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(Source: Kidney International)
Source: Kidney International - February 20, 2024 Category: Urology & Nephrology Source Type: research

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(Source: Kidney International)
Source: Kidney International - February 20, 2024 Category: Urology & Nephrology Source Type: research

Table of Contents
(Source: Kidney International)
Source: Kidney International - February 20, 2024 Category: Urology & Nephrology Source Type: research

The role of desmoglein-2 in kidney disease
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 e...
Source: Kidney International - February 20, 2024 Category: Urology & Nephrology Authors: Tong Xu, Lea Herkens, Ting Jia, Barbara M. Klinkhammer, Sebastian Kant, Claudia A. Krusche, Eva M. Buhl, Sikander Hayat, J ürgen Floege, Pavel Strnad, Rafael Kramann, Sonja Djudjaj, Peter Boor Tags: basic research Source Type: research

Disrupting circadian control of autophagy induces podocyte injury and proteinuria
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 rh ythms. Deletion of Clock in podocytes resulted in 1666 gene transcripts with the loss of circadian rhythm including autophagy genes. (Source: Kidney International)
Source: Kidney International - February 20, 2024 Category: Urology & Nephrology Authors: Lulu Wang, Han Tian, Haiyan Wang, Xiaoming Mao, Jing Luo, Qingyun He, Ping Wen, Hongdi Cao, Li Fang, Yang Zhou, Junwei Yang, Lei Jiang Tags: basic research Source Type: research

Reassuring pregnancy outcomes in women with mild COL4A3-5 –related disease (Alport Syndrome) and genetic type of disease can aid personalized counseling
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. (Source: Kidney International)
Source: Kidney International - February 18, 2024 Category: Urology & Nephrology Authors: Margriet E. Gosselink, Rozemarijn Snoek, Agne Cerkauskaite-Kerpauskiene, Sophie P.J. van Bakel, Renee Vollenberg, Henk Groen, Rimante Cerkauskiene, Marius Miglinas, Rossella Attini, K álmán Tory, Kathleen Claes, Kristel van Calsteren, Aude Servais, Marg Tags: clinical investigation Source Type: research

Reassuring pregnancy outcomes in women with mild COL4A3-5 related disease (Alport Syndrome) as the genetic type of disease can aid personalized counseling.
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. (Source: Kidney International)
Source: Kidney International - February 18, 2024 Category: Urology & Nephrology Authors: Margriet E. Gosselink, Rozemarijn Snoek, Agne Cerkauskaite-Kerpauskiene, Sophie P.J. van Bakel, Renee Vollenberg, Henk Groen, Rimante Cerkauskiene, Marius Miglinas, Rossella Attini, K álmán Tory, Kathleen Claes, Kristel van Calsteren, Aude Servais, Marg Tags: clinical investigation Source Type: research

A Neanderthal haplotype introgressed into the human genome confers protection against membranous nephropathy
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. (Source: Kidney International)
Source: Kidney International - February 14, 2024 Category: Urology & Nephrology Authors: 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 Tags: Basic Research Source Type: research

An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).
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. (Source: Kidney International)
Source: Kidney International - February 14, 2024 Category: Urology & Nephrology Authors: 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 Ge ßner, Evgenia Gurevich, Cathrine Alsaker Heier, Jill Hickman Simmons, Tracy Tags: clinical investigation Source Type: research

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