title: Association of serum concentration of TNFR1 with all-cause mortality in patients with type 2 diabetes and chronic kidney disease: follow-up of the SURDIAGENE Cohort.
abstract: OBJECTIVE
  Renal dysfunction is a key risk factor for all-cause mortality in patients with type 2 diabetes (T2D). Circulating tumor necrosis factor receptor 1 (TNFR1) was recently suggested as a strong biomarker for end-stage renal failure in T2D. However, its relevance regarding all-cause death has yet to be conclusively established. We aimed to assess the prognostic value of serum TNFR1 concentration for all-cause death in T2D and diabetic kidney disease (DKD) from the SURDIAGENE (Survie, Diabete de type 2 et Genetique) study.
  
  
  METHODS
  A total of 522 T2D patients with DKD (estimated glomerular filtration rate [eGFR] <60 and/or urinary albumin-to-creatinine ratio [uACR] >30 mg/mmol) were followed for a median duration of 48 months, and 196 deaths occurred.
  
  
  RESULTS
  Incidence rate (95% CI) for death increased as quartiles of TNFR1 concentration increased (first quartile: 4.7% patient-years [3.0-6.3%]; second quartile: 7.7% [5.4-10.0%]; third quartile: 9.3% [6.7-11.9%]; fourth quartile: 15.9% [12.2-19.5%]). In multivariate analysis taking age, diabetes duration, HbA1c, uACR, and eGFR into account, compared with the first quartile, patients from the fourth quartile had an adjusted hazard ratio for death of 2.98 (95% CI 1.70-5.23). The integrated discrimination improvement index was statistically significant when adding TNFR1 concentration to the UK Prospective Diabetes Study outcome equation (P = 0.031).
  
  
  CONCLUSIONS
  TNFR1 is a strong prognostic factor for all-cause mortality in T2D with renal dysfunction, and its clinical utility is suggested in addition to established risk factors for all-cause mortality.
authors.affiliation: Corresponding author: Samy Hadjadj, samy.hadjadj@gmail.com.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Saulnier
authors.forename: Elise
authors.initials: E
authors.lastname: Gand
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ragot
authors.forename: Grégory
authors.initials: G
authors.lastname: Ducrocq
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Halimi
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hulin-Delmotte
authors.forename: Pierre
authors.initials: P
authors.lastname: Llaty
authors.forename: David
authors.initials: D
authors.lastname: Montaigne
authors.forename: Vincent
authors.initials: V
authors.lastname: Rigalleau
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
authors.forename: Philippe
authors.initials: P
authors.lastname: Sosner
authors.forename: Philippe
authors.initials: P
authors.lastname: Zaoui
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000097:blood / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D047888:Receptors, Tumor Necrosis Factor, Type I