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Journal of the American Society of Nephrology: JASN

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https://www.readbyqxmd.com/read/28539383/glomerulosclerosis-induced-by-deficiency-of-membrane-associated-guanylate-kinase-inverted-2-in-kidney-podocytes
#1
Naritoshi Shirata, Kan-Ichiro Ihara, Kanae Yamamoto-Nonaka, Takuto Seki, Shin-Ichi Makino, Juan Alejandro Oliva Trejo, Takafumi Miyake, Hiroyuki Yamada, Kirk Nicholas Campbell, Takahiko Nakagawa, Kiyoshi Mori, Motoko Yanagita, Peter Mundel, Katsuhiko Nishimori, Katsuhiko Asanuma
Membrane-associated guanylate kinase inverted 2 (MAGI-2) is a component of the slit diaphragm (SD) of glomerular podocytes. Here, we investigated the podocyte-specific function of MAGI-2 using newly generated podocyte-specific MAGI-2-knockout (MAGI-2-KO) mice. Compared with podocytes from wild-type mice, podocytes from MAGI-2-KO mice exhibited SD disruption, morphologic abnormalities of foot processes, and podocyte apoptosis leading to podocyte loss. These pathologic changes manifested as massive albuminuria by 8 weeks of age and glomerulosclerosis and significantly higher plasma creatinine levels at 12 weeks of age; all MAGI-2-KO mice died by 20 weeks of age...
May 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28539382/il233-a-novel-il-2-and-il-33-hybrid-cytokine-ameliorates-renal-injury
#2
Marta E Stremska, Sheethal Jose, Vikram Sabapathy, Liping Huang, Amandeep Bajwa, Gilbert R Kinsey, Poonam R Sharma, Saleh Mohammad, Diane L Rosin, Mark D Okusa, Rahul Sharma
CD4(+)Foxp3(+) regulatory T cells (Tregs) protect the kidney during AKI. We previously found that IL-2, which is critical for Treg homeostasis, upregulates the IL-33 receptor (ST2) on CD4(+) T cells, thus we hypothesized that IL-2 and IL-33 cooperate to enhance Treg function. We found that a major subset of Tregs in mice express ST2, and coinjection of IL-2 and IL-33 increased the number of Tregs in lymphoid organs and protected mice from ischemia-reperfusion injury (IRI) more efficiently than either cytokine alone...
May 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28526779/the-phenotypic-spectrum-of-nephropathies-associated-with-mutations-in-diacylglycerol-kinase-%C3%AE%C2%B5
#3
Karolis Azukaitis, Eva Simkova, Mohammad Abdul Majid, Matthias Galiano, Kerstin Benz, Kerstin Amann, Clemens Bockmeyer, Radha Gajjar, Kevin E Meyers, Hae Il Cheong, Bärbel Lange-Sperandio, Therese Jungraithmayr, Véronique Frémeaux-Bacchi, Carsten Bergmann, Csaba Bereczki, Monika Miklaszewska, Dorottya Csuka, Zoltán Prohászka, Patrick Gipson, Matthew G Sampson, Mathieu Lemaire, Franz Schaefer
The recent discovery of mutations in the gene encoding diacylglycerol kinase ε (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA...
May 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28522688/polycystic-kidney-disease-without-an-apparent-family-history
#4
Ioan-Andrei Iliuta, Vinusha Kalatharan, Kairong Wang, Emilie Cornec-Le Gall, John Conklin, Marina Pourafkari, Ryan Ting, Chen Chen, Alessia C Borgo, Ning He, Xuewen Song, Christina M Heyer, Sarah R Senum, Young-Hwan Hwang, Andrew D Paterson, Peter C Harris, Korosh Khalili, York Pei
The absence of a positive family history (PFH) in 10%-25% of patients poses a diagnostic challenge for autosomal dominant polycystic kidney disease (ADPKD). In the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease, 210 affected probands underwent renal function testing, abdominal imaging, and comprehensive PKD1 and PKD2 mutation screening. From this cohort, we reviewed all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available parents of unknown disease status...
May 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28522687/integrin-linked-kinase-signaling-promotes-cyst-growth-and-fibrosis-in-polycystic-kidney-disease
#5
Archana Raman, Gail A Reif, Yuqiao Dai, Aditi Khanna, Xiaogang Li, Lindsay Astleford, Stephen C Parnell, James P Calvet, Darren P Wallace
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin...
May 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28507058/hepatocyte-nuclear-factor-1%C3%AE-regulates-urinary-concentration-and-response-to-hypertonicity
#6
Karam Aboudehen, Lama Noureddine, Patricia Cobo-Stark, Svetlana Avdulov, Shayan Farahani, Micah D Gearhart, Daniel G Bichet, Marco Pontoglio, Vishal Patel, Peter Igarashi
The transcription factor hepatocyte nuclear factor-1β (HNF-1β) is essential for normal kidney development and function. Inactivation of HNF-1β in mouse kidney tubules leads to early-onset cyst formation and postnatal lethality. Here, we used Pkhd1/Cre mice to delete HNF-1β specifically in renal collecting ducts (CDs). CD-specific HNF-1β mutant mice survived long term and developed slowly progressive cystic kidney disease, renal fibrosis, and hydronephrosis. Compared with wild-type littermates, HNF-1β mutant mice exhibited polyuria and polydipsia...
May 15, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28507057/benefit-of-ezetimibe-added-to-simvastatin-in-reduced-kidney-function
#7
John W Stanifer, David M Charytan, Jennifer White, Yuliya Lokhnygina, Christopher P Cannon, Matthew T Roe, Michael A Blazing
Efficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with ezetimibe plus simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (ezetimibe plus simvastatin versus simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms...
May 15, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28490435/home-dialysis-in-the-prospective-payment-system-era
#8
Eugene Lin, Xingxing S Cheng, Kuo-Kai Chin, Talhah Zubair, Glenn M Chertow, Eran Bendavid, Jayanta Bhattacharya
The ESRD Prospective Payment System introduced two incentives to increase home dialysis use: bundling injectable medications into a single payment for treatment and paying for home dialysis training. We evaluated the effects of the ESRD Prospective Payment System on home dialysis use by patients starting dialysis in the United States from January 1, 2006 to August 31, 2013. We analyzed data on dialysis modality, insurance type, and comorbidities from the United States Renal Data System. We estimated the effect of the policy on home dialysis use with multivariable logistic regression and compared the effect on Medicare Parts A/B beneficiaries with the effect on patients with other types of insurance...
May 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28487395/safety-of-rituximab-compared-with-steroids-and-cyclophosphamide-for-idiopathic-membranous-nephropathy
#9
Jan A J G van den Brand, Piero Ruggenenti, Antonietta Chianca, Julia M Hofstra, Annalisa Perna, Barbara Ruggiero, Jack F M Wetzels, Giuseppe Remuzzi
Guidelines recommend steroid plus cyclical cyclophosphamide (St-Cp) therapy for patients with idiopathic membranous nephropathy at high risk of progression to ESRD. Rituximab (Rtx) may be a safer alternative. In this retrospective, observational cohort study, we compared time to any adverse event (primary outcome); serious or nonserious events; partial and complete remission of the nephrotic syndrome; and a composite of doubling of serum creatinine, ESRD, or death between 100 Rtx-treated patients and 103 patients who received daily St-Cp We monitored patients with standardized protocols and adjusted for baseline characteristics by Cox regression...
May 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28483798/pregnancy-induced-sensitization-promotes-sex-disparity-in-living-donor-kidney-transplantation
#10
Bianca Bromberger, Danielle Spragan, Sohaib Hashmi, Alexander Morrison, Arwin Thomasson, Susanna Nazarian, Deirdre Sawinski, Paige Porrett
The presence of sex disparity in living donor kidney transplantation (LDKT) remains controversial. To determine if women fall behind men in LDKT evaluation, we performed an intention to treat study of 2587 candidates listed for kidney transplant at a single transplant center over 7 years. We found that women and men kidney transplant candidates engaged an equivalent type and number of prospective living donors. However, sex-specific differences in sensitization history and histocompatibility reduced the rate of LDKT for women by 30%...
May 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28476763/plasma-biomarkers-and-kidney-function-decline-in-early-and-established-diabetic-kidney-disease
#11
Steven G Coca, Girish N Nadkarni, Yuan Huang, Dennis G Moledina, Veena Rao, Jane Zhang, Bart Ferket, Susan T Crowley, Linda F Fried, Chirag R Parikh
Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (n=1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D)...
May 5, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28473637/chronic-fluid-overload-and-mortality-in-esrd
#12
Carmine Zoccali, Ulrich Moissl, Charles Chazot, Francesca Mallamaci, Giovanni Tripepi, Otto Arkossy, Peter Wabel, Stefano Stuard
Sustained fluid overload (FO) is considered a major cause of hypertension, heart failure, and mortality in patients with ESRD on maintenance hemodialysis. However, there has not been a cohort study investigating the relationship between chronic exposure to FO and mortality in this population. We studied the relationship of baseline and cumulative FO exposure over 1 year with mortality in 39,566 patients with incident ESRD in a large dialysis network in 26 countries using whole-body bioimpedance spectroscopy to assess fluid status...
May 4, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28473636/acute-declines-in-renal-function-during-intensive-bp-lowering-implications-for-future-esrd-risk
#13
Elaine Ku, George Bakris, Kirsten L Johansen, Feng Lin, Mark J Sarnak, Vito M Campese, Kenneth Jamerson, Jennifer J Gassman, Miroslaw Smogorzewski, Chi-Yuan Hsu
The magnitude of decline in renal function that should be tolerated during intensive BP lowering and its association with risk of ESRD are unclear. To determine whether the acute declines in kidney function in the intensive BP lowering arm of two trials in CKD associated with higher risk of ESRD, we performed a retrospective study of 899 African American Study of Kidney Disease and Hypertension (AASK) and 761 Modification of Diet in Renal Disease (MDRD) Trial participants previously randomized to strict versus usual BP control...
May 4, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28468822/should-statins-be-banned-from-dialysis
#14
An S De Vriese
No abstract text is available yet for this article.
May 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28465380/the-angiopoietin-tie2-signaling-axis-in-systemic-inflammation
#15
Samir M Parikh
Systemic inflammation is a hallmark of commonly encountered diseases ranging from bacterial sepsis to sterile syndromes such as major trauma. Derangements in the host vasculature contribute to the cardinal manifestations of sepsis in profound ways. Recent studies of control pathways regulating the vascular endothelium have illuminated how this single cell layer toggles between quiescence and activation to affect the development of shock and multiorgan dysfunction. This article focuses on one such control pathway, the Tie2 receptor and its ligands the angiopoietins, to describe a growing body of genetic, biochemical, mechanistic, and human studies that implicate Tie2 as a critical switch...
May 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28465379/cell-therapy-in-kidney-transplantation-focus-on-regulatory-t-cells
#16
Nicholas A Zwang, Joseph R Leventhal
Renal transplantation is the renal replacement modality of choice for suitable candidates with advanced CKD or ESRD. Prevention of rejection, however, requires treatment with nonspecific pharmacologic immunosuppressants that carry both systemic and nephrologic toxicities. Use of a patient's own suppressive regulatory T cells (Tregs) is an attractive biologic approach to reduce this burden. Here, we review the immunologic underpinnings of Treg therapy and technical challenges to developing successful cell therapy...
May 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28465378/biliary-tract-and-liver-complications-in-polycystic-kidney-disease
#17
Parminder K Judge, Charlie H S Harper, Benjamin C Storey, Richard Haynes, Martin J Wilcock, Natalie Staplin, Raph Goldacre, Colin Baigent, Jane Collier, Michael Goldacre, Martin J Landray, Christopher G Winearls, William G Herrington
Polycystic liver disease is a well described manifestation of autosomal dominant polycystic kidney disease (ADPKD). Biliary tract complications are less well recognized. We report a 50-year single-center experience of 1007 patients, which raised a hypothesis that ADPKD is associated with biliary tract disease. We tested this hypothesis using all England Hospital Episode Statistics data (1998-2012), within which we identified 23,454 people with ADPKD and 6,412,754 hospital controls. Hospitalization rates for biliary tract disease, serious liver complications, and a range of other known ADPKD manifestations were adjusted for potential confounders...
May 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28465377/synthesizing-absolute-and-relative-risks-and-the-many-unknowns-to-inform-living-kidney-donors
#18
EDITORIAL
Emilio D Poggio, Jesse D Schold
No abstract text is available yet for this article.
May 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28465376/therapeutic-considerations-for-antihyperglycemic-agents-in-diabetic-kidney-disease
#19
Joshua J Neumiller, Radica Z Alicic, Katherine R Tuttle
Diabetic kidney disease is among the most frequent complications of diabetes, with approximately 50% of patients with ESRD attributed to diabetes in developed countries. Although intensive glycemic management has been shown to delay the onset and progression of increased urinary albumin excretion and reduced GFR in patients with diabetes, conservative dose selection and adjustment of antihyperglycemic medications are necessary to balance glycemic control with safety. A growing body of literature is providing valuable insight into the cardiovascular and renal safety and efficacy of newer antihyperglycemic medications in the dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, and sodium-glucose cotransporter 2 inhibitor classes of medications...
May 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28461553/autologous-mesenchymal-stem-cells-increase-cortical-perfusion-in-renovascular-disease
#20
Ahmed Saad, Allan B Dietz, Sandra M S Herrmann, LaTonya J Hickson, James F Glockner, Michael A McKusick, Sanjay Misra, Haraldur Bjarnason, Adam S Armstrong, Dennis A Gastineau, Lilach O Lerman, Stephen C Textor
Atherosclerotic renovascular disease (RVD) reduces renal blood flow (RBF) and GFR and accelerates poststenotic kidney (STK) tissue injury. Preclinical studies indicate that mesenchymal stem cells (MSCs) can stimulate angiogenesis and modify immune function in experimental RVD. We assessed the safety and efficacy of adding intra-arterial autologous adipose-derived MSCs into STK to standardized medical treatment in human subjects without revascularization. The intervention group (n=14) received a single infusion of MSC (1...
May 1, 2017: Journal of the American Society of Nephrology: JASN
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