title: Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria.
abstract: We evaluated two urinary biomarkers reflecting different aspects of renal pathophysiology as potential determinants of incident cardiovascular disease (CVD), all-cause mortality and a reduced estimated GFR (eGFR) in patients with type 2 diabetes and microalbuminuria but without clinical features of coronary artery disease.
  
  
  
  In a prospective study of 200 patients, all received multifactorial treatment. Baseline measurements of urinary hepatocyte growth factor (HGF) and adiponectin were available for 191 patients. Cox models were adjusted for sex, age, LDL-cholesterol, smoking, HbA1c, plasma creatinine, systolic BP and urinary AER (UAER). The pre-defined endpoint of chronic kidney disease progression was a decline in the eGFR of >30% during follow-up. HRs per 1 SD increment of log-transformed values are presented.
  
  
  
  Patients had a mean ± SD age of 59 ± 9 years with a median (interquartile range) UAER of 103 (39-230) mg/24 h. During a median 6.1 years of follow-up, there were 40 incident CVD events, 26 deaths and 42 patients reached the pre-defined chronic kidney disease progression endpoint after 4.9 years (median). Higher urinary HGF was a determinant of CVD in unadjusted (HR 1.9 [95% CI 1.3, 2.8], p = 0.001) and adjusted (HR 2.0 [95% CI 1.2, 3.2], p = 0.004) models, and of all-cause mortality in unadjusted (HR 2.3 [95% CI 1.3, 3.9], p = 0.003) and adjusted (HR 2.5 [95% CI 1.3, 4.8], p = 0.005) models. A higher adiponectin level was associated with CVD in unadjusted (HR 1.4 [95% CI 1.0, 1.9], p = 0.04) and adjusted (HR 1.4 [95% CI 1.1, 2.3], p = 0.013) models, and with a decline in the eGFR of >30% in unadjusted (HR 1.6 [95% CI 1.2, 2.2], p = 0.008) and adjusted (HR 1.5 [95% CI 1.1, 2.2], p = 0.007) models.
  
  
  
  In patients with type 2 diabetes and microalbuminuria receiving multifactorial treatment, higher urinary HGF was associated with incident CVD and all-cause mortality, and higher adiponectin was associated with CVD and deterioration in renal function.
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, 2820, Gentofte, Denmark. bjos@steno.dk.
authors.forename: Bernt Johan
authors.initials: BJ
authors.lastname: von Scholten
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, 2820, Gentofte, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Reinhard
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, 2820, Gentofte, Denmark.
authors.forename: Tine W
authors.initials: TW
authors.lastname: Hansen
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, 2820, Gentofte, Denmark.|Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.|Department of Endocrinology, Slagelse Hospital, Slagelse, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Oellgaard
authors.affiliation: Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.affiliation: Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jacobsen
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, 2820, Gentofte, Denmark.|The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000401:mortality* / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000401:mortality* / Q000821:virology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers
keywords: Adiponectin; Cardiovascular disease; Hepatocyte growth factor; Macrovascular disease; Microalbuminuria; Type 2 diabetes; Urinary biomarkers