Treatment with plasma exchange (PEX) was safe, restored kidney function and led to no requirement of dialysis at three months in most children with atypical hemolytic uremic syndrome (aHUS), according to research from India.
Treatment with Soliris (eculizumab, by Alexion) is currently recommended as the first option in patients with aHUS. However, its cost and limited availability in developing regions, as well as the efficacy of PEX combined with immunosuppressants in people with anti-factor H (FH) autoantibody-associated disease, mean that PEX remains the mainstay of aHUS treatment in countries such as India.
The team at the All India Institute of Medical Sciences conducted a single-center study over 5.5 years to assess the safety and efficacy of PEX in children with aHUS.
A total of 109 patients (74 boys; mean age 7.3 years, range six months–18 years) underwent 2,024 PEX sessions — a median 17 per patient — between January 2013 and June 2018. Seventy-four of these patients (67.9%) had autoantibodies targeting FH.
The most common first aHUS manifestations were severe renal and extra-renal features, including cardiorespiratory and neurological complications. PEX was started within 24 hours of hospital admission at a median of 13 days from disease onset. PEX with immunosuppression was used in 74 patients, PEX alone in 19 and PEX followed by plasma infusions in 16. Ninety-two patients (84.4%) underwent concomitant hemodialysis.
Adverse events were usually self-limiting or mild (12.1% patients), and included chills (5.5%), vomiting/abdominal pain (3.3%), decreased blood pressure (1.6%), urticaria (1.5%), seizures (0.2%), low blood levels of calcium (0.2%), and hemorrhage (0.1%). Catheter-related adverse events were uncommon.
There were 73 patients (98.6%) with and 32 (91.4%) without anti-FH-associated disease who achieved hematological remission — normal blood cell counts — after a median six sessions. Three patients died between days 10–46 of initiating PEX and while on dialysis. Seventy-one patients experienced hematological remission within a week of PEX, 45 (60.8%) with and 26 (74.3%) without antibodies. Thirty-one more patients — 26 (35.1%) with and 5 (14.3%) without antibodies — achieved remission over the following week.
By one and three months post-PEX start, 80.8% and 89.6% patients were free from dialysis, respectively. At a median 17.5 months of follow-up, most patients had normal renal function with hypertension and/or proteinuria — abnormal amounts of protein in urine — while 15.1% had stage 2-3 chronic kidney disease. Patients with or without anti-FH antibodies did not differ at three months and at the last follow-up.
The data further showed that 18 (16.5%) patients relapsed at a median 9.1 months, eight of whom subsequently had an adverse outcome, defined as estimated glomerular filtration rate (eGFR) — a kidney function marker — lower than 30 mL/min/1.73 m2 at three months or at subsequent follow-up, or death.
At the last follow-up, 17 (15.6%) patients had an adverse outcome, including 11 (10.1%) deaths in patients with eGFR lower than 15 mL/minute/1.73 m2. Six patients died from complications of renal failure, four of septicemia, and one of cardiogenic shock, or insufficient blood being pumped by the heart.
Filter reuse and more than 20 PEX sessions per patient were independently associated with adverse events, while intravenous infusion of calcium gluconate — used to treat calcium deficiency — was protective.
“PEX is safe and associated with satisfactory short-term outcomes in children with aHUS,” the scientists stated. “In the absence of access to eculizumab, PEX remains a reasonable alternative in patients with aHUS.”