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Kidney International

Helong Dai, Alicia R Watson, Daniel Fantus, Longkai Peng, Angus W Thomson, Natasha M Rogers
Dendritic cells (DCs) are critical initiators of innate immunity in the kidney and orchestrate inflammation following ischemia-reperfusion injury. The role of the mammalian/mechanistic target of rapamycin (mTOR) in the pathophysiology of renal ischemia-reperfusion injury has been characterized. However, the influence of DC-based alterations in mTOR signaling is unknown. To address this, bone marrow-derived mTORC2-deficient (Rictor-/- ) DCs underwent hypoxia-reoxygenation and then analysis by flow cytometry...
September 3, 2018: Kidney International
Tamara Micakovic, Stamatia Papagiannarou, Euan Clark, Yalcin Kuzay, Katarina Abramovic, Jörg Peters, Carsten Sticht, Nadine Volk, Thomas Fleming, Peter Nawroth, Hans-Peter Hammes, Natalia Alenina, Hermann-Josef Gröne, Sigrid Christa Hoffmann
Diabetic nephropathy correlates more closely to defective mitochondria and increased oxidative stress in the kidney than to hyperglycemia. A key driving factor of diabetic nephropathy is angiotensin II acting via the G-protein-coupled cell membrane type 1 receptor. The present study aimed to investigate the role of the angiotensin II type 2 receptor (AT2R) at the early stages of diabetic nephropathy. Using receptor binding studies and immunohistochemistry we found that the mitochondria in renal tubules contain high-affinity AT2Rs...
September 3, 2018: Kidney International
Huai-Yu Wang, Zhao Cui, Li-Jun Xie, Li-Jie Zhang, Zhi-Yong Pei, Fang-Jin Chen, Zhen Qu, Jing Huang, Yi-Miao Zhang, Xin Wang, Fang Wang, Li-Qiang Meng, Xu-Yang Cheng, Gang Liu, Xu-Jie Zhou, Hong Zhang, Hanna Debiec, Pierre Ronco, Ming-Hui Zhao
Genome-wide associations and HLA genotyping have revealed associations between HLA alleles and susceptibility to primary membranous nephropathy. However, associations with clinical phenotypes and kidney outcome are poorly defined. We previously identified DRB1*1501 and DRB1*0301 as independent risk alleles for primary membranous nephropathy. Here, we investigated HLA associations with demographic characteristics, anti-phospholipase A2 receptor (PLA2R) antibody, treatment response and kidney outcome after a median follow-up of 52 months in 258 patients...
August 26, 2018: Kidney International
Andre Kraus, Dorien J M Peters, Bernd Klanke, Alexander Weidemann, Carsten Willam, Gunnar Schley, Karl Kunzelmann, Kai-Uwe Eckardt, Bjoern Buchholz
Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by mutations of the PKD1 gene and characterized by growth of bilateral renal cysts. Cyst growth is accompanied by regional hypoxia and induction of hypoxia-inducible factor (HIF)-1α in cyst-lining epithelial cells. To determine the relevance of HIF-1α for cyst growth in vivo we used an inducible kidney epithelium-specific knockout mouse to delete Pkd1 at postnatal day 20 or 35 to induce polycystic kidney disease of different severity and analyzed the effects of Hif-1α co-deletion and HIF-1α stabilization using a prolyl-hydroxylase inhibitor...
August 26, 2018: Kidney International
Anna Francis, David W Johnson, Jonathan Craig, Armando Teixeira-Pinto, Germaine Wong
Better prognostication of graft and patient outcomes among kidney transplant recipients with post-transplant lymphoproliferative disease (PTLD) in the rituximab era is needed to inform treatment decisions. Therefore, we sought to estimate the excess risks of death and graft loss in kidney transplant recipients with PTLD, and to determine risk factors for death. Using the ANZDATA registry, the risks of mortality and graft loss among recipients with and without PTLD were estimated using survival analysis. A group of 367 patients with PTLD (69% male, 85% white, mean age 43 years) were matched 1 to 4 to 1468 controls (69% male, 88% white, mean age 43 years), and followed for a mean of 16 years...
August 26, 2018: Kidney International
Christina M Wyatt, Stephen C Textor
No abstract text is available yet for this article.
August 26, 2018: Kidney International
Dearbhaile Dooley, Mirjan M van Timmeren, Vincent P O'Reilly, Gareth Brady, Eóin C O'Brien, Barbara Fazekas, Fionnuala B Hickey, Emma Leacy, Charles D Pusey, Frederick W K Tam, Thomas Mehrling, Peter Heeringa, Mark A Little
Current therapies for treating antineutrophil cytoplasm autoantibody (ANCA)-associated vasculitis include cyclophosphamide and corticosteroids. Unfortunately, these agents are associated with severe adverse effects, despite inducing remission in most patients. Histone deacetylase inhibitors are effective in rodent models of inflammation and act synergistically with many pharmacological agents, including alkylating agents like cyclophosphamide. EDO-S101 is an alkylating fusion histone deacetylase inhibitor molecule combining the DNA alkylating effect of Bendamustine with a pan-histone deacetylase inhibitor, Vorinostat...
August 26, 2018: Kidney International
Jianling Tao, Laura Mariani, Sean Eddy, Holden Maecker, Neeraja Kambham, Kshama Mehta, John Hartman, Weiqi Wang, Matthias Kretzler, Richard A Lafayette
Focal segmental glomerular sclerosis (FSGS) is a devastating disease with limited treatment options and poor prognosis. Activated JAK-STAT signaling has been implicated in other kidney diseases. Since new technologies allow us to better evaluate changes in systemic and renal JAK-STAT activity as it relates to kidney function, we examined this in 106 patients with biopsy-proven FSGS compared to 47 healthy control individuals. Peripheral immune function was assessed in peripheral blood mononuclear cells by phosphoflow studies before and after cytokine stimulation...
August 6, 2018: Kidney International
Lili Zhou, Shan Zhou, Peng Yang, Yuan Tian, Zhiwei Feng, Xiang-Qun Xie, Youhua Liu
The cannabinoid receptor type 2 (CB2) is a G protein-coupled seven transmembrane receptor that transmits endogenous cannabinoid signaling. The role of CB2 in the pathogenesis of kidney injury and fibrosis remains poorly understood. Here we demonstrate that CB2 was induced, predominantly in kidney tubular epithelium, in various models of kidney disease induced by unilateral ureteral obstruction, adriamycin or ischemia/reperfusion injury. In vitro, forced expression of CB2 or treatment with a CB2 agonist was sufficient to trigger matrix gene expression, whereas knockdown of CB2 by siRNA abolished transforming growth factor-β1-induced signaling and fibrogenic responses in kidney tubular cells...
August 6, 2018: Kidney International
Shunsuke Yamada, Elizabeth M Leaf, Jia Jun Chia, Timothy C Cox, Mei Y Speer, Cecilia M Giachelli
PiT-2, a type III sodium-dependent phosphate transporter, is a causative gene for the brain arteriolar calcification in people with familial basal ganglion calcification. Here we examined the effect of PiT-2 haploinsufficiency on vascular calcification in uremic mice using wild-type and global PiT-2 heterozygous knockout mice. PiT-2 haploinsufficiency enhanced the development of vascular calcification in mice with chronic kidney disease fed a high-phosphate diet. No differences were observed in the serum mineral biomarkers and kidney function between the wild-type and PiT-2 heterozygous knockout groups...
July 21, 2018: Kidney International
Cecilia Boreström, Anna Jonebring, Jing Guo, Henrik Palmgren, Linda Cederblad, Anna Forslöw, Anna Svensson, Magnus Söderberg, Anna Reznichenko, Jenny Nyström, Jaakko Patrakka, Ryan Hicks, Marcello Maresca, Barbara Valastro, Anna Collén
Development of physiologically relevant cellular models with strong translatability to human pathophysiology is critical for identification and validation of novel therapeutic targets. Herein we describe a detailed protocol for generation of an advanced 3-dimensional kidney cellular model using induced pluripotent stem cells, where differentiation and maturation of kidney progenitors and podocytes can be monitored in live cells due to CRISPR/Cas9-mediated fluorescent tagging of kidney lineage markers (SIX2 and NPHS1)...
July 20, 2018: Kidney International
Maarten Coemans, Caner Süsal, Bernd Döhler, Dany Anglicheau, Magali Giral, Oriol Bestard, Christophe Legendre, Marie-Paule Emonds, Dirk Kuypers, Geert Molenberghs, Geert Verbeke, Maarten Naesens
The evolution of kidney allograft survival remains insufficiently studied in the context of the changing donor and recipient demographics. Since European data are lacking we performed a cohort study (1986-2015) that, based on the Collaborative Transplant Study, included 108 787 recipients of brain-death kidney donors in 135 hospitals across 21 European countries. We analyzed the hazard rate of kidney failure after transplantation. Between 1986 and 1999, improvement in graft survival was more pronounced in the short term than in the long term: one-, five- and ten-year hazard rates after transplantation declined 64% (95% confidence interval, 61%-66%), 53% (49%-57%) and 45% (39%-50%), respectively...
July 20, 2018: Kidney International
Masafumi Fukagawa, Ryutaro Shimazaki, Tadao Akizawa
Secondary hyperparathyroidism (SHPT) leads to cardiovascular calcification, which affects survival and quality of life in patients with chronic kidney disease. Cinacalcet is used to control SHPT, but it may induce gastrointestinal symptoms, resulting in lower adherence and insufficient dosages. Therefore, a need exists to develop new calcimimetics that cause fewer gastrointestinal symptoms. Here we conducted a phase 3, randomized, double-blind, double-dummy trial for a head-to-head comparison of the efficacy and safety of evocalcet, a new oral calcimimetic, to the established cinacalcet...
July 20, 2018: Kidney International
Marcelo De Rosa, Francisco Azzato, Jorge E Toblli, Graciela De Rosa, Federico Fuentes, Haikady N Nagaraja, Ryan Nash, Brad H Rovin
One of the most difficult management issues in lupus nephritis (LN) is the optimal duration of maintenance immunosuppression after patients are in clinical remission. Most patients receive immunosuppression for years, based mainly on expert opinion. Prospective data are unavailable. Complicating this issue are data that patients in clinical remission can still have histologically active LN; however, the implications of this are unknown. To study this, the Lupus Flares and Histological Renal Activity at the end of Treatment study (ClinicalTrial...
July 20, 2018: Kidney International
Shinji Tanaka, Yuki Sugiura, Hisako Saito, Mai Sugahara, Yoshiki Higashijima, Junna Yamaguchi, Reiko Inagi, Makoto Suematsu, Masaomi Nangaku, Tetsuhiro Tanaka
It is unclear whether long-term sodium-glucose cotransporter 2 (SGLT2) inhibition such as that during the treatment of diabetes has deleterious effects on the kidney. Therefore, we first sought to determine whether abnormal glucose metabolism occurs in the kidneys of 22-week-old BTBR ob/ob diabetic mice. Second, the cumulative effect of chronic SGLT2 inhibition by ipragliflozin and 30% calorie restriction, either of which lowered blood glucose to a similar extent, on renal glucose metabolism was evaluated. Mass spectrometry-based metabolomics demonstrated that these diabetic mice exhibited an abnormal elevation in the renal pools of tricarboxylic acid cycle metabolites...
July 13, 2018: Kidney International
Natsuko Tokonami, Tomoaki Takata, Jan Beyeler, Iris Ehrbar, Ayumi Yoshifuji, Erik I Christensen, Johannes Loffing, Olivier Devuyst, Eric G Olinger
Uromodulin, the most abundant protein in normal urine, is essentially produced by the cells lining the thick ascending limb. There it regulates the activity of the cotransporter NKCC2 and is involved in sodium chloride handling and blood pressure regulation. Conflicting reports suggested that uromodulin may also be expressed in the distal convoluted tubule (DCT) where its role remains unknown. Using microdissection studies combined with fluorescent in situ hybridization and co-immunostaining analyses, we found a significant expression of uromodulin in mouse and human DCT at approximately 10% of thick ascending limb expression levels, but restricted to the early part of the DCT (DCT1)...
July 7, 2018: Kidney International
Alain Meyrier, Patrick Niaudet
Minimal change disease accounts for 70% to 90% of cases of nephrotic syndrome in children. It also causes nephrotic syndrome in adults, including patients older than age 60. Renal function is altered moderately in approximately 20% to 30% of patients because foot-process fusion impairs filtration of water and solutes. The glomerular filtration rate is reduced by approximately 20% to 30% and returns to baseline with remission of proteinuria. Over the past 50 years, a number of publications have reported cases of acute kidney injury occurring in approximately one-fifth to one-third of adult cases in the absence of prior or concomitant renal disease...
July 3, 2018: Kidney International
Marc Ghannoum, Robert S Hoffman, Sophie Gosselin, Thomas D Nolin, Valery Lavergne, Darren M Roberts
Historically, the clinical application of extracorporeal treatments (ECTRs), such as hemodialysis or hemoperfusion, was first intended for poisoned patients. With time, ECTRs were used almost indiscriminately to facilitate the elimination of many poisons, albeit with uncertain clinical benefit. To determine the precise role of ECTRs in poisoning situations, multiple variables need to be considered including a careful risk assessment, the poison's characteristics including toxicokinetics, alternative treatments, the patient's clinical status, and intricacies of available ECTRs, all of which are reviewed in this article...
June 26, 2018: Kidney International
Karen I López-Cayuqueo, Maria Chavez-Canales, Alexia Pillot, Pascal Houillier, Maximilien Jayat, Jennifer Baraka-Vidot, Francesco Trepiccione, Véronique Baudrie, Cara Büsst, Christelle Soukaseum, Yusuke Kumai, Xavier Jeunemaître, Juliette Hadchouel, Dominique Eladari, Régine Chambrey
Pseudohypoaldosteronism type II (PHAII) is a genetic disease characterized by association of hyperkalemia, hyperchloremic metabolic acidosis, hypertension, low renin, and high sensitivity to thiazide diuretics. It is caused by mutations in the WNK1, WNK4, KLHL3 or CUL3 gene. There is strong evidence that excessive sodium chloride reabsorption by the sodium chloride cotransporter NCC in the distal convoluted tubule is involved. WNK4 is expressed not only in distal convoluted tubule cells but also in β-intercalated cells of the cortical collecting duct...
September 2018: Kidney International
John D Bukowy, Alex Dayton, Dustin Cloutier, Julian H Lombard, Leah C Solberg Woods, Daniel A Beard, Allen W Cowley
No abstract text is available yet for this article.
September 2018: Kidney International
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