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Journal of the American Society of Nephrology: JASN

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https://www.readbyqxmd.com/read/28747315/renal-tubular-cell-derived-extracellular-vesicles-accelerate-the-recovery-of-established-renal-ischemia-reperfusion-injury
#1
Jesus H Dominguez, Yunlong Liu, Hongyu Gao, James M Dominguez, Danhui Xie, K J Kelly
Ischemic renal injury is a complex syndrome; multiple cellular abnormalities cause accelerating cycles of inflammation, cellular damage, and sustained local ischemia. There is no single therapy that effectively resolves the renal damage after ischemia. However, infusions of normal adult rat renal cells have been a successful therapy in several rat renal failure models. The sustained broad renal benefit achieved by relatively few donor cells led to the hypothesis that extracellular vesicles (EV, largely exosomes) derived from these cells are the therapeutic effector in situ We now show that EV from adult rat renal tubular cells significantly improved renal function when administered intravenously 24 and 48 hours after renal ischemia in rats...
July 26, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28739650/lysophosphatidic-acid-receptor-antagonism-protects-against-diabetic-nephropathy-in-a-type-2-diabetic-model
#2
Ming-Zhi Zhang, Xin Wang, Haichun Yang, Agnes B Fogo, Brian J Murphy, Robert Kaltenbach, Peter Cheng, Bradley Zinker, Raymond C Harris
Lysophosphatidic acid (LPA) functions through activation of LPA receptors (LPARs). LPA-LPAR signaling has been implicated in development of fibrosis. However, the role of LPA-LPAR signaling in development of diabetic nephropathy (DN) has not been studied. We examined whether BMS002, a novel dual LPAR1 and LPAR3 antagonist, affects development of DN in endothelial nitric oxide synthase-knockout db/db mice. Treatment of these mice with BMS002 from 8 to 20 weeks of age led to a significant reduction in albuminuria, similar to that observed with renin-angiotensin system inhibition (losartan plus enalapril)...
July 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28739649/persistent-microscopic-hematuria-as-a-risk-factor-for-progression-of-iga-nephropathy-new-floodlight-on-a-nearly-forgotten-biomarker
#3
EDITORIAL
Rosanna Coppo, Fernando C Fervenza
No abstract text is available yet for this article.
July 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28739648/hepatocyte-nuclear-factor-1%C3%AE-controls-mitochondrial-respiration-in-renal-tubular-cells
#4
Audrey Casemayou, Audren Fournel, Alessia Bagattin, Joost Schanstra, Julie Belliere, Stéphane Decramer, Dimitri Marsal, Marion Gillet, Nicolas Chassaing, Antoine Huart, Marco Pontoglio, Claude Knauf, Jean-Loup Bascands, Dominique Chauveau, Stanislas Faguer
AKI is a frequent condition that involves renal microcirculation impairment, infiltration of inflammatory cells with local production of proinflammatory cytokines, and subsequent epithelial disorders and mitochondrial dysfunction. Peroxisome proliferator-activated receptor γ coactivator 1-α (PPARGC1A), a coactivator of the transcription factor PPAR-γ that controls mitochondrial biogenesis and function, has a pivotal role in the early dysfunction of the proximal tubule and the subsequent renal repair. Here, we evaluated the potential role of hepatocyte nuclear factor-1β (HNF-1β) in regulating PPARGC1A expression in AKI...
July 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28739647/compensatory-distal-reabsorption-drives-diuretic-resistance-in-human-heart-failure
#5
Veena S Rao, Noah Planavsky, Jennifer S Hanberg, Tariq Ahmad, Meredith A Brisco-Bacik, Francis P Wilson, Daniel Jacoby, Michael Chen, W H Wilson Tang, David Z I Cherney, David H Ellison, Jeffrey M Testani
Understanding the tubular location of diuretic resistance (DR) in heart failure (HF) is critical to developing targeted treatment strategies. Rodents chronically administered loop diuretics develop DR due to compensatory distal tubular sodium reabsorption, but whether this translates to human DR is unknown. We studied consecutive patients with HF (n=128) receiving treatment with loop diuretics at the Yale Transitional Care Center. We measured the fractional excretion of lithium (FELi), the gold standard for in vivo assessment of proximal tubular and loop of Henle sodium handling, to assess sodium exit after loop diuretic administration and FENa to assess the net sodium excreted into the urine...
July 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28733368/moving-beyond-the-assumed-improving-fistula-success-rates
#6
EDITORIAL
Jay B Wish, Sharon M Moe
No abstract text is available yet for this article.
July 21, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28729289/class-ii-eplet-mismatch-modulates-tacrolimus-trough-levels-required-to-prevent-donor-specific-antibody-development
#7
Chris Wiebe, David N Rush, Thomas E Nevins, Patricia E Birk, Tom Blydt-Hansen, Ian W Gibson, Aviva Goldberg, Julie Ho, Martin Karpinski, Denise Pochinco, Atul Sharma, Leroy Storsley, Arthur J Matas, Peter W Nickerson
Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds <6 ng/ml and the mean tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch...
July 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28729288/urinary-extracellular-vesicles-of-podocyte-origin-and-renal-injury-in-preeclampsia
#8
Sarwat I Gilani, Ulrik Dolberg Anderson, Muthuvel Jayachandran, Tracey L Weissgerber, Ladan Zand, Wendy M White, Natasa Milic, Maria Lourdes Gonzalez Suarez, Rangit Reddy Vallapureddy, Åsa Nääv, Lena Erlandsson, John C Lieske, Joseph P Grande, Karl A Nath, Stefan R Hansson, Vesna D Garovic
Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma...
July 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28729287/bp-targets-in-ckd-mortality-and-sprint-what-have-we-learned
#9
EDITORIAL
Stephen C Textor, Gary L Schwartz
No abstract text is available yet for this article.
July 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28724775/n-degradomic-analysis-reveals-a-proteolytic-network-processing-the-podocyte-cytoskeleton
#10
Markus M Rinschen, Ann-Kathrin Hoppe, Florian Grahammer, Martin Kann, Linus A Völker, Eva-Maria Schurek, Julie Binz, Martin Höhne, Fatih Demir, Milena Malisic, Tobias B Huber, Christine Kurschat, Jayachandran N Kizhakkedathu, Bernhard Schermer, Pitter F Huesgen, Thomas Benzing
Regulated intracellular proteostasis, controlled in part by proteolysis, is essential in maintaining the integrity of podocytes and the glomerular filtration barrier of the kidney. We applied a novel proteomics technology that enables proteome-wide identification, mapping, and quantification of protein N-termini to comprehensively characterize cleaved podocyte proteins in the glomerulus in vivo We found evidence that defined proteolytic cleavage results in various proteoforms of important podocyte proteins, including those of podocin, nephrin, neph1, α-actinin-4, and vimentin...
July 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28724774/histopathology-of-veins-obtained-at-hemodialysis-arteriovenous-fistula-creation-surgery
#11
Charles E Alpers, Peter B Imrey, Kelly L Hudkins, Tomasz A Wietecha, Milena Radeva, Michael Allon, Alfred K Cheung, Laura M Dember, Prabir Roy-Chaudhury, Yan-Ting Shiu, Christi M Terry, Alik Farber, Gerald J Beck, Harold I Feldman, John W Kusek, Jonathan Himmelfarb
Stenosis from venous neointimal hyperplasia is common in native arteriovenous fistulas (AVFs). However, the preexisting histologic characteristics of veins at fistula creation, and associations thereof with baseline patient factors, have not been well characterized. In this study, we conducted histologic analysis of a segment of the vein used for anastomosis creation, obtained during AVF creation from 554 of the 602 participants in the multicenter Hemodialysis Fistula Maturation Cohort Study. We quantified intimal and medial areas and lengths of the internal and external elastic lamina by morphometry and assessed venous wall cells by immunohistochemistry, extracellular matrix with Movat stain, and calcium deposition by alizarin red stain...
July 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28720685/the-loss-of-gstm1-associates-with-kidney-failure-and-heart-failure
#12
Adrienne Tin, Robert Scharpf, Michelle M Estrella, Bing Yu, Megan L Grove, Patricia P Chang, Kunihiro Matsushita, Anna Köttgen, Dan E Arking, Eric Boerwinkle, Thu H Le, Josef Coresh, Morgan E Grams
Glutathione S-transferase mu 1 (GSTM1) encodes an enzyme that catalyzes the conjugation of electrophilic compounds with glutathione to facilitate their degradation or excretion. The loss of one or both copies of GSTM1 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of GSTM1 is also associated with incident kidney failure and heart failure, we estimated GSTM1 copy number using exome sequencing reads in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based prospective cohort of white and black participants...
July 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28720684/fsgs-as-an-adaptive-response-to-growth-induced-podocyte-stress
#13
Ryuzoh Nishizono, Masao Kikuchi, Su Q Wang, Mahboob Chowdhury, Viji Nair, John Hartman, Akihiro Fukuda, Larysa Wickman, Jeffrey B Hodgin, Markus Bitzer, Abhijit Naik, Jocelyn Wiggins, Matthias Kretzler, Roger C Wiggins
Glomerular sclerotic lesions develop when the glomerular filtration surface area exceeds the availability of podocyte foot process coverage, but the mechanisms involved are incompletely characterized. We evaluated potential mechanisms using a transgenic (podocin promoter-AA-4E-BP1) rat in which podocyte capacity for hypertrophy in response to growth factor/nutrient signaling is impaired. FSGS lesions resembling human FSGS developed spontaneously by 7 months of age, and could be induced earlier by accelerating kidney hypertrophy by nephrectomy...
July 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28720683/microrna-as-novel-exercise-mimetic-for-muscle-wasting-in-ckd
#14
EDITORIAL
Robert H Mak, Wai W Cheung
No abstract text is available yet for this article.
July 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28716959/podocyte-growing-pains-in-adaptive-fsgs
#15
EDITORIAL
Vivette D D'Agati
No abstract text is available yet for this article.
July 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28710092/a-missense-mutation-in-the-extracellular-domain-of-%C3%AE-enac-causes-liddle-syndrome
#16
Mahdi Salih, Ivan Gautschi, Miguel X van Bemmelen, Michael Di Benedetto, Alice S Brooks, Dorien Lugtenberg, Laurent Schild, Ewout J Hoorn
Liddle syndrome is an autosomal dominant form of hypokalemic hypertension due to mutations in the β- or γ-subunit of the epithelial sodium channel (ENaC). Here, we describe a family with Liddle syndrome due to a mutation in αENaC. The proband was referred because of resistant hypokalemic hypertension, suppressed renin and aldosterone, and no mutations in the genes encoding β- or γENaC. Exome sequencing revealed a heterozygous, nonconservative T>C single-nucleotide mutation in αENaC that substituted Cys479 with Arg (C479R)...
July 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28710091/intimal-hyperplasia-stenosis-and-arteriovenous-fistula-maturation-failure-in-the-hemodialysis-fistula-maturation-study
#17
Alfred K Cheung, Peter B Imrey, Charles E Alpers, Michelle L Robbin, Milena Radeva, Brett Larive, Yan-Ting Shiu, Michael Allon, Laura M Dember, Tom Greene, Jonathan Himmelfarb, Prabir Roy-Chaudhury, Christi M Terry, Miguel A Vazquez, John W Kusek, Harold I Feldman
Intimal hyperplasia and stenosis are often cited as causes of arteriovenous fistula maturation failure, but definitive evidence is lacking. We examined the associations among preexisting venous intimal hyperplasia, fistula venous stenosis after creation, and clinical maturation failure. The Hemodialysis Fistula Maturation Study prospectively observed 602 men and women through arteriovenous fistula creation surgery and their postoperative course. A segment of the vein used to create the fistula was collected intraoperatively for histomorphometric examination...
July 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28710090/the-clinical-and-economic-effect-of-vascular-access-selection-in-patients-initiating-hemodialysis-with-a-catheter
#18
Alian Al-Balas, Timmy Lee, Carlton J Young, Jeffrey A Kepes, Jill Barker-Finkel, Michael Allon
Patients in the United States frequently initiate hemodialysis with a central venous catheter (CVC) and subsequently undergo placement of a new arteriovenous fistula (AVF) or arteriovenous graft (AVG). Little is known about the clinical and economic effects of initial vascular access choice. We identified 479 patients starting hemodialysis with a CVC at a large medical center (during 2004-2012) who subsequently had an AVF (n=295) or AVG (n=105) placed or no arteriovenous access (CVC group, n=71). Compared with patients receiving an AVG, those receiving an AVF had more frequent surgical access procedures per year (1...
July 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28710089/endothelium-neutrophil-communication-via-b1-kinin-receptor-bearing-microvesicles-in-vasculitis
#19
EDITORIAL
Pierre-Louis Tharaux, Neeraj Dhaun
No abstract text is available yet for this article.
July 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28705920/nephron-remodeling-underlies-hyperkalemia-in-familial-hyperkalemic-hypertension
#20
EDITORIAL
James A McCormick, David H Ellison
No abstract text is available yet for this article.
July 13, 2017: Journal of the American Society of Nephrology: JASN
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