Preservation of Renal Function in Atypical Hemolytic Uremic Syndrome by Eculizumab: A Case Report

Abstract

Genetic mutations in complement components are associated with the development of atypical hemolytic uremic syndrome (aHUS), a rare disease with high morbidity rate triggered by infections or unidentified factors. The uncontrolled activation of the alternative pathway of complement results in systemic endothelial damage leading to progressive development of renal failure. A previously healthy 8-month-old boy was referred to our hospital because of onset of fever, vomiting, and a single episode of nonbloody diarrhea. Acute kidney injury with preserved diuresis, hemolytic anemia, and thrombocytopenia were detected, and common protocols for management of HUS were followed without considerable improvement. The persistent low levels of complement component C3 led us to hypothesize the occurrence of aHUS. In fact, the child carried a specific mutation in complement factor H (Cfh; nonsense mutation in 3514G>T, serum levels of Cfh 138 mg/L, normal range 350-750). Given the lack of response to therapy and the occurrence of kidney failure requiring dialysis, we used eculizumab as rescue therapy, a monoclonal humanized antibody against the complement component C5. One week from the first administration, we observed a significant improvement of all clinical and laboratory parameters with complete recovery from hemodialysis, even in the presence of systemic infections. Our case report shows that complement inhibiting treatment allows the preservation of renal function and avoids disease relapses during systemic infections.

Eculizumab as First-Line Therapy for Atypical Hemolytic Uremic Syndrome

“…To date, 3 case reports of treatment with eculizumab in infants have been published. 9,10,13 They describe the use of eculizumab after unsuccessful PE/PI in the neonatal period or in very young infants, in contrast to our case, in which eculizumab was used as first-line therapy in an infant for the first time. In all 3 cases, eculizumab therapy led to sustained recovery of renal function.…”

“…[8][9][10] The resulting lack of inhibition leads to uncontrolled complement activation, TMA, endothelial lesions, and platelet aggregation leading to the typical triad of HUS symptoms: hemolytic anemia, thrombocytopenia, and renal insufficiency. 5 Distinguishing aHUS from STEC-HUS, particularly in infants, is often difficult and may take several days, which may be detrimental to outcomes.…”

“…Eculizumab treatment is ongoing because previous experience has shown that interruption of treatment can lead to detrimental consequences for the patient. Giordano et al 9 reported the case of an 8-month-old boy with aHUS in whom eculizumab treatment was stopped after 18 months of remission. Forty-five days later, the patient experienced progressive reduction in platelet count and recurrence of proteinuria, despite the lack of systemic TMA symptoms.…”

Complement Activation and Kidney Injury Molecule-1–Associated Proximal Tubule Injury in Severe Preeclampsia

“…69 Complement blockade has also been reported to restore kidney function in other severe medical conditions such as atypical hemolytic uremic syndrome, shiga toxin-associated hemolytic uremic syndrome, and catastrophic antiphospholipid antibody syndrome. [70][71][72][73] Severe preeclampsia remains an unpredictable and fulminant disease, but we think there is a compelling rationale to target complement-mediated inflammation and proximal tubule injury in the treatment of preeclampsia. …”

Eculizumab in Anti-Factor H Antibodies Associated With Atypical Hemolytic Uremic Syndrome

“…6,11 In our patient, a complete recovery of neurologic functions followed eculizumab treatment, while only a partial restoration was achieved with plasma therapy, which is considered the empiric first-line treatment of aHUS. [12][13][14][15] The observed immediate and persistent recovery from dialysis after starting eculizumab confirms the efficacy of this drug in aHUS with severe renal involvement.…”