Eculizumab for Atypical Hemolytic Uremic Syndrome: Guidance for Developing Countries

Hemolytic uremic syndrome (HUS) is a heterogeneous group of disorders with the underlying pathology of thrombotic microangiopathy (TMA). With regional decline in Shiga toxin associated HUS, atypical HUS (aHUS) characterized by severe AKI, relapsing illness and extrarenal features, is increasingly identified. Since most such cases are mediated by dysregulation of the alternate complement pathway, the term complement-mediated TMA is preferred. Plasma exchanges (PEX) constitute the cornerstone of therapy of aHUS in developing countries, including for patients with anti-FH antibodies, the chief cause of pediatric aHUS in the subcontinent. However, worldwide experience with eculizumab during the past decade reports considerably better outcomes in patients with significant variants in genes encoding key complement regulators. With eculizumab poised to enter the Indian market, this article provides detailed guidance on its use. Indications for its rational use are discussed, including issues related to dosage, mode of administration, and side-effects of eculizumab and related agents. Therapy with eculizumab should be instituted promptly, with particular attention to dosage and frequency of administration. The article provides clear advice regarding meningococcal, pneumococcal and other vaccines, and the need for antibiotic prophylaxis during and following therapy with eculizumab. It also underscores key aspects for monitoring patients on complement blockade, and updates guidelines regarding discontinuation of complement inhibitors following remission, and in context of kidney transplantation. Both PEX and eculizumab are important options for managing patients with aHUS, with the choice dictated by the underlying cause, and ability to sustain either therapy in adequate doses and for sufficient duration for relapse-free outcomes.