Cryptic activity of atypical hemolytic uremic syndrome and eculizumab treatment.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening disease often related to uncontrolled complement activation. The use of eculizumab has changed the management and the outcome of aHUS, becoming the frontline treatment of the acute disease and for the prevention of relapses. We report the case of a male patient with aHUS due to complement factor H gene mutation who was shifted from plasmatherapy to eculizumab for preventing disease relapses. The shift to eculizumab was associated with a significant decrease in proteinuria, revealing disease activity otherwise unsuspected, being the classic criteria of disease activity (platelet, haptoglobin, LDH, schistocytes), all in the normal range.The condition of proteinuria as the only sign of thrombotic microangiopathy activity is here designated as "cryptic activity of aHUS."

Belingheri M ，Possenti I ，Tel F ，Paglialonga F ，Testa S ，Salardi S ，Ardissino G ... -  《-》

Eculizumab in anti-factor h antibodies associated with atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening multisystemic condition often leading to end-stage renal failure. It results from an increased activation of the alternative pathway of the complement system due to mutations of genes coding for inhibitors of this pathway or from autoantibodies directed against them. Eculizumab is a monoclonal antibody directed against complement component C5 and inhibiting the activation of the effector limb of the complement system. Its efficacy has already been demonstrated in aHUS. The present article reports for the first time the use of eculizumab in a patient presenting with aHUS associated with circulating anti-complement Factor H autoantibodies and complicated by cardiac and neurologic symptoms. Our observation highlights the efficacy of eculizumab in this form of aHUS not only on renal symptoms but also on the extrarenal symptoms. It also suggests that eculizumab should be used very promptly after aHUS presentation to prevent life-threatening complications and to reduce the risk of chronic disabilities. To obtain a complete inhibition of the effector limb activation, the advised dosage must be respected. After this initial therapy in the autoimmune aHUS form, a long-term immunosuppressive treatment should be considered, to prevent relapses by reducing anti-complement Factor H autoantibody plasma levels.

Diamante Chiodini B ，Davin JC ，Corazza F ，Khaldi K ，Dahan K ，Ismaili K ，Adams B ... -  《-》

Eculizumab as first-line therapy for atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a genetic, life-threatening, chronic disease that can affect patients of all ages. aHUS is caused by uncontrolled complement activation due to genetic defects of complement regulation. Plasma exchange or infusion has been used to manage aHUS and may transiently maintain hematologic variables in some patients, but as the underlying complement dysregulation persists, end-stage renal disease or death occurs in 33% to 40% of patients during the first clinical manifestation. Here we present a pediatric case showing that first-line eculizumab treatment successfully blocked the progression of thrombotic microangiopathy in aHUS.

Christmann M ，Hansen M ，Bergmann C ，Schwabe D ，Brand J ，Schneider W ... -  《-》

Insights from the use in clinical practice of eculizumab in adult patients with atypical hemolytic uremic syndrome affecting the native kidneys: an analysis of 19 cases.

Atypical hemolytic uremic syndrome (aHUS) is a devastating form of renal thrombotic microangiopathy. Despite plasma exchange, the standard treatment of aHUS for decades, the renal prognosis for patients with aHUS has remained poor. We assessed the off-trial use of eculizumab in adult patients with aHUS affecting the native kidneys. A retrospective study was conducted. aHUS was defined as the presence of 3 or more of the following: acute kidney injury (serum creatinine >1.4 mg/dL [120 μmol/L]), mechanical hemolytic anemia, thrombocytopenia, and the presence of thrombotic microangiopathy features in a kidney biopsy specimen. Patients who had received 4 or more weekly 900-mg infusions of eculizumab were included. 19 patients were identified through a query sent to all French nephrology centers. Evolution of kidney function, hemolysis, and thrombocytopenia after the initiation of eculizumab therapy. All patients had acute kidney injury (serum creatinine range, 2.2-17.0 mg/dL) and 12 required hemodialysis. Thirteen patients carried a mutation in 1 complement gene and 1 had anti-factor H antibodies. For first-line therapy, 16 patients underwent plasma exchange and 3 patients received eculizumab. Median time between aHUS onset and eculizumab therapy initiation was 6 (range, 1-60) days and median time to platelet count normalization after eculizumab therapy initiation was 6 (range, 2-42) days. At the 3-month follow-up, 4 patients still required dialysis, 8 had non-dialysis-dependent chronic kidney disease, and 7 had normalized kidney function. At last follow-up (range, 4-22 months), 3 patients remained dialysis dependent, 7 had non-dialysis-dependent chronic kidney disease (estimated glomerular filtration rate, 17-55 mL/min/1.73 m(2)), and 9 had normal kidney function. Risks of reaching end-stage renal disease within 3 months and 1 year of aHUS onset were reduced by half in eculizumab-treated patients compared with recent historical controls. Retrospective study and use of historical controls. Our data indicate that eculizumab improves kidney disease outcome in patients with aHUS.

Fakhouri F ，Delmas Y ，Provot F ，Barbet C ，Karras A ，Makdassi R ，Courivaud C ，Rifard K ，Servais A ，Allard C ，Besson V ，Cousin M ，Châtelet V ，Goujon JM ，Coindre JP ，Laurent G ，Loirat C ，Frémeaux-Bacchi V ... -  《-》

Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

Legendre CM ，Licht C ，Muus P ，Greenbaum LA ，Babu S ，Bedrosian C ，Bingham C ，Cohen DJ ，Delmas Y ，Douglas K ，Eitner F ，Feldkamp T ，Fouque D ，Furman RR ，Gaber O ，Herthelius M ，Hourmant M ，Karpman D ，Lebranchu Y ，Mariat C ，Menne J ，Moulin B ，Nürnberger J ，Ogawa M ，Remuzzi G ，Richard T ，Sberro-Soussan R ，Severino B ，Sheerin NS ，Trivelli A ，Zimmerhackl LB ，Goodship T ，Loirat C ... -  《-》