An open label non-inferiority randomized controlled trial evaluated alternate day prednisolone given daily during infections vs. levamisole in frequently relapsing nephrotic syndrome
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/1.73 m2 and significant steroid toxicity were excluded....
Source: Kidney International - February 13, 2024 Category: Urology & Nephrology Authors: Aditi Sinha, Kshetrimayum Ghanapriya Devi, Suprita Kalra, Kalaivani Mani, Pankaj Hari, Arvind Bagga Tags: clinical trial Source Type: research
An open label non-inferiority randomized control trial evaluated alternate day prednisolone given daily during infections vs. levamisole in frequently relapsing nephrotic syndrome.
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 assignedto receive either prednisolone (0.5-0.7 mg/kg/alternate-day, given daily during infections), orlevamisole (2-2.5 mg/kg/alternate-days) for one-year. Patients with relapses on alternate dayprednisolone at over 1 mg/kg, prior use of potent steroid-sparing therapies, eGFR under 60ml/min/1.73 m2 and significant steroid toxicity were excluded. (So...
Source: Kidney International - February 13, 2024 Category: Urology & Nephrology Authors: Aditi Sinha, Kshetrimayum Ghanapriya Devi, Suprita Kalra, Kalaivani Mani, Pankaj Hari, Arvind Bagga Tags: clinical trial Source Type: research
Ibrutinib-Associated Focal Segmental Glomerulosclerosis and the Impact of Podocin Mutations in Chronic Lymphocytic Leukemia
The Bruton ’s tyrosine kinase inhibitor Ibrutinib (IBRU) is essential for treating chronic lymphocytic leukemia (CLL).1 In CLL, BTK inhibition hinders proliferation by actin cytoskeleton destabilization and apoptosis induction.2 Unfortunately, Ibrutinib’s nonspecific binding to other kinases leads to adver se effects, including cardiac toxicity.3, S1-S2 During a phase 1b-2 study, 23% of patients experienced elevated serum creatinine and edema.4 Kidney injury linked to Ibrutinib use remains poorly understood. (Source: Kidney International)
Source: Kidney International - February 7, 2024 Category: Urology & Nephrology Authors: Jan Czogalla, Simon Schliffke, Shun Lu, Maria Schwerk, Helena Petereit, Tianran Zhang, Shuya Liu, Bernhard Dumoulin, Sydney Gies, Guochao Wu, Sonja H änzelmann, Marlies Bode, Florian Grahammer, Markus Gödel, Minna Voigtländer, Linus Butt, Carsten Bokem Tags: research letter Source Type: research
Glutamyl-prolyl-tRNA synthetase (EPRS1) drives tubulointerstitial nephritis-induced fibrosis by enhancing T cell proliferation and activity.
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 house keeping 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. (Source: Kidney International)
Source: Kidney International - February 4, 2024 Category: Urology & Nephrology Authors: 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 O Tags: basic research Source Type: research
An antigen-specific chimeric autoantibody receptor (CAAR) NK cell strategy for the elimination of anti-PLA2R1 and anti-THSD7A antibody-secreting cells
Membranous nephropathy (MN) is an antibody-mediated disease of the kidney, typically resulting in nephrotic syndrome with urinary loss of high amounts of albumin and other plasma proteins. Phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing protein 7A (THSD7A) were the first kidney autoantigens identified in adult patients with MN.1,2 Importantly, we and others could demonstrate that autoantibodies in MN are not only excellent biomarkers to monitor immunologic disease activity, but also cause the disease through the direct interaction with the autoantigen expressed on podocytes in the kidney. (...
Source: Kidney International - February 1, 2024 Category: Urology & Nephrology Authors: Larissa Seifert, Kristoffer Riecken, Gunther Zahner, Julia Hambach, Julia Hagenstein, Gudrun Dubberke, Tobias B. Huber, Friedrich Koch-Nolte, Boris Fehse, Nicola M. Tomas Tags: Research Letter Source Type: research
An antigen-specific chimeric autoantibody receptor NK cell strategy for the elimination of anti-PLA2R1 and anti-THSD7A antibody-secreting cells
Membranous nephropathy (MN) is an antibody-mediated disease of the kidney, typically resulting in nephrotic syndrome with urinary loss of high amounts of albumin and other plasma proteins. Phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing protein 7A (THSD7A) were the first renal autoantigens identified in adult patients with MN.1,2 Importantly, we and others could demonstrate that autoantibodies in MN are not only excellent biomarkers to monitor immunological disease activity, but also cause the disease through the direct interaction with the autoantigen expressed on podocytes in the kidney. ...
Source: Kidney International - February 1, 2024 Category: Urology & Nephrology Authors: Larissa Seifert, Kristoffer Riecken, Gunther Zahner, Julia Hambach, Julia Hagenstein, Gudrun Dubberke, Tobias B. Huber, Friedrich Koch-Nolte, Boris Fehse, Nicola M. Tomas Tags: research letter Source Type: research
Single-sample measured glomerular filtration rate in Malawi, South Africa, and Uganda
Measured glomerular filtration rate (mGFR) is considered the best index of kidney function.1 Various mGFR methods exist; utilising urinary or plasma clearance of exogenous markers, each with their own advantages and disadvantages.2 Most commonly, mGFR is calculated from multipoint sampling using the slope intercept method and applying the Brochner-Mortensen correction.3 Because of the time needed for the multi-sample test, between 4 and 6 hours depending on GFR, various single-sample methods have evolved to simplify the mGFR procedure while aiming to preserve accuracy. (Source: Kidney International)
Source: Kidney International - January 31, 2024 Category: Urology & Nephrology Authors: 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 Tags: research letter Source Type: research
Advancements in therapeutic development: kidney organoids and organs on a chip
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. (Source: Kidney International)
Source: Kidney International - January 29, 2024 Category: Urology & Nephrology Authors: Nahid Tabibzadeh, Ryuji Morizane Tags: Mini Review Source Type: research
Novel mitophagy inducer alleviates lupus nephritis by reducing myeloid cell activation and autoantigen presentation.
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. (Source: Kidney International)
Source: Kidney International - January 29, 2024 Category: Urology & Nephrology Authors: 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 Tags: basic research Source Type: research
Any reduction in maternal kidney mass makes a difference during pregnancy in gestational and fetal outcome.
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 0.5 g/day at referral. (Source: Kidney International)
Source: Kidney International - January 29, 2024 Category: Urology & Nephrology Authors: 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 Tags: clinical investigation Source Type: research
Advancements in Therapeutic Development: Kidney Organoids and Organs-on-a-Chip
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. (Source: Kidney International)
Source: Kidney International - January 29, 2024 Category: Urology & Nephrology Authors: Nahid Tabibzadeh, Ryuji Morizane Tags: mini review Source Type: research
Physiologic Homeostasis after Pig-to-Human Kidney Xenotransplantation
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. (Source: Kidney International)
Source: Kidney International - January 28, 2024 Category: Urology & Nephrology Authors: 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 Tags: landmark communication Source Type: research
Critical Role of histone deacetylase 3 in the regulation of kidney inflammation and fibrosis
Chronic kidney disease (CKD) is characterized by kidney inflammation and fibrosis. However, the precise mechanisms leading to kidney inflammation and fibrosis are poorly understood. Since histone deacetylase is involved in inflammation and fibrosis in other tissues, we examined the role of histone deacetylase 3 (HDAC3) in the regulation of inflammation and kidney fibrosis. HDAC3 is induced in the kidneys of animal models of CKD but mice with conditional HDAC3 deletion exhibit significantly reduced fibrosis in the kidneys compared with control mice. (Source: Kidney International)
Source: Kidney International - January 27, 2024 Category: Urology & Nephrology Authors: Yuguo Wang, Baihai Jiao, Zhaoyong Hu, Yanlin Wang Tags: Basic Research Source Type: research
Critical Role of histone deacetylase 3 in the regulation of kidney inflammation and fibrosis.
In this study, we examined the role of histone deacetylase 3 (HDAC3) in the regulation of inflammation and renal fibrosis. HDAC3 is induced in the kidneys of animal models of CKD. Mice with conditional HDAC3 deletion exhibited significantly reduced fibrosis in the kidneys compared with control mice. The expression of pro-inflammatory and pro-fibrotic genes was significantly increased in the fibrotic kidneys of control mice, which were impaired in mice with HDAC3 deletion. (Source: Kidney International)
Source: Kidney International - January 27, 2024 Category: Urology & Nephrology Authors: Yuguo Wang, Baihai Jiao, Zhaoyong Hu, Yanlin Wang Tags: basic research Source Type: research
Unbiased kidney-centric molecular categorization of chronic kidney disease as a step towards precision medicine.
Current classification of chronic kidney disease (CKD) into stages using indirect systemic measures (estimated glomerular filtration rate (eGFR) and albuminuria) is agnostic to the heterogeneity of underlying molecular processes in the kidney thereby limiting precision medicine approaches. To generate a novel CKD categorization that directly reflects within kidney disease drivers we analyzed publicly available transcriptomic data from kidney biopsy tissue. A Self-Organizing Maps unsupervised artificial neural network machine-learning algorithm was used to stratify a total of 369 patients with CKD and 46 living kidney donor...
Source: Kidney International - January 26, 2024 Category: Urology & Nephrology Authors: Anna Reznichenko, Viji Nair, Sean Eddy, Damian Fermin, Mark Tomilo, Timothy Slidel, Wenjun Ju, Ian Henry, Shawn S. Badal, Johnna D. Wesley, John T. Liles, Sven Moosmang, Julie M. Williams, Carol Moreno Quinn, Markus Bitzer, Jeffrey B. Hodgin, Laura Bariso Tags: clinical investigation Source Type: research
