Endotoxin removal therapy with Polymyxin B immobilized fiber column: a single center experience from EUPHAS2 registry

Continuous renal replacement therapy; Diagnostic markers; InfectionTerapia de reemplazo renal continua; Marcadores de diagnóstico; InfecciónTeràpia de substitució renal contínua; Marcadors diagnòstics; InfeccióAlthough the precise clinical indication for initiation of PMX-HA is widely debated in the literature, a proper patient selection and timing of treatment delivery might play a critical role in the clinical course of a specific subphenotype of septic shock (endotoxic shock). In light of this view, since 2019, we have introduced in our clinical practice a diagnostic-therapeutic flowchart to select patients that can benefit the most from the treatment proposed. In addition, we reported in this study our experience of PMX-HA in a cohort of critically ill patients admitted to our intensive care unit (ICU). We analyzed a single centre, retrospective, observational web-based database (extracted from the EUPHAS2 registry) of critically ill patients admitted to the ICU between January 2016 and May 2021 who were affected by endotoxic shock. Patients were divided according to the diagnostic-therapeutic flowchart in two groups: Pre-Flowchart (Pre-F) and Post-Flowchart (Post-F). From January 2016 to May 2021, 61 patients were treated with PMX-HA out of 531 patients diagnosed with septic shock and of these, fifty patients (82%) developed AKI during their ICU stay. The most common source of infection was secondary peritonitis (36%), followed by community-acquired pneumonia (29%). Fifty-five (90%) out of 61 patients received a second PMX-HA treatment, with a statistically significant difference between the two groups (78% of the Pre-F vs. 100% of the Post-F group, p = 0.005). In both groups, between T0 and T120, the Endotoxin Activity Assay (EAA) decreased, while the SOFA score, mean arterial pressure (MAP), and Vasoactive Inotropic Score (VIS) improved with no statistically significant difference. Furthermore, when performing a propensity score matching analysis to compare mortality between the two groups, statistically significant lower ICU and 90-day mortalities were observed in the Post-F group [p = 0.016]. Although in this experienced centre data registry, PMX-HA was associated with organ function recovery, hemodynamic improvement, and current EAA level reduction in critically ill patients with endotoxic shock. Following propensity score-matched analysis, ICU mortality and 90-day mortalities were lower in the diagnostic-therapeutic flowchart group when considering two temporal groups based on strict patient selection criteria and timing to achieve PMX. Further Randomised Control Trials focused on centre selection, adequate training and a flowchart of action when assessing extracorporeal blood purification use should be performed.This work was supported by IRRIV (The International Renal Research Institute of Vicenza) Foundation

Calciphylaxis in Hemodialysis

Calciphylaxis (CP) or uremic calcific arterial disease (CUA) is a rare, potentially fatal calcific vasculopathy characterized by calcific and thrombotic occlusion of the vessels of the subcutaneous and dermis leading to extremely painful necrotic lesions. It mainly affects patients with end-stage kidney disease (ESKD) and under long time dialysis. The only therapeutic option is represented by intravenous sodium thiosulfate. Currently, clear guidelines are lacking. We have had a good therapeutic response with doses of sodium thiosulfate in association with multidisciplinary management of the patient (vulnologist, dermatologist, nephrologist, dietitian, and cardiologist). There is limited literature on the use of DOAC therapy as a successful alternative to warfarin in patients on dialysis with calciphylaxis. The left atrial appendage closure could represent an important alternative to dicumarolics in patients with atrial fibrillation with calciphylaxis. A new perspective for the treatment of this disease is SNF472 a selective inhibitor of vascular calcification

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

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 p p = 0.04). Significant correlations were observed between eryptosis and EAA levels (Spearman rho2 = 0.50, p p 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

Bone Disease in Medullary Sponge Kidney and Effect of Potassium Citrate Treatment

Background and objectives: In medullary sponge kidney (MSK)—a common malformative renal condition in patients with calcium nephrolithiasis—hypercalciuria, incomplete distal renal tubular acidosis, and hypocitraturia are common. Clinical conditions with concomitant hypercalciuria and/or incomplete distal renal tubular acidosis are almost invariably associated with bone disease, making osteopathy highly likely in MSK, too. Patients with MSK have never been investigated for osteopathy; neither has the potential effect of potassium citrate administration (CA) on their urinary metabolic risk factors and on bone mineralization

Modeling of Internal Filtration in Theranova Hemodialyzers

High retention onset (HRO) is the designation for a new class of hemodialysis membranes. A unique characteristic of this class is the highly selective and controlled porosity resulting in sieving properties that provide a clinically desirable balance between middle/large molecular weight solute removal and albumin loss. Another defining feature of this membrane class is the relatively small fiber diameter, which produces high convective volumes in the form of internal filtration. The aim of the present study was to estimate, by semi-empirical methods, convective volumes for 2 new HRO dialyzers: Theranova 400 and Theranova 500 (Baxter International Inc., Deerfield, IL, USA). Axial blood and dialysate compartment pressure drop along with transmembrane pressure, measured in vitro with blood (Qb = 300 or 400 mL/min; Qd = 500 mL/min; net ultrafiltration rate = 0), served as input parameters for 3 different models: linear, geometric, and (non-linear) mathematical. Based on the most rigorous mathematical model, the estimated convective volumes were 1,661 mL/h (Qb = 300 mL/min) and 1,911 mL/h (Qb = 400 mL/min) for Theranova 400 and 1,864 mL/h (Qb = 300 mL/min) and 1,978 mL/h (Qb = 400 mL/min) for Theranova 500. These results suggest that the unique fiber characteristics of this new class of membranes provide substantial convective volumes without the need for exogenous substitution fluid. As such, HRO membranes are a major end-stage renal disease treatment advance in the quest to enhance the removal of larger-sized uremic toxins

Endotoxin removal therapy with Polymyxin B immobilized fiber column: a single center experience from EUPHAS2 registry

Abstract Although the precise clinical indication for initiation of PMX-HA is widely debated in the literature, a proper patient selection and timing of treatment delivery might play a critical role in the clinical course of a specific subphenotype of septic shock (endotoxic shock). In light of this view, since 2019, we have introduced in our clinical practice a diagnostic-therapeutic flowchart to select patients that can benefit the most from the treatment proposed. In addition, we reported in this study our experience of PMX-HA in a cohort of critically ill patients admitted to our intensive care unit (ICU). We analyzed a single centre, retrospective, observational web-based database (extracted from the EUPHAS2 registry) of critically ill patients admitted to the ICU between January 2016 and May 2021 who were affected by endotoxic shock. Patients were divided according to the diagnostic-therapeutic flowchart in two groups: Pre-Flowchart (Pre-F) and Post-Flowchart (Post-F). From January 2016 to May 2021, 61 patients were treated with PMX-HA out of 531 patients diagnosed with septic shock and of these, fifty patients (82%) developed AKI during their ICU stay. The most common source of infection was secondary peritonitis (36%), followed by community-acquired pneumonia (29%). Fifty-five (90%) out of 61 patients received a second PMX-HA treatment, with a statistically significant difference between the two groups (78% of the Pre-F vs. 100% of the Post-F group, p = 0.005). In both groups, between T0 and T120, the Endotoxin Activity Assay (EAA) decreased, while the SOFA score, mean arterial pressure (MAP), and Vasoactive Inotropic Score (VIS) improved with no statistically significant difference. Furthermore, when performing a propensity score matching analysis to compare mortality between the two groups, statistically significant lower ICU and 90-day mortalities were observed in the Post-F group [p = 0.016]. Although in this experienced centre data registry, PMX-HA was associated with organ function recovery, hemodynamic improvement, and current EAA level reduction in critically ill patients with endotoxic shock. Following propensity score-matched analysis, ICU mortality and 90-day mortalities were lower in the diagnostic-therapeutic flowchart group when considering two temporal groups based on strict patient selection criteria and timing to achieve PMX. Further Randomised Control Trials focused on centre selection, adequate training and a flowchart of action when assessing extracorporeal blood purification use should be performed

Identification of GDNF Gene Sequence Variations in Patients with Medullary Sponge Kidney Disease

Background and objectives: Medullary sponge kidney (MSK) is a rare nephropathy characterized by cystic anomalies of precalyceal ducts, nephrocalcinosis, renal stones, and tubule dysfunctions. Its association with various malformations and cases of familial aggregation supports the conviction that genetic factors are involved, but no genetic studies have been conducted to date. It is hypothesized that MSK is due to a disruption at the “ureteric bud/metanephric blastema” interface caused by critical developmental genes functioning abnormally

Prevalence of CKD in Northeastern Italy: Results of the INCIPE Study and Comparison with NHANES

Background and objectives: Sufficiently powered studies to investigate the CKD prevalence are few and do not cover southern Europe