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  1. Article ; Online: Defining protein expression in the kidney at large scale: from antibody validation to cytometry analysis.

    Sabo, Angela R / Winfree, Seth / El-Achkar, Tarek M

    American journal of physiology. Renal physiology

    2022  Volume 324, Issue 2, Page(s) F135–F137

    MeSH term(s) Antibodies ; Kidney ; Flow Cytometry
    Chemical Substances Antibodies
    Language English
    Publishing date 2022-12-01
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00262.2022
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  2. Article ; Online: Precision Medicine in Nephrology: An Integrative Framework of Multidimensional Data in the Kidney Precision Medicine Project.

    El-Achkar, Tarek M / Eadon, Michael T / Kretzler, Matthias / Himmelfarb, Jonathan

    American journal of kidney diseases : the official journal of the National Kidney Foundation

    2023  Volume 83, Issue 3, Page(s) 402–410

    Abstract: Chronic kidney disease (CKD) and acute kidney injury (AKI) are heterogeneous syndromes defined clinically by serial measures of kidney function. Each condition possesses strong histopathologic associations, including glomerular obsolescence or acute ... ...

    Abstract Chronic kidney disease (CKD) and acute kidney injury (AKI) are heterogeneous syndromes defined clinically by serial measures of kidney function. Each condition possesses strong histopathologic associations, including glomerular obsolescence or acute tubular necrosis, respectively. Despite such characterization, there remains wide variation in patient outcomes and treatment responses. Precision medicine efforts, as exemplified by the Kidney Precision Medicine Project (KPMP), have begun to establish evolving, spatially anchored, cellular and molecular atlases of the cell types, states, and niches of the kidney in health and disease. The KPMP atlas provides molecular context for CKD and AKI disease drivers and will help define subtypes of disease that are not readily apparent from canonical functional or histopathologic characterization but instead are appreciable through advanced clinical phenotyping, pathomic, transcriptomic, proteomic, epigenomic, and metabolomic interrogation of kidney biopsy samples. This perspective outlines the structure of the KPMP, its approach to the integration of these diverse datasets, and its major outputs relevant to future patient care.
    MeSH term(s) Humans ; Nephrology ; Precision Medicine ; Proteomics ; Kidney/pathology ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/therapy ; Renal Insufficiency, Chronic/pathology ; Acute Kidney Injury/pathology
    Language English
    Publishing date 2023-10-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604539-x
    ISSN 1523-6838 ; 0272-6386
    ISSN (online) 1523-6838
    ISSN 0272-6386
    DOI 10.1053/j.ajkd.2023.08.015
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  3. Article ; Online: Systemic Effects of Tamm-Horsfall Protein in Kidney Disease.

    LaFavers, Kaice A / El-Achkar, Tarek M

    Seminars in nephrology

    2022  Volume 42, Issue 3, Page(s) 151277

    Abstract: ... potential cation channel, subfamily M, member 2 t(TRPM2), and protection in sepsis is at least partially due ...

    Abstract Tamm-Horsfall protein (THP) is produced exclusively by the kidney, where it is released into both the urine and the circulation. Although the primary form of circulating THP is nonpolymerizing, urinary THP exists as a mix of polymerizing and nonpolymerizing forms. Urinary THP has been shown to play roles in such disparate processes as prevention of urinary tract infections and kidney stone formation, along with the regulation of multiple ion channels within the kidney. The generation of THP knockout mouse models has allowed the investigation of these phenomena and shown a prospective role for circulating THP in ischemia-reperfusion acute kidney injury as well as sepsis. Recent studies have suggested that THP is protective in ischemic injury owing to its inhibition of oxidative stress via the calcium channel transient receptor potential cation channel, subfamily M, member 2 t(TRPM2), and protection in sepsis is at least partially due to THP's promotion of macrophage function.
    MeSH term(s) Animals ; Mice ; Humans ; Uromodulin/metabolism ; Kidney/metabolism ; Acute Kidney Injury/metabolism ; Mice, Knockout ; Oxidative Stress ; TRPM Cation Channels/metabolism
    Chemical Substances Uromodulin ; TRPM2 protein, mouse ; TRPM Cation Channels
    Language English
    Publishing date 2022-11-18
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 604652-6
    ISSN 1558-4488 ; 0270-9295
    ISSN (online) 1558-4488
    ISSN 0270-9295
    DOI 10.1016/j.semnephrol.2022.10.003
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  4. Article ; Online: Computational Pathology Fusing Spatial Technologies.

    Border, Samuel / Lucarelli, Nicholas / Eadon, Michael T / El-Achkar, Tarek M / Jain, Sanjay / Sarder, Pinaki

    Clinical journal of the American Society of Nephrology : CJASN

    2023  

    Language English
    Publishing date 2023-03-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2226665-3
    ISSN 1555-905X ; 1555-9041
    ISSN (online) 1555-905X
    ISSN 1555-9041
    DOI 10.2215/CJN.0000000000000146
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  5. Article ; Online: Healthy Women Have Higher Systemic Uromodulin Levels: Identification of Uromodulin as an Estrogen Responsive Gene.

    Nanamatsu, Azuma / Micanovic, Radmila / Khan, Shehnaz / El-Achkar, Tarek M / LaFavers, Kaice A

    Kidney360

    2023  Volume 4, Issue 9, Page(s) e1302–e1307

    MeSH term(s) Female ; Humans ; Uromodulin/genetics
    Chemical Substances Uromodulin ; UMOD protein, human
    Language English
    Publishing date 2023-06-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2641-7650
    ISSN (online) 2641-7650
    DOI 10.34067/KID.0000000000000197
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  6. Article ; Online: Profiling Immune Cells in the Kidney Using Tissue Cytometry and Machine Learning.

    Winfree, Seth / Al Hasan, Mohammad / El-Achkar, Tarek M

    Kidney360

    2022  Volume 3, Issue 5, Page(s) 968–978

    Abstract: The immune system governs key functions that maintain renal homeostasis through various effector cells that reside in or infiltrate the kidney. These immune cells play an important role in shaping adaptive or maladaptive responses to local or systemic ... ...

    Abstract The immune system governs key functions that maintain renal homeostasis through various effector cells that reside in or infiltrate the kidney. These immune cells play an important role in shaping adaptive or maladaptive responses to local or systemic stress and injury. We increasingly recognize that microenvironments within the kidney are characterized by a unique distribution of immune cells, the function of which depends on this unique spatial localization. Therefore, quantitative profiling of immune cells in intact kidney tissue becomes essential, particularly at a scale and resolution that allow the detection of differences between the various "nephro-ecosystems" in health and disease. In this review, we discuss advancements in tissue cytometry of the kidney, performed through multiplexed confocal imaging and analysis using the Volumetric Tissue Exploration and Analysis (VTEA) software. We highlight how this tool has improved our understanding of the role of the immune system in the kidney and its relevance in the pathobiology of renal disease. We also discuss how the field is increasingly incorporating machine learning to enhance the analytic potential of imaging data and provide unbiased methods to explore and visualize multidimensional data. Such novel analytic methods could be particularly relevant when applied to profiling immune cells. Furthermore, machine-learning approaches applied to cytometry could present venues for nonexhaustive exploration and classification of cells from existing data and improving tissue economy. Therefore, tissue cytometry is transforming what used to be a qualitative assessment of the kidney into a highly quantitative, imaging-based "omics" assessment that complements other advanced molecular interrogation technologies.
    MeSH term(s) Acute Kidney Injury ; Humans ; Kidney/diagnostic imaging ; Machine Learning ; Software
    Language English
    Publishing date 2022-03-28
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2641-7650
    ISSN (online) 2641-7650
    DOI 10.34067/KID.0006802020
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  7. Article ; Online: Cellular and molecular interrogation of kidney biopsy specimens.

    Eadon, Michael T / Dagher, Pierre C / El-Achkar, Tarek M

    Current opinion in nephrology and hypertension

    2022  Volume 31, Issue 2, Page(s) 160–167

    Abstract: Purpose of review: Traditional histopathology of the kidney biopsy specimen has been an essential and successful tool for the diagnosis and staging of kidney diseases. However, it is likely that the full potential of the kidney biopsy has not been ... ...

    Abstract Purpose of review: Traditional histopathology of the kidney biopsy specimen has been an essential and successful tool for the diagnosis and staging of kidney diseases. However, it is likely that the full potential of the kidney biopsy has not been tapped so far. Indeed, there is now a concerted worldwide effort to interrogate kidney biopsy samples at the cellular and molecular levels with unprecedented rigor and depth. This review examines these novel approaches to study kidney biopsy specimens and highlights their potential to refine our understanding of the pathophysiology of kidney disease and lead to precision-based diagnosis and therapy.
    Recent findings: Several consortia are now active at studying kidney biopsy samples from various patient cohorts with state-of-the art cellular and molecular techniques. These include advanced imaging approaches as well as deep molecular interrogation with tools such as epigenetics, transcriptomics, proteomics and metabolomics. The emphasis throughout is on rigor, reproducibility and quality control.
    Summary: Although these techniques to study kidney biopsies are complementary, each on its own can yield novel ways to define and classify kidney disease. Therefore, great efforts are needed in order to generate an integrated output that can propel the diagnosis and treatment of kidney disease into the realm of precision medicine.
    MeSH term(s) Biopsy/methods ; Female ; Humans ; Kidney/pathology ; Kidney Diseases/diagnosis ; Kidney Diseases/genetics ; Kidney Diseases/therapy ; Male ; Precision Medicine ; Reproducibility of Results
    Language English
    Publishing date 2022-01-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1151092-4
    ISSN 1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
    ISSN (online) 1473-6543 ; 1535-3842
    ISSN 1062-4813 ; 1062-4821
    DOI 10.1097/MNH.0000000000000770
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    Zs.A 3686: Show issues Location:
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  8. Article ; Online: Autosomal dominant tubulointerstitial kidney disease: a new tool to guide genetic testing.

    LaFavers, Kaice A / El-Achkar, Tarek M

    Kidney international

    2020  Volume 98, Issue 3, Page(s) 549–552

    Abstract: Autosomal dominant tubulointerstitial disease (ADTKD) is a dominantly inherited progressive nonglomerular disease. Several factors, such as a nonspecific clinical presentation and relative rarity, impede the phenotyping of ADTKD into clinically relevant ... ...

    Abstract Autosomal dominant tubulointerstitial disease (ADTKD) is a dominantly inherited progressive nonglomerular disease. Several factors, such as a nonspecific clinical presentation and relative rarity, impede the phenotyping of ADTKD into clinically relevant subtypes and impair the appropriate implementation of genetic testing. The study by Olinger et al. describes the largest multicenter ADTKD cohort, which is likely to become a key resource. The authors also provide a new clinical tool that could guide diagnosis and genetic testing.
    MeSH term(s) Genetic Testing ; Humans ; Mucin-1/genetics ; Mutation ; Nephritis, Interstitial/diagnosis ; Nephritis, Interstitial/genetics ; Polycystic Kidney, Autosomal Dominant/diagnosis ; Polycystic Kidney, Autosomal Dominant/genetics
    Chemical Substances Mucin-1
    Language English
    Publishing date 2020-09-02
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2020.05.046
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    Zs.A 797: Show issues Location:
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  9. Article ; Online: Evolving Concepts in Uromodulin Biology, Physiology, and Its Role in Disease: a Tale of Two Forms.

    LaFavers, Kaice A / Micanovic, Radmila / Sabo, Angela R / Maghak, Lauren A / El-Achkar, Tarek M

    Hypertension (Dallas, Tex. : 1979)

    2022  Volume 79, Issue 11, Page(s) 2409–2418

    Abstract: Uromodulin (or Tamm-Horsfall protein) is a glycoprotein uniquely produced in the kidney by tubular cells of the thick ascending limb of the loop of Henle and early distal tubules. This protein exhibits bidirectional secretion in the urine and in the ... ...

    Abstract Uromodulin (or Tamm-Horsfall protein) is a glycoprotein uniquely produced in the kidney by tubular cells of the thick ascending limb of the loop of Henle and early distal tubules. This protein exhibits bidirectional secretion in the urine and in the renal interstitium and circulation. The role of this protein in maintaining renal and systemic homeostasis is becoming increasingly appreciated. Furthermore, perturbations of its functions may play a role in various diseases affecting the kidney and distant organs. In this review, we will discuss important advances in understanding its biology, highlighting the recent discoveries of its secretion and differential precursor processing that generates 2 forms: (1) a highly polymerizing form that is apically excreted in the urine and generates filaments and (2) a nonpolymerizing form that retains a polymerization inhibitory pro-peptide and is released basolaterally in the kidney interstitium and circulation, but can also be found in the urine. We will also discuss factors regulating its production and release, taking into account its intricate physiology, and propose best practices to report its levels. We also discuss breaking advances in its role in hypertension, acute kidney injury and progression to chronic disease, immunomodulation and regulating renal and systemic oxidative stress. We anticipate that this work will be a great resource for researchers and clinicians. This review will highlight the importance of defining what regulates the 2 forms of uromodulin, so that modulation of uromodulin levels and function could become a novel tool in our therapeutic armamentarium against kidney disease.
    MeSH term(s) Humans ; Uromodulin/metabolism ; Kidney/metabolism ; Acute Kidney Injury/metabolism ; Hypertension/metabolism ; Biology
    Chemical Substances Uromodulin
    Language English
    Publishing date 2022-08-12
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.122.18567
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    Zs.A 1488: Show issues Location:
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  10. Article ; Online: Increased Urinary Leukocyte Esterase Distinguishes Patients With Brushite Kidney Stones.

    Bergsland, Kristin J / Coe, Fredric L / El-Achkar, Tarek M / Worcester, Elaine M

    Kidney international reports

    2021  Volume 6, Issue 6, Page(s) 1729–1731

    Language English
    Publishing date 2021-03-27
    Publishing country United States
    Document type Journal Article
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2021.03.894
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