Article
Pediatrics
Ling Hou, Lu Yin, Yubin Wu, Chengguang Zhao, Yue Du
Summary: A structural abnormality or dysfunction of podocytes is the main cause of nephrotic syndrome. A novel potentially pathogenic variant in the TBC1D8B gene was identified in a 6-month-old boy with steroid-sensitive NS. The variant c.2717A>G (p.His906Arg) may be associated with early-onset NS in children.
FRONTIERS IN PEDIATRICS
(2021)
Article
Urology & Nephrology
Sara Falcone, Thomas Nicol, Andrew Blease, Michael J. Randles, Elizabeth Angus, Anton Page, Frederick W. K. Tam, Charles D. Pusey, Rachel Lennon, Paul K. Potter
Summary: Nephrotic syndrome is a disease characterized by severe proteinuria, hypoalbuminaemia, edema, and hyperlipidaemia. Genetic studies have identified proteins that play important roles in the signaling of the slit diaphragm, regulation of actin cytoskeleton dynamics, and cell-matrix interactions in nephrotic syndrome. In this study, a novel missense mutation in the L4a domain of the LAMA5 gene was identified in mice, leading to the development of nephrotic syndrome with histological and ultrastructural changes similar to those seen in patients. The reduced levels of LAMA5 and alteration in the matrix composition suggest the involvement of LAMA5 in the progression of nephrotic syndrome. Additionally, the genetic background of the mice affected the disease progression, indicating the influence of genetic factors in kidney diseases. Overall, this novel model provides valuable insights into the pathogenic mechanisms and potential therapeutic targets for nephrotic syndrome.
KIDNEY INTERNATIONAL
(2022)
Article
Neurosciences
Jing Chen, Gao-Bo Ye, Jin-Rong Huang, Min Peng, Wei-Yue Gu, Pin Xiong, Hong-min Zhu
Summary: This study aims to investigate the clinical and genetic characteristics of three unrelated GAMOS4 patients with TP53RK gene compound heterozygous mutations. The three patients showed facial abnormalities, developmental delays, microcephaly, and aberrant cerebral imaging. They did not have nephrotic syndrome and all survived beyond 3 years of age. This study provides new insights into the pathogenic TP53RK gene mutation spectrum and clinical phenotypes of GAMOS4.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Editorial Material
Urology & Nephrology
Tilman B. Drueke, Ziad A. Massy
Summary: Key contributors to anemia in patients with chronic kidney disease include insufficient erythropoietin production, decreased red blood cell half-life, iron deficiency, and inflammation. Proteinuria may alter erythrocyte metabolism and increase erythrocyte death in these patients.
KIDNEY INTERNATIONAL
(2021)
Article
Urology & Nephrology
Ichiro Hada, Akira Shimizu, Hiromu Takematsu, Yukino Nishibori, Toru Kimura, Toshiyuki Fukutomi, Akihiko Kudo, Noriko Ito-Nitta, Zentaro Kiuchi, Jaakko Patrakka, Naoaki Mikami, Simon Leclerc, Yoshihiro Akimoto, Yoshiaki Hirayama, Satoka Mori, Tomoko Takano, Kunimasa Yan
Summary: This study established a mouse model mimicking human idiopathic nephrotic syndrome (INS) by immunizing mice with Crb2 protein. The results highlight the causative role of anti-Crb2 autoantibody in podocyte injury in mice. This model could be useful for studying the immunologic pathogenesis of human INS.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Review
Pediatrics
Yiyang Li, Chuan Tian, Yajun Wang, Guoda Ma, Riling Chen
Summary: We report a case of an 8-year-old female patient with isolated steroid-resistant nephrotic syndrome carrying a de novo missense mutation in WT1 gene and presenting a new type of renal pathology. It is important to conduct WT1 gene testing for patients with steroid-resistant nephrotic syndrome, especially for isolated cases and female patients.
Article
Oncology
Shao-Yu Zhang, Qingfeng Fan, Anissa Moktefi, Virginie Ory, Vincent Audard, Andre Pawlak, Mario Ollero, Dil Sahali, Carole Henique
Summary: The study revealed that overproduction of CMIP in podocytes is associated with a downregulation of WT1 via two mechanisms. CMIP prevents the NF-kB-mediated transcriptional activation of WT1 and interacts with WT1 directly through its leucine-rich repeat domain. The E3 ligase activity of CMIP targets WT1 for proteasome degradation, suggesting a potential therapeutic target for podocyte diseases.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Review
Immunology
Adriel Roa-Bautista, Mahreen Sohail, Emma Wakeling, Kimberly C. Gilmour, Mark Davis, Anthony Gait, Giovanna Lucchini, David Cox, Reem Elfeky, Maaike Kusters
Summary: This case report presents a newborn with clinical features of SPLIS and severe combined immunodeficiency, with novel variants in SGPL1 and STAT1. The identification of dual diagnosis highlights the importance of comprehensive genetic testing for primary immunodeficiency in patients with similar severe clinical phenotypes in early life.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Jiwon M. Lee, Younhee Ko, Chul Ho Lee, Nara Jeon, Keum Hwa Lee, Jun Oh, Andreas Kronbichler, Moin A. Saleem, Beom Jin Lim, Jae Il Shin
Summary: This study investigated the changes in transcriptomes of human podocytes induced by IL-4 treatment and found that a few genes may be involved in IL-4-induced pathogenic effects on the transcriptome of human podocytes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Genetics & Heredity
Mahsa Sadat Asl Mohajeri, Atieh Eslahi, Zeinab Khazaii, Mohammad Reza Moradi, Reza Pazhoomand, Shima Farrokhi, Masoumeh Heidari Feizabadi, Farzaneh Alizadeh, Majid Mojarrad
Summary: A new gene, TMEM263, was found to be responsible for skeletal dysplasia in humans through whole exome sequencing (WES). This gene plays a key role in the growth hormone signaling pathway and may have a more significant impact on bone development in humans than previously thought.
Article
Urology & Nephrology
Simon Leclerc, Virginie Royal, Caroline Lamarche, Louis-Philippe Laurin
Summary: This case report describes a patient who developed minimal change disease (MCD) and severe acute kidney injury (AKI) following the Oxford-AstraZeneca COVID-19 vaccine. Treatment with glucocorticoids improved kidney function and proteinuria. Further research is needed to determine the association between MCD and COVID-19 vaccination.
AMERICAN JOURNAL OF KIDNEY DISEASES
(2021)
Article
Medicine, General & Internal
Debbie S. Gipson, Jonathan P. Troost, Cathie Spino, Samara Attalla, Joshua Tarnoff, Susan Massengill, Richard Lafayette, Virginia Vega-Warner, Sharon Adler, Patrick Gipson, Matthew Elliott, Frederick Kaskel, Damian Fermin, Marva Moxey-Mims, Richard N. Fine, Elizabeth J. Brown, Kimberly Reidy, Katherine Tuttle, Keisha Gibson, Kevin Lemley, Larry A. Greenbaum, Meredith A. Atkinson, Sangeeta Hingorani, Tarak Srivastava, Christine B. Sethna, Kevin Meyers, Cheryl Tran, Katherine M. Dell, Chia-shi Wang, Jennifer Lai Yee, Matthew G. Sampson, Rasheed Gbadegesin, J. J. Lin, Tammy Brady, Michelle Rheault, Howard Trachtman
Summary: This study examined whether there are differences in kidney health outcomes among children, adolescents, and adults with FSGS, and found that the association of FSGS with kidney survival and functional outcomes was comparable at all ages.
Article
Pediatrics
Behnaz Bazargani, Zahra Noparast, Leila Khedmat, Daryoosh Fahimi, Seyed Taher Esfahani, Mastaneh Moghtaderi, Arash Abbasi, Azadeh Afshin, Sayed Yousef Mojtahedi
Summary: The study found that rituximab (RTX) showed significant efficacy in inducing complete or partial remission in children with steroid-dependent and steroid-resistant nephrotic syndrome (SDNS, SRNS) in the short term. However, there was no significant difference in the long-term response between the two groups.
Article
Urology & Nephrology
Claire Dossier, Stephanie Bonneric, Veronique Baudouin, Theresa Kwon, Benjamin Prim, Alexandra Cambier, Anne Couderc, Christelle Moreau, Georges Deschenes, Julien Hogan
Summary: This retrospective study reported the use of low-dose obinutuzumab in children with steroid-dependent or frequently relapsing nephrotic syndrome. The results showed that all participants achieved B-cell depletion, with a median duration of 8.3 months. At 12 and 24 months, 92% and 68% of patients, respectively, were in sustained remission. Mild infusion reactions and neutropenia were observed as adverse events. The study suggested that low-dose obinutuzumab is a promising treatment option for these patients.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Pharmacology & Pharmacy
Qiongbo Huang, Xiaobin Lin, Yang Wang, Xiujuan Chen, Wei Zheng, Xiaoli Zhong, Dewei Shang, Min Huang, Xia Gao, Hui Deng, Jiali Li, Fangling Zeng, Xiaolan Mo
Summary: In this study, a prediction model for the clearance of Tacrolimus (TAC) in pediatric patients with refractory nephrotic syndrome (RNS) was established using a population pharmacokinetic (PPK) model combined with machine learning algorithms. The model accurately predicted the individual clearance of TAC, allowing for optimized initial dosing and personalized treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Claire E. Martin, Laura A. New, Noah J. Phippen, Ava Keyvani Chahi, Alexander E. Mitro, Tomoko Takano, Tony Pawson, Ivan M. Blasutig, Nina Jones
JOURNAL OF CELL SCIENCE
(2020)
Article
Cell Biology
Yujian H. Yang, Roman Istomine, Fernando Alvarez, Tho-Alfakar Al-Aubodah, Xiang Qun Shi, Tomoko Takano, Angela M. Thornton, Ethan M. Shevach, Ji Zhang, Ciriaco A. Piccirillo
Article
Urology & Nephrology
Jun Matsuda, Mirela Maier, Lamine Aoudjit, Cindy Baldwin, Tomoko Takano
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2020)
Article
Biotechnology & Applied Microbiology
Thomas Gonatopoulos-Pournatzis, Michael Aregger, Kevin R. Brown, Shaghayegh Farhangmehr, Ulrich Braunschweig, Henry N. Ward, Kevin C. H. Ha, Alexander Weiss, Maximilian Billmann, Tanja Durbic, Chad L. Myers, Benjamin J. Blencowe, Jason Moffat
NATURE BIOTECHNOLOGY
(2020)
Article
Cell Biology
Deivid C. Rodrigues, Marat Mufteev, Robert J. Weatheritt, Ugljesa Djuric, Kevin C. H. Ha, P. Joel Ross, Wei Wei, Alina Piekna, Maria A. Sartori, Loryn Byres, Rebecca S. F. Mok, Kirill Zaslavsky, Peter Pasceri, Phedias Diamandis, Quaid Morris, Benjamin J. Blencowe, James Ellis
Review
Urology & Nephrology
Jun Matsuda, Kana Asano-Matsuda, Thomas M. Kitzler, Tomoko Takano
Summary: Rho GTPases play a crucial role in regulating the actin cytoskeleton and are implicated in the pathogenesis of proteinuric glomerular diseases. These GTPases are primarily regulated by three families of proteins – GEFs, GAPs, and GDIs – with their upstream regulatory mechanisms largely unknown in podocytes. Further studies are needed to bridge the knowledge gap in the field.
KIDNEY INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Kevin C. H. Ha, Timothy Sterne-Weiler, Quaid Morris, Robert J. Weatheritt, Benjamin J. Blencowe
Summary: This study examined the differential contributions of transcriptomic regulatory layers to neuronal subtype specification, revealing that profiles of alternative splicing and polyadenylation were more effective in discriminating neuronal subtypes than gene expression patterns.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Kana Asano-Matsuda, Sajida Ibrahim, Tomoko Takano, Jun Matsuda
Summary: The initial step of urine formation involves selective filtration of plasma in the glomerulus, where a filtration barrier made up of three layers (fenestrated endothelial cells, glomerular basement membrane, and podocytes) retains blood cells and large proteins while removing waste products. Rho GTPases serve as crucial molecular switches in regulating podocyte health and barrier function, with particular focus on subcellular compartments where signaling events occur.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jingwen Song, Syed Nabeel-Shah, Shuye Pu, Hyunmin Lee, Ulrich Braunschweig, Zuyao Ni, Nujhat Ahmed, Edyta Marcon, Guoqing Zhong, Debashish Ray, Kevin C. H. Ha, Xinghua Guo, Zhaolei Zhang, Timothy R. Hughes, Benjamin J. Blencowe, Jack F. Greenblatt
Summary: Alternative polyadenylation (APA) enhances gene regulatory potential by increasing the diversity of mRNA transcripts. A study found that the transcription factor Sp1 binds RNA and is a common repressor of distal poly(A) site usage. Sp1 inhibits cleavage at distal sites by interacting with the subunits of the core cleavage and polyadenylation (CPA) machinery.
Article
Urology & Nephrology
Ichiro Hada, Akira Shimizu, Hiromu Takematsu, Yukino Nishibori, Toru Kimura, Toshiyuki Fukutomi, Akihiko Kudo, Noriko Ito-Nitta, Zentaro Kiuchi, Jaakko Patrakka, Naoaki Mikami, Simon Leclerc, Yoshihiro Akimoto, Yoshiaki Hirayama, Satoka Mori, Tomoko Takano, Kunimasa Yan
Summary: This study established a mouse model mimicking human idiopathic nephrotic syndrome (INS) by immunizing mice with Crb2 protein. The results highlight the causative role of anti-Crb2 autoantibody in podocyte injury in mice. This model could be useful for studying the immunologic pathogenesis of human INS.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Multidisciplinary Sciences
Jun Matsuda, Dina Greenberg, Sajida Ibrahim, Mirela Maier, Lamine Aoudjit, Jennifer Chapelle, Cindy Baldwin, Yi He, Nathalie Lamarche-Vane, Tomoko Takano
Summary: CdGAP and beta-PIX are major regulatory proteins interacting with Rac1 in podocytes. CdGAP interacts with beta-PIX through its basic region and promotes their translocation in podocytes. Depletion of CdGAP leads to altered cell motility and increased Rac1 and Cdc42 activities in podocytes.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Tho-Alfakar Al-Aubodah, Lamine Aoudjit, Giuseppe Pascale, Maneka A. Perinpanayagam, David Langlais, Martin Bitzan, Susan M. Samuel, Ciriaco A. Piccirillo, Tomoko Takano
Summary: Using single-cell RNA sequencing, the authors identify an extrafollicular B cell response in the blood samples of children with active INS, providing important insights into the B cell subsets in this disease.
NATURE COMMUNICATIONS
(2023)
Article
Urology & Nephrology
Ainslie M. Hildebrand, Moumita Barua, Sean J. Barbour, Karthik K. Tennankore, Daniel C. Cattran, Tomoko Takano, Ping Lam, Sacha A. De Serres, Ratna Samanta, Michelle A. Hladunewich, Todd Fairhead, Penelope Poyah, D. Danielle Bush, Brian MacLaren, Dwight Sparkes, Philip Boll, Arenn Jauhal, Rohan John, Carmen Avila-Casado, Heather N. Reich
Summary: This study aims to establish a national, patient-centered, multidimensional web-based clinical database and federated virtual biobank to conduct human-based molecular and clinical research in glomerulonephritis (GN) in Canada. The study involves recruiting adult patients from nine Canadian tertiary care centers and collecting long-term follow-up data and biospecimens to discover disease predictors and therapeutic targets for glomerulonephritis.
CANADIAN JOURNAL OF KIDNEY HEALTH AND DISEASE
(2022)
Article
Biotechnology & Applied Microbiology
Adam Kosti, Patricia Rosa de Araujo, Wei-Qing Li, Gabriela D. A. Guardia, Jennifer Chiou, Caihong Yi, Debashish Ray, Fabiana Meliso, Yi-Ming Li, Talia Delambre, Mei Qiao, Suzanne S. Burns, Franziska K. Lorbeer, Fanny Georgi, Markus Flosbach, Sarah Klinnert, Anne Jenseit, Xiufen Lei, Carolina Romero Sandoval, Kevin Ha, Hong Zheng, Renu Pandey, Aleksandra Gruslova, Yogesh K. Gupta, Andrew Brenner, Erzsebet Kokovay, Timothy R. Hughes, Quaid D. Morris, Pedro A. F. Galante, Stefano Tiziani, Luiz O. F. Penalva
Article
Rheumatology
Jessica Salituri, Natalie Patey, Tomoko Takano, Pierre Fiset, Sonia Del Rincon, Laeora Berkson, Murray Baron, Marie Hudson, M. Baron, M. Hudson, G. Gyger, J. Pope, M. Larche, N. Khalidi, A. Masetto, E. Sutton, D. Robinson, T. S. Rodriguez-Reyna, D. Smith, C. Thorne, P. R. Fortin, M. Fritzler
JOURNAL OF SCLERODERMA AND RELATED DISORDERS
(2020)