Changing the Timing of Antihypertensive Therapy to Reduce Nocturnal Blood Pressure in CKD: An 8-Week Uncontrolled Trial

Background

Nondipping status is associated with greater cardiovascular morbidity and mortality and faster progression of chronic kidney disease (CKD). We examined whether shifting 1 antihypertensive drug from morning to evening restores the circadian rhythm of blood pressure in nondipper patients with CKD.

Study Design

8-week clinical trial without a control group.

Setting & Participants

We selected from our outpatient renal clinic 32 patients with CKD with estimated glomerular filtration rate less than 90 mL/min/1.73 m² and night-day ratio of mean ambulatory blood pressure (ABP) greater than 0.9, but with normal daytime ABP (<135/85 mm Hg) to avoid the required therapy intensification.

Intervention

Shifting 1 antihypertensive drug from morning to evening.

Outcomes

Percentage of patients changing the night-day ratio of mean ABP from greater than 0.9 to 0.9 or less 8 weeks after the shift.

Measurements

Office blood pressure/ABP and proteinuria at baseline and after the shift.

Results

There were 55% men with a mean age of 67.4 ± 11.3 years and estimated glomerular filtration rate of 46 ± 12 mL/min/1.73 m². They were treated with 2.4 ± 1.4 antihypertensive drugs. After the drug shift, the night-day ratio of mean ABP decreased in 93.7% of patients, with normal circadian rhythm restored in 87.5%. The nocturnal systolic and diastolic ABP decrease was not associated with an increase in diurnal ABP and was independent from number and class of shifted drug. Office blood pressure in the morning also decreased (from 136 ± 16/77 ± 10 to 131 ± 13/75 ± 8 mm Hg; P = 0.02). Urinary protein excretion decreased from 235 ± 259 to 167 ± 206 mg/d (P < 0.001).

Limitations

Absence of a control group and patients with severe proteinuria or uncontrolled daytime ABP.

Conclusions

In nondipper patients with CKD, changing the timing of antihypertensive therapy decreases nocturnal blood pressure and proteinuria.

Index Words: Ambulatory blood pressure monitoring, chronic kidney disease, circadian rhythm, chronotherapy, nondipper status