Maria Antonietta Grignano

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• Researcher at Policlinico San Matteo Pavia Fondazione IRCCS

Alpha-1 antitrypsin deficiency (AATD) is a common genetic disorder that can manifest in a broad spectrum of clinical symptoms, ranging from asymptomatic cases to severe, progressive systemic diseases, primarily affecting the lungs and liver. Despite its prevalence, AATD is often perceived as a rare condition, which can lead to a lack of awareness a...

Background Human cytomegalovirus (HCMV) infection represents a significant complication for kidney transplant recipients (KTRs). The goal of this study was to evaluate potential immunological markers at pre-transplant in HCMV-seropositive KTRs for predicting HCMV severe reactivation (e.g treated HCMV reactivation) during the first year after transp...

The use of adenosine triphosphate (ATP) has shown promising effects in alleviating ischemic damage across various tissues. However, the penetration of ATP into kidney tubular cells presents a challenge due to their unique anatomical and physiological properties. In this study, we introduce a novel bioinspired drug delivery system utilizing extracel...

Case Report: We report a case of a 37-year-old female with kidney transplant, who was admitted at our hospital due to worsening renal function, nephrotic proteinuria, and anemia developed 21 days after the second dose of BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). Laboratory tests revealed hemolytic anemia, thrombocytopenia, and acute kidney injur...

While COVID-19’s urgency has diminished since its emergence in late 2019, it remains a significant public health challenge. Recent research reveals that the molecular intricacies of this virus are far more complex than initially understood, with numerous post-translational modifications leading to diverse proteoforms and viral particle heterogeneit...

Featured Application Mesenchymal stromal cell derived-extracellular vesicles (MSC-EVs) are considered an alter-native approach to cell therapies. They are derived from in vitro starved cells, and we demon-strated that they maintain their functional properties. For this reason, we support the idea that MSCs after starvation, otherwise discarded, cou...

Background and Aims PCSK9 inhibitors (PCSK9i) are a new class of cholesterol-lowering drugs that is gaining market share in treating hypercholesterolemia because of their effectiveness in lowering LDL cholesterol and cardiovascular risk, even in patients with kidney disease. In addition to the well-known effect of inhibiting the LDL receptor catabo...

Background and Aims PCSK9 inhibitors (PCSK9i) are a new class of cholesterol-lowering drugs that is gaining market share in treating hypercholesterolemia because of their effectiveness in lowering LDL cholesterol and cardiovascular risk, even in patients with kidney disease. In addition to the well-known effect of inhibiting the LDL receptor catabo...

Introduction: Uremic retention solutes have been alleged to induce the apoptotic program of different cell types, including peripheral blood mononuclear leukocytes (PBL), which may contribute to uremic leukopenia and immune dysfunction. Methods: The molecular effects of these solutes were investigated in uremic PBL (u-PBL) and mononuclear cell l...

Peripheral blood mononuclear leukocytes (PBL) of uremic patients (u-PBL) prematurely die by apoptosis, thus sustaining leukopenia and immune dysfunction. Uremic retention solutes have been alleged to playing a causal role in this immune cell defect. However, both the molecular identity and pro-apoptotic mechanism of these solutes remain poorly char...

We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study,...

Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS- CoV-2-specific IgG than patients with mild symptoms. In this retrospective study we considered different categories of patients defined as "vulnerable" because affected by other pathologies, such as patients with genetic and cardiovascular diseases; pa...

This work focuses on formulating liposomes to be used in isolated kidney dynamic machine perfusion in hypothermic conditions as drug delivery systems to improve preservation of transplantable organs. The need mainly arises from use of kidneys from marginal donors for transplantation that are more exposed to ischemic/reperfusion injury compared to t...

Simple Summary In this study, we explore for the first time an innovative tool for organ preservation aimed to preventing ischemia reperfusion injury (IRI) in marginal kidneys from expanded criteria donors (ECD) unsuitable for transplantation. Ex vivo hypothermic oxygenated perfusion (HOPE) with and without MSC-derived EV and normothermic reperfusi...

Donation after circulatory death (DCD) allows expansion of the donor pool. We report on 11 years of Italian experience by comparing the outcome of grafts from DCD and extracorporeal membrane oxygenation (ECMO) prior to death donation (EPD), a new donor category. We studied 58 kidney recipients from DCD or EPD and collected donor/recipient clinical...

Simple Summary The most common cause of late allograft failure is chronic active antibody-mediated rejection (ABMR), but no effective therapy is available. Different immunosuppressive drugs in combination with procedures that remove serum antibodies have been used and the results have not shown to improve graft and patient outcome, but only an incr...

Background and Aims Uncontrolled inflammation plays a relevant role in the pathogenesis of Coronavirus Disease-19 (COVID-19) and has been related to disease severity and unfavorable outcomes. Here, we studied the time trend of pro-and anti-inflammatory markers in a population of patients undergoing hemodialysis (HD) affected by COVID-19, evaluating...

Abstract: Post-transplant neutropenia (PTN) is frequently reported in the first-year after transplantation. Although prevalence and clinical consequences are widely described, there are no guidelines to manage diagnosis and treatment. We report here a case of persistent PTN occurred in a patient undergoing a kidney transplant from an AB0-incompatib...

Uncontrolled inflammation plays a relevant role in the pathogenesis of coronavirus disease-19 (COVID-19). Here, we studied the time trend of inflammatory markers in a population of hemodialysis (HD) patients affected by COVID-19, undergoing two different dialysis approaches. In a prospective study, thirty-one maintenance HD patients with COVID-19 w...

We report a preliminary experience of adjuvant therapy with Hemoperfusion (HP) in patients with Severe Acute Respiratory Syndrome-CoronaVirus 2 (SARS-CoV2) pneumonia. Currently, there are no approved treatments for CoronaVirus Disease 19 (COVID-19); however, therapeutic strategies based on the preclinical evidence include supportive measures, such...

Background and Aims Chronic antibody-mediated rejection (cABMR) is the main cause of kidney allograft failure. Currently there is no effective treatment. Extracorporeal photopheresis (ECP) is an immunomodulating therapy that acts increasing regulatory T cells and reducing effector T cells. ECP has been used with success to treat heart and lung reje...

Background and Aims Adenosine (Ado), the main substrate of ATP, is a potent endogenous anti-inflammatory nucleoside. Hypoxia induces ATP depletion, AMP extracellular increase that is phosphohydrolyzed to ADO by the enzyme ecto-5′-nucleotidase (CD73). Constitutive CD73 expression is higher in deep cortex outer medulla that is the most vulnerable reg...

Aim: Myostatin (Mstn) has been described as a trigger for the progression of atherosclerosis. In this study, we evaluated the role of Mstn in arterial remodeling in patients with end-stage renal disease (ESRD). Methods: Vascular specimens were collected from 16 ESRD patients (56.4±7.9 years) undergoing renal transplant (recipients) and 15 deceased...

Abstract Background Malnutrition and muscle wasting are common in haemodialysis (HD) patients. Their pathogenesis is complex and involves many molecules including Myostatin (Mstn), which acts as a negative regulator of skeletal muscle. The characterisation of Mstn as a biomarker of malnutrition could be useful in the prevention and management of th...

Background Living donor kidney transplantation (LDKT) is the best therapy for patients with chronic renal failure. Its advantages, compared with cadaveric transplantation, include the possibility of avoiding dialysis, the likelihood of best outcome, and donor pool expansion. Careful assessment of potential donors is important to minimize the risks...

Objective: Toll-like receptor 4 (TLR4) promotes inflammation in hemodialysis patients (HD). A soluble form of extracellular TLR4 (sTLR4) has been recently characterized, which showed the ability to attenuate TLR4 signalling. In this study, we describe the sTLR4 profile in regular HD patients. Subjects: In a cross-sectional study we enrolled fort...

Background: Kidney transplantation (KT) immunosuppression may induce bone tissue damage with bone mineral density (BMD) loss increasing bone fractures risk. Steroid therapy is considered the major player, but others factors are still under review. Patients and methods: We designed an observational retrospective cohort study to evaluate bone dama...

Background. In this study we investigated the relevance of myostatin and Hepatocyte Growth Factor (HGF) in patients undergoing hemodialysis HD and the influence of different HD modalities on their levels.Methods.We performed a prospective crossover study in which HD patients were randomized to undergo 3-month treatment periods with bicarbonate hemo...