Review
Medicine, General & Internal
Mini Michael, Arvind Bagga, Sarah E. Sartain, Richard J. H. Smith
Summary: Haemolytic uraemic syndrome (HUS) is a group of diseases that cause thrombotic microangiopathy, characterized by non-immune microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. The most common cause of HUS discussed in this review is Shiga toxin-producing Escherichia coli HUS. Identifying the trigger of thrombotic microangiopathy is crucial for personalized treatment. Complement-mediated HUS, once associated with high mortality, can now be treated with anti-complement therapies. However, the high cost of these therapies limits their use in low-income countries.
Review
Urology & Nephrology
Justo Sandino-Perez, Eduardo Gutierrez, Fernando Caravaca-Fontan, Enrique Morales, Lucia Aubert-Girbal, Ramon Delgado-Lillo, Manuel Praga
Summary: This study identified four cases of HUS following acute pancreatitis, with a mean age of 30 years and all patients being male, primarily due to excessive alcohol consumption. All patients developed progressive AKI shortly after pancreatitis onset, requiring kidney replacement therapy, but eventually showed good recovery. One patient treated with eculizumab had a faster recovery compared to others.
CLINICAL KIDNEY JOURNAL
(2021)
Article
Transplantation
Mendy ter Avest, Romy N. Bouwmeester, Caroline Duineveld, Kioa L. Wijnsma, Elena B. Volokhina, Lambertus P. W. J. van den Heuvel, David M. Burger, Jack F. M. Wetzels, Nicole C. A. J. van de Kar, Rob ter Heine
Summary: This study evaluated the pharmacokinetics and pharmacodynamics of eculizumab in patients with atypical haemolytic uraemic syndrome (aHUS) and proposed improved dosing strategies. The study found that individualized dosing strategy could improve treatment response and reduce treatment costs by prolonging the dosing interval.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Medicine, General & Internal
Sarah Dunn, Victoria Brocklebank, Andrew Bryant, Sonya Carnell, Thomas J. Chadwick, Sally Johnson, David Kavanagh, Jan Lecouturier, Michal Malina, Eoin Moloney, Yemi Oluboyede, Christopher Weetman, Edwin Kwan Soon Wong, Len Woodward, Neil Sheerin
Summary: This study aims to investigate the safety of stopping eculizumab treatment in patients with atypical haemolytic uraemic syndrome (aHUS) by monitoring disease activity and tracking thrombotic microangiopathy-related serious adverse events. It evaluates the effectiveness and feasibility of this treatment strategy.
Review
Medicine, General & Internal
Dan Pugh, Eoin D. O'Sullivan, Fiona Ai Duthie, Philip Masson, David Kavanagh
Summary: AHUS is a rare disorder characterized by abnormal complement regulatory proteins, leading to kidney failure and death in the past. However, new therapies such as terminal complement inhibition show promising outcomes, although based on very low-quality evidence from single-arm studies. Careful consideration of future data is needed for better understanding of treatment duration and adverse outcomes.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
Article
Transplantation
Shuichi Ito, Hiroshi Hataya, Akira Ashida, Riku Hamada, Tomoaki Ishikawa, Yumiko Ishikawa, Akihiko Shimono, Takao Konomoto, Tomoki Miyazawa, Masao Ogura, Kazuki Tanaka, Shoji Kagami
Summary: Eculizumab demonstrated good efficacy and tolerability in pediatric patients with aHUS in a real-world setting in Japan. The treatment led to significant improvements in platelet count, lactate dehydrogenase, and estimated glomerular filtration rate, and achieved complete TMA response, hematologic normalization, and sCr decrease in a high percentage of patients.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Immunology
Kes H. Stevens, Laura M. Baas, Thea J. A. M. van der Velden, Romy N. Bouwmeester, Niels van Dillen, Eiske M. Dorresteijn, Arjan D. van Zuilen, Jack F. M. Wetzels, Marloes A. H. M. Michels, Nicole C. A. J. van de Kar, Lambertus P. van den Heuvel
Summary: In this study, researchers established a robust ex vivo model to measure complement deposition on human GMVECs, which can be used to study the pathophysiological mechanisms of aHUS or other diseases associated with endothelial complement activation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Urology & Nephrology
Caroline Duineveld, Romy Bouwmeester, Joost W. van der Heijden, Stefan P. Berger, Nicole C. A. J. van de Kar, Jack F. M. Wetzels
Summary: This interim analysis evaluated the safety of re-treatment with eculizumab in 11 patients with suspected relapse. Results showed that re-treatment with eculizumab after relapse is safe. Transplanted patients responded better to eculizumab therapy compared to those with aHUS in native kidneys.
CLINICAL KIDNEY JOURNAL
(2021)
Article
Immunology
Irene Gomez Delgado, Fernando Corvillo, Pilar Nozal, Emilia Arjona, Alvaro Madrid, Marta Melgosa, Juan Bravo, Agnes Szilagyi, Dorottya Csuka, Nora Veszeli, Zoltan Prohaszka, Pilar Sanchez-Corral
Summary: SP-HUS is a clinically well-known disease that may have a worse prognosis than HUS associated with E. coli infections. Studies suggest that risk variants in the CFH-CFHR3-CFHR1 region could contribute to disease-predisposition to SP-HUS, and transient desialylation of complement FH by the pneumococcal neuraminidase may play a role in disease pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Yahiya Y. Syed
Summary: Ravulizumab is a humanized monoclonal antibody indicated for the treatment of aHUS, with a convenient maintenance dosage regimen compared to eculizumab, and has shown good efficacy and tolerability in clinical trials.
Article
Urology & Nephrology
Jose Portoles, Ana Huerta, Emilia Arjona, Eva Gavela, Marisa Aguera, Carlos Jimenez, Teresa Cavero, Domingo Marrero, Santiago Rodriguez de Cordoba, Fritz Diekmann
Summary: Both pre-aHUS and de novo patients showed different clinical profiles and responses to ECU treatment. Genetic studies are important in determining risks of relapse and guiding treatment decisions. ECU may be considered as a preemptive treatment for patients at moderate or high risk of recurrence.
CLINICAL KIDNEY JOURNAL
(2021)
Article
Urology & Nephrology
Muneera Alabdulqader, Khalid Alfakeeh
Summary: Atypical haemolytic uraemic syndrome (aHUS) is a rare systemic syndrome characterized by non-immune haemolytic anaemia, thrombocytopenia, and kidney injury, with most cases caused by alternative complement pathway dysregulation. However, a mutation in the diacylglycerol kinase epsilon (DGKE) gene can also lead to aHUS, theoretically affecting the coagulation pathway instead of the complement pathway. Limited data is available for the management of these patients, and ideal treatment protocols have not yet been established.
Article
Urology & Nephrology
Irene Gomez Delgado, Josue Gutierrez-Tenorio, Gloria M. Fraga Rodriguez, Teresa Cavero, Emilia Arjona, Pilar Sanchez-Corral
Summary: Dysregulation of the alternative complement pathway plays a major role in the pathogenesis of atypical haemolytic uraemic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN). Both a 66-year-old male with chronic hepatitis C virus infection and a 5-year-old boy with aHUS carried similar frameshift variants in the complement CFHR5 gene, resulting in reduced levels of factor H-related 5 (FHR-5). Lower FHR-5 levels may predispose individuals to viral and bacterial infections that trigger different renal phenotypes.
CLINICAL KIDNEY JOURNAL
(2021)
Review
Hematology
Shruti Chaturvedi, Evan M. Braunstein, Robert A. Brodsky
Summary: Antiphospholipid syndrome (APS) is an acquired thromboinflammatory disorder characterized by the presence of antiphospholipid antibodies and an increased risk of venous or arterial thrombosis, with a severe form known as catastrophic APS (CAPS). Complement activation via antiphospholipid antibodies can cause cellular injury and promote coagulation, leading to a potential increase in risk for development of severe thrombotic APS and CAPS in a subset of patients with germline variants in genes crucial for complement regulation. Complement inhibition may be a promising therapy to reduce morbidity and mortality in these patients.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Editorial Material
Hematology
Robert A. Brodsky
Summary: Evidence from a prospective study shows that discontinuing eculizumab is safe in most aHUS patients after achieving complete remission, with a relapse risk of less than 25% overall, but up to 50% in patients with rare variants in at least one complement gene.