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

Virzì, Grazia Maria; Manani, Sabrina Milan; Marturano, Davide; Clementi, Anna; Lerco, Silvia; Tantillo, Ilaria; Giuliani, Anna; Battaglia, Giovanni Giorgio; Ronco, Claudio; Zanella, Monica

doi:10.3390/jcm11236918

Cited by 3 publications

(6 citation statements)

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“…We evaluated in vivo eryptosis percentage in blood fresh samples and pWBC, pNGAL, and peritoneal cytokines (IL-1 β and IL-6), as specific peritoneal markers of peritonitis. Our in vivo results reported higher levels of eryptosis in PD patients with peritonitis and confirmed our previous data demonstrating enhanced eryptosis levels in PD patients with PD-related peritonitis compared with PD stable patients (without peritonitis and inflammatory events in the last 3 months) [23]. In our previous work, positive correlations between systemic conventional and unconventional inflammatory markers and eryptosis percentage were reported [18,23].…”

Section: Discussionsupporting

confidence: 92%

“…Recently, our group analyzed eryptosis in a PD stable population (46 patients and 17 controls) and reported an increase in eryptosis levels associated with the progressive residual diuresis and residual glomerular filtration rate (rGFR) loss, probably due to decreased uremic toxins clearance [22]. In addition, eryptosis levels were not affected by diabetes, hypertension, or cardiovascular disease in these PD [22].In addition, our group evaluated eryptosis levels in PD patients with and without peritonitis (study population: 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)and their relationship with systemic conventional(C-reactive protein) and unconventional indices (cytokines) [23]. In particular, our preliminary data show that there is a significant increase in eryptosis levels in PD patients with peritonitis and significant positive correlations between the percentage of eryptosis and all systemic inflammatory markers tested (C-reactive protein, IL-1β and IL-6) [23].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, eryptosis levels were not affected by diabetes, hypertension, or cardiovascular disease in these PD [22].In addition, our group evaluated eryptosis levels in PD patients with and without peritonitis (study population: 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)and their relationship with systemic conventional(C-reactive protein) and unconventional indices (cytokines) [23]. In particular, our preliminary data show that there is a significant increase in eryptosis levels in PD patients with peritonitis and significant positive correlations between the percentage of eryptosis and all systemic inflammatory markers tested (C-reactive protein, IL-1β and IL-6) [23]. Based on these data, we hypothesized a role for the classical and non-classical inflammatory mediators as promoters/inducers of the RBCs death in PD-related peritonitis.…”

Section: Introductionmentioning

confidence: 99%

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

Virzì,

Morisi,

Marturano

et al. 2024

IJMS

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Virzì,

Morisi,

Marturano

et al. 2024

IJMS

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“…In the case of dialysis-dependent kidney failure, there is a greater abundance of evidence compared to nondialysis-dependent cases, indicating that eryptosis plays a significant role in the context of anemia. Elevated eryptosis has been identified in hemodialysis (HD) and peritoneal dialysis patients [10]. Interestingly, eryptosis was associated with increased ESA requirements.…”

Section: Eryptosis As a Link Between Chronic Kidney Disease And Anemiamentioning

confidence: 99%

Eryptosis: a driver of anemia in chronic kidney disease

Bissinger,

Qadri,

Artunc

2023

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Anemia, characterized by a reduction in red blood cell (RBC) count or hemoglobin concentration, commonly accompanies chronic kidney disease (CKD), significantly impacting patients’ quality of life. This review delves into the multifaceted nature of anemia in CKD, with a focus on novel mechanisms, particularly the dysregulation of eryptosis or programmed cell death of RBCs, leading to shortened RBC lifespan. Recent findings Recent studies in CKD patients and mouse models revealed that eryptosis, driven by factors such as uremic toxins, inflammation, and imbalances in calcium homeostasis, plays a pivotal role in the development of renal anemia. Dysregulated eryptosis results in premature RBC destruction, exacerbating the hypoproliferative character of anemia in CKD. Summary Recognizing the intricate relationship between eryptosis and anemia in CKD opens promising prospects for improving patient outcomes and enhancing our understanding of this complex condition. Future research and therapeutic development in this area hold the potential to improve anemia treatment of CKD patients.

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“…Eryptosis is known to be involved in the pathogenesis of many clinical conditions, such as anaemia, diabetes, uremia, fever, peritonitis and dehydration [ 16 , 17 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. During sepsis, eryptosis is associated with a higher severity of disease and mortality rate [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

The Cytotoxic Effect of Septic Plasma on Healthy RBCs: Is Eryptosis a New Mechanism for Sepsis?

Marcello,

Virzì,

Marturano

et al. 2023

IJMS

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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.

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

Cited by 3 publications

References 33 publications

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

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

Eryptosis: a driver of anemia in chronic kidney disease

The Cytotoxic Effect of Septic Plasma on Healthy RBCs: Is Eryptosis a New Mechanism for Sepsis?

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