The urinary proteome as correlate and predictor of renal function in a population study
The urinary proteome as correlate and predictor of renal function in a population study
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DOI：
10.1093/ndt/gfu234
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发表时间：
2014-12-01
影响因子：
6.1
通讯作者：
Staessen, Jan A.
中科院分区：
文献类型：
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作者：
Gu, Yu-Mei;Thijs, Lutgarde;Staessen, Jan A.
我们调查了尿蛋白质组是否能改进肾功能障碍的诊断，肾功能障碍影响了超过10%的成年人。我们从人群中随机招募了797人，测量了血清肌酐、估计的肾小球滤过率(EGFR)和24小时蛋白尿。我们应用毛细管电泳质谱联用技术对肾功能不全(CKD273)或左心功能不全(HF1和HF2)的多维尿液蛋白质组分类进行了研究。对621名受试者的肾功能和整个研究人群的心血管事件发生率进行了跟踪调查。在多变量调整横断面分析中，较高的生物标志物水平单独分析或通过主成分分析合并为单因素(SF)，与较差的肾功能相关(P<0.010)。在4.8年期间，较高的Hf1和SF预测EGFR值降低(P<0.05)；较高的Hf2预测(Pa<0.049)血肌酐升高和EGFR值降低。HF1、Hf2和SF预测从慢性肾脏病2期或千分之2到千分之3的进展，尿液生物标志物1-SD增加的风险估计从38%到71%(P a千分之0.039)。HF1、Hf2和SF的重新分类净值提高了31-51%(P a PERS PERSION 0.029)。在6.1年的时间里，发生了47起心血管事件。Hf2和SF独立于基线的EGFR、24小时蛋白尿和其他辅助变量是心血管并发症的重要预测因子，1-SD增加的风险估计在32%到41%之间(P<0.047)。尿蛋白组学改进了对现有或进展中的肾功能障碍的诊断，并预测了心血管并发症。
We investigate whether the urinary proteome refines the diagnosis of renal dysfunction, which affects over 10% of the adult population.We measured serum creatinine, estimated glomerular filtration rate (eGFR) and 24-h albuminuria in 797 people randomly recruited from a population. We applied capillary electrophoresis coupled with mass spectrometry to measure multi-dimensional urinary proteomic classifiers developed for renal dysfunction (CKD273) or left ventricular dysfunction (HF1 and HF2). Renal function was followed up in 621 participants and the incidence of cardiovascular events in the whole study population.In multivariable-adjusted cross-sectional analyses, higher biomarker levels analysed separately or combined by principal component analysis into a single factor (SF), correlated (P a parts per thousand currency sign 0.010) with worse renal function. Over 4.8 years, higher HF1 and SF predicted (P a parts per thousand currency sign 0.014) lowering of eGFR; higher HF2 predicted (P a parts per thousand currency sign 0.049) increase in serum creatinine and decrease eGFR. HF1, HF2 and SF predicted progression from CKD Stages 2 or a parts per thousand currency sign2 to Stage a parts per thousand yen3, with risk estimates for a 1-SD increment in the urinary biomarkers ranging from 38 to 71% (P a parts per thousand currency sign 0.039). HF1, HF2 and SF yielded a net reclassification improvement of 31-51% (P a parts per thousand currency sign 0.029). Over 6.1 years, 47 cardiovascular events occurred. HF2 and SF, independent of baseline eGFR, 24-h albuminuria and other covariables were significant predictors of cardiovascular complications with risk estimates for 1-SD increases ranging from 32 to 41% (P a parts per thousand currency sign 0.047).The urinary proteome refines the diagnosis of existing or progressing renal dysfunction and predicts cardiovascular complications.