C5b-9肾小球沉积和肾小管α3β1整合素表达与慢性病变的发展有关，并可预测免疫球蛋白A肾病的肾功能结局。

C5b-9 glomerular deposition and tubular alpha3beta1-integrin expression are implicated in the development of chronic lesions and predict renal function outcome in immunoglobulin A nephropathy.

作者信息

Stangou Maria, Alexopoulos Efstathios, Pantzaki Afroditi, Leonstini Maria, Memmos Dimitrios

机构信息

Nephrology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.

出版信息

Scand J Urol Nephrol. 2008;42(4):373-80. doi: 10.1080/00365590801943241.

DOI:10.1080/00365590801943241

PMID:19230171

Abstract

OBJECTIVE

Tubular atrophy is one of the factors predicting poor outcome of renal function in primary immunoglobulin A nephropathy (IgAN). However, the development of tubular atrophy is a late phenomenon during the disease progression. It would be useful to identify early factors that potentially result in renal damage and could be used as early predictors of renal outcome.

MATERIAL AND METHODS

Forty-eight patients with IgAN were examined retrospectively. All patients had a renal biopsy at the beginning of the study. Histological parameters were reviewed and immunohistochemistry was performed on cryostat sections. Monoclonal antibodies used were against C5b-9, alpha3beta1-integrin, transforming growth factor-beta1 (TGF-beta1) and alpha-smooth muscle actin (alpha-SMA), and the results were correlated with histological data and long-term outcome of renal function.

RESULTS

In the glomeruli the extent of C5b-9 deposition had significant positive correlations with the degree of focal glomerulosclerosis (p=0.005), tubular atrophy (p=0.003), interstitial inflammation (p=0.005) and tubular expression of alpha3beta1 (p=0.0001). alpha3beta1 tubular expression correlated positively with the severity of proteinuria (p=0.01), number of glomerular and tubulointerstitial myofibroblasts, and the degree of tubular atrophy (p=0.0001) and interstitial monocyte infiltration (p =0.005). Tubular alpha3beta1 expression and the degree of tubular atrophy had significant implications in the development of renal failure at the beginning and at the end of follow-up, respectively.

CONCLUSIONS

Glomerular deposition of C5b-9 may participate in the development of glomerulosclerosis in IgAN. Furthermore, its positive correlation with the intensity of tubular alpha3beta1-integrin suggests a possible implication in the development of tubulointerstitial fibrosis.

摘要

目的

肾小管萎缩是预测原发性免疫球蛋白A肾病（IgAN）肾功能不良预后的因素之一。然而，肾小管萎缩的发生是疾病进展过程中的晚期现象。识别可能导致肾损伤并可作为肾脏预后早期预测指标的早期因素将很有帮助。

材料与方法

对48例IgAN患者进行回顾性研究。所有患者在研究开始时均接受了肾活检。回顾组织学参数并在冰冻切片上进行免疫组织化学检测。使用的单克隆抗体针对C5b-9、α3β1整合素、转化生长因子-β1（TGF-β1）和α-平滑肌肌动蛋白（α-SMA），结果与组织学数据及肾功能的长期预后相关。

结果

在肾小球中，C5b-9沉积程度与局灶性肾小球硬化程度（p=0.005）、肾小管萎缩程度（p=0.003）、间质炎症（p=0.005）及α3β1的肾小管表达（p=0.0001）呈显著正相关。α3β1肾小管表达与蛋白尿严重程度（p=0.01）、肾小球和肾小管间质肌成纤维细胞数量、肾小管萎缩程度（p=0.0001）及间质单核细胞浸润程度（p =0.005）呈正相关。肾小管α3β1表达程度和肾小管萎缩程度分别在随访开始和结束时对肾衰竭的发生有显著影响。