Experts make recommendations for aHUS management in adults

Guidance would aid doctors with less knowledge of the disease

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A team of five experts from across Spain got together to reach a consensus on a set of recommendations for how to best manage atypical hemolytic uremic syndrome (aHUS) in adults.

The consensus offers guidance for doctors with less experience in managing the disease. It covers the entire patient journey, from clinical suspicion to initiation and discontinuation of treatment with C5 inhibitors, the only medications approved for use in aHUS.

“The experts who participated advocate early treatment, maintenance for at least 6–12 months and treatment interruption guided by genetic background, trigger factors, risk of relapse and evolution,” the team wrote.

The recommendations were described in the study “Recommendations for the individualised management of atypical hemolytic uremic syndrome in adults,” which was published in Frontiers in Medicine.

aHUS occurs when an overly active complement system causes inflammation and blood clots in small blood vessels, especially those in the kidneys. The complement system is a part of the immune system that normally helps the body fight infection and remove damaged cells.

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Treatment specialized to the patient’s needs

While the disease is most often caused by mutations, its symptoms usually appear following a trigger event, for example, an infection. Because aHUS may not look the same for every patient, treatment should be tailored to address individual needs.

The C5 inhibitors Soliris (eculizumab) and Ultomiris (ravulizumab), which work by blocking the C5 complement protein, improve the prognosis of aHUS patients and have become the cornerstone of treatment for the disease.

But despite therapeutic advances, “guidelines are not timely updated and achieving a consensus on management recommendations remains a topic of ongoing discussion,” the researchers wrote.

To reach a consensus on general and patient-specific recommendations for managing aHUS, a scientific committee of five aHUS experts, all specialized in kidney care, reviewed the available literature from 2012-2022 and selected relevant publications about treatment approaches.

Potential recommendations for treatment initiation, monitoring, discontinuation, and post-discontinuation follow-up were proposed at an initial online meeting. General and patient-specific recommendations were evaluated by all committee members in the form of a two-part online questionnaire, and validated during a second meeting.

According to the general recommendations, patients with a clear suspicion or a confirmed diagnosis of aHUS should be treated with first-line C5 inhibitors within 24 hours of the clinical suspicion.

Treatment with C5 inhibitors should be maintained for at least six to 12 months, including at least three months of treatment after kidney function has returned to normal or remained stable. Patients at a high risk of relapse may need longer treatment.

However, treatment should be stopped before six months in patients who develop a severe infection or an allergic reaction to the medication as well as in those who fail to respond or are undergoing dialysis to replace kidney function without worsening aHUS.

Those not carrying disease-causing mutations in complement genes and showing either kidney function recovery or stability over the past three months or no severe manifestations outside the kidneys may also discontinue treatment before six months.

“The duration of treatment with C5 inhibitors, as well as when it should be interrupted, depends on the mutation and the trigger factors of aHUS and must be individualised according to each patient’s risk and evolution,” the team wrote.

They noted that while “the use of biomarkers for monitoring is currently difficult,” measuring the levels of certain complement proteins in the blood or urine may provide relevant information regarding kidney function. After discharge, patients should be monitored weekly to monthly for six months.

“Biomarkers should be widely available in routine clinical practice in the future,” the team wrote. However, “further research is needed to identify the optimal biomarkers for monitoring treatment,” they noted.

After treatment discontinuation, patients should be closely monitored and treatment should be immediately restarted in case of relapse. Also, the experts agreed patients should be aware of the warning signs and symptoms of a potential relapse.

Recommendations for 6 specific patient profiles provided

The team also provided recommendations for six specific patient profiles. For example, patients carrying mutations in complement genes or with aHUS associated with pregnancy should be treated for at least six to 12 months.

Those with aHUS associated with a kidney transplant should be treated until kidney function has recovered, as long as disease-causing mutations are not detected. Also, patients whose disease is linked to a non-kidney transplant, medications, or an autoimmune disease or infection should be treated until signs of aHUS have disappeared, unless mutations are identified.

“Although it is currently difficult to confirm the diagnosis in advance and to begin treatment with certainty, early initiation is always recommended in case of clinical suspicion of aHUS,” the team wrote, adding “treatment duration must be individualised according to [a] patient’s risk and evolution.”