> Details
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;
[...]
Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease
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- Media type: E-Article
- Title: Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease
- Contributor: 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; [...]
- imprint: American Diabetes Association, 2022
- Published in: Diabetes
- Language: English
- DOI: 10.2337/db22-0169
- ISSN: 0012-1797
- Origination:
- Footnote:
- Description: <jats:p>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.</jats:p>
- Access State: Open Access