aHUS drug Soliris helps reverse organ failure in young woman in rare case
Kidney disease due to lupus triggered sepsis, leading to aHUS for patient in China
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Prompt and intensive supportive care, which included plasma exchange and Soliris (eculizumab), successfully reversed organ failure and controlled atypical hemolytic uremic syndrome (aHUS) triggered by sepsis — a severe infection that can trigger widespread inflammation in the body — in a young woman with lupus.
That’s according to a new report detailing the case of a patient in China with kidney disease as a complication of lupus who developed sepsis while hospitalized.
Sepsis, the team noted, can activate the body’s complement system, part of the immune defense that helps fight infections, in an uncontrolled way. When the complement system becomes overactive, it can damage blood vessels and organs. This woman developed complement-mediated aHUS as a result of sepsis. In aHUS, blood clots form in small blood vessels.
Thanks to the immediate treatment the patient received, her condition improved and, at follow-up, she did not have any recurrence of aHUS, the scientists reported.
The team noted that “these findings challenge the dogma that active sepsis contraindicates complement inhibition” with a drug such as Soliris.
The young woman’s treatment was described in “Salvaging sepsis-associated atypical hemolytic uremic syndrome with terminal complement blockade: A case report,” which was published in the journal Medicine.
While it’s known that sepsis can lead to aHUS, the researchers noted that its “diagnosis is challenging due to overlapping features with septic shock [the most severe stage of sepsis], often leading to delayed recognition and high mortality.” In aHUS, symptoms include low numbers of red blood cells and of clot-forming platelets. Kidney failure can occur in some patients.
In this case, a 23-year-old woman with chronic kidney disease caused by systemic lupus erythematosus, the most common form of lupus, sought treatment at a hospital in Guizhou Province after experiencing three days of cough with sputum, fever, and worsening shortness of breath. Her kidney function was already reduced, and she had been on hemodialysis — a treatment to filter waste and water from blood, which the kidneys normally do — for two years.
Woman’s health worsens severely after hospitalization
Within 24 hours of admission, her health worsened dramatically.
The woman developed acute respiratory failure, meaning her lungs could no longer provide enough oxygen to her blood. Chest imaging showed infection in both lungs. She produced almost no urine, indicating kidney failure. She also had low blood pressure, requiring norepinephrine, a vasopressor that tightens blood vessels to increase blood pressure.
Clinicians diagnosed the woman with septic shock and placed her on a ventilator to help her breathe.
Although infection explained part of her symptoms, blood tests revealed low levels of hemoglobin, the protein in red blood cells that carries oxygen. Her platelets were also low. A blood smear showed fragmented red blood cells, called schistocytes. These findings indicated thrombotic microangiopathy, in which blood clots form in small blood vessels, destroying red blood cells and consuming platelets.
Other tests supported active destruction of red blood cells, known as hemolysis. For example, lactate dehydrogenase and bilirubin, which are released when red blood cells are destroyed, were high. Haptoglobin, a protein that binds free hemoglobin, was very low. At the same time, her creatinine, a marker of kidney function, was high, confirming acute kidney disease.
The doctors needed to determine the cause of thrombotic microangiopathy. They found that a marker of terminal complement activation, called soluble C5b-9 (sC5b-9), was very high, at 578 nanograms/mL. This confirmed uncontrolled activation of the complement system, consistent with complement-mediated aHUS.
Plasma exchange, Soliris part of intensive care given patient
The woman was given intensive supportive treatment, including mechanical ventilation, vasopressors to control blood pressure, and continuous renal replacement therapy, a slow form of dialysis. Broad-spectrum antibiotics were given for severe pneumonia, or infection and inflammation of the lungs.
Treatment for aHUS was started, with plasma exchange performed daily for 10 sessions. This procedure removes the plasma, which contains complement proteins, and replaces it with donor plasma.
Clinicians also gave the woman Soliris, an approved aHUS drug that works by inhibiting the complement protein C5. By blocking that protein, Soliris prevents the formation of C5b-9.
After about one month, platelets increased, lactate dehydrogenase decreased, and creatinine decreased to its previous level, according to the researchers. Circulating levels of C5b-9 were approximately halved. With clinical recovery, she was weaned off vasopressors and mechanical ventilation.
No infectious complications occurred during treatment with Soliris, the team noted. Follow-up imaging showed resolution of lung infiltrates.
[Soliris], combined with supportive [additional therapies] can effectively reverse multi-organ failure.
At long-term follow-up, the woman had no recurrence of aHUS.
According to the team, this case shows that in patients with sepsis and persistent low platelets despite antibiotics, testing for complement activation is crucial and “provides a roadmap for treatment efficacy.”
In a lessons learned section of the report, the researcher wrote that “[Soliris], combined with supportive continuous renal replacement therapy and plasma exchange, can effectively reverse multi-organ failure.”
