Effect of CD40 and sCD40L on renal function and survival in patients with renal artery stenosis.
Effect of CD40 and sCD40L on renal function and survival in patients with renal artery stenosis.
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DOI：
10.1161/hypertensionaha.111.00685
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Cooper CJ
中科院分区：
文献类型：
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作者：
Haller ST;Kalra PA;Ritchie JP;Chrysochou T;Brewster P;He W;Yu H;Shapiro JI;Cooper CJ
在肾损伤实验模型中，肾近端小管上皮CD40受体的激活导致纤维化和炎症。可溶性CD40配体由活化的血小板释放。CD40可溶性CD40配体在缺血性肾病患者中的作用尚不清楚。采用酶联免疫吸附法测定了来自英国曼彻斯特索尔福德皇家医院的60例肾动脉狭窄患者的血浆CD40和可溶性CD40配体水平。对CD40和可溶性CD40配体进行自然对数变换，使数据归一化。估计肾小球滤过率作为肾功能的主要指标。单因素分析显示，低基线循环CD40水平（R2=0.06, p<0.05）和基线肌酐水平（R2=0.08, p=0.022）与1年随访时肾功能丧失相关，而可溶性CD40配体与肾功能丧失无关（R2=0.02, p=ns）。在多元线性回归模型中，CD40 （p<0.02）和基线肌酐（p<0.01）继续与肾功能下降显著相关（模型R2=0.17, p<0.005）。随访期间死亡患者的基线CD40水平略低（幸存者，7.3±0.9 pg/ml, n=48，非幸存者，6.7±1.0 pg/ml, n=12, p=0.06）。CD40/可溶性CD40配体信号级联可能是参与动脉粥样硬化性肾动脉狭窄患者肾损伤发生进展的新机制。
Activation of the CD40 receptor on the proximal tubular epithelium of the kidney results in fibrosis and inflammation in experimental models of kidney injury. Soluble CD40 ligand is released by activated platelets. The role of CD40-soluble CD40 ligand in patients with ischemic renal disease is unknown. Plasma levels of CD40 and soluble CD40 ligand were measured by enzyme linked immunosorbent assay in a single center cohort of 60 patients with renal artery stenosis recruited from Salford Royal Hospital, Manchester, UK. A natural log transformation of CD40 and soluble CD40 ligand was performed to normalize the data. Estimated glomerular filtration rate was used as the primary indicator of renal function. By univariate analysis low baseline levels of circulating CD40 (R2=0.06, p<0.05) and baseline creatinine (R2=0.08, p=0.022) were associated with loss of kidney function at one-year follow-up, whereas soluble CD40 ligand was not (R2=0.02, p=ns). In a multiple linear regression model CD40 (p<0.02) and baseline creatinine (p<0.01) continued to be significantly associated with a decline in renal function (model R2=0.17, p<0.005). Baseline CD40 levels were somewhat lower in patients who died during follow-up (survivors, 7.3 ± 0.9 pg/ml, n=48 vs. non-survivors, 6.7 ± 1.0 pg/ml, n=12, p=0.06). The CD40/soluble CD40 ligand signaling cascade may be a novel mechanism contributing to the development and progression of renal injury in patients with atherosclerotic renal artery stenosis.