Delayed complement inhibition resolves pregnancy-related aHUS
Case report follows woman who developed symptoms of kidney damage
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Complement inhibitors helped a woman partially recover from atypical hemolytic uremic syndrome (aHUS) related to pregnancy despite a five-week delay in starting treatment, according to a case report.
Symptoms of kidney damage developed during the 29-year-old’s third trimester. As a result, the woman began regular hemodialysis, a procedure that helps filter blood when the kidneys aren’t able to do so. When symptoms didn’t resolve after an emergency cesarean section, her medical team performed tests and ultimately diagnosed aHUS. Several weeks after starting aHUS-specific treatment with complement inhibitors, the woman no longer required hemodialysis.
“Our case adds to the growing literature demonstrating that meaningful renal [kidney] recovery remains possible despite delayed initiation of therapy, reinforcing the need for continued diagnostic evaluation and therapeutic intervention even after the acute obstetric event has resolved,” researchers wrote.
The report, “Pregnancy-Associated Atypical Hemolytic Uremic Syndrome With Kidney Recovery Despite Delayed Initiation of Complement Blockade,” was published in Cureus Journal of Medical Science.
Complement inhibitors can help reduce aHUS disease activity
AHUS is a type of thrombotic microangiopathy (TMA), a group of diseases in which blood clots form in small blood vessels, blocking blood flow and leading to kidney damage. In aHUS, abnormal activity of the complement cascade, part of the immune system, causes blood clot formation and related symptoms. Although aHUS is often associated with genetic mutations, these mutations may remain silent until a triggering event occurs. Pregnancy is one type of trigger, because the complement cascade naturally becomes more active.
“The third trimester and postpartum period represent high-risk windows due to physiologic complement activation,” the researchers wrote.
However, other types of TMA can also occur during pregnancy, and it may be difficult to identify aHUS as the underlying cause. This identification is important, as it can guide treatment. While hemodialysis can help compensate for kidney damage regardless of TMA type, different treatments are needed to stop the excessive complement activity that specifically characterizes aHUS.
Medications called complement inhibitors, which include Soliris (eculizumab) and Ultomiris (ravulizumab-cwvz), can help reduce aHUS disease activity.
Typically, the best outcomes occur when people with aHUS begin complement inhibition soon after symptoms emerge.
“In many cases, however, the diagnosis remains uncertain at initial presentation because clinical features overlap and definitive genetic testing may not be immediately available,” the researchers wrote. “As a result, delays in targeted therapy are not uncommon in real-world clinical practice.”
Treatment began after child’s birth
In the present case, a team led by scientists from the United Arab Emirates assessed how delays affected recovery for a woman who developed aHUS during her first pregnancy. The first signs emerged at 28 weeks, when she experienced pruritus, or itching. Although her blood tests were largely normal, she had slightly low platelet levels, blood cell fragments that help with clotting, which is seen in TMA.
For the next five weeks, the woman’s doctors closely monitored her for further evidence of complications. Then, 33 weeks into her pregnancy, the woman experienced facial swelling and high blood pressure.
At this point, her blood tests showed several abnormalities. She had low platelet counts and high levels of creatinine and urea, consistent with TMA-related kidney dysfunction. Liver enzyme levels were normal, indicating that liver problems were unlikely to be the underlying cause.
Showing evidence of progressive kidney injury and lack of urine production, she started hemodialysis and delivered a healthy baby via emergency cesarean section.
“Over the ensuing days postpartum, she showed no evidence of kidney recovery and remained hemodialysis dependent,” the researchers noted. However, her platelet levels began to increase.
The fact that symptoms continued after delivery and weren’t related to liver problems made the team suspect aHUS over other TMA types. Examining a kidney sample and performing genetic testing helped them confirm the diagnosis.
This case emphasizes the importance of maintaining a high index of suspicion for complement-mediated TMA in pregnant patients with severe kidney dysfunction.
To treat aHUS, the woman began receiving Soliris five weeks after the first symptoms emerged. She later transitioned to Ultomiris.
About a month after starting complement inhibition, her symptoms and blood tests had largely resolved. She was then able to stop receiving hemodialysis.
“This underscores that dialysis dependence should not preclude initiation of complement blockade,” the team wrote.
It also supports the idea that a delayed start to complement inhibition can still help promote recovery in aHUS.
Additionally, the woman’s case has implications for diagnosis, according to the researchers.
“This case emphasizes the importance of maintaining a high index of suspicion for complement-mediated TMA in pregnant patients with severe kidney dysfunction,” they wrote.
