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Background and aims of the study. Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss Syndrome) is a rare systemic disease, included in the group of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), characterized by adult-onset asthma, blood and tissue eosinophilia with organ involvement, and small-vessel vasculitis. The disease pathogenesis is poorly understood. Immunogenetic factors may predispose to the disease. However, it has been suspected that the disease may be triggered by exogenous factors including environmental agents, infections, vaccinations, and drugs. Data about the association between individual, environmental and occupational risk factors and the development of EGPA are scarce. In this study we aimed to investigate the role of occupational agents (such as silica, farming, organic solvents and chemical agents) as well as individual agents (such as smoking habits) and their interactions, as potential risk factors for EGPA. Patients and methods. The study has a case-control design. We enrolled 111 patients with EGPA and 333 healthy controls, matched for age, sex and geographical origin. Occupational history was obtained using a structured questionnaire administered by blinded specialists in occupational medicine. The exposures to nonoccupational risk factors potentially predisposing to EGPA were assessed through the interview and through the examination of medical records. All exposures were considered until the time of EGPA diagnosis. Results. EGPA was associated with silica exposure (OR 2.26 [95% CI 1.10-4.62], p=0.026), farming (OR 2.10 [95% CI 1.19-3.73], p=0.011) and with the exposure to organic solvents (OR 2.20 [95% CI 1.14-4.2], p=0.018) at a multivariate analysis. There was a positive relationship between the duration of exposure to silica, chemical agents and the risk of developing EGPA. A multiplicative effect on risk was found for the co-exposure of silica and farming (OR 7.49 [95% CI 2.77-20.25], p

Congenital anomalies of the kidneys and urinary tract are the leading cause of end stage renal disease (ESRD) in children and young adults. CAKUT diagnosis is currently based on imaging studies and It is classified using descriptive anatomic criteria which omit the underlying pathogenetic and molecular mechanisms. Studies from our group indicate that a large fraction of CAKUT is attributable to rare genetic variants with large effect size. In particular, both point mutations and structural genomic variants (copy number variations, CNVs), detectable by whole exome sequencing (WES) or DNA microarrays, respectively, account for 10 to 30% of the cases. Nevertheless, genetic tests are often not performed or not clinically indicated, thus limiting prognosis and medical management. Here we present a new multi-institutional Italian study group on CAKUT, composed of a network of clinical and basic investigators in adult and pediatric nephrology and urology. The group aims at the recruitment and clinical characterization of 5,000 patients affected by CAKUT to conduct detailed clinical characterization and perform research DNA microarrays and WES in all patients (in collaboration with Columbia University). To date, 30 Italian centers have an approved IRB are actively enrolling for these studies or they are in the process of submitting or activating the IRB in order to start enrolling patients. We currently recruited and characterized 1,482 independent index patients. We plan to reach the target goal of 5,000 patients in four years. The deep clinical and phenotypic characterization will allow precise anatomical classification of disease. Genetic data will be use to guide deep phenotyping (ex imaging studies, metabolic tests, neurodevelopmental tests). The longitudinal design will allow identification of both genetic and non genetic prognostic factors. Finally, this project aims at a reclassification of CAKUT based on underlying molecular genetics mechanisms, in order to improve renal and overall patient outcome

Il trapianto è il trattamento di scelta per i pazienti affetti da insufficienza renale cronica terminale. La prevenzione del rigetto richiede un trattamento immunosoppressivo che deve essere protratto per tutta la durata di vita del trapianto. La personalizzazione della terapia immunosoppressiva si ritiene possa migliorare gli outcome dei trapianti attraverso un impiego più mirato dei farmaci attualmente disponibili. Lo sviluppo di trattamenti individualizzati richiede l’utilizzo di biomarcatori per stratificare il grado di rischio di danno renale che siano affidabili, riproducibili, non invasivi e poco costosi. Tra tutti il dosaggio urinario della chemochina CXCL9 si è dimostrato lo strumento più adeguato, non solo per individuare i pazienti con un rigetto acuto T cellulare in atto o in fase d’insorgenza ma anche per individuare quel sottogruppo di pazienti immunologicamente stabili che si possono definire in quiescenza immunologica33 grazie al suo elevato valore predittivo negativo. Obiettivo primario dello studio è di confermare l’elevato valore predittivo negativo di bassi livelli di CXCL9 nei pazienti clinicamente stabili che si possono definire in quiescenza immunologica. Obiettivo secondario è stato quello di esaminare i livelli urinari di CXCL9 nei pazienti con lesioni da danno mediato da cellule T, che abbia causato una disfunzione acuta o cronica del graft. La chemochina CXCL9 sembra essere un biomarcatore di quiescenza alloimmunitaria, non invasivo, ripetibile e affidabile nel selezionare i pazienti con assenza di segni di rigetto primitiva o secondaria a un’efficace terapia immunosoppressiva anti-rigetto. Il monitoraggio dell’andamento delle concentrazioni seriate di CXCL9 urinario in corso di terapia per rigetto acuto ci permette inoltre di monitorarne precocemente la risposta: la mancata normalizzazione entro la prima settimana depone per un rigetto resistente con necessità di terapie di secondo livello.

Background: Rituximab is effective for induction and maintenance of remission in ANCA-associated vasculitis; however, response to treatment is highly variable and relapse is common after its discontinuation. Biomarkers predicting response to rituximab do not exist and are needed to improve patients’ stratification. Objective: This study assesses potential genetic determinants of response to rituximab in ANCA-associated vasculitis. Methods: Genotyping of 18 candidate single nucleotide polymorphisms, chosen on the basis of a biological rationale or previous reports, was performed using TaqMan and Sequenom platforms. End-points were rituximab-failure rate at 6 months and time to rituximab-failure within a year of the first rituximab administration. Rituximab failure was defined as any form of active vasculitis requiring escalation of immunosuppressive treatment. Results: Two hundred and thirteen patients were enrolled in the primary and 109 in the replication cohorts. One single nucleotide polymorphism in the TNFSF13B regulatory gene region (BAFF) was associated with rituximab failure risk at 6 months and time to rituximab-failure in the two cohorts (respectively after meta-analysis, OR 8.8, p=0.0065; HR 7.3, p=8.5x10-06). Carriers of the risk genotype had a higher rate of detectable B-cells 6 months after rituximab (50% vs 14%, p=0.0146). This association was restricted to the PR3-ANCA patient subgroup. Conclusion: We have identified a single nucleotide polymorphism of the regulatory region of the gene BAFF that may be able to predict response to rituximab in ANCA-associated vasculitis.

INTRODUCTION World Kidney Day (WKD) started in 2006 by a memorandum of understanding between the International Federation of Kidney Foundations (IFKF) and the International Society of Nephrology (ISN) based on a proposal to “raise awareness of the importance of our kidneys to our overall health and to reduce the frequency and impact of kidney disease and its associated health problems world-wide”. In Italy the WKD was planned and conducted by the Fondazione Italiana del Rene (FIR; National Kidney Foundation of Italy), in collaboration with the Italian Society of Nephrology (SIN) and the Red Cross of Italy. Italian WKD focused on two projects called ”Square project” and “School project”. The “Square project” was intended for general population and the “School project” for students attending the fourth and fifth year of Italian high school. This is a unique initiative in the context of those carried out around the world by countries that have observed WKD. The relevance of this screening relies on the fact that this population is seldom evaluated by either pediatricians or general practitioners in the absence of overt disease. The main goal of the present study was to assess the presence of urinalysis abnormalities and their associations with hypertension and obesity in a population of adolescents participating in the Italian Kidney Day during the period 2010–2011. METHODS Study population is represented by students participating to “school project”. Data on age, gender, sport activity and general information was assessed using questionnaires. Trained personnel (nephrologists and nurses) assessed systolic and diastolic BP (SBP; DBP). Weight, height and WC were measured. BMI, Ci and WHt-ratio were calculated. HTN was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg, pre-hypertension as SBP of 120 mmHg but lower than 140 mmHg or DBP of 80 mmHg but lower than 90 mmHg. Stage-1 HTN as SBP of 140 mmHg but lower than 160 mmHg or DBP of 90 mmHg but lower than 100 mmHg, and Stage-2 HTN as SBP ≥ 160 mmHg or DBP≥ 100 mmHg. Isolated systolic hypertension (ISH) as SBP ≥ 140 mmHg and DBP ≤ 90 mmHg. According to BMI, normal weight was from 18.5 to 24.9 kg/m2, overweight from 25 to 29.9 kg/m2, class-I obesity from 30,0 to 34.9 kg/m2, class-II from 35 to 39.9 kg/m2, class-III ≥ 40 kg/m2. Normal WC was