Fujii Hideki, Kono Keiji, Nakai Kentaro, Goto Shunsuke, Kitazawa Riko, Fukagawa Masafumi, Nishi Shinichi
Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
Division of Diagnostic Molecular Pathology, Kobe University Graduate School of Medicine, Kobe, Japan ; Division of Molecular Pathology, Ehime University Graduate School of Medicine, Toon, Isehara, Japan.
Nephron Extra. 2014 Feb 28;4(1):18-25. doi: 10.1159/000358886. eCollection 2014 Jan.
BACKGROUND/AIMS: The purpose of our study was to elucidate the relationship between asymmetric dimethylarginine (ADMA) and intrarenal lesions and to determine the effect of renin-angiotensin system inhibitors (RAS-Is) on serum ADMA levels, nitric oxide (NO) synthesis and oxidative stress in normotensive patients with chronic kidney disease (CKD).
This study included 23 normotensive patients with chronic glomerulonephritis and normal or mildly impaired renal function who underwent renal biopsy. We evaluated the relationship between serum ADMA levels and intrarenal lesions, and examined renal function, urinary protein excretion, ADMA levels, NO synthesis, oxidative stress and blood pressure (BP) before and 3 months after starting the treatment with RAS-Is.
Serum ADMA levels were correlated only with arterial intimal fibroplastic thickness. Despite comparable renal function and BP, serum ADMA levels and excretion of urinary protein excretion significantly decreased, and urinary NO metabolite excretion significantly increased after starting the treatment with RAS-Is. Oxidative stress markers also tended to be reduced by the treatment.
These findings suggest that RAS-Is improve the NO system and decrease oxidative stress in normotensive patients with CKD. In addition, ADMA may be associated with intrarenal lesions and can be a useful marker for the effects of treatment in the early stages of CKD.
背景/目的:我们研究的目的是阐明不对称二甲基精氨酸(ADMA)与肾内病变之间的关系,并确定肾素 - 血管紧张素系统抑制剂(RAS-Is)对慢性肾脏病(CKD)正常血压患者血清ADMA水平、一氧化氮(NO)合成及氧化应激的影响。
本研究纳入23例慢性肾小球肾炎且肾功能正常或轻度受损的正常血压患者,这些患者均接受了肾活检。我们评估了血清ADMA水平与肾内病变之间的关系,并在开始使用RAS-Is治疗前及治疗3个月后检查了肾功能、尿蛋白排泄、ADMA水平、NO合成、氧化应激及血压(BP)。
血清ADMA水平仅与动脉内膜纤维增生厚度相关。尽管肾功能和血压相当,但开始使用RAS-Is治疗后,血清ADMA水平及尿蛋白排泄显著降低,尿NO代谢产物排泄显著增加。氧化应激标志物也有因治疗而降低的趋势。
这些发现表明,RAS-Is可改善CKD正常血压患者的NO系统并降低氧化应激。此外,ADMA可能与肾内病变有关,并且可作为CKD早期治疗效果的有用标志物。