Marianna Caterino1,2, Miriam Zacchia3, Michele Costanzo1,2,4, Giuliana Bruno5, Davide Arcaniolo6, Francesco Trepiccione3, Rosa Anna Siciliano7, Maria Fiorella Mazzeo7, Margherita Ruoppolo1,2,4, Giovambattista Capasso3. 1. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli, "Federico II", Naples, Italy. 2. CEINGE Biotecnologie Avanzate, Naples, Italy. 3. Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. 4. Associazione culturale DiSciMuS, Naples, Italy. 5. IRGS Biogem, Via Camporeale, Ariano Irpino, Avellino, Italy. 6. Urology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy. 7. Istituto di Scienze dell' Alimentazione, Avellino, Italy.
Abstract
BACKGROUND: /Aims: Renal disease is a common cause of morbidity in patients with Bardet-Biedl syndrome (BBS), however the severity of kidney dysfunction is highly variable. To date, there is little information on the pathogenesis, the risk and predictor factors for poor renal outcome in this setting. The present study aims to analyze the spectrum of urinary proteins in BBS patients, in order to potentially identify 1) disease-specific proteomic profiles that may differentiate the patients from normal subjects; 2) urinary markers of renal dysfunction. METHODS: Fourteen individuals (7 males and 7 females) with a clinical diagnosis of BBS have been selected in this study. A pool of 10 aged-matched males and 10 aged-matched females have been used as controls for proteomic analysis. The glomerular filtration rate (eGFR) has been estimated using the CKD-EPI formula. Variability of eGFR has been retrospectively assessed calculating average annual eGFR decline (ΔeGFR) in a mean follow-up period of 4 years (3-7). RESULTS: 42 proteins were significantly over- or under-represented in BBS patients compared with controls; the majority of these proteins are involved in fibrosis, cell adhesion and extracellular matrix organization. Statistic studies revealed a significant correlation between urine fibronectin (u-FN) (r2=0.28; p<0.05), CD44 antigen (r2 =0.35; p<0.03) and lysosomal alfa glucosidase ( r20.27; p<0.05) abundance with the eGFR. In addition, u-FN (r2 =0.2389; p<0.05) was significantly correlated with ΔeGFR. CONCLUSION: The present study demonstrates that urine proteome of BBS patients differs from that of normal subjects; in addition, kidney dysfunction correlated with urine abundance of known markers of renal fibrosis.
BACKGROUND: /Aims: Renal disease is a common cause of morbidity in patients with Bardet-Biedl syndrome (BBS), however the severity of kidney dysfunction is highly variable. To date, there is little information on the pathogenesis, the risk and predictor factors for poor renal outcome in this setting. The present study aims to analyze the spectrum of urinary proteins in BBSpatients, in order to potentially identify 1) disease-specific proteomic profiles that may differentiate the patients from normal subjects; 2) urinary markers of renal dysfunction. METHODS: Fourteen individuals (7 males and 7 females) with a clinical diagnosis of BBS have been selected in this study. A pool of 10 aged-matched males and 10 aged-matched females have been used as controls for proteomic analysis. The glomerular filtration rate (eGFR) has been estimated using the CKD-EPI formula. Variability of eGFR has been retrospectively assessed calculating average annual eGFR decline (ΔeGFR) in a mean follow-up period of 4 years (3-7). RESULTS: 42 proteins were significantly over- or under-represented in BBSpatients compared with controls; the majority of these proteins are involved in fibrosis, cell adhesion and extracellular matrix organization. Statistic studies revealed a significant correlation between urine fibronectin (u-FN) (r2=0.28; p<0.05), CD44 antigen (r2 =0.35; p<0.03) and lysosomal alfa glucosidase ( r20.27; p<0.05) abundance with the eGFR. In addition, u-FN (r2 =0.2389; p<0.05) was significantly correlated with ΔeGFR. CONCLUSION: The present study demonstrates that urine proteome of BBSpatients differs from that of normal subjects; in addition, kidney dysfunction correlated with urine abundance of known markers of renal fibrosis.
Authors: Valeria De Pasquale; Michele Costanzo; Rosa Anna Siciliano; Maria Fiorella Mazzeo; Valeria Pistorio; Laura Bianchi; Emanuela Marchese; Margherita Ruoppolo; Luigi Michele Pavone; Marianna Caterino Journal: Biomolecules Date: 2020-02-26