Josep M Cruzado, Anna Manonelles, Sandra Rayego, Núria Doladé, Ana Amaya-Garrido, Cristian Valera, Roser Guiteras, Jose Luis Mosquera, Michaela Jung, Sergi Codina, Laura Martínez-Valenzuela, Juliana Draibe, Carlos Couceiro, Francesc Vigués, Álvaro Madrid, M Carolina Florian, Marta Ruíz-Ortega, Anna Sola
Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS...
February 28, 2024: Kidney International
Jianchun Chen, Xiaoyong Wang, Qian He, Hai-Chun Yang, Agnes B Fogo, Raymond C Harris
Podocyte injury and loss are hallmarks of diabetic nephropathy (DN). However, the molecular mechanisms underlying these phenomena remain poorly understood. YAP (Yes-associated protein) is an important transcriptional coactivator that binds with various other transcription factors, including the TEAD family members (nuclear effectors of the Hippo pathway), that regulate cell proliferation, differentiation, and apoptosis. The present study found an increase in YAP phosphorylation at S127 of YAP and a reduction of nuclear YAP localization in podocytes of diabetic mouse and human kidneys, suggesting dysregulation of YAP may play a role in diabetic podocyte injury...
February 27, 2024: Kidney International
Lou C Duret, Tynhinane Hamidouche, Nicholas J Steers, Catherine Pons, Nicolas Soubeiran, Delphine Buret, Eric Gilson, Ali G Gharavi, Vivette D D'Agati, Marina Shkreli
Collapsing focal segmental glomerulosclerosis (FSGS), also known as collapsing glomerulopathy (CG), is the most aggressive variant of FSGS and is characterized by a rapid progression to kidney failure. Understanding CG pathogenesis represents a key step for the development of targeted therapies. Previous work implicated the telomerase protein component TERT in CG pathogenesis, as transgenic TERT expression in adult mice resulted in a CG resembling that seen in human primary CG and HIV-associated nephropathy (HIVAN)...
February 27, 2024: Kidney International
Yue Lu, Linlin Meng, Ruiqing Ren, Xinlu Wang, Wenhai Sui, Fei Xue, Lin Xie, Ang Chen, Yuxia Zhao, Jianmin Yang, Wencheng Zhang, Xiao Yu, Bo Xi, Feng Xu, Meng Zhang, Yun Zhang, Cheng Zhang
Vascular calcification is a pathological process commonly associated with atherosclerosis, chronic kidney disease, and diabetes. Paraspeckle protein NONO is a multifunctional RNA/DNA binding protein involved in many nuclear biological processes but its role in vascular calcification remains unclear. Here, we observed that NONO expression was decreased in calcified arteries of mice and patients with CKD. We generated smooth muscle-specific NONO-knockout mice and established three different mouse models of vascular calcification by means of 5/6 nephrectomy, adenine diet to induce chronic kidney failure, or vitamin D injection...
February 26, 2024: Kidney International
Michael Che, Sarah M Moran, Richard J Smith, Kevin Y M Ren, Graeme N Smith, M Khaled Shamseddin, Carmen Avila-Casado, Jocelyn S Garland
Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy (TMA), caused by uncontrolled activation of the alternative complement pathway in the setting of autoantibodies to or rare pathogenic genetic variants in complement proteins. Pregnancy may serve as a trigger and unmask aHUS/complement-mediated TMA [aHUS/CM-TMA] which has severe, life-threatening consequences. It can be difficult to diagnose aHUS/CM-TMA in pregnancy due to overlapping clinical features with other TMA syndromes including hypertensive disorders of pregnancy...
February 24, 2024: Kidney International
Pongpratch Puapatanakul, Suramath Isaranuwatchai, Ankanee Chanakul, Jerasit Surintrspanont, Kroonpong Iampenkhae, Talerngsak Kanjanabuch, Kanya Suphapeetiporn, Vivek Charu, Hani Y Suleiman, Kearkiat Praditpornsilpa, Jeffrey H Miner
Focal segmental glomerulosclerosis (FSGS) lesions have been linked to variants in COL4A3/A4/A5 genes, which are also mutated in Alport syndrome. Although it could be useful for diagnosis, quantitative evaluation of glomerular basement membrane (GBM) type IV collagen (colIV) networks is not widely used to assess these patients. To do so, we developed immunofluorescence imaging for collagen α5(IV) and α1/2(IV) on kidney paraffin sections with Airyscan confocal microscopy that clearly distinguishes GBM collagen α 3 α 4 α5(IV) and α 1 α 1 α2(IV) as two distinct layers, allowing quantitative assessment of both colIV networks...
February 22, 2024: Kidney International
Tong Xu, Lea Herkens, Ting Jia, Barbara M Klinkhammer, Sebastian Kant, Claudia A Krusche, Eva M Buhl, Sikander Hayat, Jürgen Floege, Pavel Strnad, Rafael Kramann, Sonja Djudjaj, Peter Boor
Desmosomes are multi-protein cell-cell adhesion structures supporting cell stability and mechanical stress resilience of tissues; best described in skin and heart. The kidney is exposed to various mechanical stimuli and stress, yet little is known about kidney desmosomes. In healthy kidneys, we found desmosomal proteins located at the apical-junctional complex in tubular epithelial cells. In four different animal models and patient biopsies with various kidney diseases, desmosomal components were significantly upregulated and partly miss-localized outside of the apical-junctional complexes along the whole lateral tubular epithelial cell membrane...
February 21, 2024: Kidney International
Lulu Wang, Han Tian, Haiyan Wang, Xiaoming Mao, Jing Luo, Qingyun He, Ping Wen, Hongdi Cao, Li Fang, Yang Zhou, Junwei Yang, Lei Jiang
The circadian clock influences a wide range of biological process and controls numerous aspects of physiology to adapt to the daily environmental changes caused by Earth's rotation. The kidney clock plays an important role in maintaining tubular function, but its effect on podocytes remains unclear. Here, we found that podocytes expressed CLOCK proteins, and that 2666 glomerular gene transcripts (13.4%), including autophagy related genes, had 24-hour circadian rhythms. Deletion of Clock in podocytes resulted in 1666 gene transcripts with the loss of circadian rhythm including autophagy genes...
February 20, 2024: Kidney International
Margriet E Gosselink, Rozemarijn Snoek, Agne Cerkauskaite-Kerpauskiene, Sophie P J van Bakel, Renee Vollenberg, Henk Groen, Rimante Cerkauskiene, Marius Miglinas, Rossella Attini, Kálmán Tory, Kathleen Claes, Kristel van Calsteren, Aude Servais, Margriet F C de Jong, Valentine Gillion, Liffert Vogt, Antonio Mastrangelo, Monica Furlano, Roser Torra, Kate Bramham, Kate Wiles, Elizabeth R Ralston, Matthew Hall, Lisa Liu, Michelle A Hladunewich, Titia Lely, Albertien M van Eerde
Individualized pre-pregnancy counseling and antenatal care for women with chronic kidney disease (CKD) require disease-specific data. Here, we investigated pregnancy outcomes and long-term kidney function in women with COL4A3-5 related disease (Alport Syndrome, (AS)) in a large multicenter cohort. The ALPART-network (mAternaL and fetal PregnAncy outcomes of women with AlpoRT syndrome), an international collaboration of 17 centers, retrospectively investigated COL4A3-5 related disease pregnancies after the 20th week...
February 19, 2024: Kidney International
Zewu Zhu, Bryan Bo-Ran Ho, Alyssa Chen, James Amrhein, Andreea Apetrei, Thomas Oliver Carpenter, Marise Lazaretti-Castro, Juan Manuel Colazo, Kathryn McCrystal Dahir, Michaela Geßner, Evgenia Gurevich, Cathrine Alsaker Heier, Jill Hickman Simmons, Tracy Earl Hunley, Bernd Hoppe, Christina Jacobsen, Anne Kouri, Nina Ma, Sachin Majumdar, Arnaud Molin, Natalie Nokoff, Susan M Ott, Helena Gil Peña, Fernando Santos, Peter Tebben, Lisa Swartz Topor, Yanhong Deng, Clemens Bergwitz
Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes...
February 15, 2024: Kidney International
Catalin D Voinescu, Monika Mozere, Giulio Genovese, Mallory L Downie, Sanjana Gupta, Daniel P Gale, Detlef Bockenhauer, Robert Kleta, Mauricio Arcos-Burgos, Horia C Stanescu
Class 2 HLA and PLA2R1 alleles are exceptionally strong genetic risk factors for membranous nephropathy (MN), leading, through an unknown mechanism, to a targeted autoimmune response. Introgressed archaic haplotypes (introduced from an archaic human genome into the modern human genome) might influence phenotypes through gene dysregulation. Here, we investigated the genomic region surrounding the PLA2R1 gene. We reconstructed the phylogeny of Neanderthal and modern haplotypes in this region and calculated the probability of the observed clustering being the result of introgression or common descent...
February 14, 2024: Kidney International
Aditi Sinha, Kshetrimayum Ghanapriya Devi, Suprita Kalra, Kalaivani Mani, Pankaj Hari, Arvind Bagga
Initial therapies for children with frequently relapsing nephrotic syndrome include alternate-day prednisolone that is given daily during infections, or levamisole. In this open label, non-inferiority trial, 160 patients, 2 to 18-years-old with frequent relapses, were randomly assigned to receive either prednisolone (0.5-0.7 mg/kg/alternate-day, given daily during infections), or levamisole (2-2.5 mg/kg/alternate-days) for one-year. Patients with relapses on alternate day prednisolone at over 1 mg/kg, prior use of potent steroid-sparing therapies, eGFR under 60 ml/min/1...
February 13, 2024: Kidney International
Jan Czogalla, Simon Schliffke, Shun Lu, Maria Schwerk, Helena Petereit, Tianran Zhang, Shuya Liu, Bernhard Dumoulin, Sydney Gies, Guochao Wu, Sonja Hänzelmann, Marlies Bode, Florian Grahammer, Markus Gödel, Minna Voigtländer, Linus Butt, Carsten Bokemeyer, Carsten Bergmann, Thomas Benzing, Thorsten Wiech, Victor G Puelles, Tobias B Huber
No abstract text is available yet for this article.
February 7, 2024: Kidney International
Chaelin Kang, Donghwan Yun, Haein Yoon, Minki Hong, Juhyeon Hwang, Hyun Mu Shin, Seokwoo Park, Seongmin Cheon, Dohyun Han, Kyung Chul Moon, Hye Young Kim, Eun Young Choi, Eun-Young Lee, Myung Hee Kim, Chang Wook Jeong, Cheol Kwak, Dong Ki Kim, Kook-Hwan Oh, Kwon Wook Joo, Dong-Sup Lee, Yon Su Kim, Seung Seok Han
Toxin- and drug-induced tubulointerstitial nephritis (TIN), characterized by interstitial infiltration of immune cells, frequently necessitates dialysis for patients due to irreversible fibrosis. However, agents modulating interstitial immune cells are lacking. Here, we addressed whether the housekeeping enzyme glutamyl-prolyl-transfer RNA synthetase 1 (EPRS1), responsible for attaching glutamic acid and proline to transfer RNA, modulates immune cell activity during TIN and whether its pharmacological inhibition abrogates fibrotic transformation...
February 5, 2024: Kidney International
Larissa Seifert, Kristoffer Riecken, Gunther Zahner, Julia Hambach, Julia Hagenstein, Gudrun Dubberke, Tobias B Huber, Friedrich Koch-Nolte, Boris Fehse, Nicola M Tomas
No abstract text is available yet for this article.
February 1, 2024: Kidney International
Sean Currin, Jaya A George, Christian Holm Hansen, Saraladevi Naicker, Laurie Tomlinson, Amelia Crampin, Robert Kalyesubula, Robert Newton, Wisdom P Nakanga, Dorothea Nitsch, June Fabian
No abstract text is available yet for this article.
January 31, 2024: Kidney International
Huijing Wang, Mingdi Shen, Yanhong Ma, Lan Lan, Xue Jiang, Xufeng Cen, Gangqiang Guo, Qin Zhou, Mengmeng Yuan, Jianghua Chen, Hongguang Xia, Liang Xiao, Fei Han
Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), but its mechanism of onset remains unclear. Since impaired mitophagy has been implicated in multiple organs in SLE, we hypothesized that mitophagy dysfunction is critical in the development of LN and that pharmacologically targeting mitophagy would ameliorate this disease. Therefore, lupus-prone MRL/MpJ-Faslpr (MRL/lpr) and NZBWF1/J mice were treated with a novel mitophagy inducer, UMI-77, during their onset of LN...
January 29, 2024: Kidney International
Giorgina B Piccoli, Rossella Attini, Massimo Torreggiani, Antoine Chatrenet, Ana Maria Manzione, Bianca Masturzo, Viola Casula, Elisa Longhitano, Eleonora Dalmasso, Luigi Biancone, Antonello Pani, Gianfranca Cabiddu
Little is known about the effect tubulointerstitial nephropathies have in modulating maternal-fetal outcomes in pregnancy. Therefore, we analyzed the main outcomes of pregnancy in these women to gain a better understanding of the role of a reduction in maternal kidney mass. From the Torino Cagliari Observational Study (TOCOS) cohort, we selected 529 patients with a diagnosis of tubulointerstitial disease and focused on 421 patients with chronic kidney disease (CKD) stage 1, without hypertension but with proteinuria less than 0...
January 29, 2024: Kidney International
Nahid Tabibzadeh, Ryuji Morizane
The use of animal models in therapeutic development has long been the standard practice. However, ethical concerns and the inherent species differences have prompted a reevaluation of the experimental approach in human disease studies. The urgent need for alternative model systems that better mimic human pathophysiology has led to the emergence of organoids, innovative in vitro models, to simulate human organs in vitro. These organoids have gained widespread acceptance in disease models, and drug development research...
January 29, 2024: Kidney International
Eric Judd, Vineeta Kumar, Paige M Porrett, Kelly A Hyndman, Douglas Anderson, Maggie Jones-Carr, Andrew Shunk, Daniel R Epstein, Huma Fatima, Akemi Katsurada, Ryousuke Satou, L Gabriel Navar, Jayme E Locke
Demand for kidney grafts outpaces supply, limiting kidney transplantation as a treatment for kidney failure. Xenotransplantation has the potential to make kidney transplantation available to many more patients with kidney failure, but the ability of xenografts to support human physiologic homeostasis has not been established. A brain-dead adult decedent underwent bilateral native nephrectomies followed by 10 gene-edited (four gene knockouts, six human transgenes) pig-to-human xenotransplantation. Physiologic parameters and laboratory values were measured for seven days in a critical care setting...
January 28, 2024: Kidney International
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