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Kidney International

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https://www.readbyqxmd.com/read/30420324/a-randomized-controlled-double-blind-study-comparing-the-efficacy-and-safety-of-dose-ranging-voclosporin-with-placebo-in-achieving-remission-in-patients-with-active-lupus-nephritis
#1
Brad H Rovin, Neil Solomons, William F Pendergraft, Mary Anne Dooley, James Tumlin, Juanita Romero-Diaz, Lidia Lysenko, Sandra V Navarra, Robert B Huizinga
Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN...
November 5, 2018: Kidney International
https://www.readbyqxmd.com/read/30409456/tenascin-c-protects-against-acute-kidney-injury-by-recruiting-wnt-ligands
#2
Shuangqin Chen, Haiyan Fu, Songzhao Wu, Wenjuan Zhu, Jinlin Liao, Xue Hong, Jinhua Miao, Congwei Luo, Yongping Wang, Fan Fan Hou, Lili Zhou, Youhua Liu
The development of acute kidney injury (AKI) is a complex process involving tubular, inflammatory, and vascular components, but less is known about the role of the interstitial microenvironment. We have previously shown that the extracellular matrix glycoprotein tenascin-C (TNC) is induced in fibrotic kidneys. In mouse models of AKI induced by ischemia-reperfusion injury (IRI) or cisplatin, TNC was induced de novo in the injured sites and localized to the renal interstitium. The circulating level of TNC protein was also elevated in AKI patients after cardiac surgery...
November 5, 2018: Kidney International
https://www.readbyqxmd.com/read/30415941/progression-of-diabetic-kidney-disease-and-trajectory-of-kidney-function-decline-in-chinese-patients-with-type-2-diabetes
#3
Guozhi Jiang, Andrea On Yan Luk, Claudia Ha Ting Tam, Fangying Xie, Bendix Carstensen, Eric Siu Him Lau, Cadmon King Poo Lim, Heung Man Lee, Alex Chi Wai Ng, Maggie Chor Yin Ng, Risa Ozaki, Alice Pik Shan Kong, Chun Chung Chow, Xilin Yang, Hui-Yao Lan, Stephen Kwok Wing Tsui, Xiaodan Fan, Cheuk Chun Szeto, Wing Yee So, Juliana Chung Ngor Chan, Ronald Ching Wan Ma
Diabetes is a major cause of end stage renal disease (ESRD), yet the natural history of diabetic kidney disease is not well understood. We aimed to identify patterns of estimated GFR (eGFR) trajectory and to determine the clinical and genetic factors and their associations of these different patterns with all-cause mortality in patients with type 2 diabetes. Among 6330 patients with baseline eGFR >60 ml/min per 1.73 m2 in the Hong Kong Diabetes Register, a total of 456 patients (7.2%) developed Stage 5 chronic kidney disease or ESRD over a median follow-up of 13 years (incidence rate 5...
November 2, 2018: Kidney International
https://www.readbyqxmd.com/read/30396694/natural-killer-cell-infiltration-is-discriminative-for-antibody-mediated-rejection-and-predicts-outcome-after-kidney-transplantation
#4
Saleh Yazdani, Jasper Callemeyn, Stéphane Gazut, Evelyne Lerut, Henriette de Loor, Max Wevers, Line Heylen, Carole Saison, Alice Koenig, Olivier Thaunat, Lieven Thorrez, Dirk Kuypers, Ben Sprangers, Laure-Hélène Noël, Leentje Van Lommel, Frans Schuit, Marie Essig, Wilfried Gwinner, Dany Anglicheau, Pierre Marquet, Maarten Naesens
Despite partial elucidation of the pathophysiology of antibody-mediated rejection (ABMR) after kidney transplantation, it remains largely unclear which of the involved immune cell types determine disease activity and outcome. We used microarray transcriptomic data from a case-control study (n=95) to identify genes that are differentially expressed in ABMR. Given the co-occurrence of ABMR and T-cell-mediated rejection (TCMR), we built a bioinformatics pipeline to distinguish ABMR-specific mRNA markers. Differential expression of 503 unique genes was identified in ABMR, with significant enrichment of natural killer (NK) cell pathways...
November 2, 2018: Kidney International
https://www.readbyqxmd.com/read/30389198/aldosterone-induces-albuminuria-via-matrix-metalloproteinase-dependent-damage-of-the-endothelial-glycocalyx
#5
Matthew J Butler, Raina Ramnath, Hiroyuki Kadoya, Dorinne Desposito, Anne Riquier-Brison, Joanne K Ferguson, Karen L Onions, Anna S Ogier, Hesham ElHegni, Richard J Coward, Gavin I Welsh, Rebecca R Foster, Janos Peti-Peterdi, Simon C Satchell
Aldosterone contributes to end-organ damage in heart failure and chronic kidney disease. Mineralocorticoid-receptor inhibitors limit activation of the receptor by aldosterone and slow disease progression, but side effects, including hyperkalemia, limit their clinical use. Damage to the endothelial glycocalyx (a luminal biopolymer layer) has been implicated in the pathogenesis of endothelial dysfunction and albuminuria, but to date no one has investigated whether the glomerular endothelial glycocalyx is affected by aldosterone...
October 31, 2018: Kidney International
https://www.readbyqxmd.com/read/30389199/exclusive-expression-of-transmembrane-tnf-aggravates-acute-glomerulonephritis-despite-reduced-leukocyte-infiltration-and-inflammation
#6
Martin B Müller, John M Hoppe, Andrei Bideak, Moritz Lux, Maja T Lindenmeyer, Susanna Müller, Nuru Eltrich, Bernhard Ryffel, Volker Vielhauer
Tumor necrosis factor-α (TNF) is a cytokine mediating inflammatory kidney diseases such as immune complex glomerulonephritis. Its two receptors, TNFR1 and TNFR2, play distinct roles in this process, with TNFR2 strongly required for induction of disease. In contrast to soluble TNF (sTNF), transmembrane TNF robustly activates TNFR2. Thus, we examined the functional role of transmembrane TNF by inducing heterologous nephrotoxic serum nephritis in wild-type and transgenic TNFΔ1-9,K11E knock-in mice expressing transmembrane TNF but no sTNF (memTNF mice)...
October 30, 2018: Kidney International
https://www.readbyqxmd.com/read/30385041/development-and-validation-of-a-renal-risk-score-in-anca-associated-glomerulonephritis
#7
Silke R Brix, Mercedes Noriega, Pierre Tennstedt, Eik Vettorazzi, Martin Busch, Martin Nitschke, Wolfram J Jabs, Fedai Özcan, Ralph Wendt, Martin Hausberg, Lorenz Sellin, Ulf Panzer, Tobias B Huber, Rüdiger Waldherr, Helmut Hopfer, Rolf A K Stahl, Thorsten Wiech
Predicting renal outcome in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) remains a major challenge. We aimed to identify reliable predictors of end-stage renal disease (ESRD) and to develop and validate a clinicopathologic score to predict renal outcome in ANCA-associated GN. In a prospective training cohort of 115 patients, the percentage of normal glomeruli (without scarring, crescents, or necrosis within the tuft) was the strongest independent predictor of death-censored ESRD...
October 23, 2018: Kidney International
https://www.readbyqxmd.com/read/30385040/minimally-sufficient-numbers-of-measurements-for-validation-of-24-hour-blood-pressure-monitoring-in-chronic-kidney-disease
#8
Rajiv Agarwal, Wanzhu Tu
Ambulatory blood pressure monitoring (ABPM) remains a reference standard, but the minimal number of ABPM readings required to diagnose hypertension has not been empirically validated. Among 360 patients with chronic kidney disease and 38 healthy controls, 24-hour blood pressure was recorded 2 times per hour during the night and 3 times per hour during the day. All subjects had at least 90% of the expected readings recorded. From this full set of ABPM recordings, we selected variable numbers of measurements and compared the performance of the selected readings against that of the full sample under either random or sequential sampling schemes...
October 23, 2018: Kidney International
https://www.readbyqxmd.com/read/30366682/epigenetic-regulation-of-rcan1-expression-in-kidney-disease-and-its-role-in-podocyte-injury
#9
Huilin Li, Weijia Zhang, Fang Zhong, Gokul C Das, Yifan Xie, Zhengzhe Li, Weijing Cai, Gengru Jiang, Jae Choi, Mohamad Sidani, Deborah P Hyink, Kyung Lee, Paul E Klotman, John Cijiang He
Mounting evidence suggests that epigenetic modification is important in kidney disease pathogenesis. To determine whether epigenetic regulation is involved in HIV-induced kidney injury, we performed genome-wide methylation profiling and transcriptomic profiling of human primary podocytes infected with HIV-1. Comparison of DNA methylation and RNA sequencing profiles identified several genes that were hypomethylated with corresponding upregulated RNA expression in HIV-infected podocytes. Notably, we found only one hypermethylated gene with corresponding downregulated RNA expression, namely regulator of calcineurin 1 (RCAN1)...
October 23, 2018: Kidney International
https://www.readbyqxmd.com/read/30366681/kidney-on-a-chip-untapped-opportunities
#10
REVIEW
Nureddin Ashammakhi, Katherine Wesseling-Perry, Anwarul Hasan, Elmahdi Elkhammas, Yu Shrike Zhang
The organs-on-a-chip technology has shown strong promise in mimicking the complexity of native tissues in vitro and ex vivo, and recently significant advances have been made in applying this technology to studies of the kidney and its diseases. Individual components of the nephron, including the glomerulus, proximal tubule, and distal tubule/medullary collecting duct, have been successfully mimicked using organs-on-a-chip technology and yielding strong promises in advancing the field of ex vivo drug toxicity testing and augmenting renal replacement therapies...
October 23, 2018: Kidney International
https://www.readbyqxmd.com/read/30385042/cxcl12-blockade-preferentially-regenerates-lost-podocytes-in-cortical-nephrons-by-targeting-an-intrinsic-podocyte-progenitor-feedback-mechanism
#11
Simone Romoli, Maria Lucia Angelotti, Giulia Antonelli, Santhosh Kumar Vr, Shrikant R Mulay, Jyaysi Desai, Lidia Anguiano Gomez, Dana Thomasova, Dirk Eulberg, Sven Klussmann, Maria Elena Melica, Carolina Conte, Duccio Lombardi, Laura Lasagni, Hans-Joachim Anders, Paola Romagnani
Insufficient podocyte regeneration after injury is a central pathomechanism of glomerulosclerosis and chronic kidney disease. Podocytes constitutively secrete the chemokine CXCL12, which is known to regulate homing and activation of stem cells; hence we hypothesized a similar effect of CXCL12 on podocyte progenitors. CXCL12 blockade increased podocyte numbers and attenuated proteinuria in mice with Adriamycin-induced nephropathy. Similar studies in lineage-tracing mice revealed enhanced de novo podocyte formation from parietal epithelial cells in the setting of CXCL12 blockade...
October 22, 2018: Kidney International
https://www.readbyqxmd.com/read/30360960/a-randomized-controlled-trial-of-alanyl-glutamine-supplementation-in-peritoneal-dialysis-fluid-to-assess-impact-on-biomarkers-of-peritoneal-health
#12
Andreas Vychytil, Rebecca Herzog, Paul Probst, Werner Ribitsch, Karl Lhotta, Veronika Machold-Fabrizii, Martin Wiesholzer, Michaela Kaufmann, Hermann Salmhofer, Martin Windpessl, Alexander R Rosenkranz, Rainer Oberbauer, Franz König, Klaus Kratochwill, Christoph Aufricht
In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal health. In a double-blinded, randomized crossover design, stable PD patients were treated with AlaGln (8 mM) or placebo added to PD fluid for eight weeks. As primary outcome measures, dialysate cancer-antigen 125 (CA-125) appearance rate and ex vivo stimulated interleukin-6 (IL-6) release were assessed in peritoneal equilibration tests...
October 22, 2018: Kidney International
https://www.readbyqxmd.com/read/30360959/implementing-core-outcomes-in-kidney-disease-report-of-the-standardized-outcomes-in-nephrology-song-implementation-workshop
#13
Allison Tong, Braden Manns, Angela Yee Moon Wang, Brenda Hemmelgarn, David C Wheeler, John Gill, Peter Tugwell, Robert Pecoits-Filho, Sally Crowe, Tess Harris, Wim Van Biesen, Wolfgang C Winkelmayer, Adeera Levin, Aliza Thompson, Vlado Perkovic, Angela Ju, Talia Gutman, Amelie Bernier-Jean, Andrea K Viecelli, Emma O'Lone, Jenny Shen, Michelle A Josephson, Yeoungjee Cho, David W Johnson, Bénédicte Sautenet, Marcello Tonelli, Jonathan C Craig
There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials...
October 22, 2018: Kidney International
https://www.readbyqxmd.com/read/30385039/an-open-label-randomized-controlled-trial-of-low-dose-corticosteroid-plus-enteric-coated-mycophenolate-sodium-versus-standard-corticosteroid-treatment-for-minimal-change-nephrotic-syndrome-in-adults-msn-study
#14
Philippe Rémy, Vincent Audard, Pierre André Natella, Gaëlle Pelle, Bertrand Dussol, Helene Leray-Moragues, Cecile Vigneau, Khedidja Bouachi, Jacques Dantal, Laurence Vrigneaud, Alexandre Karras, Frank Pourcine, Philippe Gatault, Philippe Grimbert, Nawelle Ait Sahlia, Anissa Moktefi, Eric Daugas, Claire Rigothier, Sylvie Bastuji-Garin, Dil Sahali
First-line therapy of minimal change nephrotic syndrome (MCNS) in adults is extrapolated largely from pediatric studies and consists of high-dose oral corticosteroids. We assessed whether a low corticosteroid dose combined with mycophenolate sodium was superior to a standard oral corticosteroid regimen. We enrolled 116 adults with MCNS in an open-label randomized controlled trial involving 32 French centers. Participants randomly assigned to the test group (n=58) received low-dose prednisone (0.5 mg/kg/day, maximum 40 mg/day) plus enteric-coated mycophenolate sodium 720 mg twice daily for 24 weeks; those who did not achieve complete remission after week 8 were eligible for a second-line regimen (increase in the prednisone dose to 1 mg/kg/day with or without Cyclosporine)...
October 20, 2018: Kidney International
https://www.readbyqxmd.com/read/30322716/properdin-binds-independent-of-complement-activation-in-an-in-vivo-model-of-anti-glomerular-basement-membrane-disease
#15
Joseph O'Flynn, Juha Kotimaa, Ria Faber-Krol, Karin Koekkoek, Ngaisah Klar-Mohamad, Angela Koudijs, Wilhelm J Schwaeble, Cordula Stover, Mohamed R Daha, Cees van Kooten
Properdin is the only known positive regulator of complement activation by stabilizing the alternative pathway convertase through C3 binding, thus prolonging its half-life. Recent in vitro studies suggest that properdin may act as a specific pattern recognition molecule. To better understand the role of properdin in vivo, we used an experimental model of acute anti-glomerular basement membrane disease with wild-type, C3- and properdin knockout mice. The model exhibited severe proteinuria, acute neutrophil infiltration and activation, classical and alternative pathway activation, and progressive glomerular deposition of properdin, C3 and C9...
October 10, 2018: Kidney International
https://www.readbyqxmd.com/read/30301568/hydroxypropyl-%C3%AE-cyclodextrin-protects-from-kidney-disease-in-experimental-alport-syndrome-and-focal-segmental-glomerulosclerosis
#16
Alla Mitrofanova, Judith Molina, Javier Varona Santos, Johanna Guzman, Ximena A Morales, G Michelle Ducasa, Jonathan Bryn, Alexis Sloan, Ion Volosenco, Jin-Ju Kim, Mengyuan Ge, Shamroop K Mallela, Matthias Kretzler, Sean Eddy, Sebastian Martini, Patricia Wahl, Santiago Pastori, Armando J Mendez, George W Burke, Sandra Merscher, Alessia Fornoni
Studies suggest that altered renal lipid metabolism plays a role in the pathogenesis of diabetic kidney disease and that genetic or pharmacological induction of cholesterol efflux protects from the development of diabetic kidney disease and focal segmental glomerulosclerosis (FSGS). Here we tested whether altered lipid metabolism contributes to renal failure in the Col4a3 knockout mouse model for Alport Syndrome. There was an eight-fold increase in the cholesterol content in renal cortexes of mice with Alport Syndrome...
October 6, 2018: Kidney International
https://www.readbyqxmd.com/read/30287079/donor-apol1-high-risk-genotypes-are-associated-with-increased-risk-and-inferior-prognosis-of-de-novo-collapsing-glomerulopathy-in-renal-allografts
#17
Dominick Santoriello, Syed A Husain, Sacha A De Serres, Andrew S Bomback, Russell J Crew, Elena-Rodica Vasilescu, Geo Serban, Eric S Campenot, Krzysztof Kiryluk, Sumit Mohan, Gregory A Hawkins, Pamela J Hicks, David J Cohen, Jai Radhakrishnan, Michael B Stokes, Glen S Markowitz, Barry I Freedman, Vivette D D'Agati, Ibrahim Batal
Collapsing focal segmental glomerulosclerosis (cFSGS) in the native kidney is associated with heavy proteinuria and accelerated renal failure. However, cFSGS in the renal allograft is less well characterized. Here we report clinico-pathologic features and APOL1 donor risk genotypes in 38 patients with de novo post-kidney transplant cFSGS. Recipients were 34% female and 26% African American. Concurrent viral infections and acute vaso-occlusion (including thrombotic microangiopathy, cortical necrosis, atheroembolization, and cardiac arrest with contralateral graft thrombosis) were present in 13% and 29% of recipients, respectively...
October 2, 2018: Kidney International
https://www.readbyqxmd.com/read/30274681/renal-transplant-recipients-receiving-loop-diuretic-therapy-have-increased-urinary-tract-infection-rate-and-altered-medullary-macrophage-polarization-marker-expression
#18
Janis Casper, Jessica Schmitz, Jan Hinrich Bräsen, Abedalrazag Khalifa, Bernhard M W Schmidt, Gunilla Einecke, Hermann Haller, Sibylle von Vietinghoff
Loop diuretics deplete the renal cortico-medullary salt gradient that has recently been established as a major modulator of immune responses. Renal transplant recipients suffer from a markedly increased rate of urinary tract infections (UTIs). Whether diuretic therapy affects renal macrophage polarization in the human kidney graft and the incidence of UTI have not been reported. In a cohort of 112 adult renal allograft recipients, loop diuretic therapy significantly correlated with the rate of UTI during five years after transplantation in uni- and multivariable regression analysis...
September 22, 2018: Kidney International
https://www.readbyqxmd.com/read/30245128/iron-attenuates-erythropoietin-production-by-decreasing-hypoxia-inducible-transcription-factor-2%C3%AE-concentrations-in-renal-interstitial-fibroblasts
#19
Norio Suzuki, Yukari Matsuo-Tezuka, Yusuke Sasaki, Koji Sato, Kenichiro Miyauchi, Koichiro Kato, Sakae Saito, Yasushi Shimonaka, Michinori Hirata, Masayuki Yamamoto
Iron is an essential mineral for oxygen delivery and for a variety of enzymatic activities, but excessive iron results in oxidative cytotoxicity. Because iron is primarily used in red blood cells, defective erythropoiesis caused by loss of the erythroid growth factor erythropoietin (Epo) elevates iron storage levels in serum and tissues. Here, we investigated the effects of iron in a mouse model of Epo-deficiency anemia, in which serum iron concentration was significantly elevated. We found that intraperitoneal injection of iron-dextran caused severe iron deposition in renal interstitial fibroblasts, the site of Epo production...
September 20, 2018: Kidney International
https://www.readbyqxmd.com/read/30249452/cd8-t-cells-modulate-autosomal-dominant-polycystic-kidney-disease-progression
#20
Emily K Kleczko, Kenneth H Marsh, Logan C Tyler, Seth B Furgeson, Bonnie L Bullock, Christopher J Altmann, Makoto Miyazaki, Berenice Y Gitomer, Peter C Harris, Mary C M Weiser-Evans, Michel B Chonchol, Eric T Clambey, Raphael A Nemenoff, Katharina Hopp
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited nephropathy. To date, therapies alleviating the disease have largely focused on targeting abnormalities in renal epithelial cell signaling. ADPKD has many hallmarks of cancer, where targeting T cells has brought novel therapeutic interventions. However, little is known about the role and therapeutic potential of T cells in ADPKD. Here, we used an orthologous ADPKD model, Pkd1 p.R3277C (RC), to begin to define the role of T cells in disease progression...
September 17, 2018: Kidney International
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