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Background : The necessity of using central venous catheters (CVCs) in hemodialysis, coupled with their associated complications, remains a critical concern in nephrology. This study aims to compare the short-term prognosis of tunneled (T-CVC) and non-tunneled (NT-CVC) CVCs in acute hemodialysis patients, specifically focusing on infection rates, malpositioning, and lumen thrombosis within the first three weeks post-insertion. Methods : A retrospective analysis was conducted on 176 CVCs placed between January and December 2023 at the Policlinico di Modena and the Ospedale Civile di Baggiovara. Patient demographics, CHA2DS2-VASc scores, and comorbid conditions were recorded at the time of catheter placement. Outcomes assessed included catheter-related infections, malpositioning, and lumen thrombosis. Statistical analyses, including Chi-square tests, Fisher's exact tests, and Kaplan-Meier survival analysis, were performed to evaluate differences between T-CVCs and NT-CVCs. Results : The sample comprised 43% females with a mean age of 69.3 years (SD 13.9) and a mean CHADS-VASC score of 3.72 (SD 1.4). Hypertension (90%) was the most prevalent comorbidity. Of the 176 CVCs, 127 were T-CVCs and 49 were NT-CVCs. Infection rates were 3.15% for T-CVCs and 8.16% for NT-CVCs ( p = 0.07). Malpositioning occurred in 0.79% of T-CVCs and 4.08% of NT-CVCs ( p = 0.47). There was one case of lumen thrombosis in the NT-CVC group. Kaplan-Meier analysis indicated a significant divergence in infection-related catheter survival favoring T-CVCs after ten days ( p = 0.034). Conclusions : While non-tunneled CVCs do not significantly alter short-term prognosis compared to tunneled CVCs, the latter show a better infection-related survival rate beyond ten days. Therefore, primary insertion of T-CVCs may be preferable when resources and clinical conditions permit, although NT-CVCs remain a viable option when immediate T-CVC insertion is challenging.

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.

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.

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.

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.

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.

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.

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.

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., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Lipopolysaccharide (LPS) or endotoxin, the major cell wall component of Gram-negative bacteria, plays a pivotal role in the pathogenesis of sepsis. It is able to activate the host defense system through interaction with Toll-like receptor 4, thus triggering pro-inflammatory mechanisms. A large amount of LPS induces inappropriate activation of the immune system, triggering an exaggerated inflammatory response and consequent extensive organ injury, providing the basis of sepsis damage. In this review, we will briefly describe endotoxin's molecular structure and its main pathogenetic action during sepsis. In addition, we will summarize the main different available methods for endotoxin detection with a special focus on the wider spectrum offered by omics technologies (genomics, transcriptomics, proteomics, and metabolomics) and promising applications of these in the identification of specific biomarkers for sepsis.

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.

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.

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.

Pluronic-coated polylipoic acid-based nanoparticles (F127@PLA-NPs) have great potential as biodegradable nanovectors for delivering active molecules to different organs in complex diseases. In this study we describe the in vivo biodistribution, safety and ability to deliver molecules of F127@PLA-NPs in healthy rats following intravenous administration. Adult rats were injected with 10 mg/kg of rhodamine B-labeled F127@PLA-NPs, and NPs fluorescence and MFI rate were measured by confocal microscopy in whole collected organs. The NPs accumulation rate was maximal in the heart, compared to the other organs. At the cellular level, myocytes and kidney tubular cells showed the highest NPs uptake. Neither histopathological lesion nor thrombogenicity were observed after NPs injection. Finally, F127@PLA-NPs were tested in vitro as miRNAs delivery nanosystem, and they showed good ability in targeting cardiomyocytes. These results demonstrated that our F127@PLA-NPs constitute a biological, minimally invasive and safe delivery tool targeting organs and cells, such as heart and kidney., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

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., (© 2021 S. Karger AG, Basel.)

Background: Recent research highlighted the potential role of circulating cell-free DNA (cfDNA), resulted by apoptosis or cell necrosis, as a prognostic marker in the setting of different clinical conditions. Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Apoptosis of renal epithelial cells is proposed as a mechanism involved in CRS type 1. In this study, we investigated cfDNA levels in patients with acute heart failure (AHF) and CRS type 1 and the possible correlation between cfDNA levels and inflammatory and apoptotic parameters., Methods: We enrolled 17 AHF patients and 15 CRS type 1 who exhibited AKI at the time of admission (caused by AHF) or developed AKI during the first 48 h from admission. cfDNA was extracted from plasma and quantified by real-time polymerase chain reaction. Plasma levels of NGAL, tumor necrosis factor-α, interleukin (IL)-6, IL-18, and caspase-3 were measured., Results: We observed significantly higher levels of cfDNA in patients with CRS type 1 than patients with AHF. Caspase-3, IL-6, IL-18, and NGAL levels resulted significantly increased in patients with CRS type 1. Moreover, a positive correlation between cfDNA levels and caspase-3 levels was found, as well as between cfDNA levels and IL-6 and renal parameters., Conclusion: Our study explores the premise of cfDNA as a marker for apoptosis and inflammation in CRS type 1 patients. cfDNA could potentially serve as an index for noninvasive monitoring of tissue damage and apoptosis in patients with AKI induced by AHF., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background: Automated peritoneal dialysis (APD) has been proved benefit from remote monitoring (RM), but evidences are limited. In this study, we compared clinical outcomes and quality of life (QoL) in two group of patients undergoing APD, with and without exposure of RM., Methods: This is a retrospective cohort study, comparing outcomes in two groups of APD patients monitored during 6 months with RM (group A: n = 35) or standard care (group B: n = 38 patients). In our clinical practice, we assign the RM system to patients who live more distant from the PD center or difficulty in moving. We evaluated emergency visits, hospitalizations, peritonitis, overhydration, and dropout. QoL was assessed with the Kidney Disease Quality of life-Short Form (KDQOL-SF). We included four additional questions focused on patient's perception of monitoring, safety and timely problems solution (Do you think that home-therapy monitoring could interfere with your privacy? Do you think that your dialysis sessions are monitored frequently enough? Do you think that dialysis-related issues are solved timely? Do you feel comfortable carrying out your home-based therapy?)., Results: The case group presented a higher comorbidity score, according to Charlson Comorbidity Index (group A: 5.0; IQR 4.0-8.0 versus group B: 4.0; IQR 3.0-6.0) (p = 0.042). The results in group A showed a reduction in the urgent visits due to acute overhydration (group A: 0.17 ± 0.45 versus group B: 0.66 ± 1.36) (p: 0.042) and in the number of disease-specific hospitalization (group A n = 2.0; 18.2% versus group B n = 7.0; 77.8%) (p = 0.022). We did not find any difference between the two groups in terms of hospitalization because of all-cause, peritonitis, overhydration, and dropout. The analysis of KDQOL-SF subscales was similar in the two groups; on the contrary, the answers of our pointed questions have showed a significant difference between the two groups (group A: 100 IQR 87.5-100.0 versus group B 87.5; IQR 75.0-100.0) (p: 0.018)., Conclusion: RM improved clinical outcomes in PD patients, reducing the emergency visits and the hospitalizations, related to nephrological problems, especially in patients with higher comorbidity score. The acceptance and satisfaction of care were better in patients monitored with RM than with standard APD.

Background: Acute cardiorenal syndrome type 1 (CRS-1) is defined by a rapid cardiac dysfunction leading to acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) is expressed on the surface of human neutrophils and epithelial cells, such as renal tubule cells, and its serum (sNGAL) and urinary have been used to predict AKI in different clinical settings., Aim: To characterize CRS-1 in a cohort of patients with acute heart diseases, evaluating the potentiality of sNGAL as an early marker of CRS-1., Methods: We performed a retrospective cohort, multi-centre study. From January 2010 to December 2011, we recruited 202 adult patients admitted to the coronary intensive care unit (CICU) with a diagnosis of acute heart failure or acute coronary syndrome. We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission., Results: Overall, enrolled patients were hemodynamically stable with a mean arterial pressure of 92 (82-107) mmHg, 55/202 (27.2%) of the patients developed CRS-1, but none of them required dialysis. Neither the NGAL delta value (AUC 0.40, 95%CI: 0.25-0.55) nor the NGAL peak (AUC 0.45, 95%CI: 0.36-0.54) or NGAL cut-off (≥ 140 ng/mL) values were statistically significant between the two groups (CRS-1 vs no-CRS1 patients). The area under the ROC curve for the prediction of CRS-1 was 0.40 (95%CI: 0.25-0.55) for the delta NGAL value and 0.45 (95%CI: 0.36-0.54) for the NGAL peak value. Finally, in multivariate analysis, the risk of developing CRS-1 was correlated with age > 60 years, urea nitrogen at admission and 24 h-urine output (AUC 0.83, SE = 60.5% SP = 93%), while sNGAL was not significantly correlated., Conclusion: In our population, sNGAL does not predict CRS-1, probably as a consequence of the mild renal injury and the low severity of heart disease. So, these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage., Competing Interests: Conflict-of-interest statement: Ronco C is a consultant of Astute Medical, OCD, Asahi Medical, Baxter, Toray Medical. None of the other authors have any financial interest related to this study to disclose. DC received an honorarium from Inverness Medical Inc. for a speech., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., (© 2020 S. Karger AG, Basel.)

Introduction: The nephrotoxicity of modern contrast media remains controversial. Novel biomarkers of kidney damage may help in identifying a subclinical structural renal injury not revealed by widely used markers of kidney function., Objective: The aim of this study was to investigate clinical (contrast-induced acute kidney injury [CI-AKI]) and subclinical CI-AKI (SCI-AKI) after intra-arterial administration of Iodixanol and Iopamidol in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2., Methods: This is a prospective observational monocentric study. Urinary sample was collected at 4-8 h after contrast medium exposure to measure neutrophil gelatinase associated lipocalin (NGAL) and the product tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), while blood samples were collected at 24 and 48 h after exposure to measure serum creatinine., Results: One hundred patients were enrolled, of whom 53 were exposed to Iodixanol and 47 to Iopamidol. Patients in Iodixanol and Iopamidol groups were comparable in terms of demographics, pre-procedural and procedural data. No patient developed CI-AKI according KDIGO criteria, while 13 patients reported SCI-AKI after exposure to iodine-based medium contrast (3 patients in Iodixanol group and 10 patients in Iopamidol group), defined by positive results of NGAL and/or [TIMP-2] × [IGFBP7]. A positive correlation was found between NGAL and [TIMP-2] × [IGFBP7] in the analysed population (Spearman's rho 0.49, p < 0.001). In logistic regression analysis, Iopamidol exposure showed higher risk for SCI-AKI compared to Iodixanol (OR 4.5 [95% CI 1.16-17.52], p = 0.030), even after controlling for eGFR and volume of contrast medium used., Conclusions: This study showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease. Further investigations on larger scale are warranted to confirm if Iopamidol exposed patients to increased risk of SCI-AKI compared to Iodixanol., (© 2020 S. Karger AG, Basel.)

Background: Catheter-related infections are important causes of morbidity in patients undergoing peritoneal dialysis (PD). There are different protocols of exit site care for the prevention of catheter-related infections. The aim of this study was to evaluate the incidence of catheter-related infections and their complications in our PD center., Methods: We performed a retrospective, observational study for all patients receiving PD in our center. We observed prevalent patients every year for 5 years. The patients performed the exit-site care three times a week, cleaning the exit site with 10% sodium hypochlorite. From 2017, update of ISPD recommendations suggests the application of antibiotic creams. We recorded the incidence rate of ESI and TI, gentamicin resistance, catheter lost, related post-ESI peritonitis and fungal infections, and we compared our results with the data in the literature., Results: Prevalent patients per year were 117.6 ± 5.5. The "time at risk" was 356.46 years. The median values of TESI (tunnel and exit site infections), TI, gentamicin resistance, related post-ESI peritonitis and fungal infection rate were similar in our results and the literature data. The ESI and the catheter lost caused by infection were significantly lower in our patients. No significant adverse effects, such as skin allergy or intolerance, were reported., Conclusions: Our results confirm the utility and the safety of routinely exit site care using 10% sodium hypochlorite. This protocol resulted similar to the data reported in the literature. Our analysis of the literature highlighted the wide variation in the infection rate of ESI and TI.

Background: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury. In this study, we evaluate the role of lipopolysaccharide (LPS) and various inflammatory markers in the developing acute kidney injury (AKI) in acute heart failure (AHF) patients., Methods: We enrolled 31 AHF patients and 20 CRS type 1 (the cause of AKI was presumed to be related to cardiac dysfunction) and 17 healthy volunteers without AHF, AKI or CKD, as control group (CTR). We assessed levels of LPS, proinflammatory cytokines (TNF-α, IL-6, IL-18), and oxidative stress marker (myeloperoxidase, MPO)., Results: We observed a significant increase in LPS, TNF-α, IL-6, IL-18 and MPO levels in CRS type 1 and AHF group compared to CTR. LPS levels resulted significantly higher in CRS type 1 patients compared with AHF (118.2 pg/mL, IQR 77.8-217.6 versus 13.5 pg/mL, IQR 12.0-17.0, p = 0.008). We found a cytokines and oxidative stress dysregulation in CRS type 1 patients compared with AHF. Furthermore, we observed a strong positive significant correlation between LPS levels and IL-6 (Spearman's rho = 0.79, p < 0.001), and IL-18 (Spearman's rho = 0.77, p < 0.001) and MPO (Spearman's rho = 0.80, p < 0.001), all confirm by simple linear regression analysis., Conclusion: CRS type 1 patients presented an increased level of LPS, pro-inflammatory cytokines, and MPO. Furthermore, there is a direct correlation between LPS and pro-inflammatory cytokines and stress oxidative marker. LPS may play a role in the pathophysiology of CRS type 1 inducing inflammation, oxidative stress and finally kidney damage.

AKI is a common clinical condition associated with the risk of developing CKD and ESKD. Sepsis is the leading cause of AKI in the intensive care unit (ICU) and accounts for nearly half of all AKI events. Patients with AKI who require dialysis have an unacceptably high mortality rate of 60%-80%. During sepsis, endothelial activation, increased microvascular permeability, changes in regional blood flow distribution with resulting areas of hypoperfusion, and hypoxemia can lead to AKI. No effective drugs to prevent or treat human sepsis-induced AKI are currently available. Recent research has identified dysfunction in energy metabolism as a critical contributor to the pathogenesis of AKI. Mitochondria, the center of energy metabolism, are increasingly recognized to be involved in the pathophysiology of sepsis-induced AKI and mitochondria could serve as a potential therapeutic target. In this review, we summarize the potential role of mitochondria in sepsis-induced AKI and identify future therapeutic approaches that target mitochondrial function in an effort to treat sepsis-induced AKI., (Copyright © 2019 by the American Society of Nephrology.)

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.

Introduction: We investigated the effects of human amniotic fluid stem cells (hAFS) and rat adipose tissue stromal vascular fraction GFP-positive cells (rSVC-GFP) in a model of cardio-renal syndrome type II (CRSII)., Methods and Results: RHF was induced by monocrotaline (MCT) in 28 Sprague-Dawley rats. Three weeks later, four million hAFS or rSVC-GFP cells were injected via tail vein. BNP, sCreatinine, kidney and heart NGAL and MMP9, sCytokines, kidney and heart apoptosis and cells (Cs) engraftment were evaluated. Cell-treated rats showed a significant reduction of serum NGAL and Creatinine compared to CRSII. In both hAFS and rSVC-GFP group, kidney protein expression of NGAL was significantly lower than in CRSII (hAFS p = 0.036 and rSVC-GFP p < 0.0001) and similar to that of controls. In both hAFS and rSVC-GFP treated rats, we observed cell engraftment in the medulla and differentiation into tubular, endothelial and SMCs cells. Apoptosis was significantly decreased in cell-treated rats (hAFS 14.07 ± 1.38 and rSVC-GFP 12.67 ± 2.96 cells/mm 2 ) and similar to controls (9.85 ± 2.1 cell/mm 2 ). TUNEL-positive cells were mainly located in the kidney medulla. Pro-inflammatory cytokines were down regulated in cell-treated groups and similar to controls. In cell-treated rats, kidney and heart tissue NGAL was not complexed with MMP9 as in CRSII group, suggesting inhibition of MMPs activity., Conclusion: Cell therapy produced improvement in kidney function in rats with CRSII. This was the result of interstitial, vessel and tubular cell engraftment leading to tubular and vessel regeneration, decreased tubular cells apoptosis and mitigated pro-inflammatory milieu. Reduction of NGLA-MMP9 complexes mainly due to decrease MMPs activity prevented further negative heart remodeling., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cardiorenal syndromes (CRS) include a scenario of clinical interactions characterized by the heart and kidney dysfunction. The crosstalk between cardiac and renal systems is clearly evidenced but not completely understood. Multi-factorial mechanisms leading to CRS do not involve only hemodynamic parameters. In fact, in recent works on organ crosstalk endothelial injury, the alteration of normal immunologic balance, cell death, inflammatory cascades, cell adhesion molecules, cytokine and chemokine overexpression, neutrophil migration, leukocyte trafficking, caspase-mediated induction of apoptotic mechanisms and oxidative stress has been demonstrated to induce distant organ dysfunction. Furthermore, new alternative mechanisms using the multi-omics approach may be implicated in the pathogenesis of cardiorenal crosstalk. The study of "omics" modifications in the setting of cardiovascular and renal disease represents an emerging area of research. Over the last years, indeed, many studies have elucidated the exact mechanisms involved in gene expression and regulation, cellular communication and organ crosstalk. In this review, we analyze epigenetics, gene expression, small non-coding RNAs, extracellular vesicles, proteomics, and metabolomics in the setting of CRS., (© 2019 S. Karger AG, Basel.)

Chronic diseases are a global concern and a leading cause of death and disability. These conditions require intensive and ongoing medical assistance to maximize outcomes and avoid the risk of frequent flare-ups and hospitalizations, which increase the cost of healthcare. Remote patient management (RPM) is a strategy that allows for accurate home monitoring of chronic patients, enabling the team to improve care through prevention and early identification of problems, with consequent timely interventions. Peritoneal dialysis (PD) is a home-based therapy representing an ideal model for testing the ability of RPM to improve clinical outcomes by allowing the 2-way link between health providers and patients. The literature and our own results confirm that RPM applied to automated peritoneal dialysis (APD) allows an efficient use of healthcare resources, helping to improve tailoring of APD prescription and to intervene early with troubleshooting, reducing the frequency of in-person visits for emergency problems. RPM-APD is today made possible by a cloud-based software providing bidirectional communication between patient's home and the hospital care team (Cycler HOMECHOICE CLARIA with SHARESOURCE platform). This approach can be useful in promptly identifying patients with higher risk of complications: a knowledge-based management permits the reduction of urgent events, and the prevention of clinical complications improving patient outcomes. In our experience, matured over 2 years in a cohort of prevalent patients, we observed a significant reduction of patient drop-out and technique failure, the number of scheduled and unscheduled hospital visits, the number of episodes of overhydration, rate of hospitalization, episodes of non-compliance to prescription, patient and hospital team time spent in travelling and management of therapy, healthcare costs and patient's expenditure, miles travelled by patients from home to hospital and vice versa. The cost/benefit analysis is strongly in favor of the RPM-APD modality versus the traditional periodic hospital visit regime., (© 2019 S. Karger AG, Basel.)

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., (© 2018 S. Karger AG, Basel.)

"Organ crosstalk" is the complex physiological communication between different body systems, and it is necessary for the optimal equilibrium and functioning of the organism. In particular, heart and kidney function is tightly connected, and interplay between these two organs occurs through a vast array of dynamic and bidirectional mechanisms. The term cardiorenal syndrome (CRS) indicates an interaction between the heart and kidneys in acute and chronic disease settings. In all types of CRS, multiple pathophysiological processes are implicated in the initiation and progression of organ injury. In addition to hemodynamic parameters, endothelial injury, immunological imbalance, cell death, inflammatory cascades, oxidative stress, neutrophil migration, leukocyte trafficking, caspase-mediated apoptosis, extracellular vesicles, small noncoding RNAs, and epigenetics play pivotal roles in the development of CRS. In this review, we will focus on neurohormonal, endocrine, and immune dysregulation and inflammation as mechanisms involved in the pathogenesis of CRS., (© 2019 S. Karger AG, Basel.)

Background: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function that leads to acute kidney injury (AKI). This study evaluated the role of lipopolysaccharide (LPS) in the development of AKI in patients with acute heart failure (AHF) and its relationship with renal parameters, to enable a better comprehension of the pathophysiology of CRS type 1., Methods: We enrolled 32 AHF patients, 15 of whom were classified as having CRS type 1. Eight of these 15 exhibited AKI at the time of admission (caused by AHF) and the other 7 developed AKI during their stay in hospital (in the first 48 h). We evaluated the plasmatic LPS concentrations as well as conventional (serum creatinine [sCr] and urea) and unconventional (neutrophil gelatinase-associated lipocalin [NGAL] and cystatin C) renal markers., Results: LPS levels were significantly higher in the CRS type 1 patients. No significant difference in LPS level was found in patients who were admitted with AKI and those developed AKI in hospital, but there was a tendency towards a higher level of LPS in CRS type 1 patients admitted with AKI. The LPS concentrations at admission were similar in CRS type 1 survivors (n = 12) and nonsurvivors (n = 3) (p = 0.22). We observed a positive correlation between LPS level and NGAL, Scr at admission and peak Scr during hospitalization and urea at admission., Conclusion: CRS type 1 patients present with an increased level of LPS and there is a direct correlation between LPS and renal parameters. This pilot research is the first study to explore the premise of LPS as novel pathophysiological factor in CRS type 1., (© 2019 S. Karger AG, Basel.)

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., (© 2018 S. Karger AG, Basel.)

Background: Peritoneal dialysis (PD) is an ideal model for testing remote monitoring (RM). In this study, we evaluated the RM application longitudinally in stable patients undergoing automated PD (APD)., Methods: This was an observational study, comparing outcomes in patients with (current patients) and without (historical data) exposure of RM. We analyzed cost-effectiveness of RM-APD measuring the number of night alarms, number of hospital visits, direct and indirect costs., Results: Changes in APD prescription were almost double in the case group (RM) compared to the control group (p = 0.0005). The need for in-person visits and nocturnal alarms was significantly less in RM-APD than in traditional APD (p = 0.01 and p = 0.002, respectively). The distance traveled by patients in the case of RM-APD was reduced by 1,134 km with a time saving of 1,554 min for patients. The overall cost reduction for the PD center in terms of time/nurse and time/physician was 2,647 and 3,673 min, respectively. All these advantages were obtained in the presence of an improved technique survival with a significant reduction of dropouts. All patients found that it is easy to use the RM system and were satisfied with the high level of interaction with the care team and with the possibility of timely resolving technical problems., Conclusion: These data confirm the long-term benefits of RM applied to APD. RM-APD is cost-effective; it allows early detection and resolution of problems, improved treatment compliance, reduction of patient's access to hospital center for technical and clinical complications with consequent savings, and improved patient's quality of life., (© 2019 S. Karger AG, Basel.)

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., (© 2019 S. Karger AG, Basel.)

The data reported in this article are related to the paper entitle "Stem cells transplantation positively modulates the heart-kidney cross talk in Cardiorenal Syndrome Type II" (Vescovo et al., 2019), which analyzed the impact of stem cells injection in cardiorenal syndrome type II. The dataset contains detailed information on apoptosis and cytokines milieu modification after injection of c-Kit-selected human amniotic fluid stem cells (hAFS) or rats vascular progenitor cells (rSVC-GFP group) in an experimental model of CRSII. The data can be useful for clarifying the paracrine effects exerted by the injected cells.

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 a microenvironment 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.

Epigenetics is defined as the heritable changes in gene expression patterns which are not directly encoded by modifications in the nucleotide DNA sequence of the genome, including higher order chromatin organization, DNA methylation, cytosine modifications, covalent histone tail modifications, and short non-coding RNA molecules. Recently, much attention has been paid to the role and the function of epigenetics and epimutations in the cellular and subcellular pathways and in the regulation of genes in the setting of both kidney and cardiovascular disease. Indeed, deregulation of histone alterations has been highlighted in a large spectrum of renal and cardiac disease, including chronic and acute renal injury, renal and cardiac fibrosis, cardiac hypertrophy and failure, kidney congenital anomalies, renal hypoxia, and diabetic renal complications. Nevertheless, the role of epigenetics in the pathogenesis and pathophysiology of cardiorenal syndromes is currently underexplored. Given the significant clinical relevance of heart-kidney crosstalk, efforts in the research for new action mechanisms concurrently operating in both pathologies are thus of maximum interest. This review focuses on epigenetic mechanisms involved in heart and kidney disease, and their possible role in the setting of cardiorenal syndromes.

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., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Inflammation and oxidative stress seem to play a pivotal role in its pathophysiology. In this in vivo study, we examined the putative role of inflammation and humoral markers in the pathogenesis of the CRS type 1., Methods: We enrolled 53 patients with acute heart failure (AHF); 17 of them developed AKI (CRS type 1). The cause of AKI was presumed to be related to cardiac dysfunction after having excluded other causes. We assessed the plasma levels of proinflammatory cytokines (TNF-α, IL-6, IL-18, sICAM, RANTES, GMCSF), oxidative stress marker (myeloperoxidase, MPO), brain natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin (NGAL) in AHF and CRS type 1 patients., Results: We observed a significant increase in IL-6, IL-18, and MPO levels in CRS type 1 group compared to AHF (p < 0.001). We found higher NGAL at admission in the CRS type 1 group compared to the AHF group (p = 0.008) and a positive correlation between NGAL and IL-6 (Spearman's rho = 0.45, p = 0.003) and between IL-6 and BNP (Spearman's rho = 0.43, p = 0.004). We observed lower hemoglobin levels in CRS type 1 patients compared to AHF patients (p < 0.05) and inverse correlation between hemoglobin and cytokines (IL-6: Spearman's rho = -0.38, p = 0.005; IL-18: Spearman's rho = -0.32, p = 0.02)., Conclusion: Patients affected by CRS type 1 present increased levels of proinflammatory cytokines and oxidative stress markers, increased levels of tissue damage markers, and lower hemoglobin levels. All these factors may be implicated in the pathophysiology of CRS type 1 syndrome., (© 2018 S. Karger AG, Basel.)

Background: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Its pathophysiology is complex and not completely understood. In this study, we examined the role of apoptosis and the caspase pathways involved., Material and Methods: We enrolled 40 acute heart failure (AHF) patients, 11 of whom developed AKI characterizing CRS type 1. We exposed the human cell line U937 to plasma from the CRS type 1 and AHF groups and then we evaluated apoptotic activity by annexin-V evaluation, determination of caspase-3, -8 and -9 levels, and BAX, BAD, and FAS gene expression., Results: We observed significant upregulation of apoptosis in monocytes exposed to CRS type 1 plasma compared to AHF, with increased levels of caspase-3 (p < 0.01), caspase-9 (p < 0.01), and caspase-8 (p < 0.03) showing activation of both intrinsic and extrinsic pathways. Furthermore, monocytes exposed to CRS type 1 plasma had increased gene expression of BAX and BAD (intrinsic pathways) (p = 0.010 for both). Furthermore, strong significant correlations between the caspase-9 levels and BAD and BAX gene expression were observed (Spearman ρ = - 0.76, p = 0.011, and ρ = - 0.72, p = 0.011)., Conclusion: CRS type 1 induces dual apoptotic pathway activation in monocytes; the two pathways converged on caspase-3. Many factors may induce activation of both intrinsic and extrinsic apoptotic pathways in CRS type 1 patients, such as upregulation of proinflammatory cytokines and hypoxia/ischemia. Further investigations are necessary to corroborate the present findings, and to better understand the pathophysiological mechanism and consequent therapeutic and prognostic implications for CRS type 1., (© 2018 S. Karger AG, Basel.)

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., (© 2018 S. Karger AG, Basel.)

Backgrounds: Dendritic cells (DCs) are antigen-presenting cells that play a central role in innate and adaptive immune responses; however, the cross talk between cardiac and renal DCs in cardiorenal syndrome (CRS) has not yet been fully elucidated. In this setting, endothelial cells (ECs) also contribute to immune responses., Summary: DC and EC activation and dysfunction have a central role in the pathogenesis of CRS. Regarding immune responses in CRS, it is unknown whether ECs may serve as antigen-presenting cells or act synergistically with DCs to actively participate in innate and adaptive immune responses. This review first focuses on the burden of concomitant heart and renal DCs in the context of CRS; it examines what is known of DCs in animal models, and proposes a central role for DCs in all types of CRS. Second, this review briefly describes the role of ECs in the context of CRS. Key Messages: Understanding the role of DCs and ECs in immune response could lead to the development of novel therapies for the prevention and treatment of CRS., (© 2018 S. Karger AG, Basel.)

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., (© 2018 S. Karger AG, Basel.)