Body composition indices as predictors of humoral response to mRNA vaccination against COVID-19 in patients on maintenance hemodialysis.

INTRODUCTION: Patients on maintenance hemodialysis show lower serological response to mRNA vaccines. Main causes that contribute to this phenomenon are uremic milieu and older age. However, there are no data on the impact of body composition parameters to humoral response. MATERIALS AND METHODS: In this retrospective study, we used data from adult patients on maintenance hemodialysis who received vaccination with 2 doses of BNT162b2. Quantitative determination of antibodies to SARS-CoV-2 spike (S) protein receptor binding domain was performed using the Elecsys immunoassay. Antibody levels higher than 0.8 and 264 U/mL were considered positive and protective, respectively. Body composition parameters were assessed using multifrequency bioelectrical impedance spectroscopy. RESULTS: Overall, 49 patients were included in the study. Three weeks after the 1st vaccination, 34% of patients, and 3 weeks and 3 months after the 2nd vaccination, 100% of patients had detectable titers. Protective titer was developed in 43% of patients 3 weeks after the 2nd vaccination and then decreased to 24% 3 months after the 2nd vaccination. More years on dialysis were correlated to the absence of protective titers. Higher prediction marker values correlated to poor antibody response, and phase angle was negatively associated with the development of protective titers. Patients with protective titers at 3 months after the 2nd vaccination had significantly lower prediction marker and higher phase angle values. CONCLUSION: Parameters of body composition correlate and affect antibody response in patients on hemodialysis. The main observation is that immunogenicity of mRNA vaccines is influenced by phase angle and prediction marker.

Percutaneous Arteriovenous Fistula Creation with the WavelinQ 4-French EndoAVF System: A Single-Center Retrospective Analysis of 30 Patients.

PURPOSE: To retrospectively assess the safety and efficacy of percutaneous arteriovenous fistula (pAVF) creation with the WavelinQ 4-F EndoAVF System. MATERIALS AND METHODS: From February 2018 to June 2020, 30 pAVFs were created in 30 consecutive patients (men; age, 55.3 years ± 13.6). Of the 30 patients, 21 (70%) were already on hemodialysis using a central venous catheter. The primary outcome measures were technical success, complications, and cannulation rate. The secondary outcome measures included the number of secondary procedures needed for cannulation, maintenance time to cannulation, and pAVF survival. RESULTS: Technical success was 100%. The adverse event rate was 6.7% (2/30), including a pseudoaneurysm of the brachial artery that developed immediately after sheath removal and an aneurysm of the anastomosis 17 days after the procedure, which was treated with a covered stent placed in the arterial side. The mean follow-up was 547 days ± 315.7 (range, 14-1,071 days). The cannulation rate was 86.7% (26/30). The mean time to cannulation was 61.3 days ± 32.5 (range, 15-135 days). The mean follow-up after cannulation was 566.2 days ± 252.7 (range, 35-1,041 days). Four pAVFs were thrombosed after cannulation, with 2 of them successfully declotted. Sixteen interventions were needed to achieve cannulation after the index procedure in 15 patients (overall, 0.53 procedures/patient). Seven maintenance endovascular interventions (following cannulation) were performed during the follow-up period in 6 patients (overall, 0.27 procedures/patient, 0.17 procedures/patient-years). For the pAVFs that were cannulated, patency was 96% at 1 year, and 82% at 2 and 3 years, according to the Kaplan-Meier survival analysis. CONCLUSIONS: This initial experience suggests that pAVF creation is safe and can be successfully performed with high maturation and long-term patency rates. Larger-scale prospective studies are needed to validate the results.

Gut barrier dysfunction, endotoxemia and inflammatory response in STEMI patients and effect of primary PCI.

BACKGROUND: Gut-derived bacterial and endotoxin translocation induce systemic inflammation, which exerts a pivotal pathogenetic role in all phases of atherosclerosis. OBJECTIVES: To investigate prospectively the gut barrier function, endotoxin translocation and inflammatory response in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary artery intervention (PPCI). METHODS: Twenty-seven patients with STEMI that underwent successful PPCI were subjected to peripheral blood sampling at 3-time points; before PPCI (day0), 24 h (day1) and 96 h (day4) after PPCI and were compared with 20 chronic coronary syndrome (CCS) patients and 11 healthy controls. Serum ZO-1, I-FABP and endotoxin concentrations were determined by ELISA. Concentrations of cytokines IL-1ß, -6, -8, -10 and TNF-α were determined by flow cytometry. RESULTS: Patients with STEMI before PPCI (day0) had increased serum ZO-1 and endotoxin, both at significantly higher levels compared to CCS patients. STEMI induced also significant increases of the cytokines IL-6, -8 and -10. After PPCI, a significant improvement of gut barrier integrity (ZO-1) and endotoxemia was observed from the first day. At day4 post PPCI, systemic endotoxin and cytokines IL-6, -8 and -10 levels were reduced to control levels. Serum ZO-1 levels were positively correlated with systemic IL-10 concentrations (r = 0.471). CONCLUSION: STEMI is associated with gut barrier dysfunction, systemic endotoxemia and inflammatory response, which improve rapidly following successful PPCI.

Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy. Histological parameters were recorded, intraepithelial CD3+ T-cells and the expression of occludin and claudin-1 in enterocytes were examined using immunohistochemistry, circulating endotoxin concentrations were determined using ELISA, and concentrations of cytokines were determined using flow cytometry. Patients with HFrEF or HFpEF had significantly higher serum endotoxin concentrations (p < 0.001), a significantly decreased intestinal occludin and claudin-1 expression (in HfrEF p < 0.01 for occludin, p < 0.05 for claudin-1, in HfpEF p < 0.01 occludin and claudin-1), and significantly increased serum concentrations of IL-6, IL-8, and IL-10 (for IL-6 and IL-10, p < 0.05 for HFrEF and p < 0.001 for HFpEF; and for IL-8, p < 0.05 for both groups) compared to controls. Occludin and claudin-1 expression inversely correlated with systemic endotoxemia (p < 0.05 and p < 0.01, respectively). Heart failure, regardless of the type of ejection fraction, results in a significant decrease in enterocytic occludin and claudin-1 expression, which may represent an important cellular mechanism for the intestinal barrier dysfunction causing systemic endotoxemia and inflammatory response.

Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

BACKGROUND: Systemic inflammation in chronic kidney disease (CKD) is associated (as a cause or effect) with intestinal barrier dysfunction and increased gut permeability, with mechanisms not yet fully understood. This study investigated different parameters of the intestinal barrier in CKD patients, especially tight junction (TJ) proteins and their possible association with systemic endotoxemia and inflammation. METHODS: Thirty-three patients with stage I-IV CKD (n = 17) or end-stage kidney disease (ESKD) (n = 16) and 11 healthy controls underwent duodenal biopsy. Samples were examined histologically, the presence of CD3+ T-lymphocytes and the expression of occludin and claudin-1 in the intestinal epithelium was evaluated by means of immunohistochemistry, circulating endotoxin concentrations were determined by means of ELISA and the concentrations of the cytokines IL-1ß, IL-6, IL-8, IL-10 and TNF-α in serum were measured using flow cytometry. RESULTS: Patients with stage I-IV CKD or ESKD had significantly higher serum endotoxin, IL-6, IL-8 and IL-10 levels compared to controls. Intestinal occludin and claudin-1 were significantly decreased, and their expression was inversely correlated with systemic endotoxemia. Regarding occludin, a specific expression pattern was observed, with a gradually increasing loss of its expression from the crypt to the tip of the villi. CONCLUSION: The expression of occludin and claudin-1 in enterocytes is significantly reduced in patients with CKD, contributing to systemic endotoxemia and inflammatory responses in these patients.

A Prospective Study of Eplerenone in the Treatment of Patients with Glomerulonephritis.

BACKGROUND: High aldosterone levels contribute to kidney disease progression, while spironolactone in combination with ACEi or ARBs can potentially reduce proteinuria and ameliorate kidney function deterioration. However, evidence on the impact of eplerenone in patients with glomerulonephritis is scarce. METHODS: In this prospective observational study, we assessed the effects of eplerenone in patients with biopsy-proven glomerulonephritis who were already treated with ACEi or ARBs. Patients received either eplerenone (25 mg daily) on top of ACEi or ARBs or standard treatment alone. Proteinuria (24 h total protein excretion), kidney function, blood pressure and serum K+ levels were assessed at 3, 6 and 12 months after the initiation of treatment. RESULTS: Sixty-six patients were included in the study. Eplerenone was administered in 30 patients, while 36 received only ACEi or ARB. Proteinuria decreased from 1768 to 1152 mg/24 h after 1 year of eplerenone treatment, while it remained stable in controls. Eplerenone showed significant impact on proteinuria in those with baseline proteinuria of >1000 mg/24 h. Patients who received eplerenone showed a reduction in systolic blood pressure, while eGFR and serum K+ levels remained stable. CONCLUSIONS: Addition of eplerenone has a beneficial effect on proteinuria in patients with glomerulonephritis and significant baseline proteinuria.

Vascular access hands-on training for young nephrologists: The fellows' experience of the N-PATH project REVAC module.

Chronic kidney disease is a major public health problem, as population studies record a prevalence of 7.2% in individuals over 30 years and is expected to increase in the future. Many of them will end up undergoing hemodialysis treatment, and vascular access is not only an essential requirement for the technique, but also a determining factor in their prognosis; for all these reasons, every nephrologist should have both theoretical and practical knowledge of vascular access; however, the practical training is generally uneven and dependent on the hospital in which you train. It is within this context that the N-PATH (Nephrology Partnership for Advancing Technology in Healthcare) program was born with the objective of training 40 young European nephrologists in theoretical and practical aspects of Interventional Nephrology. To fulfill its mission, the 2-year program is composed of four modules of 6 months each including theoretical courses and hands-on training: Renal Expert in Molecular Pathology (REMAP), Renal Expert in Vascular Access (REVAC), Renal Expert in Medical Ultrasound (REMUS), and Renal Expert in Peritoneal Dialysis (REPED). By bringing together young nephrologists from all over Europe, the goal is also to create a strong network and promote Nephrology career at the European level. This publication highlights the experience of fellows who attended the REVAC hands-on training in Milan, focused on simulation and virtual reality for vascular access, and its impact on their nephrology training.

Normal saline versus balanced crystalloids in patients with prerenal acute kidney injury and pre-existing chronic kidney disease.

INTRODUCTION: Normal saline (N/S) and Ringer's-Lactate (L/R), are administered in everyday clinical practice. Despite that, N/S increases the risk of sodium overload and hyperchloremic metabolic acidosis. In contrast, L/R has lower sodium content, significantly less chloride and contains lactates. In this study we compare the efficacy of L/R versus N/S administration in patients with prerenal acute kidney injury (AKI) and pre-established chronic kidney disease (CKD). METHODS: In this prospective open-label study we included patients with prerenal AKI and previously known CKD stage III-V without need for dialysis. Patients with other forms of AKI, hypervolemia or hyperkalemia were excluded. Patients received either N/S or L/R intravenously at a dose of 20 ml/kg body-weight/day. We studied kidney function at discharge and at 30 days, duration of hospitalization, acid-base balance and the need for dialysis. RESULTS: We studied 38 patients and 20 were treated with N/S. Kidney function improvement during hospitalization and at 30 days after discharge, was similar between the two groups. Duration of hospitalization was also similar. Anion-gap improvement as expressed with Δanion-gap between discharge and admission day was higher in those patients that received L/R in comparison to those that received N/S and pH increase (ΔpH) was slightly higher in the L/R group. No patient required dialysis. CONCLUSIONS: Administration of L/R or N/S to patients with prerenal AKI and pre-established CKD had no significant difference in short or long term kidney function but L/R showed a better profile in acid-base balance improvement and Cl- overload in comparison to N/S.

Drug-Coated Balloons for the Dysfunctional Vascular Access: An Evidence-Based Road Map to Treatment and the Existing Obstacles.

An underlying stenosis within the venous limb of a hemodialysis access circuit is the main etiology for graft and fistula dysfunction as well as other symptoms such as arm, breast, and neck swelling. Treatment options for both peripheral and central venous stenoses include plain old balloon angioplasty, angioplasty with drug-coated balloons, and stenting. This article discusses the current evidence for the use of drug-coated balloon angioplasty in this patient population.