A complicated case of atypical hemolytic uremic syndrome with frequent relapses under eculizumab

2015 ◽  
Vol 30 (6) ◽  
pp. 1039-1042 ◽  
Author(s):  
Gesa Schalk ◽  
Michael Kirschfink ◽  
Cyrill Wehling ◽  
Sara Gastoldi ◽  
Carsten Bergmann ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Complicated Case ◽  
Frequent Relapses ◽  
Uremic Syndrome

scholarly journals Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome

2018 ◽  
Vol 22 (5) ◽  
pp. 1088-1099 ◽  
Author(s):  
Madoka Fujisawa ◽  
Hideki Kato ◽  
Yoko Yoshida ◽  
Tomoko Usui ◽  
Munenori Takata ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Hemolytic Uremic Syndrome ◽  
Clinical Characteristics ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Clinical Manifestations ◽  
Total Mortality ◽  
Plasma Therapy ◽  
Laboratory Findings ◽  
Frequent Relapses ◽  
Uremic Syndrome

Abstract Background Atypical hemolytic uremic syndrome (aHUS) is caused by complement overactivation, and its presentation and prognosis differ according to the underlying molecular defects. The aim of this study was to characterize the genetic backgrounds of aHUS patients in Japan and to elucidate the associations between their genetic backgrounds, clinical findings, and outcomes. Methods We conducted a nationwide epidemiological survey of clinically diagnosed aHUS patients and examined 118 patients enrolled from 1998 to 2016 in Japan. We screened variants of seven genes related to complement and coagulation, as well as positivity for anti-CFH antibodies, and assessed clinical manifestations, laboratory findings, and clinical course. Results The most frequent genetic abnormalities were in C3 (31%) and the frequency of CFH variants was relatively low (10%) compared to Western countries. The predominant variant in this cohort was C3 p.I1157T (23%), which was related to favorable outcomes despite frequent relapses. A total of 72% of patients received plasma therapy, while 42% were treated with eculizumab. The prognosis of Japanese aHUS patients was relatively favorable, with a total mortality rate of 5.4% and a renal mortality rate of 15%. Conclusions The common occurrence of genotype C3, especially the p.I1157T variant was the characteristic of the genetic backgrounds of Japanese aHUS patients that differed from those of Caucasian patients. In addition, the favorable prognosis of patients with the unique C3 p.I1157T variant indicates that understanding the clinical characteristics of individual gene alterations is important for predicting prognosis and determining therapeutic strategies in aHUS.

scholarly journals Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anja Gäckler ◽  
Ulf Schönermarck ◽  
Vladimir Dobronravov ◽  
Gaetano La Manna ◽  
Andrew Denker ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Multicenter Trial ◽  
Efficacy And Safety ◽  
Meningococcal Infections ◽  
Phase 3 ◽  
Alternative Complement ◽  
Uremic Syndrome ◽  
Long Acting ◽  
Inhibitor Treatment

Abstract Background Atypical hemolytic uremic syndrome (aHUS) triggered by pregnancy is a rare disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor obtained through selective modifications to eculizumab, is efficacious in inhibiting complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. In this analysis, we report outcomes in a subgroup of patients from the 311 study who developed TMA postpartum. Methods This was a phase 3, multicenter trial evaluating efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete TMA response (simultaneous platelet count normalization [≥150 × 109/L], lactate dehydrogenase normalization [≤246 U/L] and 25% improvement in serum creatinine) through the 183-day initial evaluation period. Additional efficacy endpoints included time to complete TMA response, hematologic normalization, and dialysis requirement status. Results Eight patients presenting with TMA postpartum (median age of 37.7 [range; 22.1–45.2] years) were diagnosed with aHUS and received ≥1 dose of ravulizumab. Five patients (63%) were on dialysis at baseline. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 31.5 days. Hematologic normalization was observed in all patients. All patients on dialysis at baseline discontinued dialysis within 21 days after treatment with ravulizumab. All patients showed continued improvements in the estimated glomerular filtration rate from baseline to Day 183. Three possible treatment-related adverse events were observed in 2 patients (arthralgia and nasopharyngitis [both non-severe]; urinary tract infection). No deaths or meningococcal infections occurred. Conclusions Treatment with ravulizumab provided immediate and complete C5 inhibition, resulting in rapid clinical and laboratory improvements and complete TMA response through 183 days in patients with aHUS triggered by pregnancy. The safety profile observed in this subset of patients analysed is consistent with the 311 study investigating ravulizumab in patients with aHUS naïve to complement treatment. Trial registration Clinical trial identifier:NCT02949128.

scholarly journals Eculizumab-Associated Moraxella lacunata Bacteremia and Systemic Inflammatory Response Syndrome in a Toddler with Atypical Hemolytic Uremic Syndrome

2021 ◽  
Vol 15 ◽  
pp. 117955652199236
Author(s):  
Paige S Bicoll ◽  
Ashima Goyal ◽  
Neal B Blatt ◽  
Bishara J Freij
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Systemic Inflammatory Response ◽  
Upper Respiratory Tract ◽  
Invasive Bacterial Infection ◽  
Uremic Syndrome ◽  
Tract Infections ◽  
Moraxella Lacunata

Moraxella lacunata, a low-virulence Gram-negative coccobacillus, is classically associated with conjunctivitis and upper respiratory tract infections; systemic infections such as sepsis have rarely been reported, especially in children. We describe a 28-month-old girl with atypical hemolytic uremic syndrome and stage II chronic kidney disease on long-term eculizumab therapy who presented with systemic inflammatory response syndrome and was found to have Moraxella lacunata bloodstream infection. Eculizumab, a humanized monoclonal anti-C5 antibody, has been associated with susceptibility to infections with encapsulated bacteria, especially Neisseria meningitidis. This is the first report of an invasive bacterial infection with Moraxella lacunata in a pediatric eculizumab recipient.

Atypical hemolytic uremic syndrome due to DGKE mutation and response to eculizumab: lessons for the clinical nephrologist

2021 ◽  
Author(s):  
Danya Husain ◽  
Brian Barron ◽  
Anya Golkowski Barron ◽  
Ibrahim Sandokji ◽  
Olivera Marsenic ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Uremic Syndrome
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