Journal
KIDNEY INTERNATIONAL REPORTS
Volume 2, Issue 3, Pages 425-432Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ekir.2017.02.001
Keywords
CKD; creatinine; CRP; eGFR; FDP; HSP-70; proteinuria; troponin; urokinase
Categories
Funding
- Abraham J. & Phyllis Katz Foundation
- Robert W. Woodruff Health Sciences Center Fund
- Emory Heart and Vascular Center
- Katz Family Foundation Preventive Cardiology Grant
- National Institutes of Health (NIH) from the Clinical and Translational Science Award program [UL1 RR025008]
- [5P01HL101398-02]
- [1P20HL113451-01]
- [1R56HL126558-01]
- [1RF1AG051633-01]
- [R01 NS064162-01]
- [R01 HL89650-01]
- [HL095479-01]
- [1U10HL110302-01]
- [1DP3DK094346-01]
- [2P01HL086773-06A1]
- [5R01DK101350-03]
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Introduction: Soluble urokinase-type plasminogen activator receptor (suPAR) strongly predicts outcomes and incident chronic kidney disease (CKD) in patients with cardiovascular disease (CVD). Whether the association between suPAR and CKD is a reflection of its overall association with chronic inflammation and poor CVD outcomes is unclear. We examined whether CVD biomarkers, including high-sensitivity C-reactive protein (hs-CRP), fibrin-degradation products (FDPs), heat-shock protein 70 (HSP-70), and high-sensitivity troponin I (hs-TnI) were associated with a decline in kidney function in the Emory Cardiovascular Biobank cohort, in which suPAR levels were shown to be predictive of both incident CKD and CVD outcomes. Methods: We measured suPAR, hs-CRP, HSP-70, FDP, and hs-TnI plasma levels in 3282 adults (mean age 63 years, 64% male, 75% estimated glomerular filtration rate [eGFR] >60 ml/min per 1.73 m(2)). Glomerular filtration rate was estimated using Chronic Kidney Disease-Epidemiology Collaboration (eGFR) at enrollment (n = 3282) and follow-up (n = 2672; median 3.5 years). Urine protein by dipstick at baseline was available for 1335 subjects. Results: There was a weak correlation among biomarkers (r range: 0.17-0.28). hs-CRP, FDPs, hs-TnI, and suPAR were independently associated with baseline eGFR and proteinuria. The median yearly decline in eGFR was -0.6 ml/min per 1.73 m(2). hs-CRP (beta: -0.04; P = 0.46), FDPs (beta: -0.13; P = 0.08), HSP-70 (beta: 0.05; P = 0.84), or hs-TnI (beta: -0.01; P = 0.76) were associated with eGFR decline. suPAR remained predictive of eGFR decline even after adjusting for all biomarkers. Discussion: hs-CRP, FDP, HSP-70, and hs-TnI were not associated with eGFR decline. The specific association of suPAR with eGFR decline supported its involvement in pathways specific to the pathogenesis of kidney disease.
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