demonstrated an enhancement in their level of autonomy, and 87% remained stable. CONCLUSIONS: A home care assistance program ensures clinical support to a household with the purpose of improving the empowerment of the PD population and reducing the prevalence of assisted PD. Ongoing PD training at home helps patients to maintain a stable degree of autonomy and stay in their home setting, even though they present with relative attitudinal or social barriers.

[Psychological support in anxiety management for patients affected by chronic kidney disease and treated by dialysis].

Introduction: The quality of life of patients with chronic kidney disease stage V is strongly affected by the recommended therapies. Such a situation alters the state of anxiety, which expresses a perception connected to a specific context and it overlaps with trait anxiety, which evaluates relatively stable aspects of being prone to anxiety. The study aims to analyze the anxiety level of uremic patients and to demonstrate the benefit of psychological support either in person or online in order to mostly reduce the state of anxiety. Materials and methods: 23 patients treated at the Nephrology Unit of the San Bortolo Hospital in Vicenza have undergone at least 8 psychological sessions. The first and the eighth sessions have been held in person, while the others were either in person or online based on the patients' preference. The State-Trait Anxiety Inventory (STAI), which means to evaluate the current state of anxiety and aspects of being prone to anxiety, was submitted during the first and the eighth sessions. Results: Patients, before being submitted to psychological treatment, showed high rates of both State and Trait anxiety levels. After eight sessions the trait anxiety features and even better the state anxiety ones have significantly reduced both thanks to in-person or online treatments. Conclusions: A treatment of minimum eight sessions shows a significant improvement of the nephropathic patient's trait and, even better, state anxiety level and it also fosters the achievement of advanced adjustment levels compared to the new clinical status together with an improvement of the quality of life.

Contrast-Induced Encephalopathy: A Rare Complication in a Patient on Peritoneal Dialysis with Several Risk Factors.

Major adverse renal and cardiovascular events are reported for high-risk patients undergoing intra-arterial procedures, even if performed with iso-osmolar contrast media (CM). We report a case of contrast-induced encephalopathy (CIE) in a peritoneal dialysis (PD) patient, affected by diabetes, hypertension, and chronic heart failure. A 78-year-old PD patient (diuresis 1,000 mL) underwent a percutaneous angioplasty of the carotid. Immediately after the exam, he developed mental confusion and aphasia. Encephalic computed tomography scan and magnetic resonance imaging excluded ischemia or hemorrhage, but both showed cerebral edema; EEG showed right hemisphere abnormalities, sequelae of recent ischemia. Mannitol and steroids were administered to reduce edema, and additional PD exchange was performed with depurative aim. Within 2 days the patient completely recovered. CIE mimics severe neurological diseases, and it should be considered as differential diagnosis if symptoms come out soon after intra-arterial administration of CM, especially in high-risk patients. Our patient suffered from diabetes, chronic kidney disease, hypertension, chronic heart failure, which are possible contributing factors to the development of CIE. Moreover, this clinical scenario is noteworthy because the development in a patient who underwent PD had never been described before.

[Contrast Induced Encephalopathy after carotid percutaneous transluminal angioplasty in a patient with end stage renal disease undergoing peritoneal Dialysis].

Introduction. Contrast Induced Encephalopathy (CIE) belongs to Major Adverse Renal and Cardiovascular Events (MARCE) after iodinated contrast medium (IOCM), especially for high-risk patients with several comorbidities such as hypertension, diabetes, heart failure, and Chronic Kidney Disease (CKD). We report a case of CIE in a Peritoneal Dialysis (PD)-patient. Case report. A 78-year-old, affected by diabetes, hypertension, chronic heart failure, and End Stage Renal Disease (ESRD) treated with PD, underwent a carotid Percutaneous Angioplasty (PTA). Immediately after the exam, he developed mental confusion and aphasia. Encephalic CT scan and MRI excluded acute ischemia or hemorrhage but showed cerebral oedema. Mannitol and steroids were administered and additional PD exchange was performed with depurative aim. Within 2 days the patient completely recovered. Discussion. CIE mimics severe neurological diseases. It should be considered as a differential diagnosis if symptoms occur immediately after administration of IOCM, especially in high-risk patients and in case of intra-arterial injection. Clinical presentation includes transient cortical blindness, aphasia, focal neurological defects, and confusion. CIE is often a diagnosis of exclusion, and imaging plays a significant role. Symptoms generally resolve spontaneously within 24-48h, rarely in few days. Symptomatic therapy, including mannitol and steroids could be considered. In literature, CIE is reported only in a few patients affected by ESRD treated with chronic HD, and our is the first available case of a patient treated with chronic PD who developed this rare complication.

Eryptosis in Patients with Chronic Kidney Disease: A Possible Relationship with Oxidative Stress and Inflammatory Markers.

Background. Eryptosis is the programmed death of red blood cells; it may contribute to worsening anemia in chronic kidney disease (CKD). In this clinical condition, different factors induce eryptosis, such as oxidative stress, energy depletion and uremic toxins. In our study, we investigated if the progression of CKD may influence erythrocyte death levels and its relationship with oxidative stress and inflammation. Methods. We evaluated eryptosis levels in 25 CKD patients (five for each stage), as well as markers of oxidative stress and inflammation: myeloperoxidase (MPO), copper/zinc superoxide dismutase (Cu/Zn SOD) and interleukin-6 (IL-6) were evaluated in plasma samples. Results. Higher cell death rate was reported in the highest CKD stages (p < 0.05). Furthermore, we divided CKD patients into two groups (eGFR< or ≥60 mL/min/1.73 m2). Patients with eGFR < 60 mL/min/1.73 m2 had higher eryptosis levels (p < 0.001). MPO, CU/Zn SOD and IL-6 resulted significantly differently between groups (p < 0.001). Significant positive correlations were reported between eryptosis and MPO (Spearman's rho = 0.77, p = 0.01) and IL-6 (Spearman's rho = 0.52, p = 0.05) and Cu/Zn SOD. Spearman's rho = 0.6, p = 0.03). Conclusions. In patients with CKD, different factors are involved in the pathogenesis of eryptosis, in particular uremic toxins and oxidative stress and inflammatory markers. The progressive impairment of renal function may be associated with the increase in eryptosis levels, probably due to the accumulation of oxidative stress factors, inflammatory cytokines and uremic toxins.

Eryptosis in Peritoneal Dialysis-Related Peritonitis: The Potential Role of Inflammation in Mediating the Increase in Eryptosis in PD.

Background: Peritonitis and exit site infections are the main complications of patients treated with peritoneal dialysis (PD). Erythrocytes (red blood cells­RBCs) are very sensitive cells, and they are characterized by eryptosis (programmed cell death). The purpose of this research was to assess eryptosis in PD patients with PD-related peritonitis and its connection to inflammatory markers in vivo and in vitro. Material and Methods: In this study, we included 65 PD patients: 34 PD patients without systemic inflammation nor PD-related peritonitis in the previous 3 months, and 31 PD patients with an acute episode of PD-related peritonitis. We measured C-reactive protein (CRP) and cytokine (IL-1ß, IL-6, and IL-18) levels as systemic inflammatory markers. Eryptosis was evaluated by flow cytometric analyses in freshly isolated RBCs. The induction of eryptosis due to in vitro exposure to IL-1ß, IL-6, and IL-18 was verified. Results: Eryptosis was significantly higher in PD patients with peritonitis (9.6%; IQR 4.2−16.7), compared to the those in the other group (2.7%; IQR 1.6−3.9) (p < 0.0001). Significant positive correlations were noticed between eryptosis and CRP, IL-1ß, and IL-6. RBCs, incubated with greater concentrations of all cytokines in vitro, resulted in significantly higher occurrences of eryptosis in comparison with those incubated with lower concentration and with untreated cell (p < 0.05), and for those with extensive exposure (p < 0.05). Conclusion: In conclusion, we investigated a potential relationship between systemic eryptosis and the in vivo and in vitro inflammatory damage of the peritoneal membrane during peritonitis. Thus, the presented results revealed that upregulated inflammatory markers and immune system dysregulation could be the cause of high levels of systemic eryptosis during PD-related peritonitis.

In Vitro Induction of Eryptosis by Uremic Toxins and Inflammation Mediators in Healthy Red Blood Cells.

Eryptosis is the stress-induced RBC (red blood cell) death mechanism. It is known that eryptosis is largely influenced by plasma and blood composition, and that it is accelerated in patients affected by chronic kidney disease (CKD). The aim of this study is to evaluate the eryptosis rate in healthy RBCs treated with different concentration of IL-6, IL-1ß, urea and p-cresol, comparable to plasmatic level of CKD patients, at different time points. We exposed healthy RBCs to increasing concentrations of IL-6, IL-1ß, urea and p-cresol. Morphological markers of eryptosis (cell membrane scrambling, cell shrinkage and PS exposure at RBC surface) were evaluated by flow cytometric analyses. The cytotoxic effect of cytokines and uremic toxins were analyzed in vitro on healthy RBCs at 4, 8 and 24 h. Morphology of treated RBCs was dramatically deranged, and the average cell volume was significantly higher in RBCs exposed to higher concentration of all molecules (all, p < 0.001). Furthermore, healthy RBCs incubated with each molecules demonstrated a significant increase in eryptosis. Cytofluorimetric analysis of eryptosis highlighted significantly higher cell death rate in RBCs incubated with a higher concentration of both cytokines compared with RBCs incubated with a lower concentration (all, p < 0.05). In conclusion, our data show that cytokines and uremic toxins have a harmful effect on RBCs viability and trigger eryptosis. Further studies are necessary to validate these results in vivo and to associate abnormal eryptosis with cytokine levels in CKD patients. The eryptosis pathway could, moreover, become a new promising target for anemia management in CKD patients.

Subclinical AKI and Clinical Outcomes in Elderly Patients Undergoing Cardiac Surgery: Diagnostic Utility of NGAL versus Standard Creatinine Increase Criteria.

BACKGROUND: Acute kidney injury (AKI) is a common and serious postoperative complication in patients undergoing cardiac surgery and its incidence is particularly high among elderly patients. Cardiac surgery-associated AKI (CSA-AKI) represents the second most common cause of AKI in the intensive care unit but its true incidence could be underestimated, especially in elderly population. The current biomarkers of AKI are unreliable and delayed during acute changes in kidney function. In the setting of subclinical AKI (SAKI), biomarkers of tubular damage, such as NGAL, seem to be an early indicator of kidney damage. The aim of this study was to investigate NGAL utility in the SAKI diagnosis in the first 48 h after cardiac surgery and its helpfulness in predicting adverse clinical outcomes in comparison to current criteria for AKI. METHODS: This is an observational study of 72 patients admitted to San Bortolo's cardiac surgery department for elective cardiosurgical procedure enrolled over a 5-months period. All patients underwent peripheral venous sample 48 h after cardiac surgery to assess plasmatic creatinine (48Cr) and NGAL (48pNGAL) in addition to exams already foreseen by clinical practice. For each patient we studied renal, respiratory and cardiovascular outcome during hospitalization as well as 30 days and 6 months mortality. Creatinine Increase AKI (CrIAKI) was defined by 48CrI ≥0.3 mg/dL and SAKI was defined by 48pNGAL ≥100 pg/dL. We also assessed Respiratory (ArespO) as well as Cardiovascular (ACvO) outcome. RESULTS: Thirty days mortality was 8.3% (6 patients) and 6 months mortality was 12.5% (9 patients). A total of 27 patients (37.5%) presented AKI according to KDIGO (4) and 4 (5.5%) needed renal replacement therapy (RRT). SAKI was significantly associated with 30 days mortality (p = 0.0238), 6 months mortality (p = 0.002), Adverse renal outcome (ARenO) (p = 0.004) and need for RRT (p = 0.005). CrIAKI was significantly associated with 30 days mortality (p = 0.009) and ARenO (p = 0.0001), but not with 6 months mortality nor need for RRT.

[Lymphocytic leukopenia in two patients affected by polycystic kidney disease waiting for renal transplantation].

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, responsible for 10% of patients on renal replacement therapy. The disease is well known to be associated with many extrarenal manifestations. Leukopenia may also be present, even if it is not commonly identified as a typical extrarenal manifestation. Herein we describe two case reports of ADPKD patients with leukopenia. The first case is about a 47-year-old patient affected by ADPKD, regularly treated with peritoneal dialysis, who showed a progressive reduction of white blood cell count, mostly of lymphocytes. Lymphocytic leukopenia was so severe that, when he was called for transplantation from a deceased donor, he was considered temporarily not eligible. We then describe a second ADPKD patient regularly treated with peritoneal dialysis, who had stable lymphopenia for years. Six years after starting PD, it was necessary to perform bone marrow aspirate to investigate the simultaneous presence of hypogammaglobulinemia together with M-protein and to exclude monoclonal gammopathy. All the exams performed did not show any significant results, the patients were re-included in the waiting list and one of them was transplanted. Given our experience and what is reported in the literature, there seems to be enough evidence to consider leukopenia as an extrarenal manifestation of ADPKD. However, the clinical significance of leukopenia in ADPKD patients is not known. It could be interesting to investigate the leucocytes' function and if ADPKD patients with leukopenia are more susceptible to infection, or not. Moreover, it would be very useful to analyze the relationship between such manifestation and genotype/phenotype.

Electrospun Chitosan Functionalized with C12, C14 or C16 Tails for Blood-Contacting Medical Devices.

Medical applications stimulate the need for materials with broad potential. Chitosan, the partially deacetylated derivative of chitin, offers many interesting characteristics, such as biocompatibility and chemical derivatization possibility. In the present study, porous scaffolds composed of electrospun interwoven nanometric fibers are produced using chitosan or chitosan functionalized with aliphatic chains of twelve, fourteen or sixteen methylene groups. The scaffolds were thoroughly characterized by SEM and XPS. The length of the aliphatic tail influenced the physico-chemical and dynamic mechanical properties of the functionalized chitosan. The electrospun membranes revealed no interaction of Gram+ or Gram- bacteria, resulting in neither antibacterial nor bactericidal, but constitutively sterile. The electrospun scaffolds demonstrated the absence of cytotoxicity, inflammation response, and eryptosis. These results open the door to their application for blood purification devices, hemodialysis membranes, and vascular grafts.