title: Plasma growth differentiation factor-15 independently predicts all-cause and cardiovascular mortality as well as deterioration of kidney function in type 1 diabetic patients with nephropathy.
abstract: OBJECTIVE
  Growth deferentiation factor-15 (GDF-15) is involved in inflammation and apoptosis. Expression is induced in the heart in response to ischemia and in atherosclerotic plaques. The aim of this study was to investigate GDF-15 levels in relation to all-cause mortality, cardiovascular mortality and morbidity, decline in glomerular filtration rate (GFR), and progression toward end-stage renal disease (ESRD).
  
  
  METHODS
  The study was a prospective observational follow-up study including 451 type 1 diabetic patients with diabetic nephropathy (274 men, aged 42.1 +/- 0.5 years [means +/- SD], diabetes duration 28.3 +/- 8.9 years, GFR 76 +/- 33 ml/min/1.73 m(2)) and a control group of 440 patients with longstanding type 1 diabetes and persistent normoalbuminuria (232 men, aged 45.4 +/- 11.5 years, duration of diabetes 27.7 +/- 10.1 years). The patients were followed for 8.1 (0.0-12.9) years (median [range]).
  
  
  RESULTS
  Among normoalbuminuric patients, GDF-15 above the median predicted an adjusted (age, systolic blood pressure [sBP], and estimated GFR) increased risk of all-cause mortality (hazard ratio [HR] 3.6 [95% CI 1.3-10.3]; P = 0.014). Among patients with diabetic nephropathy, higher (fourth quartile) versus lower (first quartile) GDF-15 levels predict all-cause mortality (covariate-adjusted [sex, age, smoking, blood pressure, A1C, cholesterol, GFR, N-terminal prohormone B-type natriuretic peptide, antihypertensive treatment, and previous cardiovascular events]; HR 4.86 [95% CI 1.37-17.30]) as well as fatal and nonfatal cardiovascular events (adjusted HR 5.59 [1.23-25.43] and 3.55 [1.08-11.64], respectively). In addition, higher GDF-15 levels predict faster decline in GFR (P < 0.001) but not development of ESRD.
  
  
  CONCLUSIONS
  Higher levels of GDF-15 are a predictor of all-cause and cardiovascular mortality and morbidity in patients with diabetic nephropathy. Furthermore, higher levels of GDF-15 are associated with faster deterioration of kidney function.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. mlaj@steno.dk
authors.forename: Maria
authors.initials: M
authors.lastname: Lajer
authors.forename: Anders
authors.initials: A
authors.lastname: Jorsal
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000401:mortality; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000097:blood / Q000401:mortality*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D055436:Growth Differentiation Factor 15