Diagnostic and Therapeutic Aspects of Monoclonal Gammopathies of Renal Significance (MGRS): An Update.

Monoclonal gammopathy of renal significance (MGRS) refers to a group of renal disorders caused by a monoclonal immunoglobulin (MIg), secreted by a non-malignant B-cell clone. Unlike overt multiple myeloma or B-cell proliferation, MGRS does not meet those diagnostic criteria. However, it is associated with significant morbidity, due to severe renal, and sometimes systemic, lesions induced by the MIg.

Changes in 24-hour blood pressure profile after 12 weeks of dapagliflozin treatment in patients with diabetic kidney disease: an Italian multicenter prospective study.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower ambulatory blood pressure (ABP) in patients with type 2 diabetes mellitus; whether the same holds true in diabetic kidney disease (DKD) is unknown. This information is critical to the knowledge of mechanisms of nephroprotection and safety of this therapy.

Methods: This multicenter prospective study evaluates the changes in ABP after 12 weeks of dapagliflozin 10 mg/day in a cohort of patients with type 2 DKD and glomerular filtration rate (GFR) >25 mL/min/1.

mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes.

The aging process contributes significantly to the onset of chronic diseases, which are the primary causes of global mortality, morbidity, and healthcare costs. Numerous studies have shown that the removal of senescent cells from tissues extends lifespan and reduces the occurrence of age-related diseases. Consequently, there is growing momentum in the development of drugs targeting these cells.

Dendritic Cells: A Bridge between Tolerance Induction and Cancer Development in Transplantation Setting.

Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a dual role. In immunocompromised individuals, posttransplant malignancies pose a significant health concern, with DCs serving as vital players in immune responses against cancer cells.

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).

Hypoxic Inducible Factor Stabilization in Pericytes beyond Erythropoietin Production: The Good and the Bad.

The paracrine signaling pathways for the crosstalk between pericytes and endothelial cells are essential for the coordination of cell responses to challenges such as hypoxia in both healthy individuals and pathological conditions. Ischemia-reperfusion injury (IRI), one of the causes of cellular dysfunction and death, is associated with increased expression of genes involved in cellular adaptation to a hypoxic environment. Hypoxic inducible factors (HIFs) have a central role in the response to processes initiated by IRI not only linked to erythropoietin production but also because of their participation in inflammation, angiogenesis, metabolic adaptation, and fibrosis.

Safety and efficacy of tixagevimab/cilgavimab for pre-exposure prophylaxis in kidney transplant recipients: a multicenter retrospective cohort study.

Background: Immunocompromised patients show an impaired vaccine response and remain at high risk of severe COVID-19, despite vaccination. Neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed for prophylaxis and treatment. The combination tixagevimab/cilgavimab (AZD7442) has been authorized for emergency use as pre-exposure prophylaxis for COVID-19, but data on safety and efficacy in kidney transplant recipients during the Omicron period are limited.

Effects of low-sodium bread on dietary compliance and fecal cultivable bacteria in a randomized controlled pilot trial in hypertensive subjects.

High salt intake and compliance to low-sodium (LS) diets are critical in hypertension. Salt reduction in processed foods can help to achieve the target sodium intake. To verify the hypothesis that an innovative LS formulation of a traditional bread could result in a reduction of sodium intake and blood pressure, we performed a 6-month randomized controlled pilot trial on hypertensive patients.

mRNA as a medicine in nephrology: the future is now.

The successful employment of messenger RNA (mRNA) as vaccine therapy for the prevention of COVID-19 infection has spotlighted the attention of scientific community onto the potential clinical application of these molecules as innovative and alternative therapeutic approaches in different fields of medicine. As therapy, mRNAs may be advantageous due to their unique biological properties of targeting almost any genetic component within the cell, many of which may be unreachable using other pharmacological/therapeutic approaches, and encoding any proteins and peptides without the need for their transport into the nuclei of the target cells. Additionally, these molecules may be rapidly designed/produced and clinically tested.

Inflammasome pathway in kidney transplantation.

Kidney transplantation is the best available renal replacement therapy for patients with end-stage kidney disease and is associated with better quality of life and patient survival compared with dialysis. However, despite the significant technical and pharmaceutical advances in this field, kidney transplant recipients are still characterized by reduced long-term graft survival. In fact, almost half of the patients lose their allograft after 15-20 years.

Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients.

Introduction: The complete systemic deregulated biological network in patients on peritoneal dialysis (PD) is still only partially defined. High-throughput/omics techniques may offer the possibility to analyze the main biological fingerprints associated with this clinical condition.

Methods: We applied an innovative bioinformatic analysis of gene expression microarray data (mainly based on support vector machine (SVM) learning) to compare the transcriptomic profile of peripheral blood mononuclear cells (PBMCs) of healthy subjects (HS), chronic kidney disease (CKD) patients, and patients on PD divided into a microarray group (5 HS, 9 CKD, and 10 PD) and a validation group (10 HS, 15 CKD, and 15 PD).

Interventions for fatigue in people with kidney failure requiring dialysis.

Background: Fatigue is a common and debilitating symptom in people receiving dialysis that is associated with an increased risk of death, cardiovascular disease and depression. Fatigue can also impair quality of life (QoL) and the ability to participate in daily activities. Fatigue has been established by patients, caregivers and health professionals as a core outcome for haemodialysis (HD).

Hypoxic State of Cells and Immunosenescence: A Focus on the Role of the HIF Signaling Pathway.

Hypoxia activates hypoxia-related signaling pathways controlled by hypoxia-inducible factors (HIFs). HIFs represent a quick and effective detection system involved in the cellular response to insufficient oxygen concentration. Activation of HIF signaling pathways is involved in improving the oxygen supply, promoting cell survival through anaerobic ATP generation, and adapting energy metabolism to meet cell demands.

Kinetics of humoral immune response and severity of infection after three doses of SARS-CoV-2 mRNA vaccine in a large cohort of kidney transplant recipients.

Background: COVID-19 in kidney transplant recipients is associated with high morbidity and mortality. In this study we aimed to evaluate: (i) the seroconversion rate after BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine, (ii) factors associated with humoral response, (iii) clinical outcome of COVID-19 in kidney transplanted patients.

Methods: We enrolled a cohort of 743 kidney transplant recipients followed up from March 2020 until April 2022.

The Impact of the COVID-19 Pandemic on Patients With CKD: Systematic Review of Qualitative Studies.

Rationale & Objective: COVID-19 disproportionately affects people with comorbidities, including chronic kidney disease (CKD). We describe the impact of COVID-19 on people with CKD and their caregivers.

Study Design: A systematic review of qualitative studies.

mTOR-inhibitors and post-transplant diabetes mellitus: a link still debated in kidney transplantation.

The mammalian target of rapamycin inhibitors (mTOR-Is, Sirolimus, and Everolimus) are immunosuppressive drugs widely employed in kidney transplantation. Their main mechanism of action includes the inhibition of a serine/threonine kinase with a pivotal role in cellular metabolism and in various eukaryotic biological functions (including proteins and lipids synthesis, autophagy, cell survival, cytoskeleton organization, lipogenesis, and gluconeogenesis). Moreover, as well described, the inhibition of the mTOR pathway may also contribute to the development of the post-transplant diabetes mellitus (PTDM), a major clinical complication that may dramatically impact allograft survival (by accelerating the development of the chronic allograft damage) and increase the risk of severe systemic comorbidities.

Acute Kidney Injury in Kidney Transplant Patients in Intensive Care Unit: From Pathogenesis to Clinical Management.

Kidney transplantation is the first-choice treatment for end-stage renal disease (ESRD). Kidney transplant recipients (KTRs) are at higher risk of experiencing a life-threatening event requiring intensive care unit (ICU) admission, mainly in the late post-transplant period (more than 6 months after transplantation). Urosepsis and bloodstream infections account for almost half of ICU admissions in this population; in addition, potential side effects related to immunosuppressive treatment should be accounted for cytotoxic and ischemic changes induced by calcineurin inhibitor (CNI), sirolimus/CNI-induced thrombotic microangiopathy and posterior reversible encephalopathy syndrome.

Skin cancer in solid organ transplant recipients: still an open problem.

In the last two decades, the optimization of organ preservation and surgical techniques, and the personalized immunosuppression have reduced the rate of acute rejections and early post-transplant complications. However, long-term graft survival rates have not improved over time, and evidence suggest a role of chronic calcineurin inhibitor toxicity in this failure. Solid organ transplant recipients may develop chronic dysfunction/damage and several comorbidities, including post-transplant malignancies.

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.

Proteomics reveals specific biological changes induced by the normothermic machine perfusion of donor kidneys with a significant up-regulation of Latexin.

Renal normothermic machine perfusion (NMP) is an organ preservation method based on the circulation of a warm (35-37 °C) perfusion solution through the renal vasculature to deliver oxygen and nutrients. However, its biological effects on marginal kidneys are unclear. We therefore used mass spectrometry to determine the proteomic profile of kidney tissue and urine from eight organs reconditioned for 120 min using a Kidney Assist device.

New Frontiers in Sepsis-Induced Acute Kidney Injury and Blood Purification Therapies: The Role of Polymethylmethacrylate Membrane Hemofilter.

Acute kidney injury (AKI) is a common consequence of sepsis with a mortality rate of up to 40%. The pathogenesis of septic AKI is complex and involves several mechanisms leading to exacerbated inflammatory response associated with renal injury. A large body of evidence suggests that inflammation is tightly linked to AKI through bidirectional interaction between renal and immune cells.