title: The relationship between estimated glomerular filtration rate trajectory and all-cause mortality in type 2 diabetes: the Fremantle Diabetes Study.
abstract: OBJECTIVE
  To investigate the association between estimated GFR (eGFR) and all-cause mortality, including the contribution of temporal eGFR changes, in well-characterised community-based patients with type 2 diabetes.
  
  
  METHODS
  Longitudinal observational study.
  
  
  METHODS
  Participants from the Fremantle Diabetes Study Phase 1 were assessed between 1993 and 1996 and followed until end-December 2012. Cox proportional hazards modelling was used to assess the relationship between baseline eGFR category (Stage 1-5) and all-cause death, and between eGFR trajectories assigned by semiparametric group-based modelling (GBM) and all-cause death in patients with five post-baseline annual eGFR measurements.
  
  
  RESULTS
  In the full cohort (1296 patients; mean±s.d. age 64.1±11.3years, 48.6% males), 738 (56.9%) died during 12.9±6.1years of follow-up. There was a U-shaped relationship between all-cause death and eGFR category. With Stage 3 (45-59mL/min/1.73m(2)) as reference, the strongest association was for eGFR ≥90mL/min/1.73m(2) (hazard ratio (95% CI) 2.01 (1.52-2.66); P<0.001). GBM identified four linear trajectories ('low', 'medium', 'high', 'high/declining') in 532 patients with serial eGFR measurements. With medium trajectory as reference, eGFR trajectory displaced baseline eGFR category as an independent predictor of death, with low and high/declining trajectories associated with more than double the risk (2.03 (1.30-3.18) and 2.24 (1.31-3.83) respectively, P≤0.003) and associated median reductions in survival of 6.5 and 8.7years respectively.
  
  
  CONCLUSIONS
  There is a nonlinear relationship between eGFR and death in type 2 diabetes, which is at least partially explained by a sub-group of patients with an initially high but then rapidly declining eGFR.
authors.affiliation: School of Medicine and PharmacologyUniversity of Western Australia, Fremantle, Western Australia, Australia tim.davis@uwa.edu.au.
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
authors.affiliation: School of Medicine and PharmacologyUniversity of Western Australia, Fremantle, Western Australia, Australia Department of Clinical BiochemistryPathWest Laboratory Medicine WA, Perth, Western Australia, Australia School of Pathology and Laboratory MedicineUniversity of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: S A Paul
authors.initials: SA
authors.lastname: Chubb
authors.affiliation: School of Medicine and PharmacologyUniversity of Western Australia, Fremantle, Western Australia, Australia.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Davis
mesh_terms: D000368:Aged; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000401:mortality* / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors