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Journal of the American Society of Nephrology: JASN

Daniel C Cattran, Esther D Kim, Heather Reich, Michelle Hladunewich, S Joseph Kim
Although change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag between these changes and acceptable end points, such as ESRD, has limited its utility. This cohort study examined the prognostic significance of remission duration in 376 patients with biopsy-proven idiopathic/primary MGN who achieved a remission after a period of nephrotic-range proteinuria. We defined complete remission (CR), partial remission (PR), and relapse as proteinuria ≤0...
October 18, 2016: Journal of the American Society of Nephrology: JASN
Rachel E Patzer, Sudeshna Paul, Laura Plantinga, Jennifer Gander, Leighann Sauls, Jenna Krisher, Laura L Mulloy, Eric M Gibney, Teri Browne, Carlos F Zayas, William M McClellan, Kimberly Jacob Arriola, Stephen O Pastan
Georgia has the lowest kidney transplant rates in the United States and substantial racial disparities in transplantation. We determined the effectiveness of a multicomponent intervention to increase referral of patients on dialysis for transplant evaluation in the Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT), a randomized, dialysis facility-based, controlled trial involving >9000 patients receiving dialysis from 134 dialysis facilities in Georgia. In December of 2013, we selected dialysis facilities with either low transplant referral or racial disparity in referral...
October 13, 2016: Journal of the American Society of Nephrology: JASN
Donna Arvans, Yong-Chul Jung, Dionysios Antonopoulos, Jason Koval, Ignacio Granja, Mohamed Bashir, Eltayeb Karrar, Jayanta Roy-Chowdhury, Mark Musch, John Asplin, Eugene Chang, Hatim Hassan
Hyperoxaluria is a major risk factor for kidney stones and has no specific therapy, although Oxalobacter formigenes colonization is associated with reduced stone risk. O. formigenes interacts with colonic epithelium and induces colonic oxalate secretion, thereby reducing urinary oxalate excretion, via an unknown secretagogue. The difficulties in sustaining O. formigenes colonization underscore the need to identify the derived factors inducing colonic oxalate secretion. We therefore evaluated the effects of O...
October 13, 2016: Journal of the American Society of Nephrology: JASN
Afshin Parsa, Peter A Kanetsky, Rui Xiao, Jayanta Gupta, Nandita Mitra, Sophie Limou, Dawei Xie, Huichun Xu, Amanda Hyre Anderson, Akinlolu Ojo, John W Kusek, Claudia M Lora, L Lee Hamm, Jiang He, Niina Sandholm, Janina Jeff, Dominic E Raj, Carsten A Böger, Erwin Bottinger, Shabnam Salimi, Rulan S Parekh, Sharon G Adler, Carl D Langefeld, Donald W Bowden, Per-Henrik Groop, Carol Forsblom, Barry I Freedman, Michael Lipkowitz, Caroline S Fox, Cheryl A Winkler, Harold I Feldman
The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome-wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P<1×10(-6) for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD...
October 11, 2016: Journal of the American Society of Nephrology: JASN
Hessel Peters-Sengers, Stefan P Berger, Martin B A Heemskerk, Doaa Al Arashi, Jaap J Homan van der Heide, Aline C Hemke, Ineke J M Ten Berge, Mirza M Idu, Michiel G H Betjes, Arjan D van Zuilen, Luuk B Hilbrands, Aiko P J de Vries, Azam S Nurmohamed, Maarten H Christiaans, L W Ernest van Heurn, Johan W de Fijter, Frederike J Bemelman
An increasing number of elderly patients (≥65 years) receive a donor kidney from elderly donors after brain death (DBD) or after circulatory death (DCD). These organs are allocated within the Eurotransplant Senior Program, but outcomes must be evaluated. From the Dutch Organ Transplantation Registry, we selected 3597 recipients (≥18 years) who received a first DBD or DCD kidney during 2002-2012, and categorized them as young or elderly recipients receiving a graft from either a young or elderly donor, stratified by donor type...
October 11, 2016: Journal of the American Society of Nephrology: JASN
Emilee Wilhelm-Leen, Maria E Montez-Rath, Glenn Chertow
Estimates of the incidence of radiocontrast-associated nephropathy vary widely and suffer from misclassification of the cause of AKI and confounding. Using the Nationwide Inpatient Sample, we created multiple estimates of the risk of radiocontrast-associated nephropathy among adult patients hospitalized in the United States in 2009. First, we stratified patients according to the presence or absence of 12 relatively common diagnoses associated with AKI and evaluated the rate of AKI between strata. Next, we created a logistic regression model, controlling for comorbidity and acuity of illness, to estimate the risk of AKI associated with radiocontrast administration within each stratum...
September 29, 2016: Journal of the American Society of Nephrology: JASN
Kathrin Eller, Alexander R Rosenkranz
No abstract text is available yet for this article.
September 28, 2016: Journal of the American Society of Nephrology: JASN
Rosanna Coppo
IgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to ESRD. The immune and autoimmune responses that characterize IgAN indicate a potential benefit for corticosteroids. The 2012 Kidney Disease Improving Global Outcome (KDIGO) guidelines suggest giving corticosteroids to patients with rather preserved renal function (GFR>50 ml/min per 1.73 m(2)) and persistent proteinuria >1 g/d, despite 3-6 months of optimized supportive care with renin-angiotensin system blockers...
September 26, 2016: Journal of the American Society of Nephrology: JASN
Elizabeth Forsythe, Kathryn Sparks, Sunayna Best, Sarah Borrows, Bethan Hoskins, Ataf Sabir, Timothy Barrett, Denise Williams, Shehla Mohammed, David Goldsmith, David V Milford, Detlef Bockenhauer, Lukas Foggensteiner, Philip L Beales
Bardet-Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes (BBS1-19) have been identified, of which mutations in BBS1 are most common in North America and Europe. A hallmark of the disease, renal malformation is heterogeneous and is a cause of morbidity and mortality through the development of CKD. We studied the prevalence and severity of CKD in 350 patients with Bardet-Biedl syndrome-related renal disease attending the United Kingdom national Bardet-Biedl syndrome clinics to further elucidate the phenotype and identify risk indicators of CKD...
September 22, 2016: Journal of the American Society of Nephrology: JASN
Holly J Kramer, Adrienne M Stilp, Cathy C Laurie, Alex P Reiner, James Lash, Martha L Daviglus, Sylvia E Rosas, Ana C Ricardo, Bamidele O Tayo, Michael F Flessner, Kathleen F Kerr, Carmen Peralta, Ramon Durazo-Arvizu, Matt Conomos, Timothy Thornton, Jerome Rotter, Kent D Taylor, Jainwen Cai, John Eckfeldt, Han Chen, George Papanicolau, Nora Franceschini
African ancestry alleles may contribute to CKD among Hispanics/Latinos, but whether associations differ by Hispanic/Latino background remains unknown. We examined the association of CKD measures with African ancestry-specific APOL1 alleles that were directly genotyped and sickle cell trait (hemoglobin subunit β gene [HBB] variant) on the basis of imputation in 12,226 adult Hispanics/Latinos grouped according to Caribbean or Mainland background. We also performed an unbiased genome-wide association scan of urine albumin-to-creatinine ratios...
September 20, 2016: Journal of the American Society of Nephrology: JASN
Kristen L Nowak, Michel Chonchol, Talat Alp Ikizler, Heather Farmer-Bailey, Natjalie Salas, Rafia Chaudhry, Wei Wang, Gerard Smits, Isak Tengesdal, Charles A Dinarello, Adriana M Hung
Vascular endothelial dysfunction and increased arterial stiffness contribute to increased cardiovascular risk in patients with CKD who exhibit chronic systemic inflammation. Because chronic inflammation contributes to vascular dysfunction, blocking inflammation may reduce cardiovascular risk in patients with CKD. In a two-site, double-blind trial, we randomized 42 adult patients with stage 3-4 CKD who were already receiving optimal background therapy to receive either IL-1 trap rilonacept or placebo for 12 weeks...
September 19, 2016: Journal of the American Society of Nephrology: JASN
James Voelker, Paul H Berg, Matthew Sheetz, Kevin Duffin, Tong Shen, Brian Moser, Tom Greene, Samuel S Blumenthal, Ivan Rychlik, Yoram Yagil, Philippe Zaoui, Julia B Lewis
TGF-β has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-β1 activity with a TGF-β1-specific, humanized, neutralizing monoclonal antibody (TGF-β1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1...
September 19, 2016: Journal of the American Society of Nephrology: JASN
Niina Sandholm, Natalie Van Zuydam, Emma Ahlqvist, Thorhildur Juliusdottir, Harshal A Deshmukh, N William Rayner, Barbara Di Camillo, Carol Forsblom, Joao Fadista, Daniel Ziemek, Rany M Salem, Linda T Hiraki, Marcus Pezzolesi, David Trégouët, Emma Dahlström, Erkka Valo, Nikolay Oskolkov, Claes Ladenvall, M Loredana Marcovecchio, Jason Cooper, Francesco Sambo, Alberto Malovini, Marco Manfrini, Amy Jayne McKnight, Maria Lajer, Valma Harjutsalo, Daniel Gordin, Maija Parkkonen, Jaakko Tuomilehto, Valeriya Lyssenko, Paul M McKeigue, Stephen S Rich, Mary Julia Brosnan, Eric Fauman, Riccardo Bellazzi, Peter Rossing, Samy Hadjadj, Andrzej Krolewski, Andrew D Paterson, Jose C Florez, Joel N Hirschhorn, Alexander P Maxwell, David Dunger, Claudio Cobelli, Helen M Colhoun, Leif Groop, Mark I McCarthy, Per-Henrik Groop
Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6...
September 19, 2016: Journal of the American Society of Nephrology: JASN
Helen McNeill, Antoine Reginensi
In the kidney, formation of the functional filtration units, the nephrons, is essential for postnatal life. During development, mesenchymal progenitors tightly regulate the balance between self-renewal and differentiation to give rise to all nephron epithelia. Here, we investigated the functions of the Hippo pathway serine/threonine-protein kinases Lats1 and Lats2, which phosphorylate and inhibit the transcriptional coactivators Yap and Taz, in nephron progenitor cells. Genetic deletion of Lats1 and Lats2 in nephron progenitors of mice led to disruption of nephrogenesis, with an accumulation of spindle-shaped cells in both cortical and medullary regions of the kidney...
September 19, 2016: Journal of the American Society of Nephrology: JASN
Sun-Sang J Sung, Li Li, Liping Huang, Jessica Lawler, Hong Ye, Diane L Rosin, Issah S Vincent, Thu H Le, Jing Yu, Nicole Görldt, Jürgen Schrader, Mark D Okusa
CD73-derived adenosine plays an anti-inflammatory role in various organs. However, its role in renal ischemia-reperfusion injury (IRI) is controversial. We targeted CD73 mutant mice to determine the function of CD73 expressed by various renal cell types under mild IRI conditions. Mice with CD73 deletion in proximal tubules exhibited exacerbated IRI, comparable with that of CD73(-/-) mice compared with WT mice. Mice with CD73 deletions in other cell types, including cortical type 1 fibroblast-like cells, mesangial cells, macrophages, and dendritic cells, showed small or no increases in injury above control mice when subjected to threshold levels of ischemia...
September 14, 2016: Journal of the American Society of Nephrology: JASN
Lisa Buvall, Hanna Wallentin, Jonas Sieber, Svetlana Andreeva, Hoon Young Choi, Peter Mundel, Anna Greka
Tyrosine and serine/threonine signal-transduction pathways influence many aspects of cell behavior, including the spatial and temporal regulation of the actin cytoskeleton. However, little is known about how input from diverse tyrosine and serine/threonine kinases is integrated to control Rho protein crosstalk and actin remodeling, which are critically important in podocyte health and disease. Here we unveil the proteolytically-regulated, actin organizing protein synaptopodin as a coincidence detector of tyrosine versus serine/threonine phosphorylation...
September 14, 2016: Journal of the American Society of Nephrology: JASN
Rafael Kramann, Janewit Wongboonsin, Monica Chang-Panesso, Flavia G Machado, Benjamin D Humphreys
Peritubular capillary rarefaction is hypothesized to contribute to the increased risk of future CKD after AKI. Here, we directly tested the role of Gli1(+) kidney pericytes in the maintenance of peritubular capillary health, and the consequences of pericyte loss during injury. Using bigenic Gli1-CreER(t2); R26tdTomato reporter mice, we observed increased distance between Gli1(+) pericytes and endothelial cells after AKI (mean±SEM: 3.3±0.1 µm before injury versus 12.5±0.2 µm after injury; P<0.001). Using a genetic ablation model, we asked whether pericyte loss alone is sufficient for capillary destabilization...
September 13, 2016: Journal of the American Society of Nephrology: JASN
Dong Zhou, Yuan Tian, Ling Sun, Lili Zhou, Liangxiang Xiao, Roderick J Tan, Jianwei Tian, Haiyan Fu, Fan Fan Hou, Youhua Liu
Matrix metalloproteinase-7 (MMP-7), a secreted zinc- and calcium-dependent endopeptidase, is a transcriptional target of canonical Wnt/β-catenin signaling. Because Wnt/β-catenin is activated in diseased kidney, we hypothesized that urinary MMP-7 level may be used as a noninvasive surrogate biomarker for fibrotic lesions. To test this hypothesis, we conducted a cross-sectional study, measuring urinary MMP-7 levels in a cohort of 102 patients with CKD. Compared with normal subjects, patients with various kidney disorders had markedly elevated urinary levels of MMP-7...
September 13, 2016: Journal of the American Society of Nephrology: JASN
Diana I Jalal, Emily Decker, Loni Perrenoud, Kristen L Nowak, Nina Bispham, Tapan Mehta, Gerard Smits, Zhiying You, Douglas Seals, Michel Chonchol, Richard J Johnson
Hyperuricemia may contribute to endothelial dysfunction in CKD. We evaluated whether lowering serum uric acid levels with allopurinol improves endothelial dysfunction in 80 participants ≥18 years of age with stage 3 CKD and asymptomatic hyperuricemia (≥7 mg/dl in men and ≥6 mg/dl in women) randomized in a double-blinded manner to receive placebo or allopurinol for 12 weeks. Randomization was stratified according to presence or absence of diabetes mellitus. We measured vascular endothelial function by brachial artery flow-mediated dilation...
September 12, 2016: Journal of the American Society of Nephrology: JASN
Alberto Ortiz, Holger Husi, Laura Gonzalez-Lafuente, Lara Valiño-Rivas, Manuel Fresno, Ana Belen Sanz, William Mullen, Amaya Albalat, Sergio Mezzano, Tonia Vlahou, Harald Mischak, Maria Dolores Sanchez-Niño
An improved understanding of pathogenic pathways in AKI may identify novel therapeutic approaches. Previously, we conducted unbiased liquid chromatography-tandem mass spectrometry-based protein expression profiling of the renal proteome in mice with acute folate nephropathy. Here, analysis of the dataset identified enrichment of pathways involving NFκB in the kidney cortex, and a targeted data mining approach identified components of the noncanonical NFκB pathway, including the upstream kinase mitogen-activated protein kinase kinase kinase 14 (MAP3K14), the NFκB DNA binding heterodimer RelB/NFκB2, and proteins involved in NFκB2 p100 ubiquitination and proteasomal processing to p52, as upregulated...
September 12, 2016: Journal of the American Society of Nephrology: JASN
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