Department of Medicine, University of Toledo, 3000 Arlington Ave, MS 1036, Toledo, OH 43614, USA.
Hypertension. 2013 Apr;61(4):894-900. doi: 10.1161/HYPERTENSIONAHA.111.00685. Epub 2013 Feb 11.
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, United Kingdom. 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 (R(2)=0.06; P<0.05) and baseline creatinine (R(2)=0.08; P=0.022) were associated with loss of kidney function at 1-year follow-up, whereas soluble CD40 ligand was not (R(2)=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 R(2)=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 versus nonsurvivors, 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.
肾脏近端小管上皮细胞上的 CD40 受体的激活可导致实验性肾损伤模型中的纤维化和炎症。激活的血小板释放可溶性 CD40 配体。CD40-可溶性 CD40 配体在缺血性肾病患者中的作用尚不清楚。在英国曼彻斯特索尔福德皇家医院的一个单中心队列中，对 60 例肾动脉狭窄患者的血浆 CD40 和可溶性 CD40 配体水平进行了酶联免疫吸附试验测量。为了使数据标准化，对 CD40 和可溶性 CD40 配体进行自然对数转换。估计的肾小球滤过率用作肾功能的主要指标。通过单变量分析，低基线循环 CD40（R（2）=0.06；P<0.05）和基线肌酐（R（2）=0.08；P=0.022）与 1 年随访时肾功能丧失相关，而可溶性 CD40 配体则不然（R（2）=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）仍然与肾功能下降显著相关（模型 R（2）=0.17；P<0.005）。在随访期间死亡的患者的基线 CD40 水平略低（存活者，7.3±0.9 pg/mL，n=48 与非存活者，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导致动脉粥样硬化性肾动脉狭窄患者肾损伤发展和进展的新机制。
