Yang Xiaoxia, Bai Ming, Ning Xiaoxuan, Ma Feng, Liu Limin, Liu Ting, Liu Minna, Wang Hanmin, Sun Shiren
Clin Nephrol. 2018 Feb;89(2):93-103. doi: 10.5414/CN109117.
Our previous studies indicated that Bmi-1 plays an important role in hypoxia-induced tubular epithelial-mesenchymal transition and the development of kidney fibrosis in cellular and animal models. However, circulating Bmi-1 levels in human chronic kidney disease (CKD) and their relation to progression remains unknown.
We conducted a post-hoc analysis of a prospective cohort study. The blood samples and clinical data of 230 patients with glomerular CKD and 67 healthy adults were prospectively collected between January 2010 and June 2012. Serum Bmi-1 was measured using enzyme-linked immunosorbent assay (ELISA).
CKD patients had significantly higher serum Bmi-1 concentrations than the healthy controls (496.4 (363.1 - 675.4) pg/mL compared with 257.3 (235.4 - 303.8) pg/mL, p < 0.001). Serum Bmi-1 level inversely correlated with the estimated glomerular filtration rate (eGFR) (r = -0.346, p < 0.001). In addition, positive correlations were identified between serum Bmi-1 levels and serum creatinine, blood urea nitrogen, cystatin C concentration, and the severity of tubulointerstitial fibrosis (r = 0.248, p < 0.001; r = 0.245, p < 0.001; r = 0.273, p < 0.001; r = 0.536, p < 0.001, respectively). Kaplan-Meier survival curves showed that a higher serum Bmi-1 level was associated with a shorter duration of renal survival. Cox multivariate analyses further demonstrated that serum Bmi-1 concentration was an independent prognostic factor for CKD patients (HR = 6.48, p < 0.001).
CONCLUSION: Our study showed that high circulating Bmi-1 levels were associated with adverse kidney disease outcome, suggesting that Bmi-1 is a novel biomarker for glomerular CKD progression. More data from larger longitudinal studies are required to validate our findings. .
我们之前的研究表明,在细胞和动物模型中,Bmi-1在缺氧诱导的肾小管上皮-间充质转化及肾纤维化发展过程中发挥重要作用。然而,人类慢性肾脏病(CKD)患者的循环Bmi-1水平及其与疾病进展的关系尚不清楚。
我们对一项前瞻性队列研究进行了事后分析。在2010年1月至2012年6月期间前瞻性收集了230例肾小球CKD患者和67例健康成年人的血样及临床数据。采用酶联免疫吸附测定(ELISA)法检测血清Bmi-1水平。
CKD患者的血清Bmi-1浓度显著高于健康对照组(分别为496.4(363.1 - 675.4)pg/mL和257.3(235.4 - 303.8)pg/mL,p < 0.001)。血清Bmi-1水平与估算肾小球滤过率(eGFR)呈负相关(r = -0.346,p < 0.001)。此外,血清Bmi-1水平与血清肌酐、血尿素氮、胱抑素C浓度以及肾小管间质纤维化严重程度呈正相关(r分别为0.248,p < 0.001;r = 0.245,p < 0.001;r = 0.273,p < 0.001;r = 0.536,p < 0.001)。Kaplan-Meier生存曲线显示,较高的血清Bmi-1水平与肾脏存活时间较短相关。Cox多因素分析进一步表明,血清Bmi-1浓度是CKD患者的独立预后因素(HR = 6.48,p < 0.001)。
我们的研究表明,循环Bmi-1水平升高与不良肾脏疾病结局相关,提示Bmi-1是肾小球CKD进展的一种新型生物标志物。需要更多来自大型纵向研究的数据来验证我们的发现。