Impact of immunosuppressive therapy on pulmonary perfusion in kidney transplant recipients after COVID-19 illness.

Introduction: Patients who have received kidney transplants (KTR) are considered to be more susceptible to the severity of COVID-19-related illness. The transplanted patient's respiratory outcome worsened because of the ventilation-perfusion mismatch that occurs during the infection, which has been linked to endothelial damage. In this context, a reduction in immunosuppressive therapy is advisable to improve patient outcomes.

Successful Management of C3 Glomerulopathy Recurrence Post-Kidney Transplantation with Iptacopan: A Case Report.

C3 glomerulopathy (C3G) is the predominant cause of complement-mediated membranoproliferative glomerulonephritis and is considered a rare disorder caused by genetic or acquired dysregulation of the alternative complement pathway. There are no established treatment guidelines for treating kidney-transplanted recipients with C3G recurrence, as they are already on immunosuppressive protocols. Furthermore, non-complement-specific immunosuppressive drugs appear to offer limited benefits for patients with C3G in native kidneys.

Exploring Potential Complement Modulation Strategies for Ischemia-Reperfusion Injury in Kidney Transplantation.

The complement system plays a crucial role in regulating the inflammatory responses in kidney transplantation, potentially contributing to early decline in kidney function. Ischemia-reperfusion injury (IRI) is among the factors affecting graft outcomes and a primary contributor to delayed graft function. Complement activation, particularly the alternative pathway, participates in the pathogenesis of IRI, involving all kidney compartments.

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.

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.

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.

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.

Unraveling the Link between Interferon-α and Systemic Lupus Erythematosus: From the Molecular Mechanisms to Target Therapies.

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with a wide range of clinical expressions. The kidney is often affected, usually within 5 years of the onset of SLE, and lupus nephropathy (LN) carries a high risk for increased morbidity. The clinical heterogeneity of the disease is accompanied by complex disturbances affecting the immune system with inflammation and tissue damage due to loss of tolerance to nuclear antigens and the deposition of immune complexes in tissues.

mTOR inhibitors improve both humoral and cellular response to SARS-CoV-2 messenger RNA BNT16b2 vaccine in kidney transplant recipients.

Kidney transplant recipients (KTRs) have been considered as patients at higher risk of SARS-CoV-2-related disease severity, thus COVID-19 vaccination was highly recommended. However, possible interferences of different immunosuppression with development of both humoral and T cell-mediated immune response to COVID-19 vaccination have not been determined. Here we evaluated the association between mTOR-inhibitors (mTOR-I) and immune response to mRNA BNT162b2 (Pfizer-BioNTech) vaccine in KTR.

Case Report: Tocilizumab for Acute Kidney Graft Dysfunction in Patient Affected by COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was isolated in January 2020 and, on March, the WHO declared the status of a pandemic. It causes a cytokine release syndrome, called "cytokine storm," characterized by systemic inflammation involving elevated levels of cytokines and hyperactivation of immune cell; this profound alteration in the immune system led to an overshooting inflammatory response contributing to morbidity and mortality. Solid organ transplant recipients are at particularly higher risk of developing critical coronavirus disease 2019 (COVID-19) due to chronic immunosuppression; in fact, establishing the balance between infection and rejection in any transplant recipient is the principal aim when prescribing immunosuppression.

mTOR inhibition improves mitochondria function/biogenesis and delays cardiovascular aging in kidney transplant recipients with chronic graft dysfunction.

CVD remains the major cause of mortality with graft functioning in Kidney transplant recipients (KTRs), with an estimated risk of CV events about 50-fold higher than in the general population. Many strategies have been considered to reduce the CV risk such as the use of mTOR inhibitors. We evaluate whether chronic mTOR inhibition might influence CV aging in KTRs studying the molecular mechanisms involved in this effect.