Successful experience of six-year treatment of atypical hemolytic-uremic syndrome in a child with Eculizumab

Atypical hemolytic-uremic syndrome (aHUS) is an ultra-rare disease associated with uncontrolled activation of an alternative pathway of complement. Anti-complementary protection of the endothelium is disturbed by the development of systemic complement-mediated thrombotic microangiopathy. The unfavorable prognosis of overall and renal survival with aHUS without using complement-blocking antibodies (Eculizumab) is obvious. Here we present a clinical case of a patient with aHUS manifested at the age of 18 months (on the 4th day after revaccination with an attenuated oral polio vaccine). The onset of the disease was characterized by the development of microangiopathic hemolysis, thrombocytopenia and acute renal damage. A genetic study identified the heterozygous genotype of factor H (c.3653G>A (p.Cys1218Tyr)) and 2 heterozygous genetic variants (polymorphisms) in the same gene (c.2016A>G; c.2808G>T). Multigenic thrombophilia was also detected. It was represented by homo- and heterozygous genotypes of several genes (PAI: 4G/4G; MTHFR: 677 C/T; MTRR: 66 A/G; MTR: 2756 A/G; FGB: 455 G/A; ITGA2: 807 T/T). Despite the achievement of hematological remission of thrombotic microangiopathy on the background of plasma therapy, kidney function has not recovered. The severity of the condition was caused by dialysis-related renal failure (anuria), severe hypertension, and development of dilated cardiomyopathy with signs of congestive heart failure (reduction in ejection fraction to 42%). Renal biopsy revealed a mixed (glomerular and vascular) type of lesion specific for thrombotic microangiopathy involving interstitial tissue and tubules. The delayed initiation of therapy with Eculizumab allowed us to stop dialysis for more than 10 months. Up to date, this is the longest period after which a patient with aHUS did not require a renal replacement therapy. The treatment with Eculizumab, with the already existing chronic kidney damage, provided a significant improvement in their function, maintaining stable remission and improving the quality of life of the patient with aHUS. Early initiation of Eculizumab therapy in this patient could have prevented irreversible renal sclerosis. Due to the confirmed CFH genetic mutation, the girl needs lifelong therapy with Eculizumab. Its cancellation can provoke aHUS relapse with the risk of life-threatening complications.

атипичный гемолитико-уремический синдром, тромботическая микроангиопатия, плазмотерапия, мутация СFH, экулизумаб, atypical hemolytic-uremic syndrome, thrombotic microangiopathy, plasma therapy, mutation CFH, eculizumab

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