Journal of the American Society of Nephrology: JASN

Payel Sen, Alexandra Helmke, Chieh Ming Liao, Inga Sörensen-Zender, Song Rong, Jan-Hinrich Bräsen, Anette Melk, Hermann Haller, Sibylle von Vietinghoff, Roland Schmitt
BACKGROUND: Expression of SerpinB2, a regulator of inflammatory processes, has been described in the context of macrophage activation and cellular senescence. Given that mechanisms for these processes interact and can shape kidney disease, it seems plausible that SerpinB2 might play a role in renal aging, injury, and repair. METHODS: We subjected SerpinB2 knockout mice to ischemia-reperfusion injury or unilateral ureteral obstruction. We performed phagocyte depletion to study SerpinB2's role beyond the effects of macrophages and transplanted bone marrow from knockout mice to wild-type mice and vice versa to dissect cell type-dependent effects...
March 24, 2020: Journal of the American Society of Nephrology: JASN
Yan Chen, Leila R Zelnick, Ke Wang, Andrew N Hoofnagle, Jessica O Becker, Chi-Yuan Hsu, Harold I Feldman, Rupal C Mehta, James P Lash, Sushrut S Waikar, Tariq Shafi, Stephen L Seliger, Michael G Shlipak, Mahboob Rahman, Bryan R Kestenbaum
BACKGROUND: The secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. However, the clinical significance of the kidney's clearance of tubular secretory solutes is uncertain. METHODS: In this prospective cohort study, we evaluated 3416 participants with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study. We measured plasma and 24-hour urine concentrations of endogenous candidate secretory solutes at baseline, using targeted liquid chromatography-tandem mass spectrometry...
March 23, 2020: Journal of the American Society of Nephrology: JASN
Jennifer A Hollywood, Aneta Przepiorski, Randall F D'Souza, Sreevalsan Sreebhavan, Ernst J Wolvetang, Patrick T Harrison, Alan J Davidson, Teresa M Holm
BACKGROUND: Mutations in CTNS -a gene encoding the cystine transporter cystinosin-cause the rare, autosomal, recessive, lysosomal-storage disease cystinosis. Research has also implicated cystinosin in modulating the mTORC1 pathway, which serves as a core regulator of cellular metabolism, proliferation, survival, and autophagy. In its severest form, cystinosis is characterized by cystine accumulation, renal proximal tubule dysfunction, and kidney failure. Because treatment with the cystine-depleting drug cysteamine only slows disease progression, there is an urgent need for better treatments...
March 20, 2020: Journal of the American Society of Nephrology: JASN
Jun Matsuda, Mirela Maier, Lamine Aoudjit, Cindy Baldwin, Tomoko Takano
BACKGROUND: Previous studies showed that Cdc42, a member of the prototypical Rho family of small GTPases and a regulator of the actin cytoskeleton, is critical for the normal development and health of podocytes. However, upstream regulatory mechanisms for Cdc42 activity in podocytes are largely unknown. METHODS: We used a proximity-based ligation assay, BioID, to identify guanine nucleotide exchange factors that activate Cdc42 in immortalized human podocytes. We generated podocyte-specific ARHGEF7 (commonly known as β -PIX) knockout mice by crossing β -PIX floxed mice with Podocin-Cre mice...
March 18, 2020: Journal of the American Society of Nephrology: JASN
Mark R Marshall, Alain C Vandal, Janak R de Zoysa, Ruvin S Gabriel, Imad A Haloob, Christopher J Hood, John H Irvine, Philip J Matheson, David O R McGregor, Kannaiyan S Rabindranath, John B W Schollum, David J Semple, Zhengxiu Xie, Tian Min Ma, Rose Sisk, Joanna L Dunlop
BACKGROUND: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. METHODS: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility...
March 18, 2020: Journal of the American Society of Nephrology: JASN
Lola Jacquemont, Gaëlle Tilly, Michelle Yap, Tra-My Doan-Ngoc, Richard Danger, Pierrick Guérif, Florent Delbos, Bernard Martinet, Magali Giral, Yohann Foucher, Sophie Brouard, Nicolas Degauque
BACKGROUND: Identifying biomarkers to predict kidney transplant failure and to define new therapeutic targets requires more comprehensive understanding of the immune response to chronic allogeneic stimulation. METHODS: We investigated the frequency and function of CD8+ T cell subsets-including effector memory (EM) and terminally differentiated EM (TEMRA) CD8+ T cells-in blood samples from 284 kidney transplant recipients recruited 1 year post-transplant and followed for a median of 8...
March 12, 2020: Journal of the American Society of Nephrology: JASN
Jie Cui, Chase W Kessinger, Harkamal S Jhajj, Madeleine S Grau, Sanjay Misra, Peter Libby, Jason R McCarthy, Farouc A Jaffer
BACKGROUND: Arteriovenous fistulas placed surgically for dialysis vascular access have a high primary failure rate resulting from excessive inward remodeling, medial fibrosis, and thrombosis. No clinically established pharmacologic or perisurgical therapies currently address this unmet need. Statins' induction of multiple anti-inflammatory and antithrombotic effects suggests that these drugs might reduce arteriovenous fistula failure. Yet, the in vivo physiologic and molecular effects of statins on fistula patency and maturation remain poorly understood...
March 9, 2020: Journal of the American Society of Nephrology: JASN
Marina Noris, Giuseppe Remuzzi
No abstract text is available yet for this article.
March 6, 2020: Journal of the American Society of Nephrology: JASN
Alan D Salama, Mark A Little
No abstract text is available yet for this article.
March 4, 2020: Journal of the American Society of Nephrology: JASN
Sarbjit V Jassal, Janine F Farragher
No abstract text is available yet for this article.
March 4, 2020: Journal of the American Society of Nephrology: JASN
Ji-Jing Yan, Jung-Hwa Ryu, Honglin Piao, Ju Hee Hwang, Dongkyu Han, Sun-Kyung Lee, Joon Young Jang, Joongyub Lee, Tai Yeon Koo, Jaeseok Yang
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) can increase populations of myeloid-derived suppressor cells, innate immune suppressors that play an immunoregulatory role in antitumor immunity. However, the roles of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury remain unclear. METHODS: We used mouse models of ischemia-reperfusion injury to investigate whether G-CSF can attenuate renal injury by increasing infiltration of myeloid-derived suppressor cells into kidney tissue...
March 4, 2020: Journal of the American Society of Nephrology: JASN
David A Drew, Hocine Tighiouart, Jasmine Rollins, Sarah Duncan, Seda Babroudi, Tammy Scott, Daniel E Weiner, Mark J Sarnak
BACKGROUND: Neurocognitive testing shows that cognitive impairment is common among patients receiving maintenance hemodialysis. Identification of a well performing screening test for cognitive impairment might allow for broader assessment in dialysis facilities and thus optimal delivery of education and medical management. METHODS: From 2015 to 2018, in a cohort of 150 patients on hemodialysis, we performed a set of comprehensive neurocognitive tests that included the cognitive domains of memory, attention, and executive function to classify whether participants had normal cognitive function versus mild, moderate, or severe cognitive impairment...
March 4, 2020: Journal of the American Society of Nephrology: JASN
Yuting Guan, Hongbo Liu, Ziyuan Ma, Szu-Yuan Li, Jihwan Park, Xin Sheng, Katalin Susztak
BACKGROUND: Cytosine methylation is an epigenetic mark that dictates cell fate and response to stimuli. The timing and establishment of methylation logic during kidney development remains unknown. DNA methyltransferase 3a and 3b are the enzymes capable of establishing de novo methylation. METHODS: We generated mice with genetic deletion of Dnmt3a and Dnmt3b in nephron progenitor cells ( Six2 Cre Dnmt3a/3b ) and kidney tubule cells ( Ksp Cre Dnmt3a/3b ). We characterized Ksp Cre Dnmt3a/3b mice at baseline and after injury...
March 3, 2020: Journal of the American Society of Nephrology: JASN
Behzad Najafian, Camilla Tøndel, Einar Svarstad, Marie-Claire Gubler, João-Paulo Oliveira, Michael Mauer
BACKGROUND: In males with classic Fabry disease, the processes leading to the frequent outcome of ESKD are poorly understood. Defects in the gene encoding α -galactosidase A lead to accumulation of globotriaosylceramide (GL3) in various cell types. In the glomerular podocytes, accumulation of GL3 progresses with age. Of concern, podocytes are relatively resistant to enzyme replacement therapy and are poorly replicating, with little ability to compensate for cell loss. METHODS: In this study of 55 males (mean age 27 years) with classic Fabry disease genotype and/or phenotype, we performed unbiased quantitative morphometric electron microscopic studies of biopsied kidney samples from patients and seven living transplant donors (to serve as controls)...
March 3, 2020: Journal of the American Society of Nephrology: JASN
Isha S Dhande, Peter A Doris
No abstract text is available yet for this article.
March 2, 2020: Journal of the American Society of Nephrology: JASN
Varun Agrawal, Laura Plantinga, Khaled Abdel-Kader, Kurtis Pivert, Anthony Provenzano, Sandeep Soman, Michael J Choi, Bernard G Jaar
BACKGROUND: Physician burnout and emotional distress are associated with work dissatisfaction and provision of suboptimal patient care. Little is known about burnout among nephrology fellows. METHODS: Validated items on burnout, depressive symptoms, and well being were included in the American Society of Nephrology annual survey emailed to US nephrology fellows in May to June 2018. Burnout was defined as an affirmative response to two single-item questions of experiencing emotional exhaustion or depersonalization...
March 2, 2020: Journal of the American Society of Nephrology: JASN
Marc Johnsen, Torsten Kubacki, Assa Yeroslaviz, Martin Richard Späth, Jannis Mörsdorf, Heike Göbel, Katrin Bohl, Michael Ignarski, Caroline Meharg, Bianca Habermann, Janine Altmüller, Andreas Beyer, Thomas Benzing, Bernhard Schermer, Volker Burst, Roman-Ulrich Müller
BACKGROUND: Although AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance...
February 28, 2020: Journal of the American Society of Nephrology: JASN
Barbara Mara Klinkhammer, Sonja Djudjaj, Uta Kunter, Runolfur Palsson, Vidar Orn Edvardsson, Thorsten Wiech, Margret Thorsteinsdottir, Sverrir Hardarson, Orestes Foresto-Neto, Shrikant R Mulay, Marcus Johannes Moeller, Wilhelm Jahnen-Dechent, Jürgen Floege, Hans-Joachim Anders, Peter Boor
BACKGROUND: Hereditary deficiency of adenine phosphoribosyltransferase causes 2,8-dihydroxyadenine (2,8-DHA) nephropathy, a rare condition characterized by formation of 2,8-DHA crystals within renal tubules. Clinical relevance of rodent models of 2,8-DHA crystal nephropathy induced by excessive adenine intake is unknown. METHODS: Using animal models and patient kidney biopsies, we assessed the pathogenic sequelae of 2,8-DHA crystal-induced kidney damage. We also used knockout mice to investigate the role of TNF receptors 1 and 2 (TNFR1 and TNFR2), CD44, or alpha2-HS glycoprotein (AHSG), all of which are involved in the pathogenesis of other types of crystal-induced nephropathies...
February 21, 2020: Journal of the American Society of Nephrology: JASN
Lydia Hering, Masudur Rahman, Henning Hoch, Lajos Markó, Guang Yang, Annika Reil, Mina Yakoub, Vikram Gupta, Sebastian A Potthoff, Oliver Vonend, Donna L Ralph, Susan B Gurley, Alicia A McDonough, Lars C Rump, Johannes Stegbauer
BACKGROUND: Increased nerve activity causes hypertension and kidney disease. Recent studies suggest that renal denervation reduces BP in patients with hypertension. Renal NE release is regulated by prejunctional α 2A-adrenoceptors on sympathetic nerves, and α 2A-adrenoceptors act as autoreceptors by binding endogenous NE to inhibit its own release. However, the role of α 2A-adrenoceptors in the pathogenesis of hypertensive kidney disease is unknown. METHODS: We investigated effects of α 2A-adrenoceptor-regulated renal NE release on the development of angiotensin II-dependent hypertension and kidney disease...
February 21, 2020: Journal of the American Society of Nephrology: JASN
Virginie Royal, Jarcy Zee, Qian Liu, Carmen Avila-Casado, Abigail R Smith, Gang Liu, Laura H Mariani, Stephen Hewitt, Lawrence B Holzman, Brenda W Gillespie, Jeffrey B Hodgin, Laura Barisoni
BACKGROUND: The analysis and reporting of glomerular features ascertained by electron microscopy are limited to few parameters with minimal predictive value, despite some contributions to disease diagnoses. METHODS: We investigated the prognostic value of 12 electron microscopy histologic and ultrastructural changes (descriptors) from the Nephrotic Syndrome Study Network (NEPTUNE) Digital Pathology Scoring System. Study pathologists scored 12 descriptors in NEPTUNE renal biopsies from 242 patients with minimal change disease or FSGS, with duplicate readings to evaluate reproducibility...
February 21, 2020: Journal of the American Society of Nephrology: JASN
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