Heart transplant

Soliris Effectively Treats aHUS in COVID-19 Patient With Heart Transplant

Soliris (eculizumab) has been shown to effectively treat atypical hemolytic uremic syndrome (aHUS) triggered by COVID-19 in a patient who had a heart transplant five years earlier, according to a recent case study.

“We present a case of [a] 32-year-old Hispanic man with a history of heart transplantation, admitted with COVID-19 and atypical hemolytic uremic syndrome, who has been successfully treated with eculizumab, ”the researchers wrote under the name Soliris.

The study, “Atypical hemolytic uremic syndrome associated with COVID-19 and use of eculizumab therapy, ”Was published in the Journal of Nephrology.

The patient was hospitalized in December 2020 with fever, chest pain, cough and shortness of breath (dyspnea) – all indicative of infection with SARS-CoV-2, the virus that causes COVID-19. The infection was then confirmed in the hospital.

The man was diagnosed with leukemia, a cancer of the blood, at the age of 6, and received a heart transplant in 2015. In May 2020, he started showing signs of transplant rejection. He was then treated with the corticosteroid methylprednisone and bortezomib, a proteasome inhibitor used to treat diseases related to abnormal antibody production.

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In addition, he underwent plasma exchange therapy – a treatment that replaces the liquid part of the blood – and intravenous (into the vein) immune globulin (IVIG), a cocktail of antibodies.

At her last follow-up, her heart function was stable and her hypertension was under control, as was her chronic kidney disease, the researchers said.

Upon his admission to hospital, however, blood tests revealed that he had elevated levels of several inflammatory markers, including ferritin and C-reactive protein. He also suffered from sinus tachycardia – a disease that makes the heart beat faster – and high blood pressure, but no fever.

A chest CT scan revealed the presence of several frosted glass opacities – fuzzy gray areas – consistent with pneumonia associated with COVID-19. He was treated with broad-spectrum antibiotics and dexamethasone, a strong anti-inflammatory drug, given into the vein.

A urine test revealed the presence of protein and blood in the urine, both indicative of kidney failure. Further lab tests showed the patient had elevated levels of creatine kinase, a marker of muscle damage.

Clinicians suspected thrombotic microangiopathy, a condition that causes blood clots to form in small blood vessels. This suspicion developed after laboratory tests revealed signs of destruction of red blood cells, worsening kidney failure and a low platelet count.

All signs were consistent with aHUS triggered by COVID-19. The patient received daily plasma exchange for three days, but without improvement.

At this point, he began intermittent hemodialysis – a type of treatment that filters waste products from the blood, mimicking the function of the kidneys, which is usually done over a short period, usually three to five hours a day.

By day 7, her platelet count had dropped to 15,000 platelets per microliter (mcL) (normal range: 150,000 to 450,000 platelets per mcL of blood). On day 10, he underwent a kidney biopsy which revealed signs of mild thrombotic microangiopathy and aHUS.

On day 13, he began treatment with Soliris – at a dose of 900 mg per week – and continued to undergo intermittent hemodialysis three times per week. Marketed by Alexion PharmaceuticalSoliris is an approved treatment for aHUS that works by preventing overactivation of the complement system. The disease is caused by abnormal activity of the complement cascade.

Hemodialysis was stopped on day 21, or after three weeks of treatment. The patient was discharged from the hospital with instructions to continue treatment with Soliris at the same weekly dose of 900 mg for two additional doses. After that, the treatment had to be done once and then every two weeks at a higher dose of 1200 mg.

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By the time the man left the hospital, his platelet levels were within a normal range and his creatinine levels were also lower (2.29 vs. 7.75 mg / dL on admission). Of note, creatinine is a marker of kidney function, with high levels indicating poorer kidney function.

During a six-month follow-up visit, the man’s creatinine levels had fallen to 1.42 mg / dL and although he still had protein in his urine, the estimated glomerular filtration rate (eGFR ) – a measure of kidney function – was stable.

Two months later, the patient changed his medication to Ultomiris (ravulizumab), another approved treatment for aHUS marketed by Alexion. It has the same mechanism of action as Soliris, but remains active in the body for longer periods, requiring less frequent doses. He continued the treatment for at least six months.

“This may be one of the first reported cases of COVID-19-induced HUS treated with the new complement inhibitor Ravulizumab,” the researchers wrote.

At the time of manuscript preparation, the patient was in his sixth month of treatment. According to the investigators, in accordance with the wishes expressed by the patient, his care team plans to “explore the discontinuation of treatment with complement inhibitor between 6 and 12 months if the patient continues to have stable renal function and no return of ‘other symptoms’.

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