Fujii Hideki, Takiuchi Shin, Kawano Yuhei, Fukagawa Masafumi
Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
Am J Hypertens. 2008 Jun;21(6):650-6. doi: 10.1038/ajh.2008.29. Epub 2008 Mar 20.
Despite the frequent simultaneous presentation of cardiac and renal dysfunction, the relationship between these pathophysiological processes remains unclear. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase, which has been linked to endothelial dysfunction and atherosclerosis. This study elucidates the relationship between ADMA and intrarenal and coronary microvascular diseases.
In this study, we included 66 consecutive hypertensive patients with normal renal function or mild renal insufficiency (creatinine <or= 1.2 mg/dl). On the basis of their estimated glomerular filtration rate (eGFR), the patients were divided into two groups (normal group, eGFR >or=90 ml/min; renal insufficiency group, eGFR <90 ml/min). Coronary flow velocity reserve (CFVR) was measured using adenosine-triphosphate stress transthoracic Doppler echocardiography. In addition, a plasma ADMA assay, echocardiography, carotid ultrasound, and brachial-ankle pulse wave velocity measurement were performed.
The plasma ADMA level was the highest in patients with both renal insufficiency and reduced CFVR. ADMA was significantly associated with eGFR (r = -0.342, P = 0.006) and CFVR (r = -0.459, P < 0.001), and eGFR and CFVR were significantly associated with each other (r = 0.337, P = 0.006). Multiple regression analysis revealed that ADMA was an independent clinical parameter associated with both eGFR and CFVR.
Plasma ADMA is suggested to be an incipient biochemical marker of microvascular disease in both kidney and heart in hypertensive patients. ADMA might play an important role in the pathogenesis of organ damage in the kidney and heart in essential hypertension.
尽管心脏和肾脏功能障碍经常同时出现，但这些病理生理过程之间的关系仍不清楚。不对称二甲基精氨酸（ADMA）是一氧化氮（NO）合酶的内源性抑制剂，与内皮功能障碍和动脉粥样硬化有关。本研究阐明了ADMA与肾内和冠状动脉微血管疾病之间的关系。
在本研究中，我们纳入了66例连续的肾功能正常或轻度肾功能不全（肌酐≤1.2mg/dl）的高血压患者。根据他们的估计肾小球滤过率（eGFR），将患者分为两组（正常组，eGFR≥90ml/min；肾功能不全组，eGFR＜90ml/min）。使用三磷酸腺苷负荷经胸多普勒超声心动图测量冠状动脉血流储备（CFVR）。此外，还进行了血浆ADMA检测、超声心动图、颈动脉超声和臂踝脉搏波速度测量。
肾功能不全且CFVR降低的患者血浆ADMA水平最高。ADMA与eGFR（r = -0.342，P = 0.006）和CFVR（r = -0.459，P＜0.001）显著相关，且eGFR和CFVR相互之间也显著相关（r = 0.337，P = 0.006）。多元回归分析显示，ADMA是与eGFR和CFVR均相关的独立临床参数。
血浆ADMA被认为是高血压患者肾脏和心脏微血管疾病的早期生化标志物。ADMA可能在原发性高血压患者肾脏和心脏器官损伤的发病机制中起重要作用。
