Isobe Shinsuke, Ohashi Naro, Fujikura Tomoyuki, Tsuji Takayuki, Sakao Yukitoshi, Yasuda Hideo, Kato Akihiko, Miyajima Hiroaki, Fujigaki Yoshihide
Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, 431-3192, Japan.
Clin Exp Nephrol. 2015 Apr;19(2):231-9. doi: 10.1007/s10157-014-0973-2. Epub 2014 Apr 12.
The intrarenal renin-angiotensin system (RAS) plays an important role in the development of hypertension and renal damage. Disruption of diurnal blood pressure (BP) variation is an additional risk factor for renal damage. However, little is known regarding whether intrarenal RAS circadian rhythm exists or if it influences the disruption of diurnal BP and renal damage.
We investigated the circadian rhythm of urinary angiotensinogen (U-AGT) that reflects intrarenal RAS activity in 14 individuals without chronic kidney disease (CKD) and 36 CKD patients classified according to circadian BP rhythms.
BP values were higher during the daytime than during the nighttime in both individuals without CKD and CKD patients. U-AGT levels were not different between the daytime and nighttime in individuals without CKD, but were significantly higher in the daytime in CKD patients (log U-AGT/creatinine: daytime, 2.39 ± 0.99; nighttime, 2.24 ± 1.06; p = 0.001). Furthermore, in CKD patients showing a riser pattern of circadian BP, U-AGT levels did not decrease during the nighttime compared with those in the daytime (log U-AGT/creatinine: daytime, 2.51 ± 0.65; nighttime, 2.52 ± 0.71; p = 0.78). Circadian fluctuation of albuminuria and proteinuria occurred parallel to that of the U-AGT levels. U-AGT levels were significantly and positively correlated with the levels of BP and circadian fluctuation of U-AGT was correlated with diurnal BP changes.
These data suggest that the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which are associated with diurnal BP variation.
肾内肾素-血管紧张素系统（RAS）在高血压和肾损害的发生发展中起重要作用。昼夜血压（BP）变化紊乱是肾损害的另一个危险因素。然而，关于肾内RAS昼夜节律是否存在，或者它是否影响昼夜BP紊乱和肾损害，目前知之甚少。
我们调查了14名无慢性肾脏病（CKD）个体以及36名根据昼夜BP节律分类的CKD患者中反映肾内RAS活性的尿血管紧张素原（U-AGT）的昼夜节律。
无CKD个体和CKD患者的BP值均白天高于夜间。无CKD个体的U-AGT水平在白天和夜间无差异，但CKD患者白天的U-AGT水平显著更高（U-AGT/肌酐对数：白天，2.39±0.99；夜间，2.24±1.06；p = 0.001）。此外，在呈现昼夜BP上升模式的CKD患者中，U-AGT水平夜间与白天相比未降低（U-AGT/肌酐对数：白天，2.51±0.65；夜间，2.52±0.71；p = 0.78）。蛋白尿和蛋白尿的昼夜波动与U-AGT水平的波动平行。U-AGT水平与BP水平显著正相关，U-AGT的昼夜波动与昼夜BP变化相关。
这些数据表明，肾内RAS激活的昼夜节律可能导致肾损害和高血压，这与昼夜BP变化有关。
