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Journal of the American Society of Nephrology: JASN

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https://www.readbyqxmd.com/read/29142050/collectin-11-promotes-the-development-of-renal-tubulointerstitial-fibrosis
#1
Weiju Wu, Chengfei Liu, Conrad A Farrar, Liang Ma, Xia Dong, Steven H Sacks, Ke Li, Wuding Zhou
Collectin-11 is a recently described soluble C-type lectin, a pattern recognition molecule of the innate immune system that has distinct roles in host defense, embryonic development, and acute inflammation. However, little is known regarding the role of collectin-11 in tissue fibrosis. Here, we investigated collectin-11 in the context of renal ischemia-reperfusion injury. Compared with wild-type littermate controls, Collec11 deficient (CL-11(-/-) ) mice had significantly reduced renal functional impairment, tubular injury, renal leukocyte infiltration, renal tissue inflammation/fibrogenesis, and collagen deposition in the kidneys after renal ischemia-reperfusion injury...
November 15, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29127112/reduced-expression-of-glutathione-s-transferase-%C3%AE-4-promotes-vascular-neointimal-hyperplasia-in-ckd
#2
Jinlong Luo, Guang Chen, Ming Liang, Aini Xie, Qingtian Li, Qunying Guo, Rajendra Sharma, Jizhong Cheng
Neointima formation is the leading cause of arteriovenous fistula (AVF) failure. We have shown that CKD accelerates this process by transforming the vascular smooth muscle cells (SMCs) lining the AVF from a contractile to the synthetic phenotype. However, the underlying mechanisms affecting this transformation are not clear. Previous studies have shown that the α-class glutathione transferase isozymes have an important role in regulating 4-hydroxynonenal (4-HNE)-mediated proliferative signaling of cells. Here, using both the loss- and gain-of-function approaches, we investigated the role of glutathione S-transferase α4 (GSTA4) in modulating cellular 4-HNE levels for the transformation and proliferation of SMCs...
November 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29118087/overweight-and-obesity-are-predictors-of-progression-in-early-autosomal-dominant-polycystic-kidney-disease
#3
Kristen L Nowak, Zhiying You, Berenice Gitomer, Godela Brosnahan, Vincente E Torres, Arlene B Chapman, Ronald D Perrone, Theodore I Steinman, Kaleab Z Abebe, Frederic F Rahbari-Oskoui, Alan S L Yu, Peter C Harris, Kyongtae T Bae, Marie Hogan, Dana Miskulin, Michel Chonchol
The association of overweight/obesity with disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) remains untested. We hypothesized that overweight/obesity associates with faster progression in early-stage ADPKD. Overall, 441 nondiabetic participants with ADPKD and an eGFR>60 ml/min per 1.73 m(2) who participated in the Halt Progression of Polycystic Kidney Disease Study A were categorized on the basis of body mass index (BMI; calculated using nonkidney and nonliver weight) as normal weight (18...
November 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29114042/deletion-variants-of-cfhr1-and-cfhr3-associate-with-mesangial-immune-deposits-but-not-with-progression-of-iga-nephropathy
#4
Perrine Jullien, Blandine Laurent, Guillaume Claisse, Ingrid Masson, Miriana Dinic, Damien Thibaudin, Francois Berthoux, Eric Alamartine, Christophe Mariat, Nicolas Maillard
Activation of complement through the alternative pathway has a key role in the pathogenesis of IgA nephropathy (IgAN). Large, international, genome-wide association studies have shown that deletion of complement factor H-related genes 1 and 3 (CFHR3,1Δ) is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown. Here, we compared the renal outcomes of patients with IgAN according to their CFHR3,1Δ genotype. This retrospective, monocentric cohort study included 639 white patients with biopsy-proven IgAN since 1979 (mean age at diagnosis, 40...
November 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29114041/phospholipase-a2-receptor-1-epitope-spreading-at-baseline-predicts-reduced-likelihood-of-remission-of-membranous-nephropathy
#5
Barbara Seitz-Polski, Hanna Debiec, Alexandra Rousseau, Karine Dahan, Christelle Zaghrini, Christine Payré, Vincent L M Esnault, Gérard Lambeau, Pierre Ronco
The phospholipase A2 receptor (PLA2R1) is the major autoantigen in primary membranous nephropathy. Several PLA2R1 epitopes have been characterized, and a retrospective study identified PLA2R1 epitope spreading as a potential indicator of poor prognosis. Here, we analyzed the predictive value of anti-PLA2R1 antibody (PLA2R1-Ab) titers and epitope spreading in a prospective cohort of 58 patients positive for PLA2R1-Ab randomly allocated to rituximab (n=29) or antiproteinuric therapy alone (n=29). At baseline, the epitope profile (CysR, CysRC1, CysRC7, or CysRC1C7) did not correlate with age, sex, time from diagnosis, proteinuria, or serum albumin, but epitope spreading strongly correlated with PLA2R1-Ab titer (P<0...
November 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29114040/serum-response-factor-is-essential-for-maintenance-of-podocyte-structure-and-function
#6
Bing Guo, Qing Lyu, Orazio J Slivano, Ronald Dirkx, Christine K Christie, Jan Czyzyk, Aram F Hezel, Ali G Gharavi, Eric M Small, Joseph M Miano
Podocytes contain an intricate actin cytoskeleton that is essential for the specialized function of this cell type in renal filtration. Serum response factor (SRF) is a master transcription factor for the actin cytoskeleton, but the in vivo expression and function of SRF in podocytes are unknown. We found that SRF protein colocalizes with podocyte markers in human and mouse kidneys. Compared with littermate controls, mice in which the Srf gene was conditionally inactivated with NPHS2-Cre exhibited early postnatal proteinuria, hypoalbuminemia, and azotemia...
November 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29109083/activated-hedgehog-gli-signaling-causes-congenital-ureteropelvic-junction-obstruction
#7
Sepideh Sheybani-Deloui, Lijun Chi, Marian V Staite, Jason E Cain, Brain J Nieman, R Mark Henkelman, Brandon J Wainwright, S Steven Potter, Darius J Bagli, Armando J Lorenzo, Norman D Rosenblum
Intrinsic ureteropelvic junction obstruction is the most common cause of congenital hydronephrosis, yet the underlying pathogenesis is undefined. Hedgehog proteins control morphogenesis by promoting GLI-dependent transcriptional activation and inhibiting the formation of the GLI3 transcriptional repressor. Hedgehog regulates differentiation and proliferation of ureteric smooth muscle progenitor cells during murine kidney-ureter development. Histopathologic findings of smooth muscle cell hypertrophy and stroma-like cells, consistently observed in obstructing tissue at the time of surgical correction, suggest that Hedgehog signaling is abnormally regulated during the genesis of congenital intrinsic ureteropelvic junction obstruction...
November 6, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29109082/prescription-opioids-for-pain-management-in-patients-on-dialysis
#8
EDITORIAL
Beth Han, Wilson M Compton
No abstract text is available yet for this article.
November 6, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29097624/dnaj-homolog-subfamily-b-member-9-is-a-putative-autoantigen-in-fibrillary-gn
#9
Nicole K Andeen, Han-Yin Yang, Dao-Fu Dai, Michael J MacCoss, Kelly D Smith
Fibrillary GN is a rare form of GN of uncertain pathogenesis that is characterized by the glomerular accumulation of randomly arranged, nonbranching fibrils (12-24 nm) composed of Ig and complement proteins. In this study, we used mass spectrometry to comprehensively define the glomerular proteome in fibrillary GN compared with that in controls and nonfibrillary GN renal diseases. We isolated glomeruli from formalin-fixed and paraffin-embedded biopsy specimens using laser capture microdissection and analyzed them with liquid chromatography and data-dependent tandem mass spectrometry...
November 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29097623/dnaj-heat-shock-protein-family-b-member-9-is-a-novel-biomarker-for-fibrillary-gn
#10
Surendra Dasari, Mariam P Alexander, Julie A Vrana, Jason D Theis, John R Mills, Vivian Negron, Sanjeev Sethi, Angela Dispenzieri, W Edward Highsmith, Samih H Nasr, Paul J Kurtin
Fibrillary GN (FGN) is a rare primary glomerular disease. Histologic and histochemical features of FGN overlap with those of other glomerular diseases, and no unique histologic biomarkers for diagnosing FGN have been identified. We analyzed the proteomic content of glomeruli in patient biopsy specimens and detected DnaJ heat shock protein family (Hsp40) member B9 (DNAJB9) as the fourth most abundant protein in FGN glomeruli. Compared with amyloidosis glomeruli, FGN glomeruli exhibited a >6-fold overexpression of DNAJB9 protein...
November 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29097622/glomerular-disease-pathology-in-the-era-of-proteomics-from-pattern-to-pathogenesis
#11
EDITORIAL
Mark Haas
No abstract text is available yet for this article.
November 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29097621/clinical-decision-support-for-in-hospital-aki
#12
Mohammed Al-Jaghbeer, Dilhari Dealmeida, Andrew Bilderback, Richard Ambrosino, John A Kellum
AKI carries a significant mortality and morbidity risk. Use of a clinical decision support system (CDSS) might improve outcomes. We conducted a multicenter, sequential period analysis of 528,108 patients without ESRD before admission, from October of 2012 to September of 2015, to determine whether use of a CDSS reduces hospital length of stay and in-hospital mortality for patients with AKI. We compared patients treated 12 months before (181,696) and 24 months after (346,412) implementation of the CDSS. Coprimary outcomes were hospital mortality and length of stay adjusted by demographics and comorbidities...
November 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29093030/tissue-resident-lymphocytes-in-the-kidney
#13
Jan-Eric Turner, Martina Becker, Hans-Willi Mittrücker, Ulf Panzer
It has become evident that nonlymphoid tissues are populated by distinct subsets of innate and adaptive lymphocytes that are characterized by minimal exchange with recirculating counterparts. Especially at barrier sites, such as the skin, gut, and lung, these tissue-resident lymphocyte populations are ideally positioned to quickly respond to pathogens and other environmental stimuli. The kidney harbors several classes of innate and innate-like lymphocytes that have been described to contribute to this tissue-resident population in other organs, including innate lymphoid cells, natural killer cells, natural killer T cells, mucosal-associated invariant T cells, and γδ T cells...
November 1, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29093029/chromatin-conformation-links-distal-target-genes-to-ckd-loci
#14
Maarten M Brandt, Claartje A Meddens, Laura Louzao-Martinez, Noortje A M van den Dungen, Nico R Lansu, Edward E S Nieuwenhuis, Dirk J Duncker, Marianne C Verhaar, Jaap A Joles, Michal Mokry, Caroline Cheng
Genome-wide association studies (GWASs) have identified many genetic risk factors for CKD. However, linking common variants to genes that are causal for CKD etiology remains challenging. By adapting self-transcribing active regulatory region sequencing, we evaluated the effect of genetic variation on DNA regulatory elements (DREs). Variants in linkage with the CKD-associated single-nucleotide polymorphism rs11959928 were shown to affect DRE function, illustrating that genes regulated by DREs colocalizing with CKD-associated variation can be dysregulated and therefore, considered as CKD candidate genes...
November 1, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29093028/genome-wide-meta-analysis-unravels-interactions-between-magnesium-homeostasis-and-metabolic-phenotypes
#15
Tanguy Corre, Francisco J Arjona, Caroline Hayward, Sonia Youhanna, Jeroen H F de Baaij, Hendrica Belge, Nadine Nägele, Huguette Debaix, Maxime G Blanchard, Michela Traglia, Sarah E Harris, Sheila Ulivi, Rico Rueedi, David Lamparter, Aurélien Macé, Cinzia Sala, Stefania Lenarduzzi, Belen Ponte, Menno Pruijm, Daniel Ackermann, Georg Ehret, Daniela Baptista, Ozren Polasek, Igor Rudan, Toby W Hurd, Nicholas D Hastie, Veronique Vitart, Geràrd Waeber, Zoltán Kutalik, Sven Bergmann, Rosa Vargas-Poussou, Martin Konrad, Paolo Gasparini, Ian J Deary, John M Starr, Daniela Toniolo, Peter Vollenweider, Joost G J Hoenderop, René J M Bindels, Murielle Bochud, Olivier Devuyst
Magnesium (Mg(2+)) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg(2+), which is crucial for Mg(2+) homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg(2+) homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4×10(-13)) near TRPM6, which encodes an epithelial Mg(2+) channel, and rs35929 (P=2...
November 1, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29093027/thoughts-on-turning-29
#16
EDITORIAL
Josephine P Briggs
No abstract text is available yet for this article.
November 1, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29089371/fxr-tgr5-dual-agonist-prevents-progression-of-nephropathy-in-diabetes-and-obesity
#17
Xiaoxin X Wang, Dong Wang, Yuhuan Luo, Komuraiah Myakala, Evgenia Dobrinskikh, Avi Z Rosenberg, Jonathan Levi, Jeffrey B Kopp, Amanda Field, Ashley Hill, Scott Lucia, Liru Qiu, Tao Jiang, Yingqiong Peng, David Orlicky, Gabriel Garcia, Michal Herman-Edelstein, Vivette D'Agati, Kammi Henriksen, Luciano Adorini, Mark Pruzanski, Cen Xie, Kristopher W Krausz, Frank J Gonzalez, Suman Ranjit, Alexander Dvornikov, Enrico Gratton, Moshe Levi
Bile acids are ligands for the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5. We have shown that FXR and TGR5 have renoprotective roles in diabetes- and obesity-related kidney disease. Here, we determined whether these effects are mediated through differential or synergistic signaling pathways. We administered the FXR/TGR5 dual agonist INT-767 to DBA/2J mice with streptozotocin-induced diabetes, db/db mice with type 2 diabetes, and C57BL/6J mice with high-fat diet-induced obesity...
October 31, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29084809/dynamin-related-protein-1-deficiency-promotes-recovery-from-aki
#18
Heather M Perry, Liping Huang, Rebecca J Wilson, Amandeep Bajwa, Hiromi Sesaki, Zhen Yan, Diane L Rosin, David F Kashatus, Mark D Okusa
The proximal tubule epithelium relies on mitochondrial function for energy, rendering the kidney highly susceptible to ischemic AKI. Dynamin-related protein 1 (DRP1), a mediator of mitochondrial fission, regulates mitochondrial function; however, the cell-specific and temporal role of DRP1 in AKI in vivo is unknown. Using genetic murine models, we found that proximal tubule-specific deletion of Drp1 prevented the renal ischemia-reperfusion-induced kidney injury, inflammation, and programmed cell death observed in wild-type mice and promoted epithelial recovery, which associated with activation of the renoprotective β-hydroxybutyrate signaling pathway...
October 30, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29079659/novel-insights-into-the-pathogenesis-of-monogenic-congenital-anomalies-of-the-kidney-and-urinary-tract
#19
Amelie T van der Ven, Asaf Vivante, Friedhelm Hildebrandt
Congenital anomalies of the kidneys and urinary tract (CAKUT) comprise a large spectrum of congenital malformations ranging from severe manifestations, such as renal agenesis, to potentially milder conditions, such as vesicoureteral reflux. CAKUT causes approximately 40% of ESRD that manifests within the first three decades of life. Several lines of evidence indicate that CAKUT is often caused by recessive or dominant mutations in single (monogenic) genes. To date, approximately 40 monogenic genes are known to cause CAKUT if mutated, explaining 5%-20% of patients...
October 27, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29079658/renal-dysfunction-influences-the-diagnostic-and-prognostic-performance-of-high-sensitivity-cardiac-troponin-i
#20
Ian Gunsolus, Yader Sandoval, Stephen W Smith, Anne Sexter, Karen Schulz, Charles A Herzog, Fred S Apple
Measures of cardiac troponin (cTn) may have lower specificity for myocardial infarction in patients with CKD. We examined the diagnostic accuracy of baseline and serial high-sensitivity cTnI (hs-cTnI) measurements for myocardial infarction and 30- and 180-day mortality according to renal function. hs-cTnI was measured (Abbott assay) using sex-specific 99th percentiles (women, 16 ng/L; men, 34 ng/L) in 1555 adults presenting to the emergency department with symptoms suggesting ischemia (NCT02060760). Myocardial infarction was adjudicated along universal definition classification...
October 27, 2017: Journal of the American Society of Nephrology: JASN
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