膜性肾小球肾炎中的尿转化生长因子-β1

Urinary transforming growth factor-beta 1 in membranous glomerulonephritis.

作者信息

Honkanen E, Teppo A M, Törnroth T, Groop P H, Grönhagen-Riska C

机构信息

Department of Medicine, Helsinki University Central Hospital, Finland.

出版信息

Nephrol Dial Transplant. 1997 Dec;12(12):2562-8. doi: 10.1093/ndt/12.12.2562.

DOI:10.1093/ndt/12.12.2562

PMID:9430852

Abstract

BACKGROUND

Human idiopathic membranous glomerulonephritis (MGN) has a highly variable clinical course and factors determining its outcome are poorly known. Since transforming growth factor-beta 1 (TGF-beta 1) has an essential role in renal fibrogenesis, we studied the possibility to use urinary excretion of TGF-beta 1 in the assessment of progression of the disease in patients with MGN.

METHODS

Urinary TGF-beta 1 was determined in 41 patients with MGN, 25 healthy subjects, six non-proteinuric renal transplant patients, 10 patients with IgA glomerulonephritis, and seven proteinuric patients (with non-progressive diseases) using a novel, double antibody enzyme immunoassay. The results were compared with renal morphology and clinical indices of activity of MGN over 12 months.

RESULTS

The median urinary TGF-beta 1 excretion (pg/mg creatinine) was significantly higher (1730; range 60-16,970) in MGN patients than in the healthy controls (300; 30-1330; P < 0.0001). In renal allograft recipients the excretion was 840 (250-3440; P < 0.0001 vs healthy controls), in IgA GN it was 1130 (30-4910; P = 0.039), and in proteinuric patients it was 39 (29-165; P = NS). In MGN but not in the proteinuric controls or renal allograft recipients, urinary TGF-beta 1 correlated with urinary albumin excretion (r = 0.86, P < 0.0001) but no correlation with renal function or the duration of the disease was found. Urinary TGF-beta 1 at renal biopsy correlated with interstitial cellular inflammation and its excretion 1 year before the biopsy correlated with indices of sclerosis/fibrosis. Immunosuppressive therapy significantly decreased urinary TGF-beta 1 from 2800 (1610-16,960) to 840 (170-1600) pg/mg creatinine (P = 0.028). Patients with persistent nephrotic syndrome and/or declining renal function had a higher initial TGF-beta 1 excretion (median 3680; 1830-7420 pg/mg creatinine) than those entering partial or complete remission (1060; 60-1960; P = 0.003) within 12 months from sampling.

摘要

背景

人类特发性膜性肾小球肾炎（MGN）的临床病程高度可变，决定其预后的因素尚不清楚。由于转化生长因子-β1（TGF-β1）在肾纤维化形成中起关键作用，我们研究了利用尿中TGF-β1排泄量来评估MGN患者疾病进展的可能性。

方法

采用一种新型双抗体酶免疫测定法，测定了41例MGN患者、25名健康受试者、6例无蛋白尿的肾移植患者、10例IgA肾小球肾炎患者和7例蛋白尿患者（患有非进行性疾病）尿中的TGF-β1。将结果与MGN患者12个月内的肾脏形态及临床活动指标进行比较。

结果

MGN患者尿中TGF-β1排泄量中位数（pg/mg肌酐）显著高于健康对照组（1730；范围60 - 16970）（300；30 - 1330；P < 0.0001）。肾移植受者的排泄量为840（250 - 3440；与健康对照组相比P < 0.0001），IgA肾病患者为1130（30 - 4910；P = 0.039），蛋白尿患者为39（29 - 165；P = 无显著性差异）。在MGN患者中，而非蛋白尿对照组或肾移植受者中，尿TGF-β1与尿白蛋白排泄量相关（r = 0.86，P < 0.0001），但未发现与肾功能或疾病持续时间相关。肾活检时尿TGF-β1与间质细胞炎症相关，活检前1年其排泄量与硬化/纤维化指标相关。免疫抑制治疗使尿TGF-β1从2800（1610 - 16960）显著降至840（170 - 1600）pg/mg肌酐（P = 0.028）。持续性肾病综合征和/或肾功能下降的患者初始TGF-β1排泄量较高（中位数3680；1830 - 7420 pg/mg肌酐），高于在采样后12个月内进入部分或完全缓解的患者（1060；60 - 1960；P = 0.003）。