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  1. Article ; Online: Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease.

    Liu, Jiahao / Nair, Viji / Zhao, Yi-Yang / Chang, Dong-Yuan / Limonte, Christine / Bansal, Nisha / Fermin, Damian / Eichinger, Felix / Tanner, Emily C / Bellovich, Keith A / Steigerwalt, Susan / Bhat, Zeenat / Hawkins, Jennifer J / Subramanian, Lalita / Rosas, Sylvia E / Sedor, John R / Vasquez, Miguel A / Waikar, Sushrut S / Bitzer, Markus /
    Pennathur, Subramaniam / Brosius, Frank C / De Boer, Ian / Chen, Min / Kretzler, Matthias / Ju, Wenjun

    Diabetes

    2022  Volume 71, Issue 12, Page(s) 2664–2676

    Abstract: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a ... ...

    Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a proteomics analysis of plasma samples by an unbiased machine learning approach from participants (N = 58) in the Clinical Phenotyping and Resource Biobank study. In combination with standard clinical parameters, this panel improved prediction of the composite outcome of ESKD or a 40% decline in glomerular filtration rate. The panel was validated in an independent group (N = 68), who also had kidney transcriptomic profiles. One marker, plasma angiopoietin 2 (ANGPT2), was significantly associated with outcomes in cohorts from the Cardiovascular Health Study (N = 3,183) and the Chinese Cohort Study of Chronic Kidney Disease (N = 210). Glomerular transcriptional angiopoietin/Tie (ANG-TIE) pathway scores, derived from the expression of 154 ANG-TIE signaling mediators, correlated positively with plasma ANGPT2 levels and kidney outcomes. Higher receptor expression in glomeruli and higher ANG-TIE pathway scores in endothelial cells corroborated potential functional effects in the kidney from elevated plasma ANGPT2 levels. Our work suggests that ANGPT2 is a promising prognostic endothelial biomarker with likely functional impact on glomerular pathogenesis in DKD.
    MeSH term(s) Humans ; Angiopoietin-1/genetics ; Receptor, TIE-2/genetics ; Diabetic Nephropathies/genetics ; Cohort Studies ; Endothelial Cells ; Angiopoietin-2/genetics ; Angiopoietins ; Signal Transduction ; Biomarkers ; Kidney Failure, Chronic ; Disease Progression ; Diabetes Mellitus
    Chemical Substances Angiopoietin-1 ; Receptor, TIE-2 (EC 2.7.10.1) ; Angiopoietin-2 ; Angiopoietins ; Biomarkers
    Language English
    Publishing date 2022-11-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db22-0169
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Soluble ST2 and Galectin-3 and Progression of CKD.

    Alam, Mariam L / Katz, Ronit / Bellovich, Keith A / Bhat, Zeenat Y / Brosius, Frank C / de Boer, Ian H / Gadegbeku, Crystal A / Gipson, Debbie S / Hawkins, Jennifer J / Himmelfarb, Jonathan / Kestenbaum, Bryan R / Kretzler, Matthias / Robinson-Cohen, Cassianne / Steigerwalt, Susan P / Tuegel, Courtney / Bansal, Nisha

    Kidney international reports

    2018  Volume 4, Issue 1, Page(s) 103–111

    Abstract: Introduction: Cardiac biomarkers soluble ST2 (sST2) and galectin-3 may reflect cardiac inflammation and fibrosis. It is plausible that these mechanisms may also contribute to the progression of kidney disease. We examined associations of sST2 and ... ...

    Abstract Introduction: Cardiac biomarkers soluble ST2 (sST2) and galectin-3 may reflect cardiac inflammation and fibrosis. It is plausible that these mechanisms may also contribute to the progression of kidney disease. We examined associations of sST2 and galectin-3 with kidney function decline in participants with chronic kidney disease (CKD).
    Methods: This was a pooled analysis of 2 longitudinal cohorts of participants with CKD: the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS). We measured circulating concentrations of sST2 and galectin-3 at baseline. Our primary outcome was progression to estimated glomerular filtration rate (eGFR) <15 ml/min per 1.73 m
    Results: Among the 841 participants in the pooled cohort, baseline eGFR was 51 ± 27 ml/min per 1.73 m
    Conclusion: Higher concentrations of the cardiac biomarker galectin-3 may be associated with progression of CKD, highlighting potential novel mechanisms that may contribute to the progression of kidney disease.
    Language English
    Publishing date 2018-09-21
    Publishing country United States
    Document type Journal Article
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2018.09.013
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  3. Article ; Online: Integrative biology identifies shared transcriptional networks in CKD.

    Martini, Sebastian / Nair, Viji / Keller, Benjamin J / Eichinger, Felix / Hawkins, Jennifer J / Randolph, Ann / Böger, Carsten A / Gadegbeku, Crystal A / Fox, Caroline S / Cohen, Clemens D / Kretzler, Matthias

    Journal of the American Society of Nephrology : JASN

    2014  Volume 25, Issue 11, Page(s) 2559–2572

    Abstract: A previous meta-analysis of genome-wide association data by the Cohorts for Heart and Aging Research in Genomic Epidemiology and CKDGen consortia identified 16 loci associated with eGFR. To define how each of these single-nucleotide polymorphisms (SNPs) ... ...

    Abstract A previous meta-analysis of genome-wide association data by the Cohorts for Heart and Aging Research in Genomic Epidemiology and CKDGen consortia identified 16 loci associated with eGFR. To define how each of these single-nucleotide polymorphisms (SNPs) could affect renal function, we integrated GFR-associated loci with regulatory pathways, producing a molecular map of CKD. In kidney biopsy specimens from 157 European subjects representing nine different CKDs, renal transcript levels for 18 genes in proximity to the SNPs significantly correlated with GFR. These 18 genes were mapped into their biologic context by testing coregulated transcripts for enriched pathways. A network of 97 pathways linked by shared genes was constructed and characterized. Of these pathways, 56 pathways were reported previously to be associated with CKD; 41 pathways without prior association with CKD were ranked on the basis of the number of candidate genes connected to the respective pathways. All pathways aggregated into a network of two main clusters comprising inflammation- and metabolism-related pathways, with the NRF2-mediated oxidative stress response pathway serving as the hub between the two clusters. In all, 78 pathways and 95% of the connections among those pathways were verified in an independent North American biopsy cohort. Disease-specific analyses showed that most pathways are shared between sets of three diseases, with closest interconnection between lupus nephritis, IgA nephritis, and diabetic nephropathy. Taken together, the network integrates candidate genes from genome-wide association studies into their functional context, revealing interactions and defining established and novel biologic mechanisms of renal impairment in renal diseases.
    MeSH term(s) Adult ; Aged ; Databases, Genetic ; Disease Progression ; Female ; Gene Regulatory Networks/genetics ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; North America ; Polymorphism, Single Nucleotide ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/physiopathology ; Signal Transduction/genetics ; Transcription, Genetic/genetics ; Transcriptome ; Young Adult
    Language English
    Publishing date 2014-06-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2013080906
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 3344: Show issues Location:
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  4. Article ; Online: Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker.

    Ju, Wenjun / Nair, Viji / Smith, Shahaan / Zhu, Li / Shedden, Kerby / Song, Peter X K / Mariani, Laura H / Eichinger, Felix H / Berthier, Celine C / Randolph, Ann / Lai, Jennifer Yi-Chun / Zhou, Yan / Hawkins, Jennifer J / Bitzer, Markus / Sampson, Matthew G / Thier, Martina / Solier, Corinne / Duran-Pacheco, Gonzalo C / Duchateau-Nguyen, Guillemette /
    Essioux, Laurent / Schott, Brigitte / Formentini, Ivan / Magnone, Maria C / Bobadilla, Maria / Cohen, Clemens D / Bagnasco, Serena M / Barisoni, Laura / Lv, Jicheng / Zhang, Hong / Wang, Hai-Yan / Brosius, Frank C / Gadegbeku, Crystal A / Kretzler, Matthias

    Science translational medicine

    2015  Volume 7, Issue 316, Page(s) 316ra193

    Abstract: Chronic kidney disease (CKD) affects 8 to 16% people worldwide, with an increasing incidence and prevalence of end-stage kidney disease (ESKD). The effective management of CKD is confounded by the inability to identify patients at high risk of ... ...

    Abstract Chronic kidney disease (CKD) affects 8 to 16% people worldwide, with an increasing incidence and prevalence of end-stage kidney disease (ESKD). The effective management of CKD is confounded by the inability to identify patients at high risk of progression while in early stages of CKD. To address this challenge, a renal biopsy transcriptome-driven approach was applied to develop noninvasive prognostic biomarkers for CKD progression. Expression of intrarenal transcripts was correlated with the baseline estimated glomerular filtration rate (eGFR) in 261 patients. Proteins encoded by eGFR-associated transcripts were tested in urine for association with renal tissue injury and baseline eGFR. The ability to predict CKD progression, defined as the composite of ESKD or 40% reduction of baseline eGFR, was then determined in three independent CKD cohorts. A panel of intrarenal transcripts, including epidermal growth factor (EGF), a tubule-specific protein critical for cell differentiation and regeneration, predicted eGFR. The amount of EGF protein in urine (uEGF) showed significant correlation (P < 0.001) with intrarenal EGF mRNA, interstitial fibrosis/tubular atrophy, eGFR, and rate of eGFR loss. Prediction of the composite renal end point by age, gender, eGFR, and albuminuria was significantly (P < 0.001) improved by addition of uEGF, with an increase of the C-statistic from 0.75 to 0.87. Outcome predictions were replicated in two independent CKD cohorts. Our approach identified uEGF as an independent risk predictor of CKD progression. Addition of uEGF to standard clinical parameters improved the prediction of disease events in diverse CKD populations with a wide spectrum of causes and stages.
    MeSH term(s) Adult ; Aged ; Biomarkers/urine ; Biopsy ; Cell Differentiation ; Cohort Studies ; Disease Progression ; Epidermal Growth Factor/urine ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Prognosis ; Proteins/chemistry ; Regeneration ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/urine ; Transcriptome
    Chemical Substances Biomarkers ; Proteins ; Epidermal Growth Factor (62229-50-9)
    Language English
    Publishing date 2015-12-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.aac7071
    Database MEDical Literature Analysis and Retrieval System OnLINE

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