Inspra (eplerenone) is an aldosterone inhibitor, marketed by Pfizer, that is used to treat high blood pressure and congestive heart failure after a heart attack.

In Alport syndrome patients, Inspra is used to lower blood pressure and to treat proteinuria (protein in the urine). It is essential to control blood pressure in Alport patients, as high blood pressure damages the kidneys, organs that are affected by this disease. Inspra is recommended as a second-line treatment for Alport in combination with angiotensin-converting-enzyme (ACE) inhibitors.

How Inspra works

Inspra blocks the effect of a hormone called aldosterone that works to promote the retention of sodium and chloride ions. A higher concentration of sodium chloride or salt in the blood leads to an increase in the volume of the blood, causing a rise in blood pressure. Aldosterone also stimulates the excretion of potassium.

Aldosterone works by binding to so-called mineralocorticoid receptors in the kidney. Inspra blocks aldosterone’s action by binding to these receptors itself. As a consequence, the excretion of sodium chloride and water increases and potassium is retained, helping to lower blood pressure.

Independently of their effects on blood pressure, aldosterone inhibitors such as Inspra also decrease the glomerular filtration rate, or the amount of blood that passes through the kidneys every minute, thereby reducing proteinuria.

Inspra in clinical trials

Inspra has not been tested in randomized clinical trials specifically in Alport syndrome patients. However, a study in patients with chronic kidney disease assessed Inspra’s value as add-on therapy to blood-pressure-lowering medications.

The Phase 4 clinical trial (NCT00430924) included 40 people with different baseline treatments: 23 were taking ACE inhibitors, eight were using angiotensin receptor blockers (ARBs), and seven were taking ACE inhibitors and ARBs. Some patients were also using blood-pressure-lowering medications, such as beta blockers, calcium channel blockers, and furosemide. Only two patients were not taking ACE inhibitors or ARBs.

Participants were randomized to start either with an eight-week control period with only baseline treatment, followed by an eight-week period of taking Inspra in addition to their baseline treatment, or vice versa. An daily oral dose of 25 mg of Inspra was given the first week, increasing to 50 mg for the next seven weeks.

In 31 of the 40 patients, results showed that Inspra treatment lowered albuminuria (presence of albumin protein in the urine) by a statistically significant 22 percent overall. This treatment response was independent of the dose of ARBs or ACE inhibitors that patients were taking. Those on combined ARB and ACE inhibitor treatment, however, had no significant drop in albuminuria  levels while being treated with Inspra.

The blood pressure of the patients significantly decreased during Inspra treatment. Doses of ARBs or ACE inhibitors did not influence this reduction.

Additional information

Because Inspra increases the retention of potassium, potassium-rich foods such as salt substitutes, dairy products, nuts, and certain fruits and vegetable should be avoided while taking this medication.

Inspra can be dangerous for individuals with kidney disease. Alport syndrome patients should be carefully monitored when using this medication.

Common side effects of Inspra include high levels of cholesterol and triglycerides (another type of fat) in the blood.

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