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Journal of the American Society of Nephrology: JASN

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https://read.qxmd.com/read/31515244/national-trends-in-utilization-and-1-year-outcomes-with-transplantation-of-hcv-viremic-kidneys
#1
Vishnu S Potluri, David S Goldberg, Sumit Mohan, Roy D Bloom, Deirdre Sawinski, Peter L Abt, Emily A Blumberg, Chirag R Parikh, James Sharpe, K Rajender Reddy, Miklos Z Molnar, Meghan Sise, Peter P Reese
BACKGROUND: Recent pilot trials have demonstrated the safety of transplanting HCV-viremic kidneys into HCV-seronegative recipients. However, it remains unclear if allograft function is impacted by donor HCV-viremia or recipient HCV-serostatus. METHODS: We used national United States registry data to examine trends in HCV-viremic kidney use between 4/1/2015 and 3/31/2019. We applied advanced matching methods to compare eGFR for similar kidneys transplanted into highly similar recipients of kidney transplants...
September 12, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31511363/intradialytic-cerebral-hypoperfusion-as-mechanism-for-cognitive-impairment-in-patients-on-hemodialysis
#2
REVIEW
Dawn F Wolfgram
The high frequency of cognitive impairment in individuals on hemodialysis is well characterized. In-center hemodialysis patients are disproportionately affected by cognitive impairment compared with other dialysis populations, identifying hemodialysis itself as a possible factor. The pathophysiology of cognitive impairment has multiple components, but vascular-mediated cerebral injury appears to contribute based on studies demonstrating increased cerebral ischemic lesions and atrophy in brain imaging of patients on hemodialysis...
September 11, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31511362/inhibition-of-endocytosis-of-clathrin-mediated-angiotensin-ii-receptor-type-1-in-podocytes-augments-glomerular-injury
#3
Kazunori Inoue, Xuefei Tian, Heino Velazquez, Keita Soda, Zhen Wang, Christopher E Pedigo, Ying Wang, Elizabeth Cross, Marwin Groener, Jee-Won Shin, Wei Li, Hossam Hassan, Koichi Yamamoto, Peter Mundel, Shuta Ishibe
BACKGROUND: Inhibition of the renin-angiotensin system remains a cornerstone in reducing proteinuria and progression of kidney failure, effects believed to be the result of reduction in BP and glomerular hyperfiltration. However, studies have yielded conflicting results on whether podocyte-specific angiotensin II (AngII) signaling directly induces podocyte injury. Previous research has found that after AngII stimulation, β -arrestin-bound angiotensin II receptor type 1 (AT1R) is internalized in a clathrin- and dynamin-dependent manner, and that Dynamin1 and Dynamin2 double-knockout mice exhibit impaired clathrin-mediated endocytosis...
September 11, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31511361/at1r-at2r-rxfp1-functional-crosstalk-in-myofibroblasts-impact-on-the-therapeutic-targeting-of-renal-and-cardiac-fibrosis
#4
Bryna S M Chow, Martina Kocan, Matthew Shen, Yan Wang, Lei Han, Jacqueline Y Chew, Chao Wang, Sanja Bosnyak, Katrina M Mirabito-Colafella, Giannie Barsha, Belinda Wigg, Elizabeth K M Johnstone, Mohammed A Hossain, Kevin D G Pfleger, Kate M Denton, Robert E Widdop, Roger J Summers, Ross A D Bathgate, Tim D Hewitson, Chrishan S Samuel
BACKGROUND: Recombinant human relaxin-2 (serelaxin), which has organ-protective actions mediated via its cognate G protein-coupled receptor relaxin family peptide receptor 1 (RXFP1), has emerged as a potential agent to treat fibrosis. Studies have shown that serelaxin requires the angiotensin II (AngII) type 2 receptor (AT2 R) to ameliorate renal fibrogenesis in vitro and in vivo . Whether its antifibrotic actions are affected by modulation of the AngII type 1 receptor (AT1 R), which is expressed on myofibroblasts along with RXFP1 and AT2 R, is unknown...
September 11, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31511360/serious-illness-treatment-preferences-for-older-adults-with-advanced-ckd
#5
Nicolas Awad Baddour, Edward D Siew, Cassianne Robinson-Cohen, Huzaifah Salat, Olivia J Mason, Thomas G Stewart, Mohana Karlekar, Maie H El-Sourady, Loren Lipworth, Khaled Abdel-Kader
BACKGROUND: Patient-centered care for older adults with CKD requires communication about patient's values, goals of care, and treatment preferences. Eliciting this information requires tools that patients understand and that enable effective communication about their care preferences. METHODS: Nephrology clinic patients age ≥60 years with stage 4 or 5 nondialysis-dependent CKD selected one of four responses to the question, "If you had a serious illness, what would be important to you?" Condensed versions of the options were, "Live as long as possible;" "Try treatments, but do not suffer;" "Focus on comfort;" or "Unsure...
September 11, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31506292/effects-of-selonsertib-in-patients-with-diabetic-kidney-disease
#6
Glenn M Chertow, Pablo E Pergola, Fang Chen, Brian J Kirby, John S Sundy, Uptal D Patel
BACKGROUND: Apoptosis signal-regulating kinase 1 (ASK1) activation in glomerular and tubular cells resulting from oxidative stress may drive kidney disease progression. Findings in animal models identified selonsertib, a selective ASK1 inhibitor, as a potential therapeutic agent. METHODS: In a phase 2 trial evaluating selonsertib's safety and efficacy in adults with type 2 diabetes and treatment-refractory moderate-to-advanced diabetic kidney disease, we randomly assigned 333 adults in a 1:1:1:1 allocation to selonsertib (oral daily doses of 2, 6, or 18 mg) or placebo...
September 10, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31506291/does-egfr-by-any-number-mean-the-same
#7
Donald E Wesson
No abstract text is available yet for this article.
September 10, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31506290/modification-of-egfr-based-ckd-definitions-perfect-or-enemy-of-the-good
#8
Glenn M Chertow, Srinivasan Beddhu
No abstract text is available yet for this article.
September 10, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31506289/ckd-a-call-for-an-age-adapted-definition
#9
REVIEW
Pierre Delanaye, Kitty J Jager, Arend Bökenkamp, Anders Christensson, Laurence Dubourg, Bjørn Odvar Eriksen, François Gaillard, Giovanni Gambaro, Markus van der Giet, Richard J Glassock, Olafur S Indridason, Marco van Londen, Christophe Mariat, Toralf Melsom, Olivier Moranne, Gunnar Nordin, Runolfur Palsson, Hans Pottel, Andrew D Rule, Elke Schaeffner, Maarten W Taal, Christine White, Anders Grubb, Jan A J G van den Brand
Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m2 This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage...
September 10, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31501356/from-people-to-lab-rats-to-people-study-of-exercise-in-ckd
#10
EDITORIAL
Kirsten L Johansen
No abstract text is available yet for this article.
September 9, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31501355/voluntary-wheel-running-has-beneficial-effects-in-a-rat-model-of-ckd-mineral-bone-disorder-ckd-mbd
#11
Keith G Avin, Matthew R Allen, Neal X Chen, Shruthi Srinivasan, Kalisha D O'Neill, Ashley D Troutman, Garrison Mast, Elizabeth A Swallow, Mary Beth Brown, Joseph M Wallace, Teresa A Zimmers, Stuart J Warden, Sharon M Moe
BACKGROUND: Reduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality. METHODS: We tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy/+ IU ) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2-3 of CKD...
September 9, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31501354/piperacillin-tazobactam-and-antibiotic-associated-acute-kidney-injury-in-critically-ill-children
#12
Emily L Joyce, Sandra L Kane-Gill, Priyanka Priyanka, Dana Y Fuhrman, John A Kellum
BACKGROUND: There continues to be uncertainty about whether piperacillin/tazobactam (TZP) increases the risk of AKI in critically ill pediatric patients. We sought to compare rates of AKI among critically ill children treated with TZP or cefepime, an alternative frequently used in intensive care units, with and without vancomycin. METHODS: We conducted a retrospective cohort study assessing the risk of AKI in pediatric intensive care unit patients after exposure to vancomycin, TZP, and cefepime, alone or in combination, within 48 hours of admission...
September 9, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31492808/burden-of-ckd-and-cardiovascular-disease-on-life-expectancy-and-health-service-utilization-a-cohort-study-of-hong-kong-chinese-hypertensive-patients
#13
Eric Yuk Fai Wan, Esther Yee Tak Yu, Weng Yee Chin, Daniel Yee Tak Fong, Edmond Pui Hang Choi, Eric Ho Man Tang, Cindy Lo Kuen Lam
BACKGROUND: The relative effects of combinations of CKD, heart disease, and stroke on risk of mortality, direct medical costs, and life expectancy are unknown. METHODS: In a retrospective cohort study of 506,849 Chinese adults in Hong Kong with hypertension, we used Cox regressions to examine associations between all-cause mortality and combinations of moderate CKD (eGFR of 30-59 ml/min per 1.73 m2 ), severe CKD (eGFR of 15-29 ml/min per 1.73 m2 ), heart disease (coronary heart disease or heart failure), and stroke, and modeling to estimate annual public direct medical costs and life expectancy...
September 6, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31492807/a-toolbox-to-characterize-human-induced-pluripotent-stem-cell-derived-kidney-cell-types-and-organoids
#14
Jessica M Vanslambrouck, Sean B Wilson, Ker Sin Tan, Joanne Y-C Soo, Michelle Scurr, H Siebe Spijker, Lakshi T Starks, Amber Neilson, Xiaoxia Cui, Sanjay Jain, Melissa Helen Little, Sara E Howden
BACKGROUND: The generation of reporter lines for cell identity, lineage, and physiologic state has provided a powerful tool in advancing the dissection of mouse kidney morphogenesis at a molecular level. Although use of this approach is not an option for studying human development in vivo , its application in human induced pluripotent stem cells (iPSCs) is now feasible. METHODS: We used CRISPR/Cas9 gene editing to generate ten fluorescence reporter iPSC lines designed to identify nephron progenitors, podocytes, proximal and distal nephron, and ureteric epithelium...
September 6, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31488608/machine-learning-comes-to-nephrology
#15
EDITORIAL
Kevin V Lemley
No abstract text is available yet for this article.
September 5, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31488607/deep-learning-based-histopathologic-assessment-of-kidney-tissue
#16
Meyke Hermsen, Thomas de Bel, Marjolijn den Boer, Eric J Steenbergen, Jesper Kers, Sandrine Florquin, Joris J T H Roelofs, Mark D Stegall, Mariam P Alexander, Byron H Smith, Bart Smeets, Luuk B Hilbrands, Jeroen A W M van der Laak
BACKGROUND: The development of deep neural networks is facilitating more advanced digital analysis of histopathologic images. We trained a convolutional neural network for multiclass segmentation of digitized kidney tissue sections stained with periodic acid-Schiff (PAS). METHODS: We trained the network using multiclass annotations from 40 whole-slide images of stained kidney transplant biopsies and applied it to four independent data sets. We assessed multiclass segmentation performance by calculating Dice coefficients for ten tissue classes on ten transplant biopsies from the Radboud University Medical Center in Nijmegen, The Netherlands, and on ten transplant biopsies from an external center for validation...
September 5, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31488606/computational-segmentation-and-classification-of-diabetic-glomerulosclerosis
#17
Brandon Ginley, Brendon Lutnick, Kuang-Yu Jen, Agnes B Fogo, Sanjay Jain, Avi Rosenberg, Vighnesh Walavalkar, Gregory Wilding, John E Tomaszewski, Rabi Yacoub, Giovanni Maria Rossi, Pinaki Sarder
BACKGROUND: Pathologists use visual classification of glomerular lesions to assess samples from patients with diabetic nephropathy (DN). The results may vary among pathologists. Digital algorithms may reduce this variability and provide more consistent image structure interpretation. METHODS: We developed a digital pipeline to classify renal biopsies from patients with DN. We combined traditional image analysis with modern machine learning to efficiently capture important structures, minimize manual effort and supervision, and enforce biologic prior information onto our model...
September 5, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31462402/single-cell-transcriptomic-map-of-the-human-and-mouse-bladders
#18
Zhenyuan Yu, Jinling Liao, Yang Chen, Chunlin Zou, Haiying Zhang, Jiwen Cheng, Deyun Liu, Tianyu Li, Qingyun Zhang, Jiaping Li, Xiaobo Yang, Yu Ye, Zhiguang Huang, Xinyang Long, Rirong Yang, Zengnan Mo
BACKGROUND: Having a comprehensive map of the cellular anatomy of the normal human bladder is vital to understanding the cellular origins of benign bladder disease and bladder cancer. METHODS: We used single-cell RNA sequencing (scRNA-seq) of 12,423 cells from healthy human bladder tissue samples taken from patients with bladder cancer and 12,884 cells from mouse bladders to classify bladder cell types and their underlying functions. RESULTS: We created a single-cell transcriptomic map of human and mouse bladders, including 16 clusters of human bladder cells and 15 clusters of mouse bladder cells...
August 28, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31451534/cell-autonomous-hedgehog-signaling-is-not-required-for-cyst-formation-in-autosomal-dominant-polycystic-kidney-disease
#19
Ming Ma, Emilie Legué, Xin Tian, Stefan Somlo, Karel F Liem
BACKGROUND: PKD1 or PKD2 , the two main causal genes for autosomal dominant polycystic kidney disease (ADPKD), encode the multipass transmembrane proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Polycystins localize to the primary cilium, an organelle essential for cell signaling, including signal transduction of the Hedgehog pathway. Mutations in ciliary genes that build and maintain the cilium also cause renal cystic disease through unknown pathways. Although recent studies have found alterations in Hedgehog signaling in ADPKD-related models and tissues, the relationship between Hedgehog and polycystic kidney disease is not known...
August 26, 2019: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/31444275/glomerular-immunodeposits-of-patients-with-iga-nephropathy-are-enriched-for-igg-autoantibodies-specific-for-galactose-deficient-iga1
#20
Dana V Rizk, Manish K Saha, Stacy Hall, Lea Novak, Rhubell Brown, Zhi-Qiang Huang, Huma Fatima, Bruce A Julian, Jan Novak
BACKGROUND: IgA nephropathy (IgAN) is the leading primary GN worldwide. The disease is thought to result from glomerular deposition of circulating immune complexes of IgG bound to galactose-deficient IgA1 (Gd-IgA1). However, routine immunofluorescence microscopy fails to detect IgG in many kidney biopsies from patients with IgAN and the specificity of IgG in immunodeposits has not been tested. METHODS: We used remnant frozen kidney-biopsy specimens from 34 patients with IgAN; 14 were IgG-positive and 20 were IgG-negative by routine immunofluorescence microscopy...
August 23, 2019: Journal of the American Society of Nephrology: JASN
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