Francesco Scolari

Università degli Studi di Brescia | UNIBS · Department of Clinical and Experimental Sciences

Objective: Despite the increasing use of rituximab in ANCA-Associated Vasculitis (AAV), it remains unclear what the optimal dosing is, especially for maintenance of remission. A deeper understanding of post-rituximab B cell repopulation patterns may aid to better tailor treatment. Methods: This is a monocentric, retrospective study including ANC...

GWAS in IgA Nephropathy

Background and Aims Rituximab (RTX) has emerged as the first-line treatment to maintain remission in ANCA-Associated Vasculitis (AAV). However, the ideal strategy to RTX re-dosing is still unclear [1]. Method In this monocentric and retrospective study we evaluated the efficacy and safety of two RTX-based maintenance regimens in patients with AAV....

Background and Aims The start of peritoneal dialysis (PD) in patients affected by end stage renal disease (ESRD) may have a significant psychological impact. Aim of this study was to assess the most frequent reasons triggering the request of psychological referral in patients starting PD. Method A thematic analysis of the clinical diaries of the p...

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 Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder characterized by progressive bilateral renal cysts development and extrarenal phenotype, i.e. liver and/or pancreatic cysts, intracranial aneurism, hernias, mitral valve prolapse and diverticulosis. More than 90% of patients harbour...

Background and Aims Alport Syndrome (AS), the most common genetic glomerular disease, due to pathogenic variants in COL4A3-COL4A5 genes, includes three main forms: X-linked AS (XLAS, COL4A5); autosomal recessive (ARAS, biallelic pathogenic variants in COL4A3 or COL4A4); autosomal dominant (ADAS; heterozygous COL4A3 or COL4A4 variant). An expanded p...

Autosomal Dominant Tubulointerstitial Kidney Disease, a rare genetic disorder characterised by progressive chronic kidney disease, is caused by mutations in different genes including REN, encoding renin. Renin is a secreted protease composed of 3 domains: the leader peptide allowing insertion in the endoplasmic reticulum (ER), a pro-segment regulat...

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...

Primary Membranous Nephropathy (MN) is the most frequent cause of nephrotic syndrome in adults, due to a variety of auto-antibodies, most frequently against podocyte receptor PLA2R. In severe cases or when spontaneous remission is not achieved, immunosuppression is required. Cyclical therapy, based on glucocorticoids and cyclophosphamide on alterna...

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...

Background: Very small case series of patients with apolipoprotein A1 (ApoA1) amyloidosis are available. Methods: We described the clinical and echocardiographic characteristics of individuals with the pathogenic APOA1 variant Leu75Pro (p. Leu99Pro), referred for cardiac screening. Results: We enrolled 189 subjects, 54% men, median age 55 year...

Objectives: Rituximab has become the cornerstone of induction treatment in ANCA-associated vasculitis (AAV). B cell depletion may increase the risk of hypogammaglobulinemia, potentially leading to severe infections. This study aims to assess factors associated with hypogammaglobulinemia in AAV patients treated with rituximab. Methods: This retro...

Anderson-Fabry Disease (FD) is an X-linked lysosomal disorder caused by mutations in GLA, the gene encoding the lysosomal hydrolase α-galactosidase A (α-Gal A), leading to accumulation of glycosphingolipids in the lysosomes. FD is a multisystemic disorder leading to progressive cardiovascular, cerebrovascular and kidney dysfunction. Phenotypes are...

Mechanisms for the generation of anti-dsDNA autoantibodies are still not completely elucidated. One theory states that dsDNA interacts for mimicry with antibodies raised versus other antigens but molecular features for mimicry are unknown. Here we show that, at physiological acid-base balance, anti-Annexin A1 binds IgG2 dsDNA in a competitive and d...

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 signals. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. We conducted a mu...

Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is a rare inherited disorder characterized by progressive loss of kidney function, non-significant urinalysis and tubulo-interstitial fibrosis. ADTKD progresses to end stage renal disease (ESRD) in adult age. The classification of ADTKD is an evolving concept and the agreement is now that...

BACKGROUND AND AIMS Rituximab is increasingly used to induce and maintain remission in ANCA-associated vasculitis (AAV). However, it remains unclear what the optimal dosing regimen is, especially in the setting of maintenance. Clinical trials have shown that vasculitis flares are unlikely as long as B-cell depletion in peripheral blood is sustained...

Introduction Primary Focal Segmental Glomerulosclerosis (FSGS) is a rare, likely immune-mediated disease. Rituximab (RTX) may play a role in management, although data in adults are scanty. Methods We collected cases of RTX-treated primary FSGS within the Italian Society of Nephrology Immunopathology Working Group and explored response rate (24h pr...

Numerous genes for monogenic kidney diseases with classical patterns of inheritance, as well as genes for complex kidney diseases that manifest in combination with environmental factors, have been discovered. Genetic findings are increasingly used to inform clinical management of nephropathies, and have led to improved diagnostics, disease surveill...

Primary Membranous Nephropathy (PMN) is the most frequent cause of nephrotic syndrome in adults. If untreated, PMN can lead to end-stage renal disease; moreover, affected patients are at increased risk of complications typical of nephrotic syndrome such as fluid overload, deep vein thrombosis and infection. The association of PMN with HLA-DQA1 and...

Background: Dialysis and kidney transplant patients with moderate-severe COVID-19 have a high mortality rate, around 30%, that is similar in the two populations, despite differences in their baseline characteristics. In these groups, the immunology of the disease has been poorly explored. Methods: Thirty-two patients on dialysis or with kidney t...

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary nephropathy and is the fourth most common cause for end-stage renal disease in Europe. ADPKD is a systemic disease; besides the typical renal involvement, characterized by progressive cyst expansion leading to massive enlargement and distortion of the kidney archit...

Clinical Trial registry name and registration number: Zeus study, NCT02403115

Background Causative mutations in the GANAB gene have been described in only 14 families, 9 diagnosed with late-onset Autosomal Dominant Polycystic Kidney Disease (ADPKD) and 5 with Autosomal Dominant Polycystic Liver Disease (ADPLD).CaseDiagnosis of ADPKD was made in a 45-year old man during screening for hernia repair. CT scan showed enlarged cys...

Background and Aims Renal involvement in ANCA-associated vasculitis (AAV) impacts significantly on patients’ prognosis. The role of different induction regimens on remission rates and long-term renal outcomes according to renal histological characteristics has not been explored yet. Method AAV patients with biopsy-proven renal involvement were col...

The formation of neutrophil extracellular traps (NETs) is a strategy utilized by neutrophils for capturing infective agents. Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by proteolysis. A complex series of events contributes to...

Background: A cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking. Methods: We randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to ritu...

Background Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. Methods A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was per...

COVID-19 exhibits extensive patient-to-patient heterogeneity. To link immune response variation to disease severity and outcome over time, we longitudinally assessed circulating proteins as well as 188 surface protein markers, transcriptome, and T-cell receptor sequence simultaneously in single peripheral immune cells from COVID-19 patients. Condit...

Objectives: Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis. Methods: A total of 1052 SLE patie...

Objectives Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes. Methods Here we report the prospective analysis over 36 months of circulating IgG...

Background and objectives Patients with membranous nephropathy can have circulating autoantibodies against membrane-bound (phospholipase A2 receptor 1 [PLA2R1] and thrombospondin type-1 domain containing 7A [THSD7A]) and intracellular (aldose reductase, SOD2, and α-enolase) podocyte autoantigens. We studied their combined association with clinical...

In the last decades there have been important changes in the epidemiology and natural history of bacterial infection-related glomerulonephritides. Once defined as an infancy-onset acute nephritic syndrome following a streptococcal infection, and characterized by a relative benign course, infection-related glomerulonephritis nowadays also affects th...

Introduction In humans, heterozygous mutations of hepatocyte nuclear factor 1beta (HNF1B) are responsible for a dominant inherited disease with both renal and extrarenal phenotypes. HNF1B nephropathy is the umbrella term that includes the various kidney phenotypes of the disease, ranging from congenital anomalies of the kidney and urinary tract (CA...

COVID-19 might potentially give rise to a more severe infection in solid organ transplant recipients due to their chronic immunosuppression. These patients are at a higher risk of developing concurrent or secondary bacterial and fungal infections. Co-infections can increase systemic inflammation influencing the prognosis and the severity of the dis...

Context Apo A-I Leu75Pro is a rare hereditary form of amyloidosis, that mainly involves the kidney, the liver, and the testis. Objective To define the characteristics of organ damage and testis impairment in the largest cohort collected to date of men with Apo A-I Leu75Pro amyloidosis. Design, Setting and Patients Retrospective study from a prosp...

Focal segmental glomerulosclerosis (FSGS) is a pathological spectrum subtended by heterogeneous etiologies. A good knowledge of FSGS and its causes should be included in the nephrologists' clinical background, as it deeply influences the subsequent management of the affected patients. In fact, while immunosuppressive treatment should be considered...

There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN...

The outcome of kidney transplant patients with SARS‐CoV‐2 infection is still unclear. Here we describe the clinical characteristics, disease outcome and risk factors for ARDS and death of a cohort of 53 kidney transplant patients with COVID‐19. 8/53 have been handled as outpatients due to mild disease, on average with immunosuppression reduction an...

Introduction: Autosomal dominant tubulo-interstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is a rare condition associated with high variability in the age of end-stage kidney disease (ESKD). The minor allele of rs4293393, located in the promoter of the UMOD gene, is present in 19% of the population and downregulates uromodulin producti...

Background and Aims In renal transplant field, the progressive increase both of donor and recipient age has led further challenges in patient management. In this setting, the personalization of immunosuppressive therapies (IT) has been strongly suggested. We have investigated renal histology at 12 months after transplantation to assess whether surv...

Background and Aims Discordant affected relative-pairs are seen in ∼10% of families with Autosomal Dominant Polycystic Kidney Disease (ADPKD); <1% of patients exhibit very early onset (VEO) disease. Complex genotypes may result in renal disease variability beyond that predicted by the sole effect of a single PKD mutant allele, leading to the discov...

Background and Aims Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD). Its prevalence, ranging from 0.7 to 3.3%, and its reported mortality is 25-55%. Post-transplantation encapsulating peritoneal sclerosis (PT-EPS) usually occurs within two years from PD interruption due to kidney transplantatio...

Background and Aims Lupus Nephritis (LN) is the organ manifestation with the most severe prognosis in Systemic Lupus Erythematosus (SLE). Treatment options are limited due to partial efficacy, intolerance or side effects; moreover 10% of patients reach ESRD despite treatments. Rituximab (RTX) in LN is recommended as second line drug for induction o...

Background and Aims Idiopathic Focal Segmental Glomerulosclerosis (FSGS) is a rare glomerulonephritis often complicated by a chronic relapsing course frequently characterized by dependency or resistance to immunosuppressive treatment. Moreover, about half of the patients with active disease would develop end-stage renal disease within 10 years from...

Background and Aims The recent decades have witnessed significant changes in the epidemiology and clinical course of infection-related glomerulonephritis (IRGN). We analyzed the clinicopathological features and long-term outcome of adult patients with biopsy-proven IRGN followed in a large Italian referral centre. Method We included patients with...

Background and Aims Survival comparison between peritoneal dialysis (PD) and hemodialysis (HD) is still controversial. While some retrospective studies have shown better survival in PD, particularly in the first year, others have not identified this difference. The only RCT published so far showed a 3-year mortality rate similar between two groups....

Background and Aims Causative GANAB mutations have been described in only 123 families, 98 diagnosed with late-onset mild ADPKD and 35 with ADPLD. We describe a new family with mild, late-onset ADPKD due to p. R839W GANAB mutation, previously reported in an ADPLD patient requiring liver transplantation. Method Mutation analysis of PKD1, PKD2, GANA...

Background and Aims Rituximab (RTX) is one of the mainstays of ANCA-associated vasculitis (AAV) treatment. Nevertheless, studies specifically addressing the B cell repopulation in AAV patients after remission induction with RTX are still scanty and with conflicting results. Moreover, the role of B cell monitoring in the management of RTX-based main...

Background and Aims Efficacy of acute rejection (AR) therapy has always been evaluated based upon improvement of renal function. On the contrary, the degree of histological lesion (HL) regression has rarely been considered for this purpose. The main goal of this study was to evaluate the percentage of failures in HLs regression after treatment aime...

Figure: Background and Aims in Italy only a minority of uremic patients perform peritoneal dialysis (PD). In dialysis centers where PD is practiced and proposed the prevalence is no more than 23%. Proposed advantages of PD over HD are a more preserved Residual renal function (RRF), that has been associated with better survival, and better Quality...

Background and Aims Increased incidence of venous thromboembolism in active phase of vasculitis has been found by several authors. Examining large cohorts of patients, the underlying mechanisms still remain unclear. Patients with active vasculitis are not rarely exposed to heparin mainly because of dialysis, plasmafiltration or ECMO. In the high in...

Background and Aims AKI (Acute Kidney Injury) is a condition associated with elevated morbility and mortality. It determines prolonged hospitalization and severe long-term complications. AKI often complicates the course of patients’ stay in ICU (Intensive Care Units) sometimes requiring CRRT (Continuous Renal Replacement Therapy). Our aim was to pr...

Background and Aims The aim of this work is to explain the training to create a multidisciplinary team that in the future will activate the psychoeducational groups in nephrology. These groups will be support to patients and caregivers already in the waiting period from the intervention of the fistula at the beginning hemodialysis. Method The trai...

Background and Aims To date, the literature shows that HCV eradication with DAA leads to remission from HCV-related cryoglobulinemic syndrome (CS). The goal of our study is to evaluate the effect of DAA treatment on cryoglobulinemic kidney disease. Method Since 2015, 58 patients (pts) have been treated in our Centre; among them we have selected 12...

Background and Aims EDTA published data gathered between 2012 and 2016 showed greatly reduced survival in elderly prevalent dialysis patients as compared to similar aged individuals in the general population: a 70 year-old dialysis patient had a life expectancy of 5 years (instead of 16), an 80 year-old patient could expect to survive 3 years (inst...

Background and Aims Four RCTs have been published that compared on-line HDF (Ol-HDF) with HD. However, to date, an indisputable answer in determining whether patients treated with Ol-HDF had a better survival than those treated with high-flux HD (Hf-HD) has not been reached. The aim of our study was to retrospectively evaluate the impact of the dia...

The SARS-CoV-2 epidemic is pressuring health care systems worldwide. Disease outcomes in certain subgroups of patients are still scarce, and data are needed. Therefore, we describe here the experience of four dialysis centers of the Brescia Renal COVID task force. During March 2020, within an overall population of 643 hemodialysis patients, SARS-Co...

Introduction: Primary membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. The disease may have different long-term outcomes. After 10 years of follow-up, 35%-50% of the untreated patients with persistent nephrotic syndrome may die or progress to end stage renal disease. The 2012 KDIGO (Kidney Disease Improving Global Out...

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a genetically heterogeneous renal disorder leading to progressive loss of renal function. ADTKD-REN is due to rare mutations in renin, all localized in the protein leader peptide and affecting its co-translational insertion in the endoplasmic reticulum (ER). Through exome sequencing in...

Background In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of gene-disrupting variants may represent a risk factor for allograft rejection. Methods We performed a two-stage genetic association study of kidn...

Objective Neutrophil Extracellular Traps (NETs) expose modified antigens for auto-antibodies in vasculitis (SVV). Little is known on levels and removal pathways of NETs in Systemic Lupus Erythematosus (SLE), especially in lupus nephritis (LN). We determined circulating levels and defined NETs removal in large subsets of incident SLE patients, a par...

In the version of this article initially published, affiliation 38 incorrectly read “ICNU-Nephrology and Urology Department, Barcelona, Spain”; “Renal Division, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain” is the correct affiliation. The error has been corrected in the HTML and PDF versions of the article.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genom...

Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and...

Autosomal Polycystic Kidney Disease ( ADPKD) is the most common inherited renal disease. ADPKD is caused by mutations in PKD1 and PKD2, encoding polycystin 1 and 2, respectively. ADPKD is a systemic disease, with renal and extrarenal involvement. Renal disease is characterized by formation and growth of cysts, with progressive destruction of renal...

Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known. We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subje...

The suggestive locus on chromosome 7p13 encoding HECW1. (a) Mean trait values (+/- standard errors) by rs978056 genotype. (b) Regional plot of the HECW1 locus and the top signal represented by rs978056 (P = 3.3x10-5); the x-axis presents physical distance in kilobases (hg18 coordinates), and the y-axis presents −log P values for association statist...

Conditional analysis of the top three loci using all imputed markers (1000 Genomes reference, version 3). The top row depicts unconditioned discovery meta-analysis results for all the imputed markers at the (a) C1GALT1, (b) C1GALT1C1, and (c) HECW1 loci. The bottom row depicts the discovery meta-analysis results after conditioning individual cohort...