Doctors are overlooking an important test that could reduce hypertension and thus deaths in these patients.
One in three systemic lupus erythematosus patients should be tested for primary aldosteronism, but only a tiny fraction are, new Australian research suggests.
Treating primary aldosteronism could reduce hypertension and cardiovascular disease in these patients, which is a major cause of morbidity and mortality.
“Primary aldosteronism is the most common endocrine cause of secondary hypertension, with an estimated prevalence between 5% and 14% of patients with hypertension in primary care,” Associate Professor Jun Yang, co-author and Melbourne endocrine hypertension expert, and colleagues wrote.
“Yet, the diagnostic rate around the world is probably less than 1% of people who have the disease,” she told Rheumatology Republic.
The study followed around 300 adults at the Lupus Clinic at Monash Health in the past decade, who had lupus for an average of six years.
They found that around one in three participants had at least one indication for primary aldosterone testing, and around half of these had multiple indications.
Yet of the patients with at least one indication, only one in 10 were tested with plasma aldosterone to renin ratio (ARR).
Among the group who were tested, 80% were taking medications that could cause false-negatives on the ARR test, such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin II-receptor antagonists and dihydropyridine calcium channel blockers.
One in 10 tested positive on the ARR, which was defined as a result of >70pmol/L:mU/L, and half didn’t quite meet that criteria but were rated as suspicious.
“Current guidelines do not consider glucocorticoids as an interfering medication, but six of the 10 patients were taking prednisolone, including four on a daily dose of 15mg or greater,” the authors wrote.
Another seven patients were tested despite not meeting the Endocrine Society’s criteria, and two tested positive. No specific follow-ups were recorded for patients with positive or suspicious results.
Low rates of testing could have been because doctors considered primary aldosteronism to be a “rare” disease, Professor Yang said. But there may also be a lack of awareness about guideline recommendations for testing.
“Specific to this cohort, the potential attribution of hypertension to factors such as glucocorticoid use or lupus nephritis, and hypokalaemia to renal tubular acidosis or lupus nephritis with idiopathic hypokalaemia, may have allowed endocrine causes to be overlooked,” the authors wrote.
But there were also logistical barriers, with guidelines recommending patients cease medications that could potentially interfere with ARR testing – which included most conventional hypertensives.
Professor Yang said ARR testing could still be useful even in patients on these drugs, as a low or normal result for renin concentrations should trigger further investigation if those medications were known to increase renin concentrations.
New international guidelines are expected in July this year which will recommend screening all hypertension patients for primary aldosteronism.
However, more advice was needed for testing in patients with interfering medications, and guidance on how to interpret borderline results, said Professor Yang.
Co-author and rheumatologist Dr Fabien Vincent, researcher at Monash Health, said he hoped greater awareness and testing would allow for patients with primary aldosterone to be treated earlier, when they were on fewer interfering medications.
Treatments included aldosterone-blocking medications and adrenal gland removal, which could reduce blood pressure and cardiovascular risk. Spironolactone was one example, and more drugs were under development, he said.
Cardiovascular disease is a leading cause of death in lupus patients, who are at a two- or threefold higher risk than their healthy peers, and hypertension is present in up to 77% of these patients, the authors said.
Professor Yang pointed to the potentially massive improvement to quality of life, using the example of her father with previously uncontrolled hypertension who was treated for primary aldosteronism and dropped from four hypertensive medications to half a tablet daily and now has “perfect” blood pressure control.
While there was scant research on the prevalence of primary aldosteronism in lupus patients or its pathophysiology, hypertension was thought to relate to renal impairment, glucocorticoid treatment, chronic inflammation and/or disruption of the renin-angiotensin-aldosterone system, the authors said.
