In addition, such chronotherapeutic effects were not detected for olmesartan in the animal study. Based on these animal

data, we speculated that the protective effect of valsartan (but not olmesartan) against hypertension-induced organ damage differs between morning and evening dosings. In this study, a non-dipper BP pattern was corrected in 64% of the patients in the valsartan-E group, and therefore, we anticipated that renal function might be improved after switching from morning to evening dosing. However, INK1197 datasheet serum creatinine did not significantly decrease or eGFR did not significantly increase at 4 months after switching the dose regimen in the valsartan-E group. Elevated night-time BP (especially SBP) (5) and (22) and a non-dipper BP pattern (23) are potent risk factors for declines in GFR. However, whether a reduction of night-time BP or a dipper BP pattern can be a therapeutic NVP-BKM120 target to prevent progression of renal disease should still be better defined (6). After switching from morning to evening dosing, SBP slightly decreased during sleep and slightly increased during waking hours in the valsartan-E group, and consequently, the dipping state was improved in this group (64%). On the other hand, dipper BP patterns were detected in 46% of patients in the olmesartan-M group and in 42% of patients in the olmesartan-E

group.

However, in contrast to the valsartan-E group, serum creatinine decreased and eGFR increased in the olmesartan-M and-E groups. SBP during sleep significantly decreased in the olmesartan-M and olmesartan-E groups. In addition, a positive correlation between SBP during sleep and serum creatinine, and a negative correlation between SBP during sleep and the eGFR were detected. Based on these data, it is speculated that, although a dipper BP pattern was obtained in many patients in the valsartan-E group, BP reduction at night was too small to improve renal function under the present condition, ADAMTS5 which is comparable with the idea that a reduction of night-time BP rather than a dipper BP pattern is more adequate target to prevent progression of renal disease. Hermida et al. reported that the dosing of valsartan at bedtime reduced BP during sleep and improved renal function in hypertensive patients (12), findings which were different from those in this study. However, the daily dose of valsartan was 160 mg in their study and 40–80 mg in this study, which could have caused the diverse chronotherapeutic effects of valsartan. Therefore, whether the chronotherapeutic effects of valsartan are altered by the dose of the drug remains to be determined. The number of patients was relatively small in this study, which might lead to an incorrect conclusion.