Naples, Italy - Switching the dose of one antihypertensive medication from morning to night helps restore circadian rhythm to blood pressure in patients with chronic kidney disease, a new study shows [1].

"This approach is simple but very important, because it limits the phenomenon of 'nondipping' blood pressure at night, which is a well-defined risk factor for progression of kidney disease and development of cardiovascular complications," says lead author Dr Roberto Minutolo (Second University of Naples, Italy).

The study is published in the December 2007 issue of the American Journal of Kidney Diseases. The authors explain that in healthy individuals, blood pressure drops by at least 10% at night and that lack of such a nighttime decrease (known as nondipping) is associated with enhanced cardiovascular morbidity and mortality in the general population and patients with hypertension. Nondipping status, which is highly prevalent in patients with chronic kidney disease because of the typically high sodium sensitivity of these individuals, influences cardiovascular outcome in this population and is associated with a greater risk of end-stage renal disease, suggesting that normalization of circadian rhythm should be strongly pursued in these patients, they add.

They conducted a pilot study to test whether shifting one antihypertensive drug from morning to evening hours restores the normal circadian rhythm in nondipping patients with chronic kidney disease.

The study involved 32 chronic kidney disease patients who were nondippers—defined as having a night-to-day ratio of mean ambulatory blood pressure greater than 0.9. Participants were on an average of 2.4 antihypertensive drugs. One antihypertensive medication in each patient was shifted from morning to evening, and patients were followed for eight weeks. After the drug shift, the night-to-day ratio of mean ambulatory blood pressure decreased in 28 of the patients (93.7%), and normal circadian rhythm was restored in 87.5%. The nocturnal blood-pressure decrease was not associated with an increase in daytime pressure and occurred regardless of the number of antihypertensive drugs administered or which class of drug was moved, suggesting that it is brought about by better pharmacokinetics of the drugs, Minutolo et al say.

The shift to evening dosing was also associated with a significant decrease in proteinuria, which the authors point out is important, because a decrease in proteinuria in the short term predicts better renal and cardiovascular prognosis in the long term.

They conclude: "This simple intervention therefore may be considered as an additional tool to decrease the risk of cardiovascular disease in patients with chronic kidney disease. Whether changing the timing of therapy could be effective in decreasing the progression of cardiovascular and renal disease must be verified in larger studies that involve patients with chronic kidney disease with uncontrolled hypertension."

Minutolo believes that shifting at least one antihypertensive drug to the evening should be recommended to all nondipper patients. "This is an easy maneuver that hasn't specific contraindications," he told heartwire. He added, however, that he would not advise all hypertensive patients to take their medication at night without an ambulatory blood-pressure measurement, because this might expose those with a normal dip in blood pressure during the night to a higher cardiovascular risk. "Physicians must bear in mind primum non nocere, even though we all know that actually there is a large but so far undefined portion of the hypertensive population that may [benefit] from a drug shift. Therefore, the message is to check 24-hour blood pressures, at least in patients carrying the highest risk of nondipping (older, diabetic, and black patients and those with chronic kidney disease)," he commented.