title: Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial.
abstract: Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes.
authors.affiliation: Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington; nbansal@nephrology.washington.edu.
authors.forename: Nisha
authors.initials: N
authors.lastname: Bansal
authors.affiliation: Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina;
authors.forename: Myra A
authors.initials: MA
authors.lastname: Carpenter
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts;
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weiner
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts;
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
authors.affiliation: Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts;
authors.forename: Marc
authors.initials: M
authors.lastname: Pfeffer
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.affiliation: Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina;
authors.forename: Jianwen
authors.initials: J
authors.lastname: Cai
authors.affiliation: College of Medicine, Department of Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hunsicker
authors.affiliation: Division of Nephrology, University of California, San Francisco, California; and.
authors.forename: Meyeon
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio.
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.affiliation: Division of Nephrology, University of California, San Francisco, California; and.
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Liu
authors.affiliation: Division of Nephrology, University of California, San Francisco, California; and.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
mesh_terms: D015415:Biomarkers / Q000652:urine; D002318:Cardiovascular Diseases / Q000517:prevention & control* / Q000652:urine*; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control* / Q000652:urine*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005492:Folic Acid
keywords: cardiovascular disease; kidney transplantation; mortality