Loreto Gesualdo

Università degli Studi di Bari Aldo Moro | Università di Bari · Dipartimento della Emergenza e Trapianti d´Organo (DETO)

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these ind...

Pulsed electromagnetic fields (PEMF) are employed as a non-invasive medicinal therapy, especially in the orthopedic field to stimulate bone regeneration. However, the effect of PEMF on skeletal muscle cells (SkMC) has been understudied. Here, we studied the potentiality of 1.5 mT PEMF to stimulate early regeneration of human SkMC. We showed that hu...

The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect the organism against infections and support the repair of damaged tissues. Alterations in this complex machinery play a role in the pathogenesis of different diseases. Core complement proteins C3 and C5, their activation...

Background Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effect...

Diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) represent intricate challenges in diagnosis and treatment within the context of the global diabetes epidemic. As the prevalence of diabetes continues to escalate, effective management of renal complications becomes paramount. Recent advancements in comprehending the multifaceted natur...

Influenza and Coronavirus Disease 2019 (COVID-19) vaccination are recommended in both solid organ transplant (SOT) candidates and recipients. In Puglia, Southern Italy, an active vaccination offer program has been activated targeting these patients. This study aims at investigating vaccination coverage (VC) for both vaccines in a SOT patients’ coho...

Background Percutaneous renal biopsy (PRB) may subject patients to emotional distress and pain, before and during the biopsy. The aim of this study was to evaluate the effects of a complementary/non-pharmacological interventions as music therapy (MT) on anxiety, pain and satisfaction in renal patients undergoing PRB. Methods A prospective, single-...

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and...

Focal segmental glomerulosclerosis (FSGS) is a complex disease which describes different kinds of kidney defects, not exclusively linked with podocyte defects. Since nephrin mutation was first described in association with early-onset nephrotic syndrome (NS), many advancements have been made in understanding genetic patterns associated with FSGS. N...

People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions (ADR) resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of com...

There is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment especially due to vascular damage, blood-brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotro...

We propose a nonparametric compound Poisson model for underreported count data that introduces a latent clustering structure for the reporting probabilities. The latter are estimated with the model’s parameters based on experts’ opinion and exploiting a proxy for the reporting process. The proposed model is used to estimate the prevalence of chroni...

Background Age-and height-adjusted total kidney volume is currently considered the best prognosticator in patients with autosomal dominant polycystic kidney disease. We tested the ratio of urinary epidermal growth factor and monocyte chemo-tactic peptide 1 for the prediction of the Mayo Clinic Imaging Classes. Methods Urinary epidermal growth facto...

Cystinosin mediates an ATP-dependent cystine efflux from lysosomes and causes, if mutated, nephropathic cystinosis, a rare inherited lysosomal storage disease. Alternative splicing of the last exon of the cystinosin sequence produces the cystinosin-LKG isoform that is characterized by a different C-terminal region causing changes in the subcellular...

Background: Protein phosphorylation is considered a key event in signal transduction. Peripheral blood mononuclear cells (PBMCs) are a critical component of the immune system. The analysis of PBMCs phosphoproteome might help elucidate the signaling pathways essential to their biological role in health, immunological diseases and cancer. Enrichment...

Renal fibrosis is a common pathological endpoint in chronic kidney disease (CKD) that is challenging to reverse. Although myofibroblasts are mainly responsible for the accumulation of a fibrillar collagen-rich extracellular matrix (ECM) in fibrotic kidney, recent studies have unveiled their diversity in terms of proliferative and fibrotic character...

Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of th...

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...

Background: Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis and the role of IL-6 in pathogenesis is becoming increasingly important. A recent whole genome DNA methylation screening in IgAN patients identified a hypermethylated region comprising the non-coding RNA Vault RNA 2-1 (VTRNA2-1) that could explain the h...

Background: direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. Aim of this study: evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. Methods: a...

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 e...

Introduction The study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID...

GWAS in IgA Nephropathy

IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci...

Cisplatin is one of the most effective chemotherapeutic agents strongly associated with nephrotoxicity. Tubular adult renal progenitor cells (tARPC) can regenerate functional tubules and participate in the repair processes after cisplatin exposition. This study investigated the molecular mechanisms underlying the protective effect of tARPC on renal...

Background Microbiota unbalance has been proven to affect chronic kidney disease (CKD) patients and, noteworthy, microbiota composition and activity are implicated in CKD worsening. The progression of kidney failure implies an exceeding accumulation of waste compounds deriving from the nitrogenous metabolism in the intestinal milieu. Therefore, in...

Background and Aims The better understanding of the biological pathways related to chronic kidney disease (CKD) may be useful for the identification of new therapeutic targets to improve the management of CKD patients. High-throughput technologies with innovative bioinformatics approaches for data analysis are very useful to achieve this objective....

Background and Aims Sepsis is a severe and dysregulated inflammatory disease that often precedes the development of acute kidney injury (AKI) with consequent worsening outcome. Although clinical data demonstrate that high-density lipoprotein (HDL) levels drop in septic patients with a poor prognosis, little is known about the molecular basis of HDL...

Background and Aims Organoids are self-organizing 3D aggregations of cells that represent the structure and function of organs. Kidney organoids have the potential to advance the field of nephrology by providing a tool for the study of human kidney development and disease, by providing a tool for in vitro drug screening, and ultimately, for regener...

Background and Aims In general, vaccination is a well-known trigger for the onset or recurrence of glomerulonephritis or more in general autoimmune disease. Starting from the beginning of 2021 millions of people worldwide have received a vaccination of SARS-CoV2. Over the months, several cases of glomerulonephritis with a clear temporal association...

Background and Aims ADPKD is the most common form of inherited renal disease worldwide. ADPKD care has advanced over the past decade by the identification of several clinical/genetic risk factors of progression and approval of first disease-modifying drug. Further clinical outcomes research is needed to improve patient-centered clinical care; in ad...

Background and Aims HLA compatibility is a key issue in deceased and living kidney allocation, although the continuous improvement of immunosuppressive protocols might have reduced its relevance. However, an increased immunosuppression is associated with several adverse events, including the development of post-transplant neoplasia. Indeed, several...

Background and Aims Machine learning (ML) holds great promise for improving diagnostics, prognostication and theranostics in nephropathology. So far, applications have not gone much further than segmentation of tissue compartments on whole slide images (WSIs) of paraffin sections. As a proof-of-concept study, we describe the development of a diagno...

Background and Aims Direct oral anticoagulants (DOACs) are a well-known alternative to conventional antagonist of vitamin-K (avK) and have emerged as the preferred choice due to their safety and efficacy profile. However, immune modulating drugs as cyclosporine and tacrolimus, commonly used for transplant recipients, may interfere with DOACs pharma...

Background and Aims Acute kidney injury (AKI) still represents a major health public concern associated with worldwide growing incidence. Although many studies have been focused on critically ill patients admitted to ICUs, AKI occurs even in non-critical care settings, with similar consequences in terms of short- and long-outcomes. However, epidemi...

Background and Aims The SARS-CoV2 caused a pandemic disease, leading to millions of cases and fatalities worldwide. Kidney involvement is frequent and glomerular diseases (GD) have been reported in association with infection. Podocytopathies, endothelial injury with thrombotic microangiopathy are the most common histological findings in literature....

Background and Aims Partial recovery following AKI could lead to long-term consequences that predispose to chronic dysfunction and may also accelerate progression of neurocognitive impairment. In this scenario, a tight crosstalk between kidney and brain named “kidney-brain axis” seems to play a pivotal role leading to detrimental outcome for AKI pa...

Background and Aims The progression of IgA nephropathy (IgAN) has been associated with Mannose -Binding Lectin levels (both excess or deficiency). The MBL deficiency, is associated with the rs5030737, the rs1800450 and the rs1800451, who represent the “O” allele. Since lectin pathway deregulation may impact on IgA progression on native kidney we hy...

Background and Aims Renal damage in diabetes can manifest as real diabetic glomerulosclerosis (DN) or non-diabetic renal disease (NDRD). DN and NDRD differ in terms of prognosis and treatment thus kidney biopsy remains the gold standard. The iBEAt study conducted within the frame of IMI project BEAt-DKD (https://www.beat-dkd.eu/; GA No 115974) aims...

IgA Nephropathy (IgAN) is the most common form of primary glomerulonephritis and is one of the most common causes of end-stage kidney disease (ESKD) worldwide. The immunopathogenic mechanism underlying IgAN is poorly identified. Currently, the mainstay treatment of IgAN is centered on the optimization of blood pressure and a reduction in proteinuri...

Despite recent technical advances in dialysis care over the past decades, the mortality rate of critically ill patients with acute kidney injury (AKI) requiring dialysis and of chronic kidney disease (CKD) remains unacceptably high. Several preclinical studies have increased our knowledge of the principal mechanisms involved in the pathophysiology...

Here, we tested that standard eyes-closed resting-state electroencephalographic (rsEEG) rhythms may characterize patients with mild cognitive impairment due to chronic kidney disease at stages 3-4 (CKDMCI-3&4) in relation to CKDMCI patients under hemodialysis (CKDMCI-H) and mild cognitive impairment (MCI) patients with cerebrovascular disease (CVMC...

Rationale & objective: COVID-19 disproportionately affects people with co-morbidities, including chronic kidney disease (CKD). The aim of this study was to describe the impact of COVID-19 on people with CKD and their caregivers. Study design: A systematic review of qualitative studies. Setting & study populations: Primary studies that reported...

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 ex...

Introduction: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. Methods: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 we...

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 infect...

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...

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Her...

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...

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 t...

Long non-coding RNAs (lncRNAs) are a large, heterogeneous class of transcripts and key regulators of gene expression at both the transcriptional and post-transcriptional levels in different cellular contexts and biological processes. Understanding the potential mechanisms of action of lncRNAs and their role in disease onset and development may open...

Background: Antimicrobial and diagnostic stewardship (AS/DS) principles are crucial for the management of multidrug-resistant organisms (MDROs) infections. We evaluated the impact of a pro-active Infectious Disease (ID) consultation on the mortality risk of patients during an MDROs outbreak in a COVID-19 hospital. Methods: A quasi-experimental s...

Background: Congenital obstructive uropathy (COU) is a common cause of developmental defects of the urinary tract, with heterogeneous clinical presentation and outcome. Genetic analysis has the potential to elucidate the underlying diagnosis and help risk stratification. Methods: We performed a comprehensive genomic screen of 733 independent COU...

In the past years, indoxyl sulfate has been strongly implicated in kidney disease progression and contributed to cardiovascular morbidity. Moreover, as a result of its elevated albumin affinity rate, indoxyl sulfate is not adequately cleared by extracorporeal therapies. Within this scenario, although LC-MS/MS represents the conventional approach fo...

The prokaryotic, viral, fungal, and parasitic microbiome exists in a highly intricate connection with the human host. In addition to eukaryotic viruses, due to the existence of various host bacteria, phages are widely spread throughout the human body. However, it is now evident that some viral community states, as opposed to others, are indicative...

The glomerular endothelial glycocalyx (GEnGlx) forms the first part of the glomerular filtration barrier. Previously we showed that mineralocorticoid receptor (MR) activation caused GEnGlx damage and albuminuria. Here we investigated whether MR antagonism could limit albuminuria in diabetes and studied the site of action. Streptozotocin-induced dia...

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were follo...

During the past decades, the gut microbiome emerged as a key player in kidney disease. Dysbiosis-related uremic toxins together with pro-inflammatory mediators are the main factors in a deteriorating kidney function. The toxicity of uremic compounds has been well-documented in a plethora of pathophysiological mechanisms in kidney disease, such as c...

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 intera...

Several insults can lead to acute kidney injury (AKI) in native kidney and transplant patients, with diabetes critically contributing as pivotal risk factor. High glucose per se can disrupt several signaling pathways within the kidney that, if not restored, can favor the instauration of mechanisms of maladaptive repair, altering kidney homeostasis...

Donation after circulatory death (DCD) has emerged as attainable strategy to tackle the issue of organ shortage, expanding the donor pool. The DCD concept has been applied to the multiple declinations of circulatory arrest, as per the Modified Maastricht Classification. Notwithstanding, whichever the scenario, DCD donors experience a variable warm...

Previous evidence showed abnormal posterior sources of resting‐state electroencephalographic (rsEEG) delta (<4 Hz) and alpha (about 8‐12 Hz) rhythms in patients with Alzheimer's disease (AD) as cortical neural synchronization markers in quiet wakefulness. We tested whether daily computerized cognitive training (CCT), for a short period, with an app...

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 aff...

Polydopamine (PDA) is a synthetic eumelanin polymer mimicking the biopolymer secreted by mussels to attach to surfaces with a high binding strength. It exhibits unique adhesive properties and has recently attracted considerable interest as a multifunctional thin film coating. In this study, we demonstrate that a PDA coating on silica- and polymer-b...

Hepatitis C virus (HCV) adopts several immune evasion mechanisms such as interfering with innate immunity or promoting T‐cell exhaustion. However, the recent direct‐antiviral agents (DAAs) rapidly eliminate the virus, and the repercussions in terms of immune system balance are unknown. Here we compared the PBMCs transcriptomic profile of patients w...