title: Filtration Markers, Cardiovascular Disease, Mortality, and Kidney Outcomes in Stable Kidney Transplant Recipients: The FAVORIT Trial.
abstract: Cystatin C and beta-2-microglobulin (B2M) are filtration markers associated with adverse outcomes in nontransplant populations, sometimes with stronger associations than for creatinine. We evaluated associations of estimated glomerular filtration rate from cystatin C (eGFRcys), B2M (eGFRB2M), and creatinine (eGFRcr) with cardiovascular outcomes, mortality, and kidney failure in stable kidney transplant recipients using a case-cohort study nested within the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial. A random subcohort was selected (N = 508; mean age 51.6 years, median transplant vintage 4 years, 38% women, 23.6% nonwhite race) with enrichment for cardiovascular events (N = 306; 54 within the subcohort), mortality (N = 208; 68 within the subcohort), and kidney failure (N = 208; 52 within the subcohort). Mean eGFRcr, eGFRcys, and eGFRB2Mwere 46.0, 43.8, and 48.8 mL/min/1.73m2, respectively. After multivariable adjustment, hazard ratios for eGFRcysand eGFRB2M<30 versus 60+ were 2.02 (95% confidence interval [CI] 1.09-3.76; p = 0.03) and 2.56 (1.35-4.88; p = 0.004) for cardiovascular events; 3.92 (2.11-7.31) and 4.09 (2.21-7.54; both p < 0.001) for mortality; and 9.49 (4.28-21.00) and 15.53 (6.99-34.51; both p < 0.001) for kidney failure. Associations persisted with additional adjustment for baseline eGFRcr. We conclude that cystatin C and B2M are strongly associated with cardiovascular events, mortality, and kidney failure in stable kidney transplant recipients.
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA.
authors.forename: M C
authors.initials: MC
authors.lastname: Foster
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA.
authors.forename: D E
authors.initials: DE
authors.lastname: Weiner
authors.affiliation: Rhode Island Hospital, Providence, RI.
authors.forename: A G
authors.initials: AG
authors.lastname: Bostom
authors.affiliation: Department of Biostatistics, University of North Carolina, Chapel Hill, NC.
authors.forename: M A
authors.initials: MA
authors.lastname: Carpenter
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA.
authors.forename: L A
authors.initials: LA
authors.lastname: Inker
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: P
authors.initials: P
authors.lastname: Jarolim
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA.
authors.forename: A A
authors.initials: AA
authors.lastname: Joseph
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
authors.forename: J W
authors.initials: JW
authors.lastname: Kusek
authors.affiliation: The Ohio State University Medical Center, Columbus, OH.
authors.forename: T
authors.initials: T
authors.lastname: Pesavento
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: M A
authors.initials: MA
authors.lastname: Pfeffer
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Rao
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: S D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA.
authors.forename: A S
authors.initials: AS
authors.lastname: Levey
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000401:mortality*; D003404:Creatinine / Q000378:metabolism; D055316:Cystatin C / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology / Q000401:mortality*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000401:mortality* / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends*; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D007166:Immunosuppressive Agents; D001613:beta 2-Microglobulin; D003404:Creatinine
keywords: biomarker; clinical research/practice; glomerular filtration rate (GFR); kidney (native) function/dysfunction; kidney transplantation/nephrology