Bradykinin, and Treatments Targeting It, Linked to Emergency Angioedema Cases in Study

Angioedema patients in need to emergency care — being treated at a hospital’s emergency department — most often had an attack linked to bradykinin and medications that target this inflammatory molecule, a study from Croatia reports.

Such medications, called RAAS blockers, can be used to treat cardiovascular and kidney diseases.

The study, “The Incidence and Frequency of Various Causes of Angioedema in Emergency Medicine,” was published in the journal Clinical Science

Angioedema is a temporary and localized, but potentially severe, swelling of the lower layer of skin and tissue just below the skin or mucous membranes. The two main causes of attacks are associated with two biological molecules — histamine and bradykinin.

Histamine is an inflammatory molecule produced by our bodies in response to allergy triggers — insect bites, certain foods, medications – and can cause angioedema to develop.

Bradykinin, also an inflammatory mediator, causes blood vessels to dilate. Bradykinin-induced angioedema can be hereditary — including hereditary angioedema types 1 and 2 — or non-hereditary.

Medications can also cause bradykinin-induced angioedema. This is particularly true of those that block the renin-angiotensin-aldosterone system (RAAS) — which regulates kidney blood flow and blood pressure — to prevent bradykinin from degrading. High levels of bradykinin can build in a person, leading to angioedema.

Researchers set out to determine the incidence and the causes of angioedema among patients treated at hospitals on an  emergency basis. They focused on the frequency and treatment of bradykinin-induced attacks.

This study, conducted retrospectively, included 237 patients treated at two hospitals Croatia between 2009 and 2016. Patients were divided into two groups — A or B — depending on which hospital were treated at.

Data collected  included the location and duration of angioedema, other chronic diseases and their treatment, and potential triggers for inflammation (food, medications, insect bites, and chemicals). Researchers also conducted a physical examination and recorded which treatment was administered.

No statistically significant differences regarding age or comorbidities (co-occurring diseases) were seen between the two groups, but the respective causes of their angioedema attacks did differ in statistically significant ways. In both groups, however, a bradykinin-induced attack was the leading cause of emergency treatment.

Most group A patients (37.5%  of all treated at Merkur Clinical Hospital, in Zagreb) had an angioedema attack caused by RAAS  system inhibitors.

In group B, two different types of bradykinin-induced attacks — hereditary angioedema and RAAS blockers — were the leading causes of emergency treatment — 31.5% of all patients treated at Šibenik General Hospital in Šibenik.

RAAS blockers are the cornerstone of therapy for cardiovascular and kidney disease, and as their incidence has risen over the past decade, so has the use of RAAS blockers.

“In recent years, the growth of the use of RAAS blockers has resulted in an increased prevalence of angioedema,” the researchers noted. Patients they studies with RAAS-blocker-induced angioedema  also had several comorbidities.

Other causes in both groups included insect bites, use of antibiotics or analgesics, gastroesophageal reflux disease, and neoplasms (an abnormal growth of tissue, characteristic of cancer). Others had angioedema of unknown cause.

“Bradykinin-mediated AE was the main cause of emergency attendance associated with AE,” the researchers concluded.

Mild angioedema cases linked to RAAS blocker use responded to treatment with antihistamines or corticosteroids, but moderate and severe cases did not. “[This] emphasizes the need for new therapeutic solutions, especially when the patient’s airway is compromised,” the team added.