Daniela Verzola

University of Genoa | UNIGE · Dipartimento di Medicina Interna e specialità mediche (DIMI)

Microplastics (MPs) accumulate in tissues, including kidney tissue, while Bisphenol A (BPA) is a plasticizer of particular concern. At present, the combined effects of MPs and BPA are unexplored in human renal cells. Therefore, we exposed a proximal tubular cell line (PTECs) to polyethylene (PE)-MPs and BPA, both separately and in combination. When...

Cellular senescence is a condition where cells undergo a permanent cell cycle arrest, accompanied by a unique set of functional and morphological changes. While initial studies of senescence have largely focused on its role as a barrier to extended cell division and tumorigenesis, in recent years cell senescence has emerged as an important driver o...

Background Chronic kidney disease (CKD) is a progressive systemic condition characterized by numerous complications. Among these, alterations in skeletal muscle physiology, such as sarcopenia, are particularly significant, as they are associated with poor outcomes and reduced quality of life. Summary Various interventions, including pharmacological...

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...

Anti-aging therapy is the latest frontier in the world of medical science, especially for widespread diseases such as chronic kidney disease (CKD). Both renal aging and CKD are characterized by increased cellular senescence, inflammation and oxidative stress. A variety of cellular signalling mechanisms are involved in these processes, which provide...

In the last decade, extensive attention has been paid to the uremic toxin indoxyl sulphate (IS) as an inducer of cardiac fibroblast (cFib) activation and cardiac fibrosis in chronic kidney disease. At cellular level, IS engages aryl hydrocarbon receptor (AhR) and regulates many biological functions. We analysed how AhR inhibition by CH‐223191 (CH)...

There is a growing concern within the medical community about the potential burden of microplastics on human organs and tissues. In this study, we investigated by microRaman spectroscopy the presence of microplastics in human kidneys and urine. Moreover, an open-access software was developed and validated for the project, which enabled the comparis...

Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of β-galactosidase at pH 6 (SA-β-Gal) is a classic maker of senescence in cellular biology; however, the predictive role of kidney tissue SA-β-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectivel...

.Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of β-galactosidase at pH 6 (SA-β-Gal) is a classic maker of senescence in cellular biology. However the predictive role of kidney tissue SA-β-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectivel...

Identifying oncological applications for drugs that are already approved for other medical indications is considered a possible solution for the increasing costs of cancer treatment. Under the hypothesis that nutritional stress through fasting might enhance the antitumour properties of at least some non-oncological agents, by screening drug librari...

Plastic pollution became a main challenge for human beings as demonstrated by the increasing dispersion of plastic waste into the environment. Microplastics (MPs) have become ubiquitous and humans are exposed daily to inhalation or ingestion of plastic microparticles. Recent studies performed using mainly spectroscopy or spectrometry-based techniqu...

Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade infl...

Background and Aims Several studies have shown the ubiquitous presence of microplastics (plastic fragments between 5 mm and 1 μm in diameter) and nanoplastics (<1 μm) in the environment and their toxicity. Furthermore, microplastics (MPs) absorb a lot of environmental pollutants, such as bisphenol A (BPA), and release them into tissues increasing t...

Background Growing evidence shows that microplastics (MP) and their chemical derivates contaminate the environment and accumulate in the gut, liver, lungs, and kidneys. Furthermore, MP can adsorb a wide range of toxic substances (heavy metals, polycyclic aromatic hydrocarbons, Bisphenol A [B]), causing the accumulation of multiple pollutants and so...

Background and Aims Microplastics (MPs), plastic fragments less than 5mm in diameter, have been recognized as a global environmental issue. Various studies have shown their ubiquitous presence and their toxicity on marine and terrestrial fauna. Currently in humans, the presence of MP has been evidenced in lungs, placenta, blood, and liver. However,...

Arterial hypertension (AH) is a global challenge that greatly impacts cardiovascular morbidity and mortality worldwide. AH is a major risk factor for the development and progression of kidney disease. Several antihypertensive treatment options are already available to counteract the progression of kidney disease. Despite the implementation of the c...

Background An emerging hypothesis is that the activation of innate immunity in the muscle of patients with chronic kidney disease (CKD) is implicated in the development and progression of wasting and cachexia. We previously observed that Toll‐like receptor‐4 (TLR4) and its downward NF‐κB‐dependent pro‐inflammatory pathways are activated in CKD musc...

Sites and mechanisms regulating the supply of homocysteine (Hcy) to the circulation are unexplored in humans. We studied the exchange of Hcy across the forearm in CKD patients (n = 17, eGFR 20 ± 2 ml/min), in hemodialysis (HD)-treated patients (n = 14) and controls (n = 9). Arterial Hcy was ~ 2.5 folds increased in CKD and HD patients (p < 0.05-0.0...

The mechanisms by which hyperuricemia induces vascular dysfunction and contributes to cardiovascular disease are still debated. Phenotypic transition is a property of vascular smooth muscle cells (VSMCs) involved in organ damage. The aim of this study was to investigate the effects of uric acid (UA) on changes in the VSMC cytoskeleton, cell migrati...

BACKGROUND Chronic kidney disease (CKD) is characterized by increased myocardial mass despite near-normal blood pressure, suggesting the presence of a separate trigger. A potential driver is SIRPα (signal regulatory protein alpha)—a mediator impairing insulin signaling. The objective of this study is to assess the role of circulating SIRPα in CKD-i...

Background and Aim: High lipoprotein(a) [Lp(a)] is a well-established cardiovascular (CV) risk factor, but the effect of mildly elevated Lp(a) on CV health is largely unknown. Our aim was to evaluate if Lp(a) is associated with the severity of carotid atherosclerosis (CA) in the specific subset of metabolic syndrome (MetS). Patients and Methods: Su...

BACKGROUND AND AIMS Tiredness and fatigue are common symptoms in patients with chronic kidney disease (CKD), but their underlying mechanisms are unknown and treatments unavailable. Patients with CKD display abnormalities along the entire oxygen cascade, with impaired diffusive and convective oxygen transport, thus contributing to a reduced tissue o...

BACKGROUND AND AIMS Hyperuricaemia (HU) has been identified as a risk factor for hypertension and renal disease. The most widely documented pathogenetic mechanisms for the uric acid (UA) mediated vascular and renal damage are vascular inflammation and remodeling. Vascular smooth muscle cells (VSMCs) possess a distinctive property of plasticity that...

Introduction The Forkhead box protein P3 (FOXP3) is a transcription factor central to the function of regulatory T cells (Treg). Mutations in the FOXP3 gene lead to a systemic disease called immune dysregulation, polyendocrinopathy, and enteropathy, an X-linked syndrome (IPEX) characterized by the triad of early-onset intractable diarrhea, type 1 d...

Myostatin is a member of the transforming growth factor (TGF)-β superfamily. It is expressed by animal and human skeletal muscle cells where it limits muscle growth and promotes protein breakdown. Its effects are influenced by complex mechanisms including transcriptional and epigenetic regulation and modulation by extracellular binding proteins. Du...

Membranous nephropathy (MN) is one of the commonest causes of adult-onset nephrotic syndrome. We present two cases of two young women presenting with nephrotic syndrome due to Anti-phospholipase A2 Receptor (PLA2R) negative MN which was found to be associated with benign tumors. Two women in their 20s presented with nephrotic syndrome. They had no...

High‐grade gliomas (HGGs; WHO grades III and IV) are invariably lethal brain tumors. Low‐dose hyper‐radiosensitivity (HRS) of HGG is a well‐established phenomenon in vitro. However, possibly linked to the unavailability of accurate animal models of the diseases, this therapeutic effect could not be consistently translated to the animal setting, thu...

During visceral interventions, the transient clampage of supraceliac aorta causes ischemia/reperfusion (I/R) in kidneys, sometime resulting in acute renal failure; preclinical studies identified redox imbalance as the main driver of I/R injury. However, in humans, the metabolic/inflammatory responses seem to prevail on oxidative stress. We investig...

A current hypothesis is that dialysis-treated patients are “anabolic resistant” i. e., their muscle protein synthesis (MPS) response to anabolic stimuli is blunted, an effect which leads to muscle wasting and poor physical performance in aging and in several chronic diseases. The importance of maintaining muscle mass and MPS is often neglected in d...

A current hypothesis is that transforming growth factor-β signaling ligands, such as activin-A and myostatin, play a role in vascular damage in atherosclerosis and chronic kidney disease (CKD). Myostatin and activin-A bind with different affinity the activin receptors (type I or II), activating distinct intracellular signaling pathways and finally...

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...

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...

The association of hyperuricemia with cardiovascular risk, hypertension, atherosclerosis, metabolic syndrome, mortality, and chronic kidney disease has been largely described in clinical studies. Several pathogenetic mechanisms explaining uric acid mediated renal damage have been hypothesized, including crystal deposition, oxidative stress, arterio...

Chronic kidney disease (CKD) causes substantial alterations in the male endocrine system, which affect puberty, libido, and sexual function. A major effect of CKD is a reduction in testosterone levels because of both primary and hypogonadotrophic hypogonadism. In addition to impairment of pubertal growth and sexual maturation in children with CKD,...

Gout as well as asymptomatic hyperuricemia have been associated with several traditional cardiovascular risk factors and chronic kidney disease. Both in vitro studies and animal models support a role for uric acid mediating both hemodynamic and tissue toxicity leading to glomerular and tubule-interstitial damage, respectively. Nevertheless, two rec...

Background: A current, albeit unproven, hypothesis is that an acceleration of cellular senescence is involved in impaired renal repair and progression of glomerular diseases. Focal segmental glomerulosclerosis (FSGS) is a glomerular disease with a substantial risk for progression to ESRD. However, if and to what extent cell senescence predicts a n...

A low protein diet (LPD) has historically been used to delay uremic symptoms and decrease nitrogen (N)-derived catabolic products in patients with chronic kidney disease (CKD). In recent years it has become evident that nutritional intervention is a necessary approach to prevent wasting and reduce CKD complications and disease progression. While a...

Thrombolysis is the gold standard treatment for acute ischemic stroke. Besides its fibrinolytic role, recombinant tissue plasminogen activator (r-tPA) holds several non-fibrinolytic functions. Here, we investigated the potential role of r-tPA on human primary neutrophil migration in vitro. By means of modified Boyden chamber migration assay and che...

Prediabetes is often observed in patients with Metabolic Syndrome (MetS) and might be associated with metabolic and inflammatory alterations. Here, we investigated if the inflammatory molecule osteopontin (OPN) might have a prognostic impact in a cohort of MetS patients (n=85) with baseline normal glycemia or impaired fasting glucose (IFG) over one...

Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of End-Stage Renal Disease (ESRD). In addition to classical progression factors, other atherosclerosis-related factors, including hyperuricemia (HU), have been associated to the renal progression of IgAN. Increased serum uric acid...

Figure: Background and Aims Despite improved survival, patients affected by ANCA-associated vasculitis (AAV) presenting with rapidly progressive glomerulonephritis (RPGN) still remain at a higher risk of death relative to the general population. Recent findings suggest a role for the activation of the complement alternative pathway in the pathogen...

Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of End Stage Renal Disease (ESRD). In addition to the classical progression factors, including hypertension, proteinuria, and decreased renal function, other atherosclerosis-related factors, such as hypertriglyceridemia, have been...

Background and Aims Skeletal muscle is a highly adaptive tissue, however even small imbalances between protein synthesis and degradation can lead to substantial protein loss. Althought proteolysis plays a major role in the development of cachexia in CKD (chronic kidney disease), the responses of muscle protein metabolism to malnutrition had not bee...

Adaptation to a low-protein diet (LPD) involves a reduction in the rate of amino acid (AA) flux and oxidation, leading to more efficient use of dietary AA and reduced ureagenesis. Of note, the concept of 'adaptation' to low-protein intakes has been separated from the concept of 'accommodation', the latter term implying a decrease in protein synthes...

Myostatin (MSTN), a family member of the transforming growth factor (TGF)-β super family, has been detected in the tubuli of pig kidney, but its role in the human kidney is not known. In this study we observed upregulation of MSTN mRNA (~8 to 10-fold increase) both in the glomeruli and tubulointerstitium in diabetic nephropathy (DN). In DN, immunor...

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...

Background: Antihypertensive treatment by the use of RAAS inhibitors (RAAS-is) is of paramount importance in the management of slowly progressive IgA nephropathy (IgAN). With the aim of better understanding the relationship between BP behavior and progression, we looked at time-averaged SBP and time-averaged proteinuria and renal outcome in a sing...

Background: Blood pressure (BP) and arterial stiffness are known cardiovascular risk factors in hemodialysis patients. This study examines the prognostic significance of 44-h BP circadian rhythm and ambulatory arterial stiffness index (AASI) in this population. Methods: A total of 80 hemodialysis patients underwent 44-h ambulatory blood pressure...

Background: Muscle wasting from chronic kidney disease (CKD) or from defective insulin signalling results in morbidity and, ultimately, mortality. We have identified an endogenous mediator of insulin resistance, signal regulatory protein alpha (SIRPα), which leads to cachexia in mice and is associated with cachexia in patients with CKD. Methods:...

Background: Chronic kidney disease (CKD) reduces both Klotho expression and its shedding into circulation, an effect that accelerates progression and cardiovascular complications. However, the mechanisms that regulate Klotho release by the human kidney are still unknown. Methods: We measured plasma Klotho across the kidney, splanchnic organs and...

Background Inflammation, overweight and other cardiovascular risk factors might negatively impact on hypertension remission in metabolic syndrome (MetS), independently of the pharmacological treatment. Here, the potential influence of systemic inflammation (assessed by serum high‐sensitivity C‐reactive protein [hs‐CRP]) on hypertension remission wi...

Indoxyl sulfate (IS) accumulation occurs early during chronic kidney disease (CKD) progression and contributes to renal dysfunction by inducing fibrosis, inflammation, oxidative stress, and tissue remodeling. Renal toxicity of high IS concentrations (250 μ M) has been widely explored, particularly in resident tubular and glomerular cells, while the...

Growing evidence suggests the involvement of TLR4, a receptor in the innate immune system, in muscle loss in uremia. Recently, we have evaluated TLR4 in human skeletal muscle from chronic kidney disease patients, by immunohistochemistry and image analysis. Unlike the commonly-used Western blot method, immunohistochemistry allows for the observation...

Renal proximal tubular cells (PTECs) participate in several mechanisms of innate immunity, express toll‐like receptors (TLRs), and proinflammatory cytokines. Hyperuricemia may be a promoter of inflammation and renal damage. Angiotensin II (Ang II) modulate immune and inflammatory responses in renal tubular cells. With the aim to evaluate the effect...

The past two decades have witnessed tremendous progress in our understanding of the mechanisms underlying wasting and cachexia in chronic kidney disease (CKD) and in other chronic illnesses, such as cancer and heart failure. In all these conditions wasting is an effect of the activation of protein degradation in muscle, a response that increases th...

A changing paradigm of treatment of kidney transplant recipients is a new, wider approach to immunosuppression, which should take into account both antiviral and anticancer effects, in addition to cardiovascular protection. Recent observations suggest that the early introduction of mammalian target of rapamycin inhibitors (mTORi) in association wit...