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Kidney International

Patrick H Pun, Christina M Wyatt
No abstract text is available yet for this article.
March 17, 2018: Kidney International
Clifford E Kashtan, Jie Ding, Guido Garosi, Laurence Heidet, Laura Massella, Koichi Nakanishi, Kandai Nozu, Alessandra Renieri, Michelle Rheault, Fang Wang, Oliver Gross
Mutations in the genes COL4A3, COL4A4, and COL4A5 affect the synthesis, assembly, deposition, or function of the collagen IV α345 molecule, the major collagenous constituent of the mature mammalian glomerular basement membrane. These mutations are associated with a spectrum of nephropathy, from microscopic hematuria to progressive renal disease leading to ESRD, and with extrarenal manifestations such as sensorineural deafness and ocular anomalies. The existing nomenclature for these conditions is confusing and can delay institution of appropriate nephroprotective therapy...
March 15, 2018: Kidney International
Angelique L W M M Rops, Erik Jansen, Alie van der Schaaf, Elmar Pieterse, Nils Rother, Julia Hofstra, Henry B P M Dijkman, Anne-Els van de Logt, Jack Wetzels, Johan van der Vlag, Annemiek B van Spriel
Immunoglobulin A (IgA) nephropathy (IgAN), the most common glomerulonephritis worldwide, is characterized by IgA depositions in the kidney. Deficiency of CD37, a leukocyte-specific tetraspanin, leads to spontaneous development of renal pathology resembling IgAN. However, the underlying molecular mechanism has not been resolved. Here we found that CD37 expression on B cells of patients with IgAN was significantly decreased compared to B cells of healthy donors. Circulating interleukin (IL)-6 levels, but not tumor necrosis factor-α or IL-10, were elevated in Cd37-/- mice compared to wild-type mice after lipopolysaccharide treatment...
March 15, 2018: Kidney International
Jonatan Barrera-Chimal, Gabriel R Estrela, Sebastian M Lechner, Sébastien Giraud, Soumaya El Moghrabi, Shiem Kaaki, Peter Kolkhof, Thierry Hauet, Frédéric Jaisser
Acute kidney injury induced by ischemia/reperfusion is an independent risk factor for chronic kidney disease. Macrophage recruitment plays an essential role during the injury and repair phases after an ischemic episode in the kidney. Here we show that the novel non-steroidal mineralocorticoid receptor antagonist finerenone or selective myeloid mineralocorticoid receptor ablation protects against subsequent chronic dysfunction and fibrosis induced by an episode of bilateral kidney ischemia/reperfusion in mice...
March 13, 2018: Kidney International
Ibrahim Batal, Sumit Mohan, Sacha A De Serres, Elena-Rodica Vasilescu, Demetra Tsapepas, Russel J Crew, Shefali S Patel, Geo Serban, Kasi McCune, Syed A Husain, Jae-Hyung Chang, Jan M Herter, Govind Bhagat, Glen S Markowitz, Vivette D D'Agati, Mark A Hardy, Lloyd Ratner, Anil Chandraker
Ischemia-reperfusion injury increases allograft immunogenicity and enhances myeloid dendritic cell maturation and trafficking to recipient's secondary lymphoid tissue. Here, we used postreperfusion biopsies from patients who received kidney allografts from deceased donors between 2006 and 2009 to assess the impact of ischemia-reperfusion damage and myeloid dendritic cell density on subsequent allograft rejection episodes. Histologic changes of severe ischemia-reperfusion damage in postreperfusion biopsies were found to be associated with subsequent rejection episodes and suboptimal allograft survival...
March 13, 2018: Kidney International
Martin Höhne, Christian K Frese, Florian Grahammer, Claudia Dafinger, Giuliano Ciarimboli, Linus Butt, Julia Binz, Matthias J Hackl, Mahdieh Rahmatollahi, Martin Kann, Simon Schneider, Mehmet M Altintas, Bernhard Schermer, Thomas Reinheckel, Heike Göbel, Jochen Reiser, Tobias B Huber, Rafael Kramann, Tamina Seeger-Nukpezah, Max C Liebau, Bodo B Beck, Thomas Benzing, Andreas Beyer, Markus M Rinschen
In diseases of many parenchymatous organs, heterogeneous deterioration of individual functional units determines the clinical prognosis. However, the molecular characterization at the level of such individual subunits remains a technological challenge that needs to be addressed in order to better understand pathological mechanisms. Proteinuric glomerular kidney diseases are frequent and assorted diseases affecting a fraction of glomeruli and their draining tubules to variable extents, and for which no specific treatment exists...
March 9, 2018: Kidney International
Peter P Toth, Jamie P Dwyer, Christopher P Cannon, Helen M Colhoun, Daniel J Rader, Ashish Upadhyay, Michael J Louie, Andrew Koren, Alexia Letierce, Jonas Mandel, Maciej Banach
Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30-59 ml/min/1.73 m2 , to those without impaired renal function eGFR ≥60 ml/min/1...
March 8, 2018: Kidney International
Marcello Tonelli, Natasha Wiebe, Matthew T James, Scott W Klarenbach, Braden J Manns, Pietro Ravani, Giovanni F M Strippoli, Brenda R Hemmelgarn
In older people with chronic kidney disease (CKD) and comorbidities, the risk of death or disability may overshadow the risk of kidney failure. To help refine this we did a retrospective population-based cohort study to evaluate the relative likelihood of adverse outcomes as functions of age and comorbidity burden among 47,228 adults with severe non-dialysis dependent CKD. We identified comorbidities using 29 validated algorithms applied to administrative data and assessed death, end-stage renal disease (ESRD), cardiovascular disease (CVD) events, and long-term care...
March 7, 2018: Kidney International
Jürgen Floege, Kate Tsirtsonis, Jan Iles, Tilman B Drueke, Glenn M Chertow, Patrick Parfrey
The calcimimetic cinacalcet is used to treat secondary hyperparathyroidism in patients receiving dialysis, and asymptomatic hypocalcemia is often observed following its initiation. Here we investigated the incidence, predictors and therapeutic consequences of hypocalcemia by a post hoc analysis of the randomized, double-blind, placebo-controlled EValuation Of Cinacalcet Hydrochloride Therapy to Lower CardioVascular Events (EVOLVE) trial. Hypocalcemia was classified as mild (total serum calcium 8.0-8.39 mg/dL), moderate (7...
March 7, 2018: Kidney International
Vandana Dua Niyyar, W Charles O'Neill
Sonography is increasingly being performed by clinicians and has applications throughout the spectrum of nephrology, including acute and chronic renal failure, urinary obstruction, cystic disease, pain, hematuria, transplantation, kidney biopsy, temporary and permanent vascular access, and assessment of fluid status. The skill is relatively easily acquired, expedites patient care, and enhances the practice of nephrology. However, the lack of exposure in most training programs remains a major obstacle.
February 22, 2018: Kidney International
Quan Hong, Lu Zhang, Bhaskar Das, Zhengzhe Li, Bohan Liu, Guangyan Cai, Xiangmei Chen, Peter Y Chuang, John Cijiang He, Kyung Lee
Podocyte injury and loss contribute to the progression of glomerular diseases, including diabetic kidney disease. We previously found that the glomerular expression of Sirtuin-1 (SIRT1) is reduced in human diabetic glomeruli and that the podocyte-specific loss of SIRT1 aggravated albuminuria and worsened kidney disease progression in diabetic mice. SIRT1 encodes an NAD-dependent deacetylase that modifies the activity of key transcriptional regulators affected in diabetic kidneys, including NF-κB, STAT3, p53, FOXO4, and PGC1-α...
February 22, 2018: Kidney International
Naila Rabbani, Paul J Thornalley
Advanced glycation end products (AGEs) are stable posttranslational modifications of proteins formed by the spontaneous reaction with glucose and related metabolites. Important AGEs quantitatively are methylglyoxal (MG)-derived hydroimidazolone MG-H1, Nε -carboxymethyl-lysine (CML), and glucosepane. They contribute to the development of chronic kidney disease (CKD). Cellular proteolysis of AGE-modified proteins forms AGE free adducts, glycated amino acids, which are cleared by the kidneys and excreted in urine...
February 22, 2018: Kidney International
Tushar J Vachharajani, Anil K Agarwal, Arif Asif
Exhausted vasculature is not uncommon in patients receiving long-term hemodialysis treatment. Certain patients exhaust their peripheral veins and do not retain the venous capital necessary for fistula creation. Others suffer from severe peripheral arterial disease and despite the presence of adequate venous capital are not able to receive an arteriovenous access successfully. Most importantly, in the case of occluded central veins, the creation of an arteriovenous access in the arms or thighs would be futile, even if peripheral veins and/or arteries were available...
February 21, 2018: Kidney International
Christina B Ching, Sudipti Gupta, Birong Li, Hanna Cortado, Nicholas Mayne, Ashley R Jackson, Kirk M McHugh, Brian Becknell
The signaling networks regulating antimicrobial activity during urinary tract infection (UTI) are incompletely understood. Interleukin-6 (IL-6) levels increase with UTI severity, but the specific contributions of IL-6 to host immunity against bacterial uropathogens are unknown. To clarify this we tested whether IL-6 activates the Stat3 transcription factor, to drive a program of antimicrobial peptide gene expression in infected urothelium during UTI. Transurethral inoculation of uropathogenic Escherichia coli led to IL-6 secretion, urothelial Stat3 phosphorylation, and activation of antimicrobial peptide transcription, in a Toll-like receptor 4-dependent manner in a murine model of cystitis...
February 20, 2018: Kidney International
Christina M Wyatt, Glenn M Chertow
No abstract text is available yet for this article.
February 20, 2018: Kidney International
Yasmine Neirijnck, Antoine Reginensi, Kirsten Y Renkema, Filippo Massa, Vladimir M Kozlov, Haroun Dhib, Ernie Mhf Bongers, Wout F Feitz, Albertien M van Eerde, Veronique Lefebvre, Nine Vam Knoers, Mansoureh Tabatabaei, Herbert Schulz, Helen McNeill, Franz Schaefer, Michael Wegner, Elisabeth Sock, Andreas Schedl
Congenital abnormalities of the kidney and the urinary tract (CAKUT) belong to the most common birth defects in human, but the molecular basis for the majority of CAKUT patients remains unknown. Here we show that the transcription factor SOX11 is a crucial regulator of kidney development. SOX11 is expressed in both mesenchymal and epithelial components of the early kidney anlagen. Deletion of Sox11 in mice causes an extension of the domain expressing Gdnf within rostral regions of the nephrogenic cord and results in duplex kidney formation...
February 16, 2018: Kidney International
Ingeborg M Bajema, Suzanne Wilhelmus, Charles E Alpers, Jan A Bruijn, Robert B Colvin, H Terence Cook, Vivette D D'Agati, Franco Ferrario, Mark Haas, J Charles Jennette, Kensuke Joh, Cynthia C Nast, Laure-Hélène Noël, Emilie C Rijnink, Ian S D Roberts, Surya V Seshan, Sanjeev Sethi, Agnes B Fogo
We present a consensus report pertaining to the improved clarity of definitions and classification of glomerular lesions in lupus nephritis that derived from a meeting of 18 members of an international nephropathology working group in Leiden, Netherlands, in 2016. Here we report detailed recommendations on issues for which we can propose adjustments based on existing evidence and current consensus opinion (phase 1). New definitions are provided for mesangial hypercellularity and for cellular, fibrocellular, and fibrous crescents...
February 16, 2018: Kidney International
Christoph Kopp, Peter Linz, Carolin Maier, Peter Wabel, Matthias Hammon, Armin M Nagel, Daniela Rosenhauer, Stephan Horn, Michael Uder, Friedrich C Luft, Jens Titze, Anke Dahlmann
Long-term elevated blood sugar levels result in tissue matrix compositional changes in patients with diabetes mellitus type 2 (T2DM). We hypothesized that hemodialysis patients with T2DM might accumulate more tissue sodium than control hemodialysis patients. To test this,23 Na magnetic resonance imaging (23 Na MRI) was used to estimate sodium in skin and muscle tissue in hemodialysis patients with or without T2DM. Muscle fat content was estimated by1 H MRI and tissue sodium content by23 Na MRI pre- and post-hemodialysis in ten hemodialysis patients with T2DM and in 30 matched control hemodialysis patients...
February 15, 2018: Kidney International
Maxim Durand, Florian Dubois, Cécile Dejou, Eugénie Durand, Richard Danger, Mélanie Chesneau, Carole Brosseau, Pierrick Guerif, Jean-Paul Soulillou, Nicolas Degauque, Jean-François Eliaou, Magali Giral, Nathalie Bonnefoy, Sophie Brouard
Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process...
February 15, 2018: Kidney International
Sara Desideri, Karen L Onions, Yan Qiu, Raina D Ramnath, Matthew J Butler, Christopher R Neal, Matthew L R King, Andrew E Salmon, Moin A Saleem, Gavin I Welsh, C Charles Michel, Simon C Satchell, Andrew H J Salmon, Rebecca R Foster
Increased urinary albumin excretion is a key feature of glomerular disease but has limitations as a measure of glomerular permeability. Here we describe a novel assay to measure the apparent albumin permeability of single capillaries in glomeruli, isolated from perfused kidneys cleared of red blood cells. The rate of decline of the albumin concentration within the capillary lumen was quantified using confocal microscopy and used to calculate apparent permeability. The assay was extensively validated and provided robust, reproducible estimates of glomerular albumin permeability...
February 9, 2018: Kidney International
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