Licia Peruzzi | Università degli Studi di Torino (original) (raw)

Papers by Licia Peruzzi

Cells

Early diagnosis and effective therapy are essential for improving the overall prognosis and quali... more Early diagnosis and effective therapy are essential for improving the overall prognosis and quality of life of patients with nephropathic cystinosis. The severity of kidney dysfunction and the multi-organ involvement as a consequence of the increased intracellular concentration of cystine highlight the necessity of accurate monitoring of intracellular cystine to guarantee effective treatment of the disease. Cystine depletion is the only available treatment, which should begin immediately after diagnosis, and not discontinued, to significantly slow progression of renal and extra-renal organ damage. This review aims to discuss the importance of the close monitoring of intracellular cystine concentration to optimize cystine depletion therapy. In addition, the role of new biomarkers in the management of the disease, from timely diagnosis to implementing treatment during follow-up, is overviewed.

Journal of Nephrology, 2022

Background Primary hyperoxalurias (PHs) are rare autosomal recessive diseases of the glyoxylate m... more Background Primary hyperoxalurias (PHs) are rare autosomal recessive diseases of the glyoxylate metabolism; PH1 is caused by mutations in the AGXT gene, PH2 in GRHPR and PH3 in HOGA1. Methods Here we report the first large multi-center cohort of Italian PH patients collected over 30 years (1992–2020 median follow-up time 8.5 years). Complete genotype was available for 94/95 PH1 patients and for all PH2 (n = 3) and PH3 (n = 5) patients. Symptoms at onset were mainly nephrolithiasis (46.3%) and nephrocalcinosis (33.7%). Median age at onset of symptoms and diagnosis were 4.0 years and 9.9 years, respectively. Results Fifty-four patients (56.8%) were diagnosed after chronic kidney disease. Sixty-three patients (66.3%) developed end stage kidney disease (median age 14.0 years). Twenty-one patients had a kidney-only transplant and, among them, seven had a second kidney transplant combined with liver transplant. A combined kidney–liver transplant was carried out in 29 patients and a sequen...

Orphanet Journal of Rare Diseases, 2021

Background Rare diseases are chronic and life-threatening disorders affecting < 1 person every... more Background Rare diseases are chronic and life-threatening disorders affecting < 1 person every 2,000. For most of them, clinical symptoms and signs can be observed at birth or childhood. Approximately 80% of all rare diseases have a genetic background and most of them are monogenic conditions. In addition, while the majority of these diseases is still incurable, early diagnosis and specific treatment can improve patients’ quality of life. Transplantation is among the therapeutic options and represents the definitive treatment for end-stage organ failure, both in children and adults. The aim of this paper was to analyze, in a large cohort of Italian patients, the main rare genetic diseases that led to organ transplantation, specifically pointing the attention on the pediatric cohort. Results To the purpose of our analysis, we considered heart, lung, liver and kidney transplants included in the Transplant Registry (TR) of the Italian National Transplantation Center in the 2002–2019...

Italian Journal of Pediatrics, 2020

Background The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to... more Background The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting. Methods We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment. Results The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serio...

International Journal of Molecular Sciences, 2020

Dent disease (DD), an X-linked renal tubulopathy, is mainly caused by loss-of-function mutations ... more Dent disease (DD), an X-linked renal tubulopathy, is mainly caused by loss-of-function mutations in CLCN5 (DD1) and OCRL genes. CLCN5 encodes the ClC-5 antiporter that in proximal tubules (PT) participates in the receptor-mediated endocytosis of low molecular weight proteins. Few studies have analyzed the PT expression of ClC-5 and of megalin and cubilin receptors in DD1 kidney biopsies. About 25% of DD cases lack mutations in either CLCN5 or OCRL genes (DD3), and no other disease genes have been discovered so far. Sanger sequencing was used for CLCN5 gene analysis in 158 unrelated males clinically suspected of having DD. The tubular expression of ClC-5, megalin, and cubilin was assessed by immunolabeling in 10 DD1 kidney biopsies. Whole exome sequencing (WES) was performed in eight DD3 patients. Twenty-three novel CLCN5 mutations were identified. ClC-5, megalin, and cubilin were significantly lower in DD1 than in control biopsies. The tubular expression of ClC-5 when detected was i...

Italian Journal of Pediatrics, 2019

Background: paucity of interlobular bile ducts is an important observation at liver biopsy in the... more Background: paucity of interlobular bile ducts is an important observation at liver biopsy in the diagnostic work-up of neonatal cholestasis. To date, other than in the Alagille syndrome, syndromic paucity of interlobular bile ducts has been documented in four cholestatic neonates with HFN1β mutations. A syndromic phenotype, known as renal cysts and diabetes syndrome (RCAD), has been identified. This is usually characterized by a wide clinical spectrum, including renal cysts, maturity-onset diabetes of the young, exocrine pancreatic insufficiency, urogenital abnormalities and a not well established liver involvement. Herein we report a novel case of paucity of interlobular bile ducts due to an HFN1β defect. Case presentation: A 5-week-old boy was admitted to our department for cholestatic jaundice with increased gamma-glutamyl transpeptidase and an unremarkable clinical examination. He had been delivered by Caesarian section at 38 weeks' gestation from unrelated parents, with a birth weight of 2600 g (3rd percentile). Screening for cholestatic diseases, including Alagille syndrome, was negative except for a minor pulmonary artery stenosis at echocardiography and a doubt of a thoracic butterfly hemivertebra. The finding of hyperechogenic kidneys with multiple bilateral cortical cysts at ultrasound examination, associated with moderately impaired renal function with proteinuria, polyuria and metabolic acidosis, was suggestive of ciliopathy. A liver biopsy was performed revealing paucity of interlobular bile ducts, thus the diagnosis of Alagille syndrome was reconsidered. Although genetic tests for liver cholestatic diseases were performed with negative results for Alagille syndrome (JAG1 and NOTCH2), a de-novo missense mutation of HNF1β gene was detected. At 18 months of age our patient has persistent cholestasis and his itching is not under satisfactory control. Conclusions: Alagille syndrome may not be the only syndrome determining paucity of interlobular bile ducts in neonates presenting with cholestasis and renal impairment, especially in small for gestational age newborns. We suggest that HNF1β deficiency should also be ruled out, taking into consideration HNF1β mutations, together with Alagille syndrome, in next generation sequencing strategies in neonates with cholestasis, renal impairment and/or paucity of interlobular bile ducts at liver biopsy.

Transplantation, Jan 20, 2018

BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft ... more BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking. We analyzed data of 313 patients in the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, with an observation period of 3.3 years (range, 1 - 5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score. Presumptive BKPyVAN (defined as sustained (>3 weeks) high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49/311 (15.8%) of patients, and biopsy-proven BKPyVAN in 14/313 (4.5%). BKPyV viremia was observed in 115/311 patients (36.7%), of whom 11 of 115 (9.6%) developed viremia late, ie, after the second year posttransplant. In 6/48 patients (12.5%) with high-level viremia and in 3/14 (21.4%) with BKPyVAN this respective event occurred late. According to multivaria...

Nature reviews. Endocrinology, Jan 29, 2018

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by pheno... more Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-rel...

Bacterial Infections and the Kidney, 2017

Acute pyelonephritis is a common disorder prevalently affecting young women, that may be severe i... more Acute pyelonephritis is a common disorder prevalently affecting young women, that may be severe in the elderly, in diabetics, in pregnant women and in immunosuppressed patients. The aim of this chapter is to try to elucidate some nebulous points, also through our own experience, regarding the relationship with vesico-ureteral reflux in adults, the frequency of complication with abscesses, the need for CT or magnetic resonance imaging, the long-term evolution. Acute pyelonephritis (APN) in the native kidney is a common disorder prevalently affecting young women. It is responsible for more than 100,000 hospitalizations per year in the U.S. APN is usually a benign disease, but it may be severe in the elderly, in diabetics, in pregnant women, and in immunosuppressed patients. Complicated APN may present renal abscesses or transformation into emphysematous pyelonephritis (EP). A pathogenic role is played by sexual activity, genetic predisposition, and urinary instrumentation. The correlation between APN and vesicoureteral reflux (VUR) in adults has not been clearly determined. The most common etiologic agent both in adults and in children is Escherichia coli. Diagnosis of APN is mainly clinical, but only CT or magnetic resonance are able to establish the exact definition and extent of the renal parenchymal lesions and to detect abscesses. The frequency of abscesses is largely underestimated in the literature and in clinical practice. The most severe cases of APN should be treated, at least at the onset, with parenteral antibiotics, and the patients should be hospitalized. Antibiotic treatment should include fluoroquinolone or a broad spectrum cephalosporin associated or not with an aminoglycoside for 10–14 days. Abscesses require longer treatment, and drainage may be necessary in large ones. The long-term evolution of APN seems favorable, even though cortical scar formation, development of proteinuria, or renal failure have been reported.

Pediatric Nephrology, 2016

Background There is a need for early identification of children with immunoglobulin A nephropathy... more Background There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. Methods Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN,

Nephrology Dialysis Transplantation, 2016

Delivery patterns of recommended chronic kidney disease care in clinical practice: administrative... more Delivery patterns of recommended chronic kidney disease care in clinical practice: administrative claims-based analysis and systematic literature review. Clin Exp Nephrol 2008; 12: 41-52 41. Wu IW, Wang SY, Hsu KH et al. Multidisciplinary predialysis education decreases the incidence of dialysis and reduces mortality-a controlled cohort study based on the NKF/DOQI guidelines. Nephrol Dial Transplant 2009; 24: 3426-3433 42. Chen YR, Yang Y, Wang SC et al. Multidisciplinary care improves clinical outcome and reduces medical costs for pre-end-stage renal disease in Taiwan. Nephrology (Carlton) 2014; 19: 699-707 43. Cho EJ, Park HC, Yoon HB et al. Effect of multidisciplinary pre-dialysis education in advanced chronic kidney disease: propensity score matched cohort analysis.

Journal of Nephrology, 2016

Updated genetic testing of Italian patients referred with a clinical diagnosis of primary hyperox... more Updated genetic testing of Italian patients referred with a clinical diagnosis of primary hyperoxaluria.

Contributions to Nephrology

Kidney international. Supplement, 1993

We previously demonstrated that gliadin, a lectinic component of gluten, induces IgA mesangial de... more We previously demonstrated that gliadin, a lectinic component of gluten, induces IgA mesangial deposits in orally immunized mice, binds in vitro polymeric IgA and cultured rat mesangial cells modulating their arachidonic acid metabolism. We investigated the effects of gliadin and other environmental lectins on some mesangial cell functions, including synthesis and release of cytokines and lipid mediators. Several lectins, particularly gliadin, affected the mRNA expression of c-myc and c-fos, two proto-oncogenes involved in the transcriptional enhancement of the gene cascade, which are markers of cell growth, differentiation and mitosis. Lectins modulated the ability of cultured rat mesangial cells to express mRNA for cytokines involved in the inflammation and in the regulation of the immune response. TNF-alpha and IL-6 mRNA transcription were enhanced by gliadin and other lectins, and TNF release was variably increased. Conversely, IL-1 production was less affected or slightly depre...

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Minerva urologica e nefrologica = The Italian journal of urology and nephrology, 1994

From 1981 to 1992, 81 children affected by idiopathic nephrotic syndrome were treated in our Divi... more From 1981 to 1992, 81 children affected by idiopathic nephrotic syndrome were treated in our Division. The majority were males (74%), with mean age at diagnosis of 4.8 (0-14)) years. They had a mean follow-up of 5.7 (0.5-11) years. The renal function at diagnosis was normal in all cases, proteinuria was selective in 86.4% of the cases. 28 children with somehow atypical behaviour underwent renal biopsy. In this negatively selected group the more frequent histologic forms were focal segmental glomerular sclerosis (33.5%), minimal change disease (37.4%), IgM mesangial glomerulonephritis (16.6%), membranous nephropathy (12.5%). First choice drug was in all cases prednisone. In the last years the trend for steroid therapy was to adopt long protocols (16 weeks), with a total dose of 105-133 mg/kg per therapeutic cycle. About 90% of children had a favourable response to steroids, but half of them were frequent relapser. In these cases the long term stable remission was obtained with steroi...

Nutrition, 2000

The purpose of this study was to determine the reference, bivariate, and tolerance intervals of t... more The purpose of this study was to determine the reference, bivariate, and tolerance intervals of the whole-body impedance vector in Italian children. This was a cross-sectional, multicenter study, and participants were chosen from the general school population. The impedance vector (standard, tetrapolar analysis at 50-kHz frequency) was measured in 3110 subjects, ages 2 to 15 y, and 2044 healthy children (1014 male and 1030 female) with weight and height within the 95th percentile were selected for the analysis (resistance-reactance graph method). The age-specific 95% confidence intervals of mean vectors and the 95%, 75%, and 50% tolerance intervals for individual vector measurements were plotted using resistance and reactance components standardized by the subject's height. Mean vectors from both sexes with separate 95% confidence ellipses were considered as representative of eight different age groups, from 2 to 13 y. There was a statistically significant sex effect on vector distribution from boys and girls in the age group of 14 to 15 y. The impedance vector distribution of children was also compared with healthy adult subjects (354 male and 372 female, age 15 to 85 y). There was a progressive, statistically significant vector shortening from age 2 to 15 y toward the adults' vector position. In conclusion, we established the trajectory followed by the mean impedance vector in children over ages 2 to 15 y and also obtained the reference, bivariate, and 95%, 75%, and 50% tolerance intervals of the impedance vector by age for healthy children, with which the vectors from children with altered body composition can be tested.

Nephrology Dialysis Transplantation, 1996

Background. The renal minimal lesion disease induced in rats by adriamycin (ADR) is generally tho... more Background. The renal minimal lesion disease induced in rats by adriamycin (ADR) is generally thought to be consequent to a direct cytotoxic effect of this drug on glomerular epithelial cells. Only recently an altered synthesis of mediators, including reactive oxygen species and monocyte-macrophage cytokines, has been hypothesized. Methods. A mouse strain (nude) bearing a congenital thymic aplasia is a suitable experimental animal to evaluate the role of immune reactions in the development of ADR nephropathy, provided mouse susceptibility to its toxic effect. Therefore, experimental mice were divided into three groups (G) each receiving adriamycin 7.5 mg/kg b.w.: GA (15 heterozygous nu/O mice with normal immune system); GB (15 homozygous nu/nu athymic mice); GC (15 homozygous nu/nu mice which were also splenectomized, irradiated, and treated with anti-asialo Gml antibody to abolish NK and decrease macrophage activity). All animals were maintained under pathogen-free conditions. Urinary proteins, albumin and TNF-a excretion were measured. Results. After 14 days the proteinuria was 43.8 + 1.7 ug/min in GA, 30.2 + 2.9 ug/min in GB (P< 0.05) and 12.2 ±2.8 ug/min in GC (GA vs GC, P<0.0001; GB vs GC, P<0.05). Albuminuria gave a similar profile. TNF-a urinary excretion was significantly higher in GA (17.3 + 3.2 mU/min) than in GB (5 + 0.6 mU/min, P<0.00\) and GC (3.2±0.9 mU/min, P< 0.001). A significant correlation was found in GA between urinary TNF-a and protein losses (1^ = 0.63 P<0.0001). Kidney tissue homogenates failed to show in each experimental group any evidence of mRNA encoding for TNF-a, which was detectable in peripheral mononuclear cells from GA and GB, but undetectable in GC mice. Segmental effacements of glomerular epithelial cell foot process

Nephrology Dialysis Transplantation, 2012

Introduction and Aims: Recent studies have implicated potassium (K +) as a major factor in the de... more Introduction and Aims: Recent studies have implicated potassium (K +) as a major factor in the development of uremic neuropathy, with strong correlations noted between nerve dysfunction and serum K + concentration. The present study utilized a K + clamp strategy to investigate whether hyperkalaemia plays a causal role in nerve dysfunction in end-stage kidney disease (ESKD). Methods: Neurophysiological studies wereundertaken in five haemodialysis patients during a modified dialysis session, using nerve excitability testing, a clinical technique that assesses nerve membrane potential and ion channel function.All patients had a pre-dialysis K + greater than 5mmol/L. The serum K + level was "clamped" (fixed) for the first 3 hours of dialysis by adding K + to the dialysate (concentration 5.0-5.5mmol/L). Following this clamped period, the dialysatewas changed back to a low K + concentration to allow its removal during the remainder of the dialysis session. Patient and dialysate K+ concentrations were measured every hour during the first 3hrs and at the termination of dialysis. Studies were undertaken prior to and during the K + clamp period and following cessation of dialysis. Results were compared to nerve function data collected in the same patients during routine dialysis sessions. Results: All patients demonstrated significant nerve function abnormalities reflective of nerve membrane depolarizationin pre-dialysis recordings (p<0.01). After the 3hr clamp period, patient serum K + remainedelevated (5.04mmol/L) and nerve excitability remained highly abnormal. In contrast, studies undertaken during routine 'unclamped' dialysis sessions demonstrated significant improvement in both serum potassium concentration (3.58mmol/L) and nerve function after 3 hours. Importantly, after release of the K + clamp and a further 4hrs of dialysis against low K + dialysate patient serum K + was significantly reduced (p=0.01)and nerve excitability values returned towards the normal range. Conclusions: The current study has established a causal relationship between serum K + and nerve dysfunction in haemodialysis patients. From a clinical perspective, these studies suggest that strict K + control may represent a potential neuroprotective strategy in ESKD.

Journal of Urology, 2005

Obstructive uropathies, including posterior urethral valves (PUVs) and kidney hypodysplasia, are ... more Obstructive uropathies, including posterior urethral valves (PUVs) and kidney hypodysplasia, are the most frequent cause of renal failure in children. The role of renin-angiotensin system genes in renal and urinary tract development has been observed in experimental models. The aim of this study was to investigate the distribution of angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin receptor type 1 (ATR1) genetic polymorphisms in children affected by chronic renal failure due to renal hypodysplasia associated with posterior urethral valves or without urethral abnormalities. The study included 50 children (21 with hypodysplasia associated with PUVs, 7 with obstructive uropathy and 22 with pure hypodysplasia) and 50 healthy subjects matched for sex and geographic origin. ACE ID, AGT TC and ATR1 AC gene polymorphisms were assayed in all patients with standard polymerase chain reaction techniques. ACE II was expressed more in patients with PUVs compared to those with other dysplasias and controls (43% vs 7% and 10%, respectively, chi-square test p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), while ATR1 AA was significantly less represented in patients with hypodysplasia compared to controls (38% vs 56%, chi-square test p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). ACE DD and AGT genotypes were not distributed differently in patients with PUVs compared to those with other dysplasias and controls. To our knowledge this is the first report associating severe congenital uropathies and renal hypodysplasia with decreased renin-angiotensin system activity associated with the ACE II genotype and a possible functional imbalance among ATR1 receptors.