Asymmetric dimethylarginine is a novel biomarker for CKD

不对称二甲基精氨酸（ADMA）在心血管疾病（CVD）和慢性肾脏疾病（CKD）的发病机制中起重要作用。我们最近发现ADMA是普通人群动脉粥样硬化的新标志物，在CKD动物模型中参与肾小球硬化和小管间质纤维化。然而，ADMA是否可以作为CVD或CKD患者肾损害严重程度的生物标志物尚不清楚。因此，我们研究了1)ADMA与1-5期CKD患者CVD替代标志物（如PWV和LVMI）之间的关系，以及2)109例活检证实的IgA肾病（IgAN）患者血浆ADMA水平是否与肾组织损伤的严重程度相关，并可能预测疾病进展。1)血浆ADMA水平随着CKD分期的进展而升高。逐步回归分析显示，年龄和eGFR是ADMA的独立决定因素。此外，ADMA水平与PVW和lvmi密切相关。2)IgAN患者的ADMA水平高于年龄、性别和平均egfr匹配的健康志愿者。ADMA水平与肾小球和小管间质损伤的严重程度相关。多元逐步回归分析显示，ADMA（而非蛋白尿）是我们受试者中eGFR年降低率评估的疾病进展的独立决定因素。本研究表明，ADMA不仅可以作为CVD的一种新的生物标志物，还可以作为CKD患者肾损伤进展的一种新的生物标志物。

Asymmetric dimethylarginine(ADMA) plays important roles in the pathogenesis of cardiovascular disease(CVD) as well as chronic kidney disease(CKD). We have recently found that ADMA is a novel marker for atherosclerosis in general population and is involved in glomerular sclerosis and tubulointerstitial fibrosis in an animal model of CKD. However, it is still unclear whether ADMA could be a biomarker for CVD or severity of renal damage in CKD patients remains unknown. So, we investigated 1) the relationship between ADMA and surrogate markers for CVD such as PWV and LVMI in patients with stage 1-5 CKD and 2) whether plasma levels of ADMA were associated with severity of the renal tissue damage and could be a predictor of the disease progression in 109 biopsy-proven IgA nephropathy(IgAN) patients.1) Plasma ADMA levels were increased as the CKD stage was progressed. Stepwise regression analysis revealed that age and eGFR were independent determinants for ADMA. Further, ADMA levels were strongly associated with PVW and LVMI.2) ADMA levels were higher in IgAN patients than age-, sex-and mean eGFR-matched healthy volunteers. ADMA levels were associated with the severity of glomerular and tubulointerstitial injury. Multiple stepwise regression analysis revealed that ADMA, but not proteinuria was an independent determinant for the disease progression assessed by annual reduction rates of eGFR in our subjects.The present study suggest that ADMA could be a novel biomarker for not only CVD but also progression of renal injury in CKD patients.