title: Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial.
abstract: Cardiovascular risk remains high in kidney transplant recipients (KTRs) despite improved kidney function after transplant. Urinary markers of kidney fibrosis and injury may help to reveal mechanisms of this risk. In a case-cohort study among stable KTRs who participated in the FAVORIT trial, we measured four urinary proteins known to correlate with kidney tubulointerstitial fibrosis on biopsy (urine alpha 1 microglobulin [α1m], monocyte chemoattractant protein-1 [MCP-1], procollagen type I [PINP] and type III [PIIINP] N-terminal amino peptide) and evaluated associations with cardiovascular disease (CVD) events (n = 300) and death (n = 371). In adjusted models, higher urine α1m (hazard ratio [HR] per doubling of biomarker 1.40 [95% confidence interval [CI] 1.21, 1.62]), MCP-1 (HR 1.18 [1.03, 1.36]), and PINP (HR 1.13 [95% CI 1.03, 1.23]) were associated with CVD events. These three markers were also associated with death (HR per doubling α1m 1.51 [95% CI 1.32, 1.72]; MCP-1 1.31 [95% CI 1.13, 1.51]; PINP 1.11 [95% CI 1.03, 1.20]). Higher concentrations of urine α1m, MCP-1, and PINP may identify KTRs at higher risk for CVD events and death. These markers may identify a systemic process of fibrosis involving both the kidney and cardiovascular system, and give new insights into mechanisms linking the kidney with CVD.
authors.affiliation: Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA.|Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA.
authors.forename: M
authors.initials: M
authors.lastname: Park
authors.affiliation: Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, WA.
authors.forename: R
authors.initials: R
authors.lastname: Katz
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA.|General Internal Medicine Section, San Francisco Veterans Affairs Hospital, San Francisco, CA.|Division of General Internal Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
authors.forename: M G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA.
authors.forename: D
authors.initials: D
authors.lastname: Weiner
authors.affiliation: Department of Pathology, University of Vermont, Burlington, VT.
authors.forename: R
authors.initials: R
authors.lastname: Tracy
authors.affiliation: Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA.
authors.forename: V
authors.initials: V
authors.lastname: Jotwani
authors.affiliation: Division of Preventive Medicine, Department of Preventive Medicine and Public Health, University of California San Diego, San Diego, CA.
authors.forename: J
authors.initials: J
authors.lastname: Hughes-Austin
authors.affiliation: Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CA.|Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA.
authors.forename: F
authors.initials: F
authors.lastname: Gabbai
authors.affiliation: Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Division of Cardiology, Brigham and Women's Hospital, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Pfeffer
authors.affiliation: Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, WA.
authors.forename: N
authors.initials: N
authors.lastname: Bansal
authors.affiliation: Rhode Island Hospital, Providence, RI.
authors.forename: A
authors.initials: A
authors.lastname: Bostom
authors.affiliation: Departments of Medicine and Epidemiology, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: O
authors.initials: O
authors.lastname: Gutierrez
authors.affiliation: Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Sarnak
authors.affiliation: Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA.
authors.forename: A
authors.initials: A
authors.lastname: Levey
authors.affiliation: Division of Preventive Medicine, Department of Preventive Medicine and Public Health, University of California San Diego, San Diego, CA.|Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CA.|Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA.
authors.forename: J H
authors.initials: JH
authors.lastname: Ix
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control / Q000652:urine*; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis; D005492:Folic Acid / Q000008:administration & dosage; D006801:Humans; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000652:urine*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005492:Folic Acid
keywords: biomarker; cardiovascular disease; clinical research/practice; kidney disease; kidney transplantation/nephrology