Urinary excretion of soluble tumour necrosis factor receptor 1 as a marker of increased risk of progressive kidney function deterioration in patients with primary chronic glomerulonephritis
Urinary excretion of soluble tumour necrosis factor receptor 1 as a marker of increased risk of progressive kidney function deterioration in patients with primary chronic glomerulonephritis
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DOI：
10.1093/ndt/gfq310
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发表时间：
2010-12-01
影响因子：
6.1
通讯作者：
Czekalski, Stanislaw
中科院分区：
文献类型：
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作者：
Idasiak-Piechocka, Ilona;Oko, Andrzej;Czekalski, Stanislaw
背景资料。肿瘤坏死因子a是一种强有力的促炎细胞因子，其在肾脏的作用是由两种膜受体(TNFR)介导的，即TNFR1和TNFR2。在几种肾脏疾病中，肿瘤坏死因子受体和肿瘤坏死因子受体的表达均增加，并与受体从细胞膜上脱落有关。在肾小球肾炎(GN)的实验模型中，血清中的TNFRs浓度升高，尿液中的TNFRs排泄增加。本研究旨在探讨肾小球肾炎患者尿中肿瘤坏死因子受体1的排泄及其与肾损害临床指标的关系。同时还评估了基础尿TNFR1排泄量作为肾功能损害进展预测指标的价值。材料和方法。55名新诊断的、经活检证实的原发肾炎患者被纳入研究。在所有患者和20名健康受试者中，用酶联免疫吸附试验测定了UTNFR1。在患者中，评估了肾功能损害进展的危险因素(ECCR降低、肾病综合征、高血压和肾脏形态损害的强度)。然后介绍相应的治疗方法，并对患者进行了4年的随访。肾功能损害的进展被定义为ECCR>；在随访期间减少5毫升/分钟/1.73米(2)/年。评估基础肿瘤坏死因子受体1(TNFR1)排泄量与肿瘤进展的关系。肾小球肾炎患者尿肿瘤坏死因子受体1排泄量(4039.2+/-3801.5 pg/mgcr)高于正常对照组(1358.9+/-927.8 pg/mgcr，P<0.00002)。与ECCR呈显著负相关(sr=0.464，P<0.01)，与蛋白尿呈正相关(sr=0.463，P<0.01)。在13例患者中，ECCR在随访期间明显降低。Logistic回归分析显示，肾活检标本中肿瘤坏死因子受体1的排泄量和3863.3 pg/mgcr可预测肾功能损害的进展和进展性间质纤维化。尿TNFR1排泄量显著升高可作为新诊断GN患者肿瘤坏死因子α途径活化的良好标志，并可作为进行性肾功能损害的潜在可改变危险因素。
Background. The effects of tumor necrosis factor a (TNF a), a potent proinflammatory cytokine, in the kidneys are mediated by two membrane receptors (TNFR), TNFR1 and TNFR2. The expression of both TNF and TNFRs increases in several kidney diseases and is associated with the shedding of the receptors out of the cell membranes. In an experimental model of glomerulonephritis (GN), elevated concentrations of TNFRs in serum and TNFRs excretion in urine were demonstrated. The aim of this study was evaluation of urinary excretion of TNFR1 and its relationship with the clinical markers of kidney injury in patients with GN. The value of basal urinary TNFR1 excretion as a prognostic indicator of the progression of kidney function impairment was also assessed.Material and Methods. Fifty-five patients with newly diagnosed, biopsy-proven primary GN were included in the study. In all patients, and in 20 healthy subjects, UTNFR1 was measured using an ELISA. In the patients, risk factors of the progression of impairment of kidney function (reduced eCcr, nephrotic syndrome, hypertension and intensity of morphological lesions in the kidneys) were evaluated. The appropriate treatment was then introduced and the patients were in follow-up for 4 years. The progression of kidney function impairment was defined as a reduction of eCcr > 5 mL/min/1.73 m(2)/year during follow-up. The association of basal TNFR1 excretion with the progression was evaluated.Results. Urinary excretion of TNFR1 in the patients with GN (4039.2 +/- 3801.5 pg/mgCr) was greater than in the healthy subjects (1358.9 +/- 927.8 pg/mgCr, P < 0,00002). A significant negative correlation between TNFR1 excretion and eCcr (Sr = 0.464, P < 0.01) and a positive correlation between TNFR1 excretion and proteinuria (Sr = 0,463, P < 0.01) were found. In 13 patients, a marked reduction of eCcr was observed during follow-up. Logistic regression analysis revealed that TNFR1 excretion > 3863.3 pg/mgCr predicts progression of renal function impairment along with advanced interstitial fibrosis in the kidney biopsy specimens at presentation.Conclusion. Markedly elevated urinary TNFR1 excretion may be considered as a good marker of an activated TNF alpha-pathway in patients with newly diagnosed GN and as a potentially modifiable risk factor of progressive kidney function impairment.