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A simple urine test might help clinicians figure out whether their patients aren't responding to antihypertensive therapy because of true resistance or because of nonadherence, a small study suggested.

Among patients evaluated at a hypertension clinic, 25% were at least partially nonadherent to their antihypertensive regimens based on the results of a urine-based assay that detected the 40 most commonly prescribed medications, according to , of the University of Leicester in England, and colleagues.

Nonadherence was associated with higher blood pressure, with the most dramatic differences seen when comparing those who were totally nonadherent -- no prescribed drugs detected in their urine -- with those who were adherent, the researchers reported online in .

"Screening for nonadherence to antihypertensive treatment by high-performance liquid chromatography-tandem mass spectrometry-based urine analysis is a simple, noninvasive diagnostic test with a potential to better stratify patients prior to treatment escalations and expensive and irreversible procedures such as renal denervation," they wrote.

But cost could be an issue. Although each urine test costs only about 30 British pounds ($50 U.S.), the analyzer itself costs about 150,000 British pounds (about $250,000 U.S.).

"Future large multicenter studies will be needed to provide estimates of direct biochemical nonadherence to treatment in other populations and evaluate the cost-effectiveness of this screening method in the context of overall expenditure for management of resistant hypertension," the authors wrote.

The degree of adherence to drug therapies influences the control of multiple chronic health conditions, including hypertension, and poor adherence might account for at least some of the 10% to 20% of patients with hypertension who are considered resistant to therapy.

There are, however, no reliable ways to measure adherence to antihypertensives, reflected by the wide range of reported rates of poor adherence (3% to 65%).

Tomaszewski and colleagues assessed the ability of high-performance liquid chromatography-tandem mass spectrometry-based urine analysis to identify nonadherence in patients being evaluated in a specialist hypertension clinic. The study included 208 patients (mean age 57), of whom 125 were new referrals from primary care, 66 were follow-up patients who had inadequately controlled blood pressure, and 17 were being considered for renal denervation.

The urine tests revealed that 10.1% of the patients had no traces of any of their prescribed antihypertensives (totally nonadherent) and 14.9% were taking only some of their antihypertensives (partially nonadherent).

The combined rate of total or partial nonadherence was highest for those coming in for follow-up visits for inadequate blood pressure control (37.9%).

There also was an "alarmingly high" rate of total nonadherence detected in patients who were being considered for renal denervation (23.5%).

"A majority of these patients in any secondary/tertiary care center would routinely undergo many additional tests and procedures in search of the explanation for their apparent unresponsiveness to standard therapy prescribed by primary care," the researches pointed out. "Our data suggest that in 20% of such patients, these investigations (along with follow-up appointments and exposure to unnecessary additional treatment) could be potentially avoided if ... urine analysis was used as a routine screening for nonadherence."

, of the University of Cambridge -- who said the rate of nonadherence among patients who were being evaluated as candidates for renal denervation was a "shock" -- detailed the consequences of placing the "resistant" tag on a patient with hypertension, including more drug prescriptions, doctor visits, referrals to specialists, tests, and interventions, as well as the accompanying increases in cost.

"The consequences become most serious when an intervention is ineffective and irreversible, and this unfortunately now seems to be the case for renal denervation," he wrote in an accompanying editorial, pointing to the failure of the SYMPLICITY HTN-3 trial.

He further described the challenges of assessing whether a patient is taking his or her medication, and said that "[the current findings], and the enabling comprehensive mass spectrometry assay for all commonly used antihypertensive drugs, solve at a stroke the problem of monitoring adherence and should rapidly transform practice."

"No longer need we guess whether patients have resistant hypertension," Brown wrote. "We can know."

Tomaszewski and colleagues acknowledged some limitations of their analysis, including missing 24-hour blood pressure readings for about a quarter of the patients, the small number of renal denervation candidates, the use of a single spot urine analysis, the potential for bias from unmeasured confounders, and the lack of information on indirect measures of non-adherence against which the results of the urine test could be compared.

From the American Heart Association:

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