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Disturbed circadian rhythm of the intrarenal renin-angiotensin system: relevant to nocturnal hypertension and renal damage

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgements

This study was supported by grants from the Salt Science Research Foundation (Awarded to Naro OHASHI, no. 1230) and Young Investigator Research Projects of Hamamatsu University School of Medicine in 2011 (Awarded to Naro OHASHI) and in 2012 (Awarded to Naro OHASHI and Shinsuke ISOBE).

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Authors and Affiliations

  1. Internal Medicine 1, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, 431-3192, Japan

    Shinsuke Isobe, Naro Ohashi, Tomoyuki Fujikura, Takayuki Tsuji, Hideo Yasuda, Hiroaki Miyajima & Yoshihide Fujigaki

  2. Blood Purification Unit, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, 431-3192, Japan

    Yukitoshi Sakao & Akihiko Kato

  3. Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan

    Yoshihide Fujigaki

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  1. Shinsuke Isobe
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  2. Naro Ohashi
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  4. Takayuki Tsuji
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Correspondence to Naro Ohashi.

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Isobe, S., Ohashi, N., Fujikura, T. et al. Disturbed circadian rhythm of the intrarenal renin-angiotensin system: relevant to nocturnal hypertension and renal damage. Clin Exp Nephrol 19, 231–239 (2015). https://doi.org/10.1007/s10157-014-0973-2

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  • DOI: https://doi.org/10.1007/s10157-014-0973-2

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