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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Patients with end-stage kidney disease (ESKD) have altered immunity. Patients on hemodialysis (HD) present a coexistence of immunodeficiency and activation of the immune system. We evaluated the immunophenotypic profile induced by the medium cut-off of Theranova filter during a single HD session in the same individual. Methods: This pilot observational study explored 11 patients (75 ± 8 years and 73% male). Blood samples were collected prior to (predialytic, PRE) and after 4 h (postdialytic, POST) standard HD session with a medium cut-off, polyarylethersulfone and polyvinylpyrrolidone blend, BPA-free membrane. We performed an immunophenotyping characterization by using flow cytometry. We evaluated eryptosis RBCs and HLA-DR expression on monocytes and Treg cells. Results: The percentages of eryptosis in lymphocytes (CD3+), lymphocyte T helper (CD3+ and CD4+) cells, and monocytes (CD45+ and CD14+) were similar pre- and post-HD. On the contrary, HLA-DR expression and Treg cell numbers significantly decreased after HD. Conclusions: Many studies have focused on the comparison between healthy volunteers and HD patients, but very few have focused on the changes that occur after an HD session in the same individual. With this pilot observational study, we have revealed an immunomodulation driven by HD treatment with Theranova filter. Our preliminary results can be considered to be a hypothesis, generating and stimulating further studies with better designs and larger populations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening multiple-organ dysfunction induced by infection and is one of the leading causes of mortality and critical illness worldwide. The pathogenesis of sepsis involves the alteration of several biochemical pathways such as immune response, coagulation, dysfunction of endothelium and tissue damage through cellular death and/or apoptosis. Recently, in vitro and in vivo studies reported changes in the morphology and in the shape of human red blood cells (RBCs) causing erythrocyte death (eryptosis) during sepsis. Characteristics of eryptosis include cell shrinkage, membrane blebbing, and surface exposure to phosphatidylserine (PS), which attract macrophages. The aim of this study was to evaluate the in vitro induction of eryptosis on healthy RBCs exposed to septic plasma at different time points. Furthermore, we preliminary investigated the in vivo levels of eryptosis in septic patients and its relationship with Endotoxin Activity Assay (EAA), mortality and other biological markers of inflammation and oxidative stress. We enrolled 16 septic patients and 16 healthy subjects (no systemic inflammation in the last 3 months) as a control group. At diagnosis, we measured Interleukin-6 (IL-6) and Myeloperoxidase (MPO). For in vitro study, healthy RBCs were exposed to the plasma of septic patients and CTR for 15 min, 1, 2, 4 and 24 h. Morphological markers of death and eryptosis were evaluated by flow cytometric analyses. The cytotoxic effect of septic plasma on RBCs was studied in vitro at 15 min, 1, 2, 4 and 24 h. Healthy RBCs incubated with plasma from septic patients went through significant morphological changes and eryptosis compared to those exposed to plasma from the control group at all time points (all, p < 0.001). IL-6 and MPO levels were significantly higher in septic patients than in controls (both, p < 0.001). The percentage of AnnexinV-binding RBCs was significantly higher in septic patients with EAA level ≥0.60 (positive EAA: 32.4%, IQR 27.6–36.2) compared to septic patients with EAA level <0.60 (negative EAA: 14.7%, IQR 5.7–30.7) (p = 0.04). Significant correlations were observed between eryptosis and EAA levels (Spearman rho2 = 0.50, p < 0.05), IL-6 (Spearman rho2 = 0.61, p < 0.05) and MPO (Spearman rho2 = 0.70, p < 0.05). In conclusion, we observed a quick and great cytotoxic effect of septic plasma on healthy RBCs and a strong correlation with other biomarkers of severity of sepsis. Based on these results, we confirmed the pathological role of eryptosis in sepsis and we hypothesized its use as a biomarker of sepsis, potentially helping physicians to face important treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Cell-free plasma DNA (cfDNA) is circulating extracellular DNA arising from cell death mechanisms (apoptosis, necrosis, etc.). It is commonly existent in healthy individuals, but its ranks increase in diverse clinical circumstances, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. In patients with advanced chronic kidney disease, cfDNA is connected to inflammation, and it has been associated with higher mortality. Caspase-3 plays a dominant role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis and progression of chronic kidney disease (CKD). The aim of this pilot study was the evaluation of cfDNA levels and caspase-3 concentrations in patients with chronic kidney disease, in order to investigate the potential role of these molecules, deriving from inflammatory and apoptotic mechanisms, in the progression of renal damage. Methods: We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating their levels based on CKD stage. We also explored correlations between cfDNA and caspase-3 levels in CKD patients and between cfDNA and caspase-3 levels and serum creatinine and urea in this population. Results: We observed that cfDNA and caspase-3 levels were higher in patients with CKD compared to healthy subjects, in particular in patients with advanced renal disease (CKD stage 5). A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea were also noticed. Conclusions: Patients with chronic kidney disease show higher levels of cfDNA and caspase-3 levels compared to the control group. Based on these preliminary results, we speculated that the worsening of renal damage and the increase in uremic toxin concentration could be associated with higher levels of cfDNA and caspase-3 levels, thus reflecting the potential role of inflammation and apoptosis in the progression of CKD. Future studies should focus on the validation of these promising preliminary results. [ABSTRACT FROM AUTHOR]

Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), represent a general, public health urgency, causing a heavy burden to global health care systems. Moreover, AKI is a frequent complication of hospitalization, and it is associated with short-term morbidity and mortality rate greater than 50%, as a result of its relationship with other severe complications. Furthermore, multiple pathophysiologic processes are involved in AKI, such as cellular death, apoptosis, mesenchymal transition, cellular infiltration, inflammation, cytokines release, coagulation, and complement activation. Since increasing evidence highlighted the central role of the immune system in AKI pathophysiology, several efforts have been made to delineate the link between this disease and the different population of immune cells. This narrative review aims to describe the role played by dendritic cells (DCs) in AKI, with a special focus on recent findings suggesting DCs suppression as a promising strategy to prevent AKI negative side effects and ameliorate renal injury and dysfunction. Furthermore, we briefly summarize the main characteristics of innovative high-throughput techniques, including as genomics, transcriptomics, proteomics, and metabolomics in the context of AKI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Peritonitis and exit site infections are the main complications of patients treated with peritoneal dialysis (PD). Erythrocytes (red blood cells—RBCs) 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-1β, 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-1β, 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-1β, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-1β, 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-1β, 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. [ABSTRACT FROM AUTHOR]

Neutrophil gelatinase-associated lipocalin (NGAL) is a lipocalin involved in the immune response and is significantly high in the peritoneal dialytic effluent (PDE) of peritoneal dialysis (PD) patients with inflammation of the peritoneum membrane (peritonitis). The focus of this study was to match two different techniques for peritoneal NGAL evaluation: NGAL point-of-care test-POCT (NGAL Dipstick—NGALds) versus the laboratory-based NGAL assay and with the white cell count in PDE. In this study, we included 30 PD patients: 17 with peritonitis and 13 without. Peritoneal NGAL was tested by a turbidimetric immunoassay and by NGALds. We noticed a good positive linear correlation between the POCT results and the laboratory-based test and between the peritoneal NGALds and white cell count in PDE (both, p < 0.01). NGALds values resulted in being elevated in patients with peritonitis (300 ng/mL, IQR 300–600) in comparison to patients without (100 ng/mL, IQR 50–150) (p < 0.01). Furthermore, the NGALds test was performed in a median time of 20 mins (IQR 18–21) in comparison with the median time of 65 mins (IQR 55–69) necessary for the laboratory-based test (p < 0.01). The results of the NGALds were coherent with the laboratory-based NGAL and with the white cell count in PDE; furthermore, it was a user-friendly method with real-time findings. NGALds could be an extra tool for the diagnosis of peritonitis, helpful at the bedside of the patient, shortening the length of diagnosis, and if the laboratory-based NGAL test is not accessible. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Cardiac surgery is a leading cause of acute kidney injury (AKI). Such AKI patients may develop progressive chronic kidney disease (CKD). Others, who appear to have sustained no permanent loss of function (normal serum creatinine), may still lose renal functional reserve (RFR). Methods We extended the follow-up in the observational 'Preoperative RFR Predicts Risk of AKI after Cardiac Surgery' study from hospital discharge to 3 months after surgery for 86 (78.2%) patients with normal baseline estimated glomerular filtration rate (eGFR), and re-measured RFR with a high oral protein load. The primary study endpoint was change in RFR. Study registration at clinicaltrials.gov Identifier: NCT03092947, ISRCTN Registry: ISRCTN16109759. Results At 3 months, three patients developed new CKD. All remaining patients continued to have a normal eGFR (93.3 ± 15.1 mL/min/1.73 m2). However, when stratified by post-operative AKI and cell cycle arrest (CCA) biomarkers, AKI patients displayed a significant decrease in RFR {from 14.4 [interquartile range (IQR) 9.5 − 24.3] to 9.1 (IQR 7.1 − 12.5) mL/min/1.73 m2; P < 0.001} and patients without AKI but with positive post-operative CCA biomarkers also experienced a similar decrease of RFR [from 26.7 (IQR 22.9 − 31.5) to 19.7 (IQR 15.8 − 22.8) mL/min/1.73 m2; P < 0.001]. In contrast, patients with neither clinical AKI nor positive biomarkers had no such decrease of RFR. Finally, of the three patients who developed new CKD, two sustained AKI and one had positive CCA biomarkers but without AKI. Conclusions Among elective cardiac surgery patients, AKI or elevated post-operative CCA biomarkers were associated with decreased RFR at 3 months despite normalization of serum creatinine. Larger prospective studies to validate the use of RFR to assess renal recovery in combination with biochemical biomarkers are warranted. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a life-threatening condition often associated with a high incidence of multiple organs injury. Several papers suggested the immune response by itself, with the production of humoral inflammatory mediators, is crucial in determining organ injury. However, little is known of how sepsis directly induces organ injury at the cellular levels. To assess this point, we set up an in vitro study to investigate the response of renal tubular cells (RTCs), monocytes (U937) and hepatocytes (HepG2) after 24 h-incubation with septic patients' plasma. Methods: We enrolled 26 septic patients ("test" group). We evaluated cell viability, apoptosis and necrosis by flow cytometer. Caspase-3,-8,-9 and cytochrome-c concentrations have been analyzed using the Human enzyme-linked immunosorbent assay kit. Results: We found that a decrease of cell viability in all cell lines tested was associated to the increase of apoptosis in RTCs and U937 (p < 0.0001) and increase of necrosis in HepG2 (p < 0.5). The increase of apoptosis in RTCs and U937 cells was confirmed by higher levels of caspase-3 (p < 0.0001). We showed that apoptosis in both RTCs and U937 was triggered by the activation of the intrinsic pathway, as caspase-9 and cytochrome-c levels significantly increased (p < 0.0001), while caspase-8 did not change. This assumption was strengthened by the significant correlation of caspase-9 with both cytochrome-c (r = 0.73 for RTCs and r = 0.69 for U937) and caspase-3 (r = 0.69 for RTCs and r = 0.63 for U937). Conclusion: Humoral mediators in septic patients' plasma induce apoptosis. This fact suggests that apoptosis inhibitors should be investigated as future strategy to reduce sepsis-induced organ damages. [ABSTRACT FROM AUTHOR]

Backgound: This study was aimed at evaluating the presepsin and procalcitonin levels to predict adverse postoperative complications and mortality in cardiac surgery patients. Methods: A total of 122 cardiac surgery patients were enrolled for the study. Presepsin and procalcitonin levels were measured 48 h after the procedure. The primary endpoints were adverse renal, respiratory, and cardiovascular outcomes and mortality. Results: Presepsin and procalcitonin levels were significantly higher in patients with adverse renal and respiratory outcome (p < 0.001 and 0.0081). The presepsin levels were significantly higher in patients with adverse cardiovascular outcome (p = 0.023) and the procalcitonin values in patients with sepsis (p = 0.0013). Presepsin levels were significantly higher in patients who died during hospitalization (382 pg/mL, interquartile range [IQR] 243–717.5 vs. 1,848 pg/mL, IQR 998–5,451.5, p = 0.049). In addition, the predictive value for in-hospital, 30-days, and 6-months mortality was higher for presepsin, with a significant difference between the 2 biomarkers (p = 0.025, p = 0.035, p = 0.003; respectively). Presepsin and procalcitonin seem to have comparable predictive value for adverse renal, cardiovascular, and respiratory outcome in cardiac surgery patients. Although a positive trend was notable for presepsin and adverse renal outcome (area under the ROC [receiver operating characteristic] curves [AUC] of 0.760, 95% CI 0.673–0.833 versus procalcitonin: AUC 0.692; 95% CI 0.601–0.773): no statistically significant difference was evident between the AUC of the 2 biomarkers (p = 0.25). Conclusions: Presepsin and -procalcitonin seem to have comparable predictive value for -adverse renal, cardiovascular, and respiratory outcome in cardiac surgery patients. Also, presepsin possesses a better predictive value for in-hospital, 30-days, and 6-months mortality. [ABSTRACT FROM AUTHOR]

Background. The renal assist device (RAD) is a blood purification system containing viable renal tubular epithelial cells (TECs) that has been proposed for the treatment of acute kidney injury (AKI) and multiple organ failure. Perfluorocarbons (PFCs) are oxygen carriers used for organ preservation in transplantation. The aim of this study was to investigate the effect of PFCs on hypoxia- and sepsis-induced TEC injury and on renal CD133+ progenitor differentiation in amicroenvironment similar to the RAD. Methods. TECs were seeded in a polysulphone hollow fibre under hypoxia or cultured with plasma from 10 patients with sepsis-associated AKI in the presence or absence of PFCs and were tested for cytotoxicity (XTT assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay, caspases, enzyme-linked immunosorbent assay, Fas/Fas Ligand pathway activation), mitochondrial activity, cell polarity [transepithelial electrical resistance (TEER)] and adenosine triphosphate production. The effect of PFCs on proliferation and differentiation of human CD133+ progenitors was also studied. Results. In the presence of PFCs, TECs seeded into the polysulphone hollow fibre showed increased viability and expression of insulin-like growth factor 1, hepatocyte growth factor and macrophage-stimulating protein. Plasma from septic patients induced TEC apoptosis, disruption of oxidative metabolism, alteration of cell polarity and albumin uptake, down-regulation of the tight junction protein ZO-1 and the endocytic receptor megalin on the TEC surface. These detrimental effects were significantly reduced by PFCs. Moreover, PFCs induced CD133+ renal progenitor cell proliferation and differentiation towards an epithelial/tubular-like phenotype. Conclusions. PFCs improved the viability and metabolic function of TECs seeded within a polysulphone hollow fibre and subjected to plasma from septic AKI patients. Additionally, PFCs promoted differentiation towards a tubular/epithelial phenotype of CD133+ renal progenitor cells. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Although acute kidney injury (AKI) frequently complicates cardiac operations, methods to determine AKI risk in patients without underlying kidney disease are lacking. Renal functional reserve (RFR) can be used to measure the capacity of the kidney to increase glomerular filtration rate under conditions of physiologic stress and may serve as a functional marker that assesses susceptibility to injury. We sought to determine whether preoperative RFR predicts postoperative AKI. Methods We enrolled 110 patients with normal resting glomerular filtration rates undergoing elective cardiac operation. Preoperative RFR was measured by using a high oral protein load test. The primary end point was the ability of preoperative RFR to predict AKI within 7 days of operation. Secondary end points included the ability of a risk prediction model, including demographic and comorbidity covariates, RFR, and intraoperative variables to predict AKI, and the ability of postoperative cell cycle arrest markers at various times to predict AKI. Results AKI occurred in 15 patients (13.6%). Preoperative RFR was lower in patients who experienced AKI ( p < 0.001) and predicted AKI with an area under the receiver operating characteristic curve (AUC) of 0.83 (95% confidence interval [CI]: 0.70 to 0.96). Patients with preoperative RFRs not greater than 15 mL · min −1 · 1.73 m −2 were 11.8 times more likely to experience AKI (95% CI: 4.62 to 29.89 times, p < 0.001). In addition, immediate postoperative cell cycle arrest biomarkers predicted AKI with an AUC of 0.87. Conclusions Among elective cardiac surgical patients with normal resting glomerular filtration rates, preoperative RFR was highly predictive of AKI. A reduced RFR appears to be a novel risk factor for AKI, and measurement of RFR preoperatively can identify patients who are likely to benefit from preventive measures or to select for use of biomarkers for early detection. Larger prospective studies to validate the use of RFR in strategies to prevent AKI are warranted. ClinicalTrials.gov identifier: NCT03092947 , ISRCTN Registry: ISRCTN16109759. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) diagnosis is based on a rise in serum creatinine and/or fall in urine output. It has been shown that there are patients that fulfill AKI definition but do not have AKI, and there are also patients with evidence of renal injury who do not meet any criteria for AKI. Recently the innovative and emerging proteomic technology has enabled the identification of novel biomarkers that allow improved risk stratification. Methods: Tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7) were measured to a cohort of 719 consecutive patients admitted to Intensive Care Unit (ICU). The primary endpoint was the evaluation of clinical performances of the biomarkers focusing on the probability do develop AKI in the first 7 days. Results: The Kaplan-Meier analysis considering the first 7 days of ICU stay suggested a lower risk of developing AKI (p < 0.0001) for patients with a negative (<0.3; TIMP-2*IGFBP7) test. Conclusion: (TIMP-2*IGFBP7) at ICU admission has a good performance in predicting AKI, especially in the first 4 days in ICU. [ABSTRACT FROM AUTHOR]

Introduction: Ultrasound and colorDoppler technique, which is relatively inexpensive, rapid, non-invasive and repeatable is a powerful tool used for early diagnosis of vascular access (VA) complications in hemodialysis patients. To date a standard and widely comprehensible echocolorDoppler (ECD) protocol is not available. Materials and Methods: A simple step-by-step protocol based on anatomical and hemodynamic parameters of VA has been developed during a 3-years VA ECD follow-up. It consists of an ECD study scheme. The algorithm created involves the calculation of brachial artery flow, description of artero-venous and/or graft-vascular anastomosis and efferent vessel and/or graft. Results: The algorithm allows to formulate a medical report that takes into account both anatomic and hemodynamic parameters of the VA. Reduction of complications and the prevention of chronic complications as well as the early detection of acute problems were achieved. Discussion and Conclusion: The creation of a step-by-step protocol may simplify the multidisciplinary management of VA, its monitoring and the early diagnosis of its complications. [ABSTRACT FROM AUTHOR]