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Kidney Week

Abstract: FR-PO1058

Chronotherapy of Renin-Angiotensin System (RAS) Inhibitor Ameliorates Renal Damage via Suppression of Intrarenal RAS Activity

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Aoki, Taro, Hamamatsu University School of Medicine, Hamamatsu, SHIZUOKA, Japan
  • Ohashi, Naro, Hamamatsu University School of Medicine, Hamamatsu, SHIZUOKA, Japan
  • Isobe, Shinsuke, Hamamatsu University School of Medicine, Hamamatsu, SHIZUOKA, Japan
  • Ishigaki, Sayaka, Hamamatsu University School of Medicine, Hamamatsu, SHIZUOKA, Japan
  • Matsuyama, Takashi, Hamamatsu University School of Medicine, Hamamatsu, SHIZUOKA, Japan
  • Fujikura, Tomoyuki, Hamamatsu University School of Medicine, Hamamatsu, SHIZUOKA, Japan
  • Kato, Akihiko, Hamamatsu University School of Medicine, Hamamatsu, SHIZUOKA, Japan
  • Yasuda, Hideo, Hamamatsu University School of Medicine, Hamamatsu, SHIZUOKA, Japan
Background

We have shown that intrarenal RAS with chronic kidney disease (CKD) patients is activated and that intrarenal RAS activity contributes to blood pressure (BP) elevation, abnormal circadian rhythm of BP and renal damage. Moreover, changing the administration time of RAS inhibitors from morning to evening, namely chronotherapy, decreases BP and ameliorates renal damage during nighttime. However, it has not been clarified whether chronotherapy changes intrarenal RAS activity and the change of intrarenal RAS activity by chronotherapy reflects the change of BP and renal damage.

Methods

We recruited 34 CKD patients who took RAS inhibitors in the morning (sex: 22 males / 12 females, age: 60.2±19.4 years, estimated glomerular filtration rate (eGFR): 34.8±30.8 ml/min/1.73 m2). We collected urine during daytime and nighttime, respectively, and evaluated urinary albumin (U–Alb) and urinary angiotensinogen (U–AGT), a surrogate marker for intrarenal RAS activity. Ambulatory BP monitoring was conducted at 30–min intervals during the daytime and nighttime. Thereafter, the same experiments were made after 4.1±0.5 days from change of the administration time. The ratios of clinical parameters morning dosing against evening dosing were defined as M/E ratio.

Results

The excretion levels of U–Alb and U–AGT during daytime and nighttime were significantly decreased by chronotherapy in all CKD patients. M/E ratio of U–Alb had significant and positive relationships with M/E ratio of U–AGT.
Moreover, there were significant and positive relationships between M/E ratio of U–Alb and U–AGT during nighttime (β=0.73 and p=0.005), but not daytime (β=0.39 and p=0.098) in the CKD patients whose eGFR is less than 45 ml/min/1.73m2. In addition, significant and positive relationships were found between M/E ratio of U–Alb and U–AGT during nighttime (β=1.04 and p <0.001), but not daytime (β=0.52 and p=0.074) in the CKD patients who have nondipper or riser patterns when the night–to–day ratio of systolic BP is 0.90–1.00 or >1.00, respectively.

Conclusion

The present study indicated that chronotherapy of RAS inhibitor improved renal damage via intrarenal RAS suppression in CKD patients. This effect was more remarkable in patients with highly impaired renal function and nocturnal hypertension.