Caterino Marianna, Zacchia Miriam, Costanzo Michele, Bruno Giuliana, Arcaniolo Davide, Trepiccione Francesco, Siciliano Rosa Anna, Mazzeo Maria Fiorella, Ruoppolo Margherita, Capasso Giovambattista
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli, "Federico II", Naples, Italy.
CEINGE Biotecnologie Avanzate, Naples, Italy.
Kidney Blood Press Res. 2018;43(2):389-405. doi: 10.1159/000488096. Epub 2018 Mar 8.
/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.
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).
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.
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.
/目的：肾脏疾病是巴德-比德尔综合征（BBS）患者发病的常见原因，然而肾功能障碍的严重程度差异很大。迄今为止，关于这种情况下肾功能不良的发病机制、风险和预测因素的信息很少。本研究旨在分析BBS患者尿蛋白谱，以便潜在地识别：1）可能将患者与正常受试者区分开来的疾病特异性蛋白质组学特征；2）肾功能障碍的尿标志物。
本研究选取了14例临床诊断为BBS的个体（7例男性和7例女性）。选取10例年龄匹配的男性和10例年龄匹配的女性作为蛋白质组学分析的对照。使用CKD-EPI公式估算肾小球滤过率（eGFR）。在平均4年（3 - 7年）的随访期内，通过计算平均每年eGFR下降值（ΔeGFR）对eGFR的变异性进行回顾性评估。
与对照组相比，BBS患者中有42种蛋白质显著高表达或低表达；这些蛋白质大多数参与纤维化、细胞黏附和细胞外基质组织。统计学研究显示，尿纤连蛋白（u-FN）（r2 = 0.28；p < 0.05）、CD44抗原（r2 = 0.35；p < 0.03）和溶酶体α-葡萄糖苷酶（r2 = 0.27；p < 0.05）的丰度与eGFR之间存在显著相关性。此外，u-FN（r2 = 0.2389；p < 0.05）与ΔeGFR显著相关。
本研究表明，BBS患者的尿蛋白质组与正常受试者不同；此外，肾功能障碍与已知肾纤维化标志物的尿丰度相关。
