Filtration Markers, Cardiovascular Disease, Mortality, and Kidney Outcomes in Stable Kidney Transplant Recipients: The FAVORIT Trial

Am J Transplant. 2017 Sep;17(9):2390-2399. doi: 10.1111/ajt.14258. Epub 2017 Mar 30.

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 eGFRB2M were 46.0, 43.8, and 48.8 mL/min/1.73m2 , respectively. After multivariable adjustment, hazard ratios for eGFRcys and 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.

Keywords: biomarker; clinical research/practice; glomerular filtration rate (GFR); kidney (native) function/dysfunction; kidney transplantation/nephrology.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • Creatinine / metabolism
  • Cystatin C / metabolism
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / diagnosis
  • Graft Rejection / etiology
  • Graft Rejection / mortality*
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Failure, Chronic / mortality*
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Mortality / trends*
  • Postoperative Complications
  • Prognosis
  • Risk Factors
  • Survival Rate
  • beta 2-Microglobulin / metabolism

Substances

  • Biomarkers
  • Cystatin C
  • Immunosuppressive Agents
  • beta 2-Microglobulin
  • Creatinine