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Seminars in Nephrology

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https://www.readbyqxmd.com/read/29291764/translating-knowledge-into-therapy-for-acute-kidney-injury
#1
REVIEW
Mark de Caestecker, Raymond Harris
No therapies have been shown to improve outcomes in patients with acute kidney injury (AKI). Given the high morbidity and mortality associated with AKI this represents an important unmet medical need. A common feature of all of the therapeutic development efforts for AKI is that none were driven by target selection or preclinical modeling that was based primarily on human data. This is important when considering a heterogeneous and dynamic condition such as AKI, in which in the absence of more accurate molecular classifications, clinical cohorts are likely to include patients with different types of injury at different stages in the injury and repair continuum...
January 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29291763/proteomics-and-metabolomics-for-aki-diagnosis
#2
REVIEW
David Marx, Jochen Metzger, Martin Pejchinovski, Ryan Bruce Gil, Maria Frantzi, Agnieszka Latosinska, Iwona Belczacka, Silke Sophie Heinzmann, Holger Husi, Jerome Zoidakis, Matthias Klingele, Stefan Herget-Rosenthal
Acute kidney injury (AKI) is a severe and frequent condition in hospitalized patients. Currently, no efficient therapy of AKI is available. Therefore, efforts focus on early prevention and potentially early initiation of renal replacement therapy to improve the outcome in AKI. The detection of AKI in hospitalized patients implies the need for early, accurate, robust, and easily accessible biomarkers of AKI evolution and outcome prediction because only a narrow window exists to implement the earlier-described measures...
January 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29291762/advances-in-renal-cell-imaging
#3
REVIEW
Georgina Gyarmati, Hiroyuki Kadoya, Ju-Young Moon, James L Burford, Nariman Ahmadi, Inderbir S Gill, Young-Kwon Hong, Bálint Dér, János Peti-Peterdi
A great variety of cell imaging technologies are used routinely every day for the investigation of kidney cell types in applications ranging from basic science research to drug development and pharmacology, clinical nephrology, and pathology. Quantitative visualization of the identity, density, and fate of both resident and nonresident cells in the kidney, and imaging-based analysis of their altered function, (patho)biology, metabolism, and signaling in disease conditions, can help to better define pathomechanism-based disease subgroups, identify critical cells and structures that play a role in the pathogenesis, critically needed biomarkers of disease progression, and cell and molecular pathways as targets for novel therapies...
January 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29291761/precision-medicine-for-acute-kidney-injury-aki-redefining-aki-by-agnostic-kidney-tissue-interrogation-and-genetics
#4
REVIEW
Krzysztof Kiryluk, Andrew S Bomback, Yim-Ling Cheng, Katherine Xu, Pablo G Camara, Raul Rabadan, Peter A Sims, Jonathan Barasch
Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase...
January 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29291760/bringing-renal-biopsy-interpretation-into-the-molecular-age-with-single-cell-rna-sequencing
#5
REVIEW
Andrew F Malone, Haojia Wu, Benjamin D Humphreys
The renal biopsy provides critical diagnostic and prognostic information to clinicians including cases of acute kidney injury, chronic kidney disease, and allograft dysfunction. Today, biopsy specimens are read using a combination of light microscopy, electron microscopy, and indirect immunofluorescence, with a limited number of antibodies. These techniques all were perfected decades ago with only incremental changes since then. By contrast, recent advances in single-cell genomics are transforming scientists' ability to characterize cells...
January 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29291759/phenotyping-of-acute-kidney-injury-beyond-serum-creatinine
#6
REVIEW
Dennis G Moledina, Chirag R Parikh
Acute kidney injury (AKI) is a common complication in hospitalized patients and is associated with adverse short- and long-term outcomes. AKI is diagnosed by serum creatinine (SCr)-based consensus definitions that capture an abrupt decrease in glomerular filtration rate associated with AKI. However, SCr-based AKI definitions lack sensitivity and specificity for diagnosing structural kidney injury. Moreover, AKI is a heterogeneous condition consisting of distinct phenotypes based on its etiology, prognosis, and molecular pathways, and that may potentially require different therapies...
January 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29291758/pathologic-perspectives-on-acute-tubular-injury-assessment-in-the-kidney-biopsy
#7
REVIEW
Gilbert W Moeckel
The molecular mechanisms in acute tubular injury (ATI) are complex and enigmatic. Moreover, we currently lack validated tissue injury markers that can be integrated into the kidney biopsy analysis to guide nephrologists in their patient's management of AKI. Although recognizing the ATI lesion by light microscopy is fairly straightforward, the staging of tubular lesions in the context of clinical time course and etiologic mechanism currently is not adapted to the renal pathology practice. To the clinician, the exact time point when an ischemic or toxic injury has occurred often is not known and cannot be discerned from the review of the biopsy sample...
January 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29291757/expanding-the-role-for-kidney-biopsies-in-acute-kidney-injury
#8
REVIEW
Sushrut S Waikar, Gearoid M McMahon
Acute kidney injury (AKI) is a highly heterogeneous, common, and potentially devastating condition associated with markedly increased hospital length of stay, cost, mortality, and morbidity. Expanding the role for kidney biopsies in AKI may offer fresh insights into disease heterogeneity, molecular mechanisms, and therapeutic targets. A number of challenges face investigators and clinicians considering research biopsies in AKI: ensuring patient safety, ensuring the ethical conduct of research studies, and maximizing the scientific yield of the kidney tissue obtained...
January 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29291756/introduction-understanding-human-aki
#9
EDITORIAL
Lloyd G Cantley
No abstract text is available yet for this article.
January 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110763/clinical-genetic-testing-for-apol1-are-we-there-yet
#10
REVIEW
Bessie A Young, Stephanie Malia Fullerton, James G Wilson, Kerri Cavanaugh, Erika Blacksher, Clarence Spigner, Jonathan Himmelfarb, Wylie Burke
End-stage renal disease (ESRD) disproportionately affects African Americans, who are two to four times more likely than European Americans to develop ESRD. Two independent variants of the apolipoprotein L1 (APOL1) gene, G1 and G2, have been associated with a 7- to 10-fold greater risk of developing nondiabetic ESRD in African Americans. Those who inherit two risk variants (G1/G1, G2/G2, or G1/G2) are also more likely to develop ESRD at a younger age and to have progression of chronic kidney disease. Currently, it is not known what proportion of persons with high-risk genotypes will develop ESRD in the general population, the exact mechanism of injury for APOL1-related risk, its relation to environmental exposures, or whether patients with comorbid conditions are more likely to develop ESRD...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110762/apol1-nephrotoxicity-what-does-ion-transport-have-to-do-with-it
#11
REVIEW
Opeyemi A Olabisi, John F Heneghan
Apolipoprotein L1 (APOL1) protein is the human serum factor that protect human beings against Trypanosoma brucei brucei, the cause of trypanosomiasis. Subspecies of T b brucei that cause human sleeping sickness-T b gambiense and T b rhodesiense evolved molecular mechanisms that enabled them to evade killing by APOL1. Sequence changes (termed G1 and G2) in the APOL1 gene that restored its ability to kill T b rhodesiense also increase the risk of developing glomerular diseases and accelerate progression to end-stage kidney disease...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110761/the-cell-biology-of-apol1
#12
REVIEW
John F O'Toole, Leslie A Bruggeman, Sethu Madhavan, John R Sedor
The association of variants in the APOL1 gene, which encodes apolipoprotein L1 (APOL1), with progressive nondiabetic kidney diseases in African Americans has prompted intense investigation into the function(s) of APOL1. APOL1 is an innate immune effector that protects human beings from infection by some trypanosomal parasites. We review the data characterizing APOL1 trypanolytic function, which has been a basis for studies of APOL1 function in mammalian cells. Subsequently, we discuss the studies that use animal models, mammalian cell culture models, and kidney biopsy tissue to discover the mechanisms of variant APOL1-associated kidney diseases...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110760/apolipoprotein-l1-gene-effects-on-kidney-transplantation
#13
REVIEW
Barry I Freedman, Jayme E Locke, Amber M Reeves-Daniel, Bruce A Julian
The pathogenesis of many common etiologies of nephropathy has been informed by recent molecular genetic breakthroughs. It now is apparent that the ethnic disparity in the risk for nondiabetic chronic kidney disease between African Americans and European Americans is explained largely by variation in the apolipoprotein L1 gene (APOL1). The presence of two APOL1 renal risk variants markedly increases an individual's risk for kidney disease. In transplantation, kidneys from deceased African Americans with two APOL1 renal risk variants have shorter survival intervals after engraftment, regardless of the ethnicity of the recipient...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110759/the-expanding-role-of-apol1-risk-in-chronic-kidney-disease-and-cardiovascular-disease
#14
REVIEW
Michelle M Estrella, Rulan S Parekh
Variants of the APOL1 gene, found primarily in individuals of African descent, are associated with various forms of kidney disease and kidney disease progression. Recent studies evaluating the association of APOL1 with cardiovascular disease have yielded conflicting results, and the potential role in cardiovascular disease remains unclear. In this review, we summarize the observational studies linking the APOL1 risk variants with chronic kidney and cardiovascular disease among persons of African descent.
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110758/apol1-renal-risk-variants-fertile-soil-for-hiv-associated-nephropathy
#15
REVIEW
Jeffrey B Kopp, Jurgen Heymann, Cheryl A Winkler
Apolipoprotein L1 (APOL1) genetic variants are potent risk factors for glomerular disease, but one or more additional factors are required for expression of glomerular disease. Uncontrolled or poorly controlled human immunodeficiency virus (HIV) infection is the most potent susceptibility factor for APOL1 nephropathy that has been identified to date. APOL1 variants are associated with HIV-associated nephropathy (HIVAN), a podocyte disease, but not with HIV-immune complex disease, primarily a disease of the mesangium...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110757/a-brief-history-of-apol1-a-gene-evolving
#16
REVIEW
David J Friedman
APOL1 kidney risk variants lead to high rates of kidney disease in people of recent African ancestry. These risk variants are very common and confer a large increase in risk of kidney disease. This unusual combination of high frequency and large effect size occurs because the risk variants also appear to have beneficial properties. The risk variants show enhanced protective effects against certain pathogens, particularly the trypanosomes that cause African sleeping sickness. Here, we consider the origins and evolution of the primate-only APOL1 gene...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110756/apol1-nephropathy-a-population-genetics-and-evolutionary-medicine-detective-story
#17
REVIEW
Etty Kruzel-Davila, Walter G Wasser, Karl Skorecki
Common DNA sequence variants rarely have a high-risk association with a common disease. When such associations do occur, evolutionary forces must be sought, such as in the association of apolipoprotein L1 (APOL1) gene risk variants with nondiabetic kidney diseases in populations of African ancestry. The variants originated in West Africa and provided pathogenic resistance in the heterozygous state that led to high allele frequencies owing to an adaptive evolutionary selective sweep. However, the homozygous state is disadvantageous and is associated with a markedly increased risk of a spectrum of kidney diseases encompassing hypertension-attributed kidney disease, focal segmental glomerulosclerosis, human immunodeficiency virus nephropathy, sickle cell nephropathy, and progressive lupus nephritis...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110755/introduction-apol1-associated-kidney-disease
#18
EDITORIAL
Martin R Pollak
No abstract text is available yet for this article.
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/28863795/erratum
#19
(no author information available yet)
No abstract text is available yet for this article.
September 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/28863794/immunoadsorption-in-autoimmune-diseases-affecting-the-kidney
#20
REVIEW
Georg Stummvoll, Martin Aringer, Ammon Handisurya, Kurt Derfler
Autoantibodies play an important role in the pathophysiology of renal involvement in systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic vasculitis, and anti-glomerular basement membrane disease (or Goodpasture syndrome). Direct removal of autoantibodies therefore has been tried in various ways, first by plasma exchange. Today, immunoadsorption is the extracorporeal method that most effectively removes (pathogenic) immune complexes and antibodies. Although past data have shown efficacy and biocompatibility of immunoadsorption in (renal) SLE, it is still an experimental and expensive procedure, and evidence from randomized controlled trials is needed...
September 2017: Seminars in Nephrology
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