Wijnhoven Tessa J M, Geelen Joyce M, Bakker Marinka, Lensen Joost F M, Rops Angelique L W M M, Kramer Andrea B, Navis Gerjan, van den Hoven Mabel J W, van der Vlag Johan, Berden Jo H M, Wetzels Jack F M, van den Heuvel Lambert P W J, Monnens Leo A H, van Kuppevelt Toin H
Department of Matrix Biochemistry, Nijmegen Centre for Molecular Life Sciences, Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Nephrol Dial Transplant. 2007 Oct;22(10):2886-93. doi: 10.1093/ndt/gfm301. Epub 2007 May 25.
Minimal change nephrotic syndrome (MCNS) is the most frequent form of nephrotic syndrome in childhood. In the glomerular basement membrane (GBM) of adult patients with MCNS, a reduced expression of a specific heparan sulphate (HS) domain has been reported. In children with MCNS, urinary activity of the HS-degrading enzyme heparanase was increased. It is, therefore, possible that a decreased GBM HS expression is associated with the pathogenesis of proteinuria in patients with MCNS.
In this study, HS in glomeruli of five adult and six paediatric patients with MCNS were analysed by immunofluorescence staining using four different antibodies, each defining a specific sulphated HS domain. The pediatric patients were subdivided into three groups depending on the presence or absence of podocyte foot process effacement, the level of proteinuria and prednisone administration at the time of the biopsy. In addition, kidneys of rats with adriamycin nephropathy (ADRN), a model for MCNS, were included in the study.
Expression of sulphated HS domains was not aberrant in adult or paediatric patients compared with control subjects. Children with and without proteinuria had the same HS content. In contrast, rats with ADRN showed a decreased glomerular expression of sulphated HS domains.
These results suggest that in patients with MCNS proteinuria is not associated with major changes in glomerular expression of sulphated HS domains.
微小病变型肾病综合征(MCNS)是儿童肾病综合征最常见的类型。据报道,成年MCNS患者的肾小球基底膜(GBM)中特定硫酸乙酰肝素(HS)结构域的表达降低。在儿童MCNS患者中,HS降解酶乙酰肝素酶的尿活性增加。因此,GBM中HS表达降低可能与MCNS患者蛋白尿的发病机制有关。
在本研究中,使用四种不同抗体通过免疫荧光染色分析了五名成年和六名儿童MCNS患者肾小球中的HS,每种抗体可识别特定的硫酸化HS结构域。根据活检时足细胞足突消失情况、蛋白尿水平和泼尼松给药情况,将儿科患者分为三组。此外,MCNS模型阿霉素肾病(ADRN)大鼠的肾脏也纳入了研究。
与对照组相比,成年或儿科患者硫酸化HS结构域的表达没有异常。有蛋白尿和无蛋白尿的儿童HS含量相同。相比之下,ADRN大鼠的肾小球硫酸化HS结构域表达降低。
这些结果表明,MCNS患者的蛋白尿与硫酸化HS结构域的肾小球表达的主要变化无关。