GENETIC BACKGROUND OF ATYPICAL HEMOLYTIC-UREMIC SYNDROME AND ITS INFLUENCE ON THE COURSE OF DISEASE AND THERAPEUTIC EFFECTS

2019 ◽  
Vol 72 (10) ◽  
Author(s):  
Ewelina Użarowska ◽  
Michał Kościółek ◽  
Anna Wójcicka
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Genetic Background ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Therapeutic Effects ◽  
Course Of Disease ◽  
Uremic Syndrome

scholarly journals Atypical hemolytic uremic syndrome

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 217-225 ◽  
Author(s):  
Vahid Afshar-Kharghan
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Turnaround Time ◽  
Point Of View ◽  
High Rate ◽  
Close Monitoring ◽  
Adequate Treatment ◽  
Course Of Disease ◽  
Multiple Organs ◽  
Uremic Syndrome

Abstract Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) that affects multiple organs and the kidneys in particular. aHUS can be sporadic or familial and is most commonly caused by dysregulation of the alternative complement pathway. The initial attack of aHUS can occur at any age, and is associated with a high rate of progression to end stage renal disease. Many aHUS patients relapse in the native or transplanted kidneys, and require close monitoring and long-term management. Availability of anticomplement therapy has revolutionized the management of aHUS, and can change the natural course of aHUS by inducing hematologic remission, improving or stabilizing kidney functions, and preventing graft failure. As a result, it is important to succeed in the challenging task of differentiating aHUS from other TMAs and initiate adequate treatment early during the course of disease. Considering the high cost of currently available anticomplement therapy, it is important also from a financial point of view to accurately diagnose aHUS early during the course of disease and determine the necessary length of therapy. This highlights the need for development of precise complement functional and genetic studies with rapid turnaround time.

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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