Complete renal recovery following delayed therapy with eculizumab in atypical hemolytic uremic syndrome

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening illness characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Plasma therapy, previously considered the primary treatment for this condition, is associated with death and permanent kidney injury in over 50% of patients. Eculizumab, a monoclonal antibody that blocks C5, is far more effective and is the current treatment of choice, but it is not widely available. An 18-month-old boy presented with AKI, anemia, and normal platelet count. While managed initially as proliferative antineutrophil cytoplasmic antibody-associated glomerulonephritis, a diagnosis of partial HUS was suggested by low levels of complement C3, complement factor I (CFI) and complement Factor B (CFB), and histological changes suggesting microangiopathy without thrombi. Later, next-generation sequencing indicated homozygous pathogenic mutations in CFI and heterozygous variations in C3 and CFB. Corticosteroid pulses and plasmapheresis were ineffective in resolving the need for dialysis, and hypertension was refractory to polytherapy. Therapy with eculizumab, initiated only after 5 months on dialysis, was associated with rapid increase in urine output, control of hypertension, and slow but complete renal recovery. Dialysis was discontinued after 5 months of eculizumab therapy, and renal function has been within normal range after 33 months of initiating therapy with eculizumab. Our case emphasizes that a diagnosis of aHUS should be considered in the appropriate clinical setting even in the absence of thrombocytopenia. Kidney biopsy and genetic testing are useful in confirming the diagnosis. Therapy with eculizumab in patients with severe AKI may be associated with complete renal recovery even if therapy is delayed by several months.