aHUS Triggered by Pregnancy Similar to Other Forms, Triggers

Atypical hemolytic uremic syndrome (aHUS) that is triggered by pregnancy is similar to aHUS caused by other triggers, and responds similarly to treatment, a new study suggests.

The study, “Pregnancy-triggered atypical hemolytic uremic syndrome (aHUS): a Global aHUS Registry analysis,” was published in the Journal of Nephrology. It was funded by Alexion Pharmaceuticals.

aHUS is caused by the abnormal activation of part of the immune system called the complement cascade. While genetic mutations can predispose individuals toward developing aHUS, they alone do not cause the disease. In almost all cases, a trigger event, like an infection, also is needed.

It is well-established that pregnancy can act as a trigger for aHUS. However, it is not yet clear how aHUS triggered by pregnancy compares to aHUS associated with other triggers.

In the new study, an international team of researchers conducted a series of analyses to compare the two disease entities using data from the Global aHUS Registry (NCT01522183).

“The objective of this study was to use Global aHUS Registry data to compare the clinical characteristics and renal outcomes, with and without eculizumab [Soliris] treatment, in women with [pregnancy-triggered] aHUS with those in women of childbearing age with aHUS but without identified triggers,” the researchers wrote.

The team identified 51 women in whom aHUS had been triggered by pregnancy (p-aHUS). Among these patients, more than half (54.9%) first experienced symptoms while pregnant; the rest (45.1%) first developed symptoms after giving birth.

In all but one of these women, the pregnancy that triggered aHUS was the first time they had been pregnant.

Researchers also identified 397 women of childbearing age in whom aHUS had been triggered by other factors (non-p-aHUS). In total, 33 of these women had been pregnant at some point, but the pregnancy had not been documented as a trigger for the disease. In 18 of them, the pregnancy occurred before the onset of aHUS symptoms.

Most demographic and clinical characteristics were comparable between the p-aHUS and non-p-aHUS groups. For example, average age at diagnosis was about 30 years, and just more than 40% of the women in both groups had a clearly identifiable cause of aHUS (i.e., an underlying genetic mutation affecting complement activity).

Outcomes and treatments also were generally similar between the two groups.

A few notable differences were highlighted. For instance, the average time from initial symptom manifestation to diagnosis was shorter for women with p-aHUS (0.5 months) than for those with non-p-aHUS (4.5 months).

Notably, about half of the patients in both groups were treated with Soliris (eculizumab), an approved aHUS treatment developed by Alexion that works by blocking complement activation.

In both p-aHUS and non-p-aHUS groups, treatment with Soliris significantly reduced the risk of end-stage renal (kidney) disease, a condition in which the kidneys are no longer able to function properly.

Soliris treatment also improved kidney function in both groups. Broadly, responses to treatment with Soliris were comparable in p-aHUS and non-p-aHUS.

“Our results showed that both groups were similar in several demographic and clinical characteristics, as well as in their response to [Soliris],” the researchers wrote.

“Similarity in response [to Soliris treatment] indicates similar disease pathophysiology [biological disease processes] in p-aHUS and aHUS not associated with identifiable triggers,” they wrote.

Among p-aHUS patients, rates of pregnancy complications were generally fairly high. For example, more than half (54.9%) of p-aHUS patients had preeclampsia, a condition characterized by high blood pressure accompanied by liver and kidney damage. About a third (33.3%) of p-aHUS patients had a particular severe type of preeclampsia, called HELLP syndrome.

Notably, rates of these complications did not vary significantly based on whether or not women had been treated with Soliris.