Article
Urology & Nephrology
Thomas Barbour, Marie Scully, Gema Ariceta, Spero Cataland, Katherine Garlo, Nils Heyne, Yosu Luque, Jan Menne, Yoshitaka Miyakawa, Sung-Soo Yoon, David Kavanagh
Summary: Ravulizumab demonstrates long-term efficacy and safety in adults with aHUS, providing additional clinical benefits beyond 6 months of treatment, with most adverse events occurring early during the initial evaluation period and decreasing over time.
KIDNEY INTERNATIONAL REPORTS
(2021)
Article
Urology & Nephrology
Gema Ariceta, Bradley P. Dixon, Seong Heon Kim, Gaurav Kapur, Teri Mauch, Stephan Ortiz, Marc Vallee, Andrew E. Denker, Hee Gyung Kang, Larry A. Greenbaum
Summary: Ravulizumab rapidly improved hematologic and kidney parameters in complement inhibitor-naive children with atypical hemolytic uremic syndrome, showing no unexpected safety concerns.
KIDNEY INTERNATIONAL
(2021)
Article
Urology & Nephrology
Gianluigi Ardissino, Donata Cresseri, Francesca Tel, Antenore Giussani, Stefania Salardi, Martina Sgarbanti, Bice Strumbo, Sara Testa, Valentina Capone, Samantha Griffini, Elena Grovetti, Massimo Cugno, Mirco Belingheri, Chiara Tamburello, Evangeline Millicent Rodrigues, Michela Perrone, Massimo Cardillo, Grazia Corti, Dario Consonni, Lucrezia Furian, Silvana Tedeschi, Piergiorgio Messa, Claudio Beretta
Summary: This study presents experience with KTx in aHUS patients, showing that prophylactic use of Eculizumab can significantly reduce relapse rates. Tailored timing of Eculizumab doses based on classical complement pathway activity for each patient has also shown positive results.
JOURNAL OF NEPHROLOGY
(2021)
Article
Immunology
Margarita Lopez-Trascasa, Angel Alonso-Melgar, Marta Melgosa-Hijosa, Laura Espinosa-Roman, Maria Dolores Lledin-Barbancho, Eugenia Garcia-Fernandez, Santiago Rodriguez de Cordoba, Pilar Sanchez-Corral
Summary: Pathogenic gain-of-function mutations in complement Factor B were found to be the cause of atypical HUS in 2007. A four-month-old boy diagnosed with hypocomplementemic aHUS in 2000 suffered severe complications and end-stage renal disease by the age of 3, eventually undergoing a combined liver and kidney transplantation in 2009. After experiencing post-transplant complications, including B-cell non-Hodgkin lymphoma and liver rejection, the patient currently maintains normal kidney and liver functions 12 years post-surgery, suggesting that CLKT was an acceptable therapeutic option.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Josh Cone, Lida Kimmel, Yuchun Zhang, Krista Johnson, Douglas Sheridan, Paul Tamburini
Summary: This study used size exclusion chromatography (SEC) in combination with multiangle light scattering to investigate the formation of immune complexes when a patient is exposed to two different anti-complement component 5 (C5) antibodies. It was found that the inclusion of additional antibodies led to the formation of larger complexes, indicating the incorporation of multiple antibodies and C5 molecules. Similar results were observed when fluorescently labeled antibodies were spiked into human plasma. Further research is needed to understand the pharmacodynamic and pharmacokinetic properties of these complexes and to develop strategies to prevent their formation in patients.
Article
Pediatrics
Kazuki Tanaka, Brigitte Adams, Alvaro Madrid Aris, Naoya Fujita, Masayo Ogawa, Stephan Ortiz, Marc Vallee, Larry A. Greenbaum
Summary: The study demonstrated that pediatric patients with aHUS who switched from chronic eculizumab to ravulizumab treatment experienced stable kidney and hematologic parameters, with low occurrence of adverse events.
PEDIATRIC NEPHROLOGY
(2021)
Article
Health Care Sciences & Services
Agnieszka Furmanczyk-Zawiska, Anna Kubiak-Dydo, Ewelina Uzarowska-Gaska, Marta Kotlarek-Lysakowska, Katarzyna Salata, Monika Kolanowska, Michal Swierniak, Pawel Gaj, Beata Leszczynska, Maria Daniel, Krystian Jazdzewski, Magdalena Durlik, Anna Wojcicka
Summary: Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by genetic defects, with variable clinical outcomes, including renal failure. This study presents cases of five family members affected by aHUS, demonstrating the highly variable penetrance of the disease.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Urology & Nephrology
Caroline Duineveld, Romy N. Bouwmeester, Kioa L. Wijnsma, F. J. Bemelman, J. W. van der Heijden, S. P. Berger, L. P. W. J. van den Heuvel, Nicole C. A. J. van de Kar, Jack F. M. Wetzels
Summary: Kidney transplantation in aHUS patients in the Netherlands is performed without eculizumab prophylaxis, and eculizumab therapy is given in case of posttransplant aHUS recurrence. The study found a recurrence rate of 23% without eculizumab prophylaxis, and eculizumab treatment effectively improved or stabilized kidney function in most patients.
KIDNEY INTERNATIONAL REPORTS
(2023)
Article
Biochemistry & Molecular Biology
I-Ru Chen, Chiu-Ching Huang, Siang-Jyun Tu, Guei-Jane Wang, Ping-Chin Lai, Ya-Ting Lee, Ju-Chen Yen, Ya-Sian Chang, Jan-Gowth Chang
Summary: This single-cell sequencing study confirms the importance of immune cell dysregulation in the pathogenesis of aHUS, providing valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Maryam Saleem, Sana Shaikh, Zheng Hu, Nicola Pozzi, Anuja Java
Summary: Thrombotic microangiopathy (TMA) is a condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury caused by endothelial cell damage and microthrombi formation. Membranous nephropathy can be either primary, associated with circulating autoantibodies, or secondary, associated with infections, drugs, cancer, or other autoimmune diseases. Differentiating between primary and secondary TMA as well as primary and secondary membranous nephropathy is crucial for timely treatment, but can be challenging for clinicians, particularly after kidney transplant.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Vicky Brocklebank, Patrick R. Walsh, Kate Smith-Jackson, Thomas M. Hallam, Kevin J. Marchbank, Valerie Wilson, Theophile Bigirumurame, Tina Dutt, Emma K. Montgomery, Michal Malina, Edwin K. S. Wong, Sally Johnson, Neil S. Sheerin, David Kavanagh
Summary: Our study demonstrates the efficacy of eculizumab in improving ESKD-free survival in patients with complement-mediated atypical hemolytic uremic syndrome. The response to eculizumab treatment is influenced by the underlying genotype and clinical characteristics.
Review
Medicine, General & Internal
Ana Avila, Eva Gavela, Asuncion Sancho
Summary: Thrombotic microangiopathy is a rare but serious complication affecting kidney transplant recipients, characterized by systemic or localized symptoms. Treatment options include plasma exchange and complement blockade.
FRONTIERS IN MEDICINE
(2021)
Article
Urology & Nephrology
Massimo Cugno, Valentina Capone, Samantha Griffini, Elena Grovetti, Giulia Pintarelli, Luigi Porcaro, Emilio Clementi, Gianluigi Ardissino
Summary: This study reports on the experience with eculizumab maintenance treatment in patients with aHUS. The interval between eculizumab doses was adjusted based on CCP activity, with the goal of maintaining CCP activity below 30% to prevent relapse. Patients who received eculizumab regularly at tailored intervals showed no relapse during the observation period, and there was an inverse correlation between CCP activity and eculizumab circulating levels.
JOURNAL OF NEPHROLOGY
(2022)
Article
Immunology
Shirley Pollack, Israel Eisenstein, Adi Mory, Tamar Paperna, Ayala Ofir, Hagit Baris-Feldman, Karin Weiss, Nora Veszeli, Dorottya Csuka, Revital Shemer, Fabian Glaser, Zoltan Prohaszka, Daniella Magen
Summary: The study identified a rare novel homozygous activating deletion in the C3 gene associated with atypical hemolytic uremic syndrome (aHUS), highlighting the critical role of the disrupted C3-TED domain in the disease mechanism.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Min-Hua Tseng, Shih-Hua Lin, Jeng-Daw Tsai, Mai-Szu Wu, I-Jung Tsai, Yeu-Chin Chen, Min-Chih Chang, Wen-Chien Chou, Yee-Hsuan Chiou, Chiu-Ching Huang
Summary: Atypical hemolytic uremic syndrome (aHUS) is a rare but life-threatening systemic disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, caused by dysregulation of the complement pathway. Molecular analysis and pathogenesis have improved the diagnosis and development of treatment for aHUS. Diagnosis of aHUS relies on the presence of TMA with normal ADAMTS13 activity and excludes known secondary causes. Complement blockade with anti-C5 monoclonal antibody is the recommended first-line therapy for aHUS.
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
(2023)
Article
Endocrinology & Metabolism
Fabiola Carrara, Piero Ruggenenti, Annalisa Perna, Ilian Petrov Iliev, Flavio Gaspari, Silvia Ferrari, Nadia Stucchi, Antonio Bossi, Roberto Trevisan, Giuseppe Remuzzi, Aneliya Parvanova
Summary: The study aimed to investigate the prediction of glomerular filtration rate (GFR) decline in hypertensive, non-proteinuric type 2 diabetic patients by examining changes in glomerular hemodynamic parameters. Results showed that an increased Ra/Re ratio and longer duration of arterial hypertension were independently associated with GFR decline. These findings suggest that glomerular hypoperfusion and chronic ischemic injury related to pre-glomerular arteriolar narrowing play a role in early GFR decline in this patient population.
ACTA DIABETOLOGICA
(2022)
Review
Immunology
Marina Noris, Miriam Galbusera
Summary: The complement and hemostatic systems have functional interactions and play important roles in regulating immune response and preventing bleeding. Both systems involve proteins that activate each other and regulate the function of endothelial cells, platelets, and immune cells. Dysregulation of either system can lead to severe thromboinflammatory events.
IMMUNOLOGICAL REVIEWS
(2023)
Review
Immunology
Erica Daina, Monica Cortinovis, Giuseppe Remuzzi
Summary: Dysregulation and accelerated activation of the alternative pathway of complement play important roles in kidney diseases, and complement-directed therapies have shown potential for treatment. Although there have been successful cases, incorporating these therapies into clinical practice still faces challenges.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Endocrinology & Metabolism
Aneliya Parvanova, Manuela Abbate, Aina Maria Yanez, Miquel Bennasar-Veny, Angel Arturo Lopez-Gonzalez, Jose Ignacio Ramirez-Manent, Ilian Petrov Iliev, Sergio Fresneda, Maria Arias-Fernandez, Giuseppe Remuzzi, Piero Ruggenenti
Summary: This study investigated the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in prediabetes, visceral obesity, and preserved kidney function, and explored the association between MAFLD and hyperfiltration. It was found that MAFLD was more frequent in hyperfiltering subjects and was independently associated with hyperfiltration, as well as potentiated the age-related decline in estimated glomerular filtration rate (eGFR).
DIABETES RESEARCH AND CLINICAL PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Piera Trionfini, Elena Romano, Marco Varinelli, Lorena Longaretti, Paola Rizzo, Roberta Giampietro, Annalina Caroli, Sistiana Aiello, Marta Todeschini, Federica Casiraghi, Giuseppe Remuzzi, Ariela Benigni, Susanna Tomasoni
Summary: Induced pluripotent stem cells (iPSC) have the potential for cell therapy due to their self-renewal and differentiation capabilities. However, the high production costs and limited use for acute conditions hinder their applications. An allogeneic iPSC-based strategy may overcome these issues, but immune rejection is a concern. In this study, CRISPR/Cas9 was used to create hypoimmunogenic iPSCs that can differentiate into liver cells, providing a cost-effective and off-the-shelf opportunity for liver disease cell therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Norberto Perico, Giuseppe Remuzzi, Matthew D. Griffin, Paul Cockwell, Alexander P. Maxwell, Federica Casiraghi, Nadia Rubis, Tobia Peracchi, Alessandro Villa, Marta Todeschini, Fabiola Carrara, Bernadette A. Magee, Piero L. Ruggenenti, Stefano Rota, Laura Cappelletti, Veronica Mcinerney, Tomas P. Griffin, Md Nahidul Islam, Martino Introna, Olga Pedrini, Josee Golay, Andrew A. Finnerty, Jon Smythe, Willem E. Fibbe, Stephen J. Elliman, Timothy O'Brien, NEPHSTROM Trial Consortium
Summary: The NEPHSTROM study evaluates the safety, tolerability, and preliminary efficacy of ORBCEL-M cell therapy in adults with type 2 diabetes and progressive diabetic kidney disease. The results show that ORBCEL-M cell therapy is safe and well-tolerated in the lowest dose cohort, and significantly reduces the decline rate of eGFR over 18 months.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Medicine, General & Internal
Damiano Baldassarre, Licia Iacoviello, Roberta Baetta, Maria Carla Roncaglioni, Gianluigi Condorelli, Giuseppe Remuzzi, Gianfranco Gensini, Luigi Frati, Walter Ricciardi, Pier Giulio Conaldi, Antonio Uccelli, Fabio Blandini, Silvano Bosari, Giovanni Scambia, Massimo Fini, Antonio Di Malta, Mauro Amato, Fabrizio Veglia, Alice Bonomi, Catherine Klersy, Francesca Colazzo, Martino Pengo, Francesca Gorini, Luciana Auteri, Giuseppe Ferrante, Marta Baviera, Giuseppe Ambrosio, Alberico Catapano, Alessandro Gialluisi, Alexis Elias Malavazos, Serenella Castelvecchio, Massimiliano Marco Corsi-Romanelli, Rosanna Cardani, Maria Teresa La Rovere, Valentina Agnese, Bianca Pane, Daniele Prati, Laura Spinardi, Giovanna Liuzzo, Eloisa Arbustini, Maurizio Volterrani, Marco Visconti, Jose Pablo Werba, Stefano Genovese, Grzegorz Bilo, Cecilia Invitti, Anna Di Blasio, Carolina Lombardi, Andrea Faini, Debora Rosa, Luisa Ojeda-Fernandez, Andreana Foresta, Amalia De Curtis, Augusto Di Castelnuovo, Simonetta Scalvini, Antonia Pierobon, Alessandra Gorini, Luca Valenti, Livio Luzi, Annarosa Racca, Manuela Bandi, Elena Tremoli, Lorenzo Menicanti, Gianfranco Parati, Giulio Pompilio
Summary: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial aiming to compare the effectiveness of an educational and motivational mobile health intervention with usual care in reducing cardiovascular risk. The trial plans to enrol approximately 80,000 subjects without overt cardiovascular diseases and evaluate the short-term endpoints, as well as conduct a long-term follow-up to assess the incidence of major adverse cardiovascular events.
Editorial Material
Surgery
Giuseppe Remuzzi
UPDATES IN SURGERY
(2023)
Article
Multidisciplinary Sciences
Matteo Breno, Marina Noris, Nadia Rubis, Aneliya Ilieva Parvanova, Davide Martinetti, Sara Gamba, Lucia Liguori, Caterina Mele, Rossella Piras, Silvia Orisio, Elisabetta Valoti, Marta Alberti, Olimpia Diadei, Elena Bresin, Miriam Rigoldi, Silvia Prandini, Tiziano Gamba, Nadia Stucchi, Fabiola Carrara, Erica Daina, Ariela Benigni, ORIGIN Study Grp
Summary: This study conducted a genetic association study on the outcome of COVID-19 in a homogeneous population from Bergamo province, which was heavily impacted by the SARS-CoV-2 pandemic in Europe. The results showed an association between the 3p21.31 locus and disease severity, with a stronger effect in severely ill patients. Additionally, transcriptome-wide association study identified eQTLs for LZTFL1 and CCR9, and 17 previously unreported loci were suggestive for an association with COVID-19 severity or susceptibility.
Article
Multidisciplinary Sciences
Angelo M. Lavecchia, Polyxeni Mantzouratou, Domenico Cerullo, Monica Locatelli, Sara Conti, Matteo Tironi, Fabio Sangalli, Daniela Corna, Carlamaria Zoja, Giuseppe Remuzzi, Christodoulos Xinaris
Summary: Research shows that activation of thyroid hormone (TH) signaling can counteract cellular remodeling and pathological alterations caused by diabetes, providing a potential approach for the treatment of diabetes and its complications.
Article
Radiology, Nuclear Medicine & Medical Imaging
Anna Caroli, Giulia Villa, Paolo Brambilla, Matias Trillini, Kanishka Sharma, Sandro Sironi, Giuseppe Remuzzi, Norberto Perico, Andrea Remuzzi
Summary: This study presents and validates a diffusion MRI (DWI)-based method for quantifying total kidney and cyst volume (TCV) and characterizing non-cystic tissue microstructure in autosomal dominant polycystic kidney disease (ADPKD). DWI shows potential in ADPKD to assess and predict disease progression, evaluate the impact of novel therapies, and identify microcysts and peritubular interstitial fibrosis in non-cystic kidney tissue.
EUROPEAN RADIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Federica Casiraghi, Marta Todeschini, Manuel Alfredo Podesta, Marilena Mister, Barbara Ruggiero, Matias Trillini, Camillo Carrara, Olimpia Diadei, Alessandro Villa, Ariela Benigni, Giuseppe Remuzzi
Summary: Immune dysregulation plays a key role in the pathogenesis of steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS). However, no major B- or T-cell alterations have been described for adults, unlike in pediatric cases. This study found that patients with SDNS/FRNS have expansion of memory B cells and reduced memory Tregs. The levels of CD45RO(+) Tregs at baseline may help predict which patients will achieve sustained remission following rituximab infusion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Monica Locatelli, Daniela Rottoli, Rayan Mahmoud, Mauro Abbate, Daniela Corna, Domenico Cerullo, Susanna Tomasoni, Giuseppe Remuzzi, Carlamaria Zoja, Ariela Benigni, Daniela Macconi
Summary: In BTBR ob/ob mice with type 2 diabetic nephropathy, peritubular capillaries show endothelial cell abnormalities and basement membrane thickening. Remodeling and focal loss of the endothelial glycocalyx were observed in diabetic kidneys, and ACEi treatment preserved the glycocalyx and attenuated the ultrastructural abnormalities of peritubular capillaries.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Primary Health Care
Livio Garattini, Michela Bozzetto, Giuseppe Remuzzi, Nick Freemantle, Alessandro Nobili
Article
Immunology
Behdad Afzali, Marina Noris, Bart N. Lambrecht, Claudia Kemper
Summary: Hyperactivation of the complement system is implicated in the pathology of COVID-19, with potential therapeutic benefits through complement inhibition. Latest research progress suggests targeting complement components for treatment may be beneficial in mitigating excessive inflammation and thrombosis in severe COVID-19 cases.
NATURE REVIEWS IMMUNOLOGY
(2022)