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)
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
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
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
Gema Ariceta, Fadi Fakhouri, Lisa Sartz, Benjamin Miller, Vasilis Nikolaou, David Cohen, Andrew M. Siedlecki, Gianluigi Ardissino
Summary: Discontinuation of eculizumab in patients with aHUS carries risks of TMA recurrence and renal failure. A thorough assessment of risk factors prior to discontinuing eculizumab is essential for patient management.
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
Public, Environmental & Occupational Health
Lisa Byrne, Amy Douglas, Naomi Launders, Gauri Godbole, Richard Lynn, Carol Inward, Claire Jenkins
Summary: This study provides robust estimates of paediatric HUS incidence in England, Wales, Northern Ireland, and the Republic of Ireland and describes the characteristics of the condition. The study finds variations in the incidence of typical HUS based on country, age, gender, and ethnicity, and identifies the limitations of the current surveillance system for monitoring STEC and capturing HUS cases.
EPIDEMIOLOGY AND INFECTION
(2023)
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
Multidisciplinary Sciences
Prakriti Roy, Sophie E. van Peer, Martin M. de Witte, Godelieve A. M. Tytgat, Henrike E. Karim-Kos, Martine van Grotel, Cees P. van de Ven, Annelies M. C. Mavinkurve-Groothuis, Johannes H. M. Merks, Roland P. Kuiper, Janna A. Hol, Geert O. R. Janssens, Ronald R. de Krijger, Marjolijn C. J. Jongmans, Jarno Drost, Alida F. W. van der Steeg, Annemieke S. Littooij, Marc H. W. A. Wijnen, Harm van Tinteren, Marry M. van den Heuvel-Eibrink
Summary: Centralization of care for pediatric renal tumors in the Netherlands has significantly improved survival rates and contributed to the development of innovative treatments.
Article
Medicine, General & Internal
Geminiganesan Sangeetha, Jaippreetha Jayaraj, Swathi Ganesan, Sreeapoorva Puttagunta
Summary: Complement-mediated kidney disease, specifically atypical haemolytic uraemic syndrome (aHUS), is a rare thrombotic microangiopathy characterized by haemolytic anaemia, thrombocytopenia, and acute kidney injury. Unlike other diseases, aHUS presents without a diarrheal prodrome and often requires genetic testing for diagnosis. Early differentiation from other thrombotic microangiopathies is crucial for improving patient outcomes.
Article
Urology & Nephrology
Jingnan Feng, Ke Xu, Xinmiao Shi, Lu Xu, Lili Liu, Fang Wang, Xuhui Zhong, Guozhen Liu, Jinxi Wang, Pei Gao, Jie Ding, Shengfeng Wang, Siyan Zhan
Summary: This study provides the first population-based data on the incidence of HUS in urban China. The age and seasonal distributions of HUS in urban China differ from those in most developed countries, indicating a difference in etiology. The average medical cost of HUS per patient is significantly higher than the national average for all inpatients in the same period.
Editorial Material
Medicine, General & Internal
Azhar Ali Khan, Muhammad Usman Ahraf, Usman Javaid
Summary: This case study presents a young boy diagnosed with atypical HUS, who showed improvement after treatment including plasmapheresis and IV Methylprednisolone, although Rituximab was not administered due to affordability issue.
JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
(2021)
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.
Article
Medicine, General & Internal
Alicia Darwin, Leonger Malpica, Jugraj Dhanoa, Hamza Hashmi
Summary: Haemolytic uraemic syndrome (HUS) encompasses typical HUS associated with Shiga toxin and atypical aHUS associated with overactivation of the alternative complement pathway. Drug-induced aHUS cases vary in presentation, emphasizing the importance of early detection and treatment.
Editorial Material
Pharmacology & Pharmacy
Bradley P. Dixon, Ashley Sabus
Summary: The study describes the practical benefits of using ravulizumab 100 mg/mL in the treatment of aHUS, including the reduction of yearly infusions and shorter infusion times. These benefits improve the infusion experience for patients and caregivers.
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
(2022)
Article
Immunology
Edwin K. S. Wong, Thomas M. Hallam, Vicky Brocklebank, Patrick R. Walsh, Kate Smith-Jackson, Victoria G. Shuttleworth, Thomas E. Cox, Holly E. Anderson, Paul Nigel Barlow, Kevin James Marchbank, Claire L. Harris, David Kavanagh
Summary: MPGN, C3G, aHUS, and AMD are closely linked to dysfunction of the AP, with rare genetic variants in the CFH gene causing deficiencies in the FH protein. Careful biochemical assessment of these variants is crucial for accurate clinical decisions and patient management.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Ophthalmology
Nikolaos Tzoumas, Dean Hallam, Claire L. Harris, Majlinda Lako, David Kavanagh, David H. W. Steel
Summary: Age-related macular degeneration has been recently associated with abnormal complement activation, indicating it as a disease of general complement dysregulation. Researchers are exploring the molecular impact of related mutations/polymorphisms and identifying various therapeutic avenues for the disease.
SURVEY OF OPHTHALMOLOGY
(2021)
Review
Hematology
Christoph Q. Schmidt, Hubert Schrezenmeier, David Kavanagh
Summary: This article examines a rare blood disease and kidney disease, as well as other complement-related diseases. It finds that these diseases share similar etiology and clinical presentations, with an imbalance in complement activation leading to thrombotic events that can be reduced by inhibiting the complement pathway for better patient outcomes.
Article
Immunology
Ola Kamala, Talat H. Malik, Thomas M. Hallam, Thomas E. Cox, Yi Yang, Falguni Vyas, Saimir Luli, Chloe Connelly, Beth Gibson, Kate Smith-Jackson, Harriet Denton, Isabel Y. Pappworth, Lei Huang, David Kavanagh, Matthew C. Pickering, Kevin J. Marchbank
Summary: The study demonstrated that using a murine version of homodimeric mini-FH for treating C3G in murine models showed higher affinity and avidity, as well as enhanced complement regulatory function. Delivery of mini-FH constructs through gene therapy can enhance complement regulation in vivo, supporting its application as a novel treatment strategy for diseases like C3G.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nikolaos Tzoumas, David Kavanagh, Heather J. Cordell, Andrew J. Lotery, Praveen J. Patel, David H. Steel
Summary: The study investigated the association between CFI gene variants and age-related macular degeneration (AMD) and found that CFI variants associated with low Factor I levels predicted thinner macular and retinal thicknesses and higher AMD risk, while CFI variants associated with normal Factor I levels did not have any impact. CFH gene variant was associated with thinner macular and retinal thicknesses, while ARMS2 gene variant did not influence thickness. These findings highlight the significance of CFI variants as reliable predictors of reduced macular thickness and AMD, and the importance of CFH gene variant in early pathogenesis.
HUMAN MOLECULAR GENETICS
(2022)
Article
Pathology
Nikolai Tschernoster, Florian Erger, Patrick R. Walsh, Bairbre McNicholas, Margareta Fistrek, Sandra Habbig, Anna-Lena Schumacher, Kat Folz-Donahue, Christian Kukat, Mohammad R. Toliat, Christian Becker, Holger Thiele, David Kavanagh, Peter Nuernberg, Bodo B. Beck, Janine Altmueller
Summary: Complement factor H (CFH) and its related proteins play a crucial role in regulating the alternative pathway of the complement system. However, analyzing structural variants (SVs) of the CFH gene cluster is challenging due to sequence homology. In this study, a new molecular combing technology was applied to detect and visualize SVs within the CFH gene cluster, improving the understanding of its structural haplotypes and identifying new SVs in patients with renal pathologies.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
Article
Medicine, General & Internal
Sarah Henderson, Rosalyn Ardill, Ben Reynolds, David Kavanagh
Summary: A male child initially presented well but later deteriorated and required renal replacement therapy. Renal biopsy and further investigations revealed membranoproliferative glomerulonephritis (MPGN) and the presence of antifactor H antibodies. Treatment with rituximab and mycophenolate mofetil resulted in reduction of antibody titres, decreased proteinuria, and normalization of renal function.
Article
Urology & Nephrology
Andrew S. Bomback, David Kavanagh, Marina Vivarelli, Matthias Meier, Yaqin Wang, Nicholas J. A. Webb, Angelo J. Trapani, Richard J. H. Smith
Summary: This study aims to evaluate the efficacy and safety of Iptacopan in C3G patients. The study design is a randomized, double-blind, placebo-controlled Phase III trial, and the primary endpoint is the reduction in proteinuria and improvement in kidney function.
KIDNEY INTERNATIONAL REPORTS
(2022)
Review
Hematology
Gemma L. Thonnpson, David Kavanagh
Summary: Thrombotic microangiopathy (TMA) is a disease characterized by low platelet count, microangiopathic hemolytic anemia, and organ damage. TMAs can present with a variety of clinical manifestations due to different underlying pathophysiology. Kidney involvement is common due to its susceptibility to endothelial damage and microvascular occlusion. Rapid assessment, diagnosis, and treatment are necessary for TMAs due to their high morbidity and mortality rates.
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2022)
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.
Article
Immunology
Thomas M. M. Hallam, Thomas E. E. Cox, Kate Smith-Jackson, Vicky Brocklebank, April J. J. Baral, Nikolaos Tzoumas, David H. H. Steel, Edwin K. S. Wong, Victoria G. G. Shuttleworth, Andrew J. J. Lotery, Claire L. L. Harris, Kevin J. J. Marchbank, David Kavanagh
Summary: Age-related macular degeneration (AMD) is associated with genetic pathways, and genetic variants in complement factor H and factor I are linked to the disease. Sensitive assays are needed for personalized treatment to determine the functional significance of individual genetic variants. Research suggests that certain genetic variants may competitively inhibit the activity of normal proteins, which could impact the pharmacological replacement therapy for dry AMD.
FRONTIERS IN IMMUNOLOGY
(2022)
Meeting Abstract
Hematology
David Kavanagh
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2023)
Meeting Abstract
Urology & Nephrology
Bradley Dixon, Alvaro Domingo Madris-Aris, Brigette Adams, David Kavanagh, Hee Gyung Kang, Jimmy Wang, Katherine Garlo, Kazuki Tanaka, Larry Greenbaum, Masayo Ogawa, Nils Heyne, Seong Heon Kim, Spero Cataland, Sung-Soo Yoon, Yoshitaka Miyakawa, Yosu Luque, Melissa Muff-Luett
Article
Ophthalmology
Amy Jones, Stuart MacGregor, Xikun Han, James Francis, Claire Harris, David Kavanagh, Andrew Lotery, Nadia Waheed
Summary: This study investigates the relationship between rare genetic variants and complement factor I (CFI) levels, as well as the association between CFI levels and risk of advanced age-related macular degeneration (AAMD). The study finds that low circulating CFI levels are associated with an increased risk of AAMD, and provides genetic evidence to support this relationship.
OPHTHALMOLOGY SCIENCE
(2022)
Meeting Abstract
Hematology
April Joy Baral, Claire Mckinley, Rosie Fellows, Thomas Hallam, Thomas Cox, Daniel Payne, Stephen Richards, Alexandra Pike, Richard Kelly, Morag Griffin, Peter Hillmen, Kevin Marchbank, David Kavanagh, Darren Newton, Claire Harris
BRITISH JOURNAL OF HAEMATOLOGY
(2022)