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Journal of the American Society of Nephrology : JASN

https://read.qxmd.com/read/36446431/negative-modulation-of-b-cell-activation-by-mc1r-signaling-protects-against-membranous-nephropathy
#1
JOURNAL ARTICLE
Bohan Chen, Xuejing Guan, William Gunning, Yan Ge, Amira Gohara, Lance Dworkin, Rujun Gong
BACKGROUND: The pituitary neuropeptide melanocortins, and specifically ACTH, have recently emerged as a novel therapeutic modality for membranous nephropathy (MN). However, the mechanism(s) of action remains elusive. METHODS: Passive Heymann nephritis (PHN), a model of MN, was induced in wild-type (WT) rats and melanocortin 1 receptor (MC1R) knockout (KO) rats generated by the CRISPR/Cas9 technology, followed by treatment with various melanocortin agents, including Repository Corticotropin Injection, the non-steroidogenic pan-MCR agonist NDP-MSH, and the selective MC1R agonist MS05...
November 29, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36446430/risk-stratification-to-predict-renal-survival-in-anti-gbm-disease
#2
JOURNAL ARTICLE
Lauren Floyd, Sebastian Bate, Abdul Kafagi, Nina Brown, Jennifer Scott, Mukunthan Srikantharajah, Marek Mysilvecek, Graeme Reid, Faten Aqeel, Doubravka Frausova, Marek Kollar, Phuong Le Kieu, Bilal Khurshid, Ajay Dhaygude, Vladimir Tesar, Stephen McAdoo, Mark Little, Duvuru Geetha, Silke Brix
Anti-glomerular basement membrane (GBM) disease is a rare, aggressive vasculitis with no validated prediction tools to assist its management. We investigated a retrospective multicenter international cohort with the aim to transfer the Renal Risk Score (RRS) and to identify patients that benefit from rescue immunosuppressive therapy. Of a total 191 patients, 174 patients were included in the final analysis (57% female, median age 59 years). Using Cox and Kaplan-Meier methods, the RRS was found to be a strong and effective predictor for end stage kidney disease (ESKD) with a model concordance of C=0...
November 29, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36418185/reproductive-healthcare-is-a-key-component-of-comprehensive-care-for-adolescents-with-ckd
#3
JOURNAL ARTICLE
Monica Reynolds, Andrea Oliverio, Celina Brunson, Marva Moxey-Mims
No abstract text is available yet for this article.
November 23, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36414418/cell-cycle-and-senescence-regulation-by-podocyte-histone-deacetylase-1-and-2
#4
JOURNAL ARTICLE
Paulina Medina Rangel, Elizabeth Cross, Chang Liu, Christopher Pedigo, Xuefei Tian, Elena Guitierrez-Calabres, Soichiro Nagata, Anupama Priyadarshini, Gabriel Lerner, Patricia Bunda, Sudhir Perincheri, Jianlei Gu, Hongyu Zhao, Ying Wang, Kazunori Inoue, Shuta Ishibe
Background: Intact expression of podocyte histone deacetylases (HDAC) during development is essential for maintaining a normal glomerular filtration barrier due to its role in modulating DNA damage and preventing premature senescence. Methods: Germline podocyte-specific Hdac1 and 2 ( Hdac1/2 ) double knockout mice were generated to examine the importance of these enzymes during development. Results: Podocyte-specific loss of Hdac1/2 in mice resulted in severe proteinuria, kidney failure, and collapsing glomerulopathy...
November 22, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36414417/genetic-variants-in-arhgef6-cause-congenital-anomalies-of-the-kidneys-and-urinary-tract-in-humans-mice-and-frogs
#5
JOURNAL ARTICLE
Verena Klämbt, Florian Buerger, Chunyan Wang, Thomas Naert, Karin Richter, Theresa Nauth, Anna-Carina Weiss, Tobias Sieckmann, Ethan Lai, Dervla Connaughton, Steve Seltzsam, Nina Mann, Amar Majmundar, Chen-Han Wu, Ana Onuchic-Whitford, Shirlee Shril, Sophia Schneider, Luca Schierbaum, Rufeng Dai, Mir Reza Bekheirnia, Marieke Joosten, Omer Shlomovitz, Asaf Vivante, Ehud Banne, Shrikant Mane, Richard P Lifton, Karin Kirschner, Andreas Kispert, Georg Rosenberger, Klaus-Dieter Fischer, Soeren Lienkamp, Mirjam Zegers, Friedhelm Hildebrandt
Background About 40 disease genes have been described to date for isolated congenital anomalies of the kidneys and urinary tract (CAKUT), the most common cause of childhood chronic kidney disease. However, these genes account for only 20% of cases. ARHGEF6, a guanine nucleotide exchange factor that is implicated in such biologic processes as cell migration and focal adhesion, acts downstream of integrin linked kinase (ILK) and parvin proteins. A genetic variant of ILK that causes murine renal agenesis abrogates the interaction of ILK with a murine focal adhesion protein encoded by Parva , leading to CAKUT in mice with this variant...
November 22, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36396331/treatment-effect-of-the-sglt2-inhibitor-empagliflozin-on-chronic-syndrome-of-inappropriate-antidiuresis-results-of-a-randomized-double-blind-placebo-controlled-crossover-trial
#6
JOURNAL ARTICLE
Julie Refardt, Cornelia Imber, Rianne Nobbenhuis, Clara O Sailer, Aaron Haslbauer, Sophie Monnerat, Cemile Bathelt, Deborah R Vogt, Manfred Berres, Bettina Winzeler, Stephanie A Bridenbaugh, Mirjam Christ-Crain
BACKGROUND: The syndrome of inappropriate antidiuresis (SIAD) is characterized by a reduction of free water excretion with consecutive hypotonic hyponatremia and is therefore challenging to treat. The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin promotes osmotic diuresis via urinary glucose excretion, likely leading to increased electrolyte free water clearance. METHODS: In this randomized, double-blind, placebo-controlled, crossover trial, we compared 4-week treatment with empagliflozin 25 mg/d to placebo in outpatients with chronic SIAD-induced hyponatremia...
November 17, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36396330/changes-in-glomerular-volume-sclerosis-and-ischemia-at-5-years-after-kidney-transplantation-incidence-and-correlation-with-late-graft-failure
#7
JOURNAL ARTICLE
Aleksandar Denic, Marija Bogojevic, Rashmi Subramani, Walter D Park, Byron H Smith, Mariam P Alexander, Joseph P Grande, Aleksandra Kukla, Carrie A Schinstock, Andrew J Bentall, Andrew D Rule, Mark D Stegall
BACKGROUND: Histology can provide insight into the biology of renal allograft loss. However, studies are lacking that use quantitative morphometry to simultaneously assess changes in mean glomerular volume and in the percentages of globally sclerosed glomeruli (GSG) and ischemic-appearing glomeruli in surveillance biopsies over time to determine whether such changes are correlated with late graft failure. METHODS: We used digital scans of surveillance biopsies (at implantation and at 1 and 5 years after-transplantation) to morphometrically quantify glomerular volume and the percentages of GSG and ischemic-appearing glomeruli in a cohort of 835 kidney transplants...
November 17, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36368777/national-projections-for-clinical-implications-of-race-free-creatinine-based-gfr-estimating-equations
#8
JOURNAL ARTICLE
James A Diao, Gloria J Wu, Jason K Wang, Isaac S Kohane, Herman A Taylor, Hocine Tighiouart, Andrew S Levey, Lesley A Inker, Neil R Powe, Arjun K Manrai
BACKGROUND: The National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease recently recommended a new race-free creatinine-based equation for eGFR. The effect on recommended clinical care across race and ethnicity groups is unknown. METHODS: We analyzed nationally representative cross-sectional questionnaires and medical examinations from 44,360 participants collected between 2001 and 2018 by the National Health and Nutrition Examination Survey...
November 11, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36351762/the-role-of-platelet-derived-growth-factor-in-focal-segmental-glomerulosclerosis
#9
JOURNAL ARTICLE
Ting Jia, Tong Xu, Bart Smeets, Eva Miriam Buhl, Marcus Johannes Moeller, Jürgen Floege, Barbara Mara Klinkhammer, Peter Boor
BACKGROUND: FSGS is the final common pathway to nephron loss in most forms of severe or progressive glomerular injury. Although podocyte injury initiates FSGS, parietal epithelial cells (PECs) are the main effectors. Because PDGF takes part in fibrotic processes, we hypothesized that the ligand PDGF-B and its receptor PDGFR- β participate in the origin and progression of FSGS. METHODS: We challenged Thy1.1 transgenic mice, which express Thy1.1 in the podocytes, with anti-Thy1...
November 9, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36351761/artificial-intelligence-you-can-trust-what-matters-beyond-performance-when-applying-artificial-intelligence-to-renal-histopathology
#10
REVIEW
John O O Ayorinde, Federica Citterio, Matteo Landrò, Elia Peruzzo, Tuba Islam, Simon Tilley, Geoffrey Taylor, Victoria Bardsley, Pietro Liò, Alex Samoshkin, Gavin J Pettigrew
Although still in its infancy, artificial intelligence (AI) analysis of kidney biopsy images is anticipated to become an integral aspect of renal histopathology. As these systems are developed, the focus will understandably be on developing ever more accurate models, but successful translation to the clinic will also depend upon other characteristics of the system.In the extreme, deployment of highly performant but "black box" AI is fraught with risk, and high-profile errors could damage future trust in the technology...
November 9, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36344066/can-kidney-organoid-xenografts-accelerate-therapeutic-development-for-genetic-kidney-disorders
#11
JOURNAL ARTICLE
Ting-Chun Kuo, Dalia N Cabrera-Barragan, Marta Lopez-Marfil, Diana O Lopez-Cantu, Dario R Lemos
A number of genetic kidney diseases can now be replicated experimentally, using kidney organoids generated from human pluripotent stem cells. This methodology holds great potential for drug discovery. Under in vitro conditions, however, kidney organoids remain developmentally immature, develop scarce vasculature, and may contain undesired off-target cell types. Those critical deficiencies limit their potential as disease-modeling tools. Orthotopic transplantation under the kidney capsule improves the anatomic maturity and vascularization of kidney organoids, while reducing off-target cell content...
November 7, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36332973/slit-diaphragms-junctions-that-never-sleep
#12
EDITORIAL
Iain A Drummond
No abstract text is available yet for this article.
November 4, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36332972/mrna-covid-19-vaccines-and-their-risk-to-induce-a-relapse-of-glomerular-diseases
#13
EDITORIAL
Andreas Kronbichler, Hans-Joachim Anders
No abstract text is available yet for this article.
November 4, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36332971/a-population-based-analysis-of-the-risk-of-glomerular-disease-relapse-after-covid-19-vaccination
#14
JOURNAL ARTICLE
Mark Canney, Mohammad Atiquzzaman, Amanda M Cunningham, Yuyan Zheng, Lee Er, Steven Hawken, Yinshan Zhao, Sean J Barbour
BACKGROUND: Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination. METHODS: In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available)...
November 4, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36302600/the-new-kidney-focused-companies-a-privatized-approach-to-value-based-care-and-addressing-social-determinants-of-health
#15
JOURNAL ARTICLE
Eugene Lin, Gaurav Dave, Abhijit V Kshirsagar
No abstract text is available yet for this article.
October 27, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36302599/early-effect-of-the-circular-model-of-kidney-allocation-in-the-united-states
#16
JOURNAL ARTICLE
Chethan M Puttarajappa, Sundaram Hariharan, Xingyu Zhang, Amit Tevar, Rajil Mehta, Vikraman Gunabushanam, Puneet Sood, William Hoffman, Sumit Mohan
BACKGROUND: In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system on the basis of distance from donor hospital to transplant center within/outside a radius of 250 nautical miles. The effect of this policy on kidney discards and logistics is unknown. METHODS: We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared with a pre-KAS250 cohort from the preceding 2 years...
October 27, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36302598/long-read-sequencing-identifies-novel-pathogenic-intronic-variants-in-gitelman-syndrome
#17
JOURNAL ARTICLE
Daan Viering, Marguerite Hureaux, Kornelia Neveling, Femke Latta, Michael Kwint, Anne Blanchard, Martin Konrad, René Bindels, Karl-Peter Schlingmann, Rosa Vargas-Poussou, Jeroen de Baaij
Background: Gitelman syndrome is a salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. It is caused by homozygous recessive or compound heterozygous pathogenic variants in SLC12A3 , which encodes the Na+ -Cl- cotransporter (NCC). In up to 10% of patients with Gitelman syndrome, current genetic techniques detect only one specific pathogenic variant. This study aimed to identify a second pathogenic variant in introns, splice sites, or promoters to increase the diagnostic yield. Methods: Long read sequencing of SLC12A3 was performed in 67 DNA samples from individuals with suspected Gitelman syndrome in whom a single likely pathogenic or pathogenic variant was previously detected...
October 27, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36302597/genomic-disorders-in-chronic-kidney-disease-across-the-lifespan
#18
JOURNAL ARTICLE
Miguel Verbitsky, Sarathbabu Krishnamurthy, Priya Krithivasan, Daniel Hughes, Atlas Khan, Maddalena Marasa, Natalie Vena, Jun Zhang, Tze Lim, Joseph Glessner, Pavan Khosla, Chunhua Weng, Ning Shang, Yufeng Shen, George Hripcsak, Hakon Hakonarson, Iuliana Ionita-Laza, Brynn Levy, Eimear Kenny, Ruth Loos, Krzysztof Kiryluk, Simone Sanna-Cherchi, David Crosslin, Susan Furth, Bradley Warady, Robert Igo, Sudha Iyengar, Craig Wong, Afshin Parsa, Harold Feldman, Ali Gharavi
Background: Genomic Disorders (GDs) are associated with many comorbid outcomes, including chronic kidney disease (CKD). Identification of GDs has diagnostic utility. Methods: We examined the prevalence of GDs among participants in the Chronic Kidney Disease in Children (CKiD) cohort II (N=248), Chronic Renal Insufficiency Cohort study (CRIC, N = 3,375), Columbia University CKD Biobank (CU-CKD, N=1,146), and the Family Investigation of Nephropathy and Diabetes (FIND, N=1,318) compared to 30,746 controls. We also performed a phenome-wide association analysis (PheWAS) of GDs in the electronic MEdical Records and GEnomics (eMERGE; N=11,146) cohort...
October 27, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36288905/testican-2-is-associated-with-reduced-risk-of-incident-eskd
#19
JOURNAL ARTICLE
Donghai Wen, Linda Zhou, Zihe Zheng, Aditya Surapaneni, Christie Ballantyne, Ron Hoogeveen, Michael Shlipak, Sushrut Waikar, Ramachandra Vasan, Paul Kimmel, Ruth Dubin, Rajat Deo, Harold Feldman, Peter Ganz, Josef Coresh, Morgan Grams, Eugene Rhee
Background: Testican-2 was recently identified as a podocyte-derived protein that is released into circulation by the kidneys and is positively correlated with estimated glomerular filtration rate (eGFR) and eGFR slope. However, whether higher testican-2 levels are associated with lower risk of end stage kidney disease (ESKD) is unknown. Methods: Aptamer-based proteomics assessed blood testican-2 levels among participants in the African American Study of Kidney Disease and Hypertension (AASK, n=703), the Chronic Renal Insufficiency Cohort (CRIC) study (n=3,196), and the Atherosclerosis Risk in Communities (ARIC) study (n=4,378)...
October 26, 2022: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/36288904/distinguishing-among-hco-3-co-3-and-h-as-substrates-of-proteins-that-appear-to-be-bicarbonate-transporters
#20
JOURNAL ARTICLE
Seong-Ki Lee, Rossana Occhipinti, Fraser J Moss, Mark D Parker, Irina I Grichtchenko, Walter F Boron
BACKGROUND: Differentiating among HCO3 - , CO3 = , and H+ movements across membranes has long seemed impossible. We now seek to discriminate unambiguously among three alternate mechanisms: the inward flux of 2 HCO3 - (mechanism 1), the inward flux of 1 CO3 = (mechanism 2), and the CO2 /HCO3 - -stimulated outward flux of 2 H+ (mechanism 3). METHODS: As a test case, we use electrophysiology and heterologous expression in Xenopus oocytes to examine SLC4 family members that appear to transport "bicarbonate" ("HCO3 - ")...
October 26, 2022: Journal of the American Society of Nephrology: JASN
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