PMMA dialyzers modulate both humoral and cell-mediate immune response to anti-COVID-19 vaccine (BNT162b2) in a cohort of chronic hemodialyzed patients.

Patients on hemodialysis (HD) have a high risk of death from COVID-19. We evaluated the humoral and cell-mediated immune response to BNT162b2 (Pfizer-BioNTech) vaccine in HD patients, comparing HD with Poly-methyl-methacrylate (PMMA) and HD with Polysulphone (PS). Samples were collected before vaccination (T0) and 14-days after the 2ndvaccine (T2) in a TG (TG, n = 16-Foggia) and in a VG (CG, n = 36-Novara). Anti-SARS-CoV-2-Ig were titrated in the cohort 2-weeks after the 2nddose of vaccine. In the Testing-Group, serum neutralizing antibodies (NAb) were assayed and PBMCs isolated from patients were thawed, counted and stimulated with SARS-CoV-2 IGRA stimulation tube set. All patients had a positive ab-response, except in a case. PMMA-patients had higher levels of anti-SARS-CoV-2 IgG (p = 0.031); VG data confirmed these findings (p < 0.05). NAb evaluation: PMMA patients passed the positive cut-off value, while in PS group only only 1/8 patient did not respond. PMMA patients showed higher percentages of anti-SARS-CoV-2 S1/RBD-Ig after a complete vaccine schedule (p = 0.028). Interferon-gamma release: PMMA patients showed significantly higher release of IFNγ (p = 0.014). The full vaccination course provided sufficient protection against SARS-CoV-2 across the entire cohort, regardless of dialyzer type. After vaccination, PMMA patients show a better immune response, both humoral and cellular, at the end of the vaccination course than PS patients.

Enhancing Immune Protection in Hemodialysis Patients: Role of the Polymethyl Methacrylate Membrane.

End-stage renal disease (ESRD) is characterized by deep disorders in both innate and adaptive immune systems that imply unbalance deactivation and immunosuppression. The central, widely recognized factors responsible for this immune dysregulation are uremia, uremic toxin retention, hemodialysis membrane biocompatibility, and related cardiovascular complications. Recently, several studies strengthened the concept that dialysis membranes are not considered as a simple diffusive/adsorptive device but as a platform to personalize a dialysis approach to improve the quality of life of ESRD patients. Therefore, understanding of the molecules associated with altered immune response is crucial and could lead to therapeutically intervention or adaptation of the dialysis procedure itself for the management of immunological dysfunction of ESRD patients. The polymethyl methacrylate (PMMA)-based membrane is characterized by a symmetrical structure with large-sized pores, providing a better hydrophobic and cationic adsorption capacity compared to the other synthetic membranes. Together with hydrophobic interactions, the high adsorption rate of cytokines (i.e., IL-6) can also be enhanced by the size of nano-pores placed on the membrane surface. PMMA membranes exhibit adsorptive properties for a large amount of uremic toxins including p-cresol and indoxyl sulfate, as well as ß2-microglobulin characterized by higher molecular weight, maintaining the diffusive clearance of small molecules like urea with a great biocompatibility. Besides exerting a strong anti-inflammatory effects in line with the improvement of immune responses in patients undergoing dialysis, PMMA also plays a role in modulating adaptive immune response, i.e., can clear blood from soluble CD40, a natural antagonist of the CD40/CD40L signaling that acts inhibiting immunoglobulin production by B cells. This review provides an overview of the main concepts and current understanding of immune dysfunction in hemodialysis and summarizes the recent findings regarding PMMA-based dialysis as potential strategy to restore immune balance in ESRD patients.

Nutrition-Based Management of Inflammaging in CKD and Renal Replacement Therapies.

Access to renal transplantation guarantees a substantial improvement in the clinical condition and quality of life (QoL) for end-stage renal disease (ESRD) patients. In recent years, a greater number of older patients starting renal replacement therapies (RRT) have shown the long-term impact of conservative therapies for advanced CKD and the consequences of the uremic milieu, with a frail clinical condition that impacts not only their survival but also limits their access to transplantation. This process, referred to as "inflammaging," might be reversible with a tailored approach, such as RRT accompanied by specific nutritional support. In this review, we summarize the evidence demonstrating the presence of several proinflammatory substances in the Western diet (WD) and the positive effect of unprocessed food consumption and increased fruit and vegetable intake, suggesting a new approach to reduce inflammaging with the improvement of ESRD clinical status. We conclude that the Mediterranean diet (MD), because of its modulative effects on microbiota and its anti-inflammaging properties, may be a cornerstone in a more precise nutritional support for patients on the waiting list for kidney transplantation.

Molecular Mechanisms of Premature Aging in Hemodialysis: The Complex Interplay Between Innate and Adaptive Immune Dysfunction.

Hemodialysis (HD) patient are known to be susceptible to a wide range of early and long-term complication such as chronic inflammation, infections, malnutrition, and cardiovascular disease that significantly affect the incidence of mortality. A large gap between the number of people with end-stage kidney disease (ESKD) and patients who received kidney transplantation has been identified. Therefore, there is a huge need to explore the underlying pathophysiology of HD complications in order to provide treatment guidelines. The immunological dysregulation, involving both the innate and adaptive response, plays a crucial role during the HD sessions and in chronic, maintenance treatments. Innate immune system mediators include the dysfunction of neutrophils, monocytes, and natural killer (NK) cells with signaling mediated by NOD-like receptor P3 (NLRP3) and Toll-like receptor 4 (TLR4); in addition, there is a significant activation of the complement system that is mediated by dialysis membrane-surfaces. These effectors induce a persistent, systemic, pro-inflammatory, and pro-coagulant milieu that has been described as inflammaging. The adaptive response, the imbalance in the CD4+/CD8+ T cell ratio, and the reduction of Th2 and regulatory T cells, together with an altered interaction with B lymphocyte by CD40/CD40L, have been mainly implicated in immune system dysfunction. Altogether, these observations suggest that intervention targeting the immune system in HD patients could improve morbidity and mortality. The purpose of this review is to expand our understanding on the role of immune dysfunction in both innate and adaptive response in patients undergoing hemodialysis treatment.

Pregnancy in end-stage renal disease patients on dialysis: how to achieve a successful delivery.

Pregnancy in women with chronic kidney disease has always been considered as a challenging event both for the mother and the fetus. Over the years, several improvements have been achieved in the outcome of pregnant chronic renal patients with increasing rates of successful deliveries. To date, evidence suggests that the stage of renal failure is the main predictive factor of worsening residual kidney function and complications in pregnant women. Moreover, the possibility of success of the pregnancy depends on adequate depurative and pharmacological strategies in patients with end-stage renal disease. In this paper, we propose a review of the current literature about this topic presenting our experience as well.

A single-center cohort study to define the role of pretransplant biopsy score in the long-term outcome of kidney transplantation.

BACKGROUND: The role of pretransplant biopsy in defining the quality of kidney grafts is still debated. The aim of this study was to investigate the influence of pretransplant biopsy score on long-term graft outcome. METHODS: In a retrospective cohort study, we analyzed 372 recipients of single kidney transplantation (SKT) from deceased donors between 1997 and 2007, with an available pretransplant biopsy. We evaluated 5- and 10-year graft survival, incidence of delayed graft function, and estimated glomerular filtration rate at 1 and 5 years. RESULTS: Graft survival at 5 and 10 years was significantly better for recipients with a score of 0 compared to transplants with a score of 1 to 5, whereas we did not observe any significant difference among transplants with a score of 1 through 4. Survival of kidneys with a score of 5 was significantly worse compared to grafts with a score of 1 to 4. In a multivariate Cox model, only pretransplant histological score was significantly associated with graft survival. Transplants with a score of 0 and 5 had the best and the worst graft function, respectively, both at 1 and 5 years, whereas we did not observe any difference among patients with a score of 1 through 4. In a multivariate logistic regression, pretransplant histological score was independently associated with the prevalence of an estimated glomerular filtration rate less than 30 mL/min at 5 years. Finally, delayed graft function rate was significantly higher in recipients with a score of 5 compared to patients with a score of 1 to 4 and score of 0. CONCLUSIONS: Our data suggest that 1) pretransplant histological score may predict long-term graft outcome and 2) allocation of kidneys with a score of 4 to SKT provides an acceptable long-term graft function and survival.

Impact of transplant nephrectomy on retransplantation: a single-center retrospective study.

PURPOSE: Kidney retransplantation is the best treatment option for transplanted patients returning to dialysis. The aim of this study was to explore the effect of removal of a failed graft on the outcome of a subsequent transplant. METHODS: We identified 140 patients who underwent retransplantation at our institution. Retrospective comparison was performed between patients undergoing kidney retransplantation with (group A, n = 28) and without (group B, n = 112) preliminary nephrectomy. Graft and patient survival were calculated by the Kaplan-Meier method. RESULTS: After a mean follow-up of 64.5 months, patients survival was comparable between the two groups (group A = 68.6 vs. group B = 63.5 months; p = 0.6). Mean graft survival was 65.5 versus 56.0 months in group A and B, respectively (p = 0.14). Surgical complications after retransplantation were significantly higher in group A compared to group B (57.1 vs. 19.6 %; p = 0.0002). There was no significant difference between the two groups in the panel reactive antibody level at the time of retransplantation (group A = 20 % vs. group B = 32 %; p = 0.22). The acute rejection rate was 35.7 % in group A and 25 % in group B (p = 0.36). The risk of delayed graft function was not significantly increased in group A (p = 0.63). Finally, 2 years after retransplantation, patients who had not undergone nephrectomy had lower serum creatinine concentrations (1.3 vs. 1.7 mg/dl; p = 0.01) and higher estimated GFR (77.9 vs. 59.3 ml/min/1.73 m(2); p = 0.02). CONCLUSION: Our experience shows that there is no advantage in performing allograft nephrectomy before retransplantation, and that this procedure does not seem to significantly influence the survival of a subsequent graft.

Update on pregnancy in chronic kidney disease.

The occurrence of pregnancy in patients with chronic kidney disease (CKD) has been considered a dangerous event both for the mother and for the fetus. However, increasing evidence shows that the stage of CKD is the leading factor that can predict possible acceleration in the declining of renal function and complications of pregnancy. This review summarizes recent data on pregnancy in patients with CKD, dialysis and kidney transplantation.