8,820 results match your criteria Journal of the American Society of Nephrology : JASN[Journal]


Staying the Course: Through End of Life in ESRD.

J Am Soc Nephrol 2019 Feb 19. Epub 2019 Feb 19.

Internal Medicine/Nephrology, University of Michigan, Ann Arbor, Michigan

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http://dx.doi.org/10.1681/ASN.2019010020DOI Listing
February 2019

Lower Extremity Amputation and Health Care Utilization in the Last Year of Life among Medicare Beneficiaries with ESRD.

J Am Soc Nephrol 2019 Feb 19. Epub 2019 Feb 19.

Division of Nephrology, Department of Medicine and the Kidney Research Institute, University of Washington, Seattle, Washington.

Background: Lower extremity amputation is common among patients with ESRD, and often portends a poor prognosis. However, little is known about end-of-life care among patients with ESRD who undergo amputation.

Methods: We conducted a mortality follow-back study of Medicare beneficiaries with ESRD who died in 2002 through 2014 to analyze patterns of lower extremity amputation in the last year of life compared with a parallel cohort of beneficiaries without ESRD. Read More

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http://dx.doi.org/10.1681/ASN.2018101002DOI Listing
February 2019

Overall and Site-Specific Cancer Mortality in Patients on Dialysis and after Kidney Transplant.

J Am Soc Nephrol 2019 Feb 14. Epub 2019 Feb 14.

School of Public Health, University of Sydney, Sydney, Australia.

Patients with ESRD have a substantially increased cancer risk, but few studies have examined the patterns of cancer mortality along a patient's journey from dialysis to transplantation.

Methods: We identified all Australian patients on dialysis and patients with transplants from 1980 to 2014 from the Australia and New Zealand Dialysis and Transplant Registry. Using standardized mortality ratios (SMRs), we compared cancer mortality among patients on dialysis and patients with transplants versus the general population (overall and by age, sex, year, and site); we also performed a subgroup analysis excluding patients with preexisting cancers. Read More

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http://dx.doi.org/10.1681/ASN.2018090906DOI Listing
February 2019
2 Reads
9.343 Impact Factor

Letter to the Editor.

J Am Soc Nephrol 2019 Feb 13. Epub 2019 Feb 13.

Adult Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel

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http://dx.doi.org/10.1681/ASN.2018121226DOI Listing
February 2019

Long-Range Chromatin Interactions in the Kidney.

J Am Soc Nephrol 2019 Feb 13. Epub 2019 Feb 13.

Renal-Electrolyte and Hypertension Division, Department of Medicine and

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http://dx.doi.org/10.1681/ASN.2019010044DOI Listing
February 2019

Authors' Reply.

J Am Soc Nephrol 2019 Feb 13. Epub 2019 Feb 13.

Department of Nuclear Medicine, Physiology and PET, Rigshospitalet, Glostrup, Denmark.

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http://dx.doi.org/10.1681/ASN.2019010049DOI Listing
February 2019

Integrated Functional Genomic Analysis Enables Annotation of Kidney Genome-Wide Association Study Loci.

J Am Soc Nephrol 2019 Feb 13. Epub 2019 Feb 13.

Department of Anatomic Pathology,

Background: Linking genetic risk loci identified by genome-wide association studies (GWAS) to their causal genes remains a major challenge. Disease-associated genetic variants are concentrated in regions containing regulatory DNA elements, such as promoters and enhancers. Although researchers have previously published DNA maps of these regulatory regions for kidney tubule cells and glomerular endothelial cells, maps for podocytes and mesangial cells have not been available. Read More

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http://dx.doi.org/10.1681/ASN.2018030309DOI Listing
February 2019

Spliced XBP1 Rescues Renal Interstitial Inflammation Due to Loss of in Collecting Ducts.

J Am Soc Nephrol 2019 Feb 11. Epub 2019 Feb 11.

Departments of Internal Medicine and

Background: encodes a resident protein in the endoplasmic reticulum membrane that, when mutated, causes human autosomal dominant polycystic liver disease. Selective inactivation of in all distal nephron segments in embryonic mouse kidney results in polycystin-1-mediated polycystic kidney disease (PKD). It also activates the Ire1-Xbp1 branch of the unfolded protein response, producing Xbp1s, the active transcription factor promoting expression of specific genes to alleviate endoplasmic reticulum stress. Read More

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http://dx.doi.org/10.1681/ASN.2018060614DOI Listing
February 2019
1 Read
9.343 Impact Factor

Treatment with 2,4-Dihydroxybenzoic Acid Prevents FSGS Progression and Renal Fibrosis in Podocyte-Specific Knockout Mice.

J Am Soc Nephrol 2019 Feb 8. Epub 2019 Feb 8.

Division of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts;

Background: Although studies have identified >55 genes as causing steroid-resistant nephrotic syndrome (SRNS) and localized its pathogenesis to glomerular podocytes, the disease mechanisms of SRNS remain largely enigmatic. We recently reported that individuals with mutations in COQ6, a coenzyme Q (also called CoQ, CoQ, or ubiquinone) biosynthesis pathway enzyme, develop SRNS with sensorineural deafness, and demonstrated the beneficial effect of CoQ for maintenace of kidney function.

Methods: To study function in podocytes, we generated a podocyte-specific knockout mouse ( ) model and a transient siRNA-based knockdown in a human podocyte cell line. Read More

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http://dx.doi.org/10.1681/ASN.2018060625DOI Listing
February 2019
2 Reads

Iron, Hepcidin, and Death in Human AKI.

J Am Soc Nephrol 2019 Feb 8. Epub 2019 Feb 8.

Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Background: Iron is a key mediator of AKI in animal models, but data on circulating iron parameters in human AKI are limited.

Methods: We examined results from the ARF Trial Network study to assess the association of plasma catalytic iron, total iron, transferrin, ferritin, free hemoglobin, and hepcidin with 60-day mortality. Participants included critically ill patients with AKI requiring RRT who were enrolled in the study. Read More

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http://dx.doi.org/10.1681/ASN.2018100979DOI Listing
February 2019
1 Read
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Cardiopulmonary Resuscitation in Outpatient Dialysis Clinics: Perception of Futility?

J Am Soc Nephrol 2019 Feb 7. Epub 2019 Feb 7.

Division of Nephrology, University Health Network, Toronto, Ontario, Canada

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http://dx.doi.org/10.1681/ASN.2019010046DOI Listing
February 2019
1 Read

Outcomes for Hemodialysis Patients Given Cardiopulmonary Resuscitation for Cardiac Arrest at Outpatient Dialysis Clinics.

J Am Soc Nephrol 2019 Feb 7. Epub 2019 Feb 7.

Duke Clinical Research Institute.

Background: Out-of-hospital cardiac arrest, the leading cause of death among patients on hemodialysis, occurs frequently within outpatient dialysis centers. Practice guidelines recommend resuscitation training for all dialysis clinic staff and on-site defibrillator availability, but the extent of staff involvement in cardiopulmonary resuscitation (CPR) efforts and its association with outcomes is unknown.

Methods: We used data from the Cardiac Arrest Registry to Enhance Survival and the Centers for Medicare & Medicaid Services dialysis facility database to identify patients who had cardiac arrest within outpatient dialysis clinics between 2010 and 2016 in the southeastern United States. Read More

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http://dx.doi.org/10.1681/ASN.2018090911DOI Listing
February 2019
1 Read

Systemic Succinate Homeostasis and Local Succinate Signaling Affect Blood Pressure and Modify Risks for Calcium Oxalate Lithogenesis.

J Am Soc Nephrol 2019 Feb 6. Epub 2019 Feb 6.

Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel;

Background: In the kidney, low urinary citrate increases the risk for developing kidney stones, and elevation of luminal succinate in the juxtaglomerular apparatus increases renin secretion, causing hypertension. Although the association between stone formation and hypertension is well established, the molecular mechanism linking these pathophysiologies has been elusive.

Methods: To investigate the relationship between succinate and citrate/oxalate levels, we assessed blood and urine levels of metabolites, renal protein expression, and BP (using 24-hour telemetric monitoring) in male mice lacking slc26a6 (a transporter that inhibits the succinate transporter NaDC-1 to control citrate absorption from the urinary lumen). Read More

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http://dx.doi.org/10.1681/ASN.2018030277DOI Listing
February 2019

T Cells Play a Causal Role in Diastolic Dysfunction during Uremic Cardiomyopathy.

J Am Soc Nephrol 2019 Feb 6. Epub 2019 Feb 6.

Emory Transplant Center, Department of Surgery, and.

Background: Uremic cardiomyopathy, characterized by left ventricular hypertrophy, diastolic dysfunction, and impaired myocardial strain, contributes to increased cardiovascular mortality in patients with CKD. Emerging evidence suggests a pathogenic role for T cells during chronic heart failure.

Methods: To determine whether T cells contribute to uremic cardiomyopathy pathogenesis, we modeled this condition by inducing CKD 5/6th nephrectomy in mice. Read More

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http://dx.doi.org/10.1681/ASN.2017101138DOI Listing
February 2019
1 Read

Frailty and Changes in Cognitive Function after Kidney Transplantation.

J Am Soc Nephrol 2019 Feb 24;30(2):336-345. Epub 2019 Jan 24.

Departments of Epidemiology,

Background: Restoration of kidney function after kidney transplant generally improves cognitive function. It is unclear whether frail recipients, with higher susceptibility to surgical stressors, achieve such post-transplant cognitive improvements or whether they experience subsequent cognitive decline as they age with a functioning graft.

Methods: In this two-center cohort study, we assessed pretransplant frailty (Fried physical frailty phenotype) and cognitive function (Modified Mini-Mental State Examination) in adult kidney transplant recipients. Read More

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http://dx.doi.org/10.1681/ASN.2018070726DOI Listing
February 2019

Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population.

J Am Soc Nephrol 2019 Feb 24;30(2):346-353. Epub 2019 Jan 24.

Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota.

Background: Morbidity and mortality vary seasonally. Timing and severity of influenza seasons contribute to those patterns, especially among vulnerable populations such as patients with ESRD. However, the extent to which influenza-like illness (ILI), a syndrome comprising a range of potentially serious respiratory tract infections, contributes to mortality in patients with ESRD has not been quantified. Read More

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http://dx.doi.org/10.1681/ASN.2018060581DOI Listing
February 2019
3 Reads

Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients.

J Am Soc Nephrol 2019 Feb 17;30(2):201-215. Epub 2019 Jan 17.

Division of Nephrology,

Background: Whole-exome sequencing (WES) finds a CKD-related mutation in approximately 20% of patients presenting with CKD before 25 years of age. Although provision of a molecular diagnosis could have important implications for clinical management, evidence is lacking on the diagnostic yield and clinical utility of WES for pediatric renal transplant recipients.

Methods: To determine the diagnostic yield of WES in pediatric kidney transplant recipients, we recruited 104 patients who had received a transplant at Boston Children's Hospital from 2007 through 2017, performed WES, and analyzed results for likely deleterious variants in approximately 400 genes known to cause CKD. Read More

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http://dx.doi.org/10.1681/ASN.2018060575DOI Listing
February 2019
7 Reads

Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities.

J Am Soc Nephrol 2019 Feb 14;30(2):187-200. Epub 2019 Jan 14.

Division of Nephrology, Department of Medicine, Stony Brook University, Stony Brook, New York; and

Inhibition of vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling is a common therapeutic strategy in oncology, with new drugs continuously in development. In this review, we consider the experimental and clinical evidence behind the diverse nephrotoxicities associated with the inhibition of this pathway. We also review the renal effects of VEGF inhibition's mediation of key downstream signaling pathways, specifically MAPK/ERK1/2, endothelial nitric oxide synthase, and mammalian target of rapamycin (mTOR). Read More

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http://dx.doi.org/10.1681/ASN.2018080853DOI Listing
February 2019
1 Read

Manipulation of Nephron-Patterning Signals Enables Selective Induction of Podocytes from Human Pluripotent Stem Cells.

J Am Soc Nephrol 2019 Feb 11;30(2):304-321. Epub 2019 Jan 11.

Department of Kidney Development, Institute of Molecular Embryology and Genetics, and

Background: Previous research has elucidated the signals required to induce nephron progenitor cells (NPCs) from pluripotent stem cells (PSCs), enabling the generation of kidney organoids. However, selectively controlling differentiation of NPCs to podocytes has been a challenge.

Methods: We investigated the effects of various growth factors in cultured mouse embryonic NPCs during three distinct steps of nephron patterning: from NPC to pretubular aggregate, from the latter to epithelial renal vesicle (RV), and from RV to podocyte. Read More

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http://dx.doi.org/10.1681/ASN.2018070747DOI Listing
February 2019
2 Reads

Producing Purer Podocytes.

J Am Soc Nephrol 2019 Feb 11;30(2):183-184. Epub 2019 Jan 11.

Division of Nephrology,

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http://dx.doi.org/10.1681/ASN.2018101045DOI Listing
February 2019

Hepatocyte Growth Factor-Secreting Mesothelial Cell Sheets Suppress Progressive Fibrosis in a Rat Model of CKD.

J Am Soc Nephrol 2019 Feb 11;30(2):261-276. Epub 2019 Jan 11.

Department of Medicine, Kidney Center.

Background: Although hepatocyte growth factor (HGF) has antifibrotic effects and is involved in angiogenesis and vasodilation, systemic administration of HGF to prevent kidney fibrosis is not a feasible strategy for suppressing interstitial fibrosis in patients with CKD.

Methods: We investigated a novel therapy involving HGF transgenic cell sheets grown in culture from human mesothelial cells and administered to rats with unilateral ureteral obstruction (UUO). We compared progression of fibrosis in rats with UUO that received one of five interventions: HGF-transgenic mesothelial cell sheets transplanted to the kidney surface, HGF-transgenic mesothelial cell sheets transplanted to thigh, mesotherial cell sheets transplanted to kidney, no sheets, or HGF injections. Read More

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http://dx.doi.org/10.1681/ASN.2018050556DOI Listing
February 2019

New Insights into the Mechanism of NO Selectivity in the Human Kidney Chloride Channel ClC-Ka and the CLC Protein Family.

J Am Soc Nephrol 2019 Feb 11;30(2):293-302. Epub 2019 Jan 11.

Dulbecco Telethon Laboratory, Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Genova, Italy; and

Background: The mechanism of anion selectivity in the human kidney chloride channels ClC-Ka and ClC-Kb is unknown. However, it has been thought to be very similar to that of other channels and antiporters of the CLC protein family, and to rely on anions interacting with a conserved Ser residue (Ser) at the center of three anion binding sites in the permeation pathway S. In both CLC channels and antiporters, mutations of Ser alter the anion selectivity. Read More

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http://dx.doi.org/10.1681/ASN.2018060593DOI Listing
February 2019
2 Reads

Activation and Proliferation of PD-1 Kidney Double-Negative T Cells Is Dependent on Nonclassical MHC Proteins and IL-2.

J Am Soc Nephrol 2019 Feb 8;30(2):277-292. Epub 2019 Jan 8.

Department of Pathology.

Background: CD4 CD8 double-negative (DN) T cells with innate-like properties represent a significant component of T cells in human and mouse kidneys. They spontaneously proliferate in the steady state and protect against ischemic AKI. However, the mechanisms regulating DN T cell homeostasis and responses to external danger signals from "sterile" inflammation remain poorly understood. Read More

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http://dx.doi.org/10.1681/ASN.2018080815DOI Listing
February 2019
6 Reads
9.343 Impact Factor

IL-34-Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL- Mice.

J Am Soc Nephrol 2019 Feb 8;30(2):244-259. Epub 2019 Jan 8.

Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and

Background: In people with SLE and in the MRL- lupus mouse model, macrophages and autoantibodies are central to lupus nephritis. IL-34 mediates macrophage survival and proliferation, is expressed by tubular epithelial cells (TECs), and binds to the cFMS receptor on macrophages and to a newly identified second receptor, PTPRZ.

Methods: To investigate whether IL-34-dependent intrarenal and systemic mechanisms promote lupus nephritis, we compared lupus nephritis and systemic illness in MRL- mice expressing IL-34 and IL-34 knockout (KO) MRL- mice. Read More

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http://www.jasn.org/lookup/doi/10.1681/ASN.2018090901
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http://dx.doi.org/10.1681/ASN.2018090901DOI Listing
February 2019
4 Reads

Lipid Peroxidation Drives Renal Cyst Growth through Activation of TMEM16A.

J Am Soc Nephrol 2019 Feb 3;30(2):228-242. Epub 2019 Jan 3.

Department of Physiology, University of Regensburg, Regensburg, Germany; and

Background: Transepithelial chloride secretion, through the chloride channels cystic fibrosis transmembrane conductance regulator (CFTR) and TMEM16A (anoctamin 1), drives cyst enlargement in polycystic kidney disease (PKD). Polycystic kidneys are hypoxic, and oxidative stress activates TMEM16A. However, mechanisms for channel activation in PKD remain obscure. Read More

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http://dx.doi.org/10.1681/ASN.2018010039DOI Listing
February 2019
4 Reads

A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney Transplantation.

J Am Soc Nephrol 2019 Feb 3;30(2):355-365. Epub 2019 Jan 3.

Urology Division, Renal Transplant Service and

Background: Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD).

Methods: In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. Read More

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http://www.jasn.org/lookup/doi/10.1681/ASN.2018060656
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http://dx.doi.org/10.1681/ASN.2018060656DOI Listing
February 2019
5 Reads
9.343 Impact Factor

Readmissions Metrics in Hemodialysis: Do the Specifics Matter?

J Am Soc Nephrol 2019 Feb 3;30(2):184-186. Epub 2019 Jan 3.

William B. Schwartz Division of Nephrology, Tufts Medical Center, Boston, Massachusetts

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http://dx.doi.org/10.1681/ASN.2018101033DOI Listing
February 2019

Prior Hospitalization Burden and the Relatedness of 30-Day Readmissions in Patients Receiving Hemodialysis.

J Am Soc Nephrol 2019 Feb 3;30(2):323-335. Epub 2019 Jan 3.

Division of Nephrology, Department of Medicine and.

Background: Thirty-day readmissions are common in patients receiving hemodialysis and costly to Medicare. Because patients on hemodialysis have a high background hospitalization rate, 30-day readmissions might be less likely related to the index hospitalization than in patients with other conditions.

Methods: In adults with Medicare receiving hemodialysis in the United States, we used multinomial logistic regression to evaluate whether prior hospitalization burden was associated with increased 30-day readmissions unrelated to index hospitalizations with a discharge date from January 1, 2013 to December 31, 2014. Read More

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http://dx.doi.org/10.1681/ASN.2018080858DOI Listing
February 2019

Erratum.

Authors:

J Am Soc Nephrol 2019 Jan;30(1):182

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http://dx.doi.org/10.1681/ASN.2018111096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317597PMC
January 2019

Nucleophosmin Phosphorylation as a Diagnostic and Therapeutic Target for Ischemic AKI.

J Am Soc Nephrol 2019 Jan;30(1):50-62

Renal Section, Boston University Medical Center, Boston, Massachusetts; and

Ischemic AKI lacks a urinary marker for early diagnosis and an effective therapy. Differential nucleophosmin (NPM) phosphorylation is a potential early marker of ischemic renal cell injury and a therapeutic target. Differential NPM phosphorylation was assessed by mass spectrometry in NPM harvested from murine and human primary renal epithelial cells, fresh kidney tissue, and urine before and after ischemic injury. Read More

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http://dx.doi.org/10.1681/ASN.2018040401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317607PMC
January 2019
1 Read

Improving Clinical Outcomes in the Era of Information Ubiquity.

Authors:
Robert M Califf

J Am Soc Nephrol 2019 Jan;30(1):7-12

Duke Forge, Duke University School of Medicine, Durham, North Carolina;

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http://dx.doi.org/10.1681/ASN.2018111128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317594PMC
January 2019

Simple Postoperative AKI Risk (SPARK) Classification before Noncardiac Surgery: A Prediction Index Development Study with External Validation.

J Am Soc Nephrol 2019 Jan 18;30(1):170-181. Epub 2018 Dec 18.

Department of Internal Medicine,

Background: Researchers have suggested models to predict the risk of postoperative AKI (PO-AKI), but an externally validated risk index that can be practically implemented before patients undergo noncardiac surgery is needed.

Methods: We performed a retrospective observational study of patients without preexisting renal failure who underwent a noncardiac operation (≥1 hour) at two tertiary hospitals in Korea. We fitted a proportional odds model for an ordinal outcome consisting of three categories: critical AKI (defined as Kidney Disease Improving Global Outcomes AKI stage ≥2, post-AKI death, or dialysis within 90 days after surgery), low-stage AKI (defined as PO-AKI events not fulfilling the definition of critical AKI), and no PO-AKI. Read More

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http://www.jasn.org/lookup/doi/10.1681/ASN.2018070757
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http://dx.doi.org/10.1681/ASN.2018070757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317608PMC
January 2019
4 Reads

Postoperative AKI-Prevention Is Better than Cure?

J Am Soc Nephrol 2019 Jan 18;30(1):4-6. Epub 2018 Dec 18.

Adult Critical Care Unit and Department of Renal Medicine and Transplantation, The Royal London Hospital, Barts Health National Health Service Trust, London, United Kingdom; and.

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http://dx.doi.org/10.1681/ASN.2018111127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317595PMC
January 2019

Growth of the ESKD Population: Progress or Peril?

Authors:
Allan J Collins

J Am Soc Nephrol 2019 Jan 17;30(1):3-4. Epub 2018 Dec 17.

School of Medicine, University of Minnesota, Minneapolis, Minnesota

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http://dx.doi.org/10.1681/ASN.2018111135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317602PMC
January 2019

Kir4.1/Kir5.1 Activity Is Essential for Dietary Sodium Intake-Induced Modulation of Na-Cl Cotransporter.

J Am Soc Nephrol 2019 Feb 17;30(2):216-227. Epub 2018 Dec 17.

Department of Pharmacology, New York Medical College, Valhalla, New York

Background: Dietary sodium intake regulates the thiazide-sensitive Na-Cl cotransporter (NCC) in the distal convoluted tubule (DCT). Whether the basolateral, inwardly rectifying potassium channel Kir4.1/Kir5. Read More

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http://dx.doi.org/10.1681/ASN.2018080799DOI Listing
February 2019

Projecting ESRD Incidence and Prevalence in the United States through 2030.

J Am Soc Nephrol 2019 Jan 17;30(1):127-135. Epub 2018 Dec 17.

Arbor Research Collaborative for Health, Ann Arbor, Michigan; and Departments of.

Background: Population rates of obesity, hypertension, diabetes, age, and race can be used in simulation models to develop projections of ESRD incidence and prevalence. Such projections can inform long-range planning for ESRD resources needs.

Methods: We used an open compartmental simulation model to estimate the incidence and prevalence of ESRD in the United States through 2030 on the basis of wide-ranging projections of population obesity and ESRD death rates. Read More

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http://dx.doi.org/10.1681/ASN.2018050531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317596PMC
January 2019

Expression Profiling of Fibroblasts in Chronic and Acute Disease Models Reveals Novel Pathways in Kidney Fibrosis.

J Am Soc Nephrol 2019 Jan 13;30(1):80-94. Epub 2018 Dec 13.

Department of Pathology, University of Michigan, Ann Arbor, Michigan; and

Background: Renal interstitial fibrosis results from activation and proliferation of fibroblasts to myofibroblasts, secretion and accumulation of extracellular matrix, and displacement of normal renal tubules. In contrast to chronic renal disease, acute injury may be repaired, a process that includes a decrease in the number of myofibroblasts in the interstitium and degradation of the accumulated extracellular matrix, leaving little evidence of prior injury.

Methods: To investigate whether activated fibroblasts demonstrate changes in gene expression that correspond with regression after acute injury but are not observed in chronic models of fibrosis, we used microarrays to analyze gene expression patterns among fibroblast populations at different stages of injury or repair. Read More

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http://dx.doi.org/10.1681/ASN.2018060644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317603PMC
January 2019
1 Read

Quantity and Reporting Quality of Kidney Research.

J Am Soc Nephrol 2019 Jan 13;30(1):13-22. Epub 2018 Dec 13.

Division of Nephrology, Medizinische Klinik and Poliklinik IV, Klinikum der Universität München, Ludwig Maximilians University München, Munich, Germany

Background: In 2004, researchers reported that the number of nephrology clinical trials was low and that the reporting quality of such trials was suboptimal. Furthermore, the number or quality of preclinical kidney-related studies has not been systematically evaluated.

Methods: We performed a systematic review of randomized clinical trials published in 1966-2017 (listed in the Cochrane Library) and preclinical studies published in 1945-2017 (listed in PubMed). Read More

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http://dx.doi.org/10.1681/ASN.2018050515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317598PMC
January 2019
1 Read

The MEK Inhibitor Trametinib Ameliorates Kidney Fibrosis by Suppressing ERK1/2 and mTORC1 Signaling.

J Am Soc Nephrol 2019 Jan 10;30(1):33-49. Epub 2018 Dec 10.

Diabetic Kidney Disease Centre, Renal Unit, Barts Health National Health Service Trust, The Royal London Hospital, London, UK; and.

Background: During kidney fibrosis, a hallmark and promoter of CKD (regardless of the underlying renal disorder leading to CKD), the extracellular-regulated kinase 1/2 (ERK1/2) pathway, is activated and has been implicated in the detrimental differentiation and expansion of kidney fibroblasts. An ERK1/2 pathway inhibitor, trametinib, is currently used in the treatment of melanoma, but its efficacy in the setting of CKD and renal fibrosis has not been explored.

Methods: We investigated whether trametinib has antifibrotic effects in two mouse models of renal fibrosis-mice subjected to unilateral ureteral obstruction (UUO) or fed an adenine-rich diet-as well as in cultured primary human fibroblasts. Read More

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http://dx.doi.org/10.1681/ASN.2018020209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317609PMC
January 2019

Investigating the Relationship between Cerebral Blood Flow and Cognitive Function in Hemodialysis Patients.

J Am Soc Nephrol 2019 Jan 7;30(1):147-158. Epub 2018 Dec 7.

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK;

Background: The immediate and longer-term effects of hemodialysis on cerebral circulation, cerebral structure, and cognitive function are poorly understood.

Methods: In a prospective observational cohort study of 97 adults (median age 59 years) receiving chronic hemodialysis, we used transcranial Doppler ultrasound to measure cerebral arterial mean flow velocity (MFV) throughout dialysis. Using a well validated neuropsychological protocol, we assessed cognitive function during and off dialysis and after 12 months of treatment. Read More

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http://dx.doi.org/10.1681/ASN.2018050462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317612PMC
January 2019

Survival among Veterans Obtaining Dialysis in VA and Non-VA Settings.

J Am Soc Nephrol 2019 Jan 7;30(1):159-168. Epub 2018 Dec 7.

Health Services Research and Development, Durham Veterans Affairs Health Care System, Durham, North Carolina.

Background: Outcomes of veterans with ESRD may differ depending on where they receive dialysis and who finances this care, but little is known about variation in outcomes across different dialysis settings and financial arrangements.

Methods: We examined survival among 27,241 Veterans Affairs (VA)-enrolled veterans who initiated chronic dialysis in 2008-2011 at () VA-based units, () community-based clinics through the Veterans Affairs Purchased Care program (VA-PC), () community-based clinics under Medicare, or () more than one of these settings ("dual" care). Using a Cox proportional hazards model, we compared all-cause mortality across dialysis settings during the 2-year period after dialysis initiation, adjusting for demographic and clinical characteristics. Read More

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http://www.jasn.org/lookup/doi/10.1681/ASN.2018050521
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http://dx.doi.org/10.1681/ASN.2018050521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317601PMC
January 2019
6 Reads

DNA Methyltransferase 1 Controls Nephron Progenitor Cell Renewal and Differentiation.

J Am Soc Nephrol 2019 Jan 5;30(1):63-78. Epub 2018 Dec 5.

III. Department of Medicine,

Background: Nephron number is a major determinant of long-term renal function and cardiovascular risk. Observational studies suggest that maternal nutritional and metabolic factors during gestation contribute to the high variability of nephron endowment. However, the underlying molecular mechanisms have been unclear. Read More

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http://dx.doi.org/10.1681/ASN.2018070736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317605PMC
January 2019
3 Reads

Morphological Processes of Foot Process Effacement in Puromycin Aminonucleoside Nephrosis Revealed by FIB/SEM Tomography.

J Am Soc Nephrol 2019 Jan 4;30(1):96-108. Epub 2018 Dec 4.

Department of Anatomy and Life Structure and.

Background: Foot process effacement is one of the pathologic indicators of podocyte injury. However, the morphologic changes associated with it remain unclear.

Methods: To clarify the developmental process, we analyzed puromycin nephrotic podocytes reconstructed from serial focused-ion beam/scanning electron microscopy (FIB/SEM) images. Read More

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http://dx.doi.org/10.1681/ASN.2018020139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317610PMC
January 2019
1 Read

Endogenous Notch Signaling in Adult Kidneys Maintains Segment-Specific Epithelial Cell Types of the Distal Tubules and Collecting Ducts to Ensure Water Homeostasis.

J Am Soc Nephrol 2019 Jan 4;30(1):110-126. Epub 2018 Dec 4.

Pediatrics and Rare Diseases Group and

Background: Notch signaling is required during kidney development for nephron formation and principal cell fate selection within the collecting ducts. Whether Notch signaling is required in the adult kidney to maintain epithelial diversity, or whether its loss can trigger principal cell transdifferentiation (which could explain acquired diabetes insipidus in patients receiving lithium) is unclear.

Methods: To investigate whether loss of Notch signaling can trigger principal cells to lose their identity, we genetically inactivated and , inactivated the Notch signaling target , or induced expression of a Notch signaling inhibitor in all of the nephron segments and collecting ducts in mice after kidney development. Read More

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http://dx.doi.org/10.1681/ASN.2018040440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317606PMC
January 2019
1 Read

Sex-Related Disparities in CKD Progression.

J Am Soc Nephrol 2019 Jan 3;30(1):137-146. Epub 2018 Dec 3.

Department of Medicine, Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois.

Background: In the United States, incidence of ESRD is 1.5 times higher in men than in women, despite men's lower prevalence of CKD. Prior studies, limited by inclusion of small percentages of minorities and other factors, suggested that men have more rapid CKD progression, but this finding has been inconsistent. Read More

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http://dx.doi.org/10.1681/ASN.2018030296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317604PMC
January 2019
7 Reads

Advantages of Single-Nucleus over Single-Cell RNA Sequencing of Adult Kidney: Rare Cell Types and Novel Cell States Revealed in Fibrosis.

J Am Soc Nephrol 2019 Jan 3;30(1):23-32. Epub 2018 Dec 3.

Division of Nephrology, Department of Medicine and

Background: A challenge for single-cell genomic studies in kidney and other solid tissues is generating a high-quality single-cell suspension that contains rare or difficult-to-dissociate cell types and is free of both RNA degradation and artifactual transcriptional stress responses.

Methods: We compared single-cell RNA sequencing (scRNA-seq) using the DropSeq platform with single-nucleus RNA sequencing (snRNA-seq) using sNuc-DropSeq, DroNc-seq, and 10X Chromium platforms on adult mouse kidney. We validated snRNA-seq on fibrotic kidney from mice 14 days after unilateral ureteral obstruction (UUO) surgery. Read More

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http://dx.doi.org/10.1681/ASN.2018090912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317600PMC
January 2019
1 Read

Association of Blood Pressure Trajectories in Early Life with Subclinical Renal Damage in Middle Age.

J Am Soc Nephrol 2018 Dec 12;29(12):2835-2846. Epub 2018 Nov 12.

Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College, Xi'an Jiaotong University and Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, People's Republic of China.

Background: Although high BP is one of the most important factors affecting renal function, whether longitudinal BP trajectories in early life course are associated with renal function damage in later life is unclear.

Methods: To investigate the correlation between BP trajectories from childhood to adulthood and renal function in middle age, we used group-based trajectory models to identify BP trajectories in 2430 individuals (aged 6-15 years old at baseline) participating in the ongoing Hanzhong Adolescent Hypertension Cohort. We tested the association between these trajectories and subclinical renal damage in middle age, adjusting for several covariates. Read More

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http://www.jasn.org/lookup/doi/10.1681/ASN.2018030263
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http://dx.doi.org/10.1681/ASN.2018030263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287870PMC
December 2018
7 Reads

The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial.

J Am Soc Nephrol 2018 Dec 12;29(12):2890-2899. Epub 2018 Nov 12.

Sydney School of Public Health, Faculty of Medicine and Health, Sydney, Australia;

Background: The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear.

Methods: In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP<130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Read More

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http://dx.doi.org/10.1681/ASN.2018040443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287867PMC
December 2018
8 Reads