Dual therapy manages aHUS with high blood pressure: Case report
Combining Ultomirus, blood pressure med ‘promising strategy’ in treatment
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Doctors successfully used a combination of Ultomiris (ravulizumab) and a blood pressure medication called sacubitril/valsartan to manage a case of atypical hemolytic uremic syndrome (aHUS) complicated by extremely high blood pressure.
Researchers said it was the first reported case of the treatment combo being used to manage aHUS with this common complication.
They described the case in the study, “C3 mutation-associated atypical hemolytic uremic syndrome with severe renal dysfunction and hypertensive emergency successfully treated with ravulizumab and sacubitril/valsartan: a case report,” published in BMC Nephrology. The work was funded by Japan’s Ministry of Health, Labor and Welfare.
aHUS is an inflammatory disorder in which part of the immune system called the complement cascade becomes overactive, leading tiny clots to form in blood vessels throughout the body. This can cause damage to organs, particularly the kidneys. Often, people with aHUS have underlying mutations in complement-related genes; these mutations don’t cause the disease outright but may set the stage for it to develop.
Ultomiris is an approved aHUS treatment that works by blocking the complement cascade. Although Ultomiris has proven effective for aHUS, recent data suggest complement-blocking medicines such as Ultomiris may not be effective for restoring kidney function in people experiencing a hypertensive emergency. Hypertensive emergency, or HE, essentially means that a person is experiencing extremely high blood pressure accompanied by organ damage. This often occurs in aHUS, and it can lead to kidney damage that’s independent of the complement cascade, the researchers said.
“Although early initiation of [complement-inhibiting treatment] is crucial for renal [kidney] recovery in aHUS, renal outcomes in cases complicated by HE are often suboptimal,” the researchers wrote. “In patients presenting with HE, renal survival appears less robust than in those without HE, suggesting complement-independent [blood vessel] injury superimposed on complement dysregulation in such cases.”
Case shows how man with anemia, kidney dysfunction improved
Here, researchers reported the case of a 57-year-old Japanese man who was referred to their hospital due to progressive anemia — meaning low levels of hemoglobin, the protein that carries oxygen in red blood cells — and kidney dysfunction. Initial lab testing indicated the man probably had aHUS or a related disease, as his platelet counts were low and there were signs of red blood cell destruction. His blood pressure was also very high, which, combined with kidney damage, indicated HE. The man was immediately given medications to bring down his blood pressure while additional testing was run.
Further testing confirmed the diagnosis of aHUS, while ruling out autoimmune disorder, digestive symptoms, or respiratory distress, with genetic testing showing the man carried a mutation in the gene encoding a complement protein called C3. The researchers noted that the man’s specific mutation has previously been documented among Western populations, but this is the first documented case of this particular mutation affecting someone in Japan. The researchers said that a COVID-19 infection about two months before the man’s hospitalization may have acted as the trigger for the development of aHUS.
After the aHUS diagnosis was confirmed, the man started treatment with Ultomiris. This led to a gradual improvement in kidney function — he initially needed dialysis, but was able to discontinue dialysis about two weeks after starting Ultomiris.
Shortly after initiating Ultomiris, a kidney biopsy was taken. This revealed no signs of extensive scarring, but there were still indications of kidney damage due to high blood pressure. The man was started on treatment with sacubitril/valsartan, a combination blood pressure medication sold under the name Entresto (generics are available) as a treatment for heart failure. His condition continued to improve, and he was discharged from the hospital soon after. His kidney function has continued to show improvement over a year of follow-up, the researchers said.
“Although HE is a common manifestation of [aHUS], to the best of our knowledge, this is the first reported case of aHUS complicated by HE treated with a combination of [Ultomiris] and sacubitril/valsartan,” the researchers concluded.
The scientists stressed that further studies are needed to clarify the therapeutic success of this treatment combination. Still, they said this patient’s experience suggests that adding sacubitril/valsartan or similar blood pressure medicines to Ultomiris “may represent a promising strategy to improve kidney outcomes in aHUS complicated by HE.”
Ultomiris is sold by Alexion, AstraZeneca Rare Disease, which was not involved in this study.
