title: Urinary angiotensinogen as a potential biomarker of diabetic nephropathy.
abstract: BACKGROUND
  Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mediator of diabetic nephropathy. Urinary angiotensinogen, a novel biomarker of the intrarenal RAAS, is associated with progressive kidney injury. In this study, the authors investigated the determinants of urinary angiotensinogen and its associations with staging of diabetic nephropathy.
  
  
  METHODS
  Random urine samples were collected from the patients with type 2 diabetes with normoalbuminuria (n = 52), microalbuminuria (n = 52) and macroalbuminuria (n = 51) for the measurement of angiotensinogen by sensitive and specific ELISAs. Control samples were collected from healthy volunteers (n = 20) who had normal albuminuria and renal function.
  
  
  RESULTS
  Urinary angiotensinogen was higher in microalbuminuric and macroalbuminuric diabetes than in controls [63.44 (interquartile range, IQR: 22.08, 174.8) versus 398.38 (IQR: 205.03, 673.68) versus 9.12 (IQR: 3.76, 23.82) ng/mg creatinine, respectively, P < 0.001]. In diabetes with normoalbuminuria, urinary angiotensinogen was also higher than in controls [16.42 (IQR: 7.69, 34.71) versus 9.12 (IQR: 3.76, 23.82) ng/mg creatinine, P = 0.047]. The performance of the biomarker in differentiating each stage of type 2 diabetes from controls was illustrated by receiver-operating characteristic curves. The areas under the curve for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes using urine angiotensinogen (ng/mg creatinine) were 0.62 (95% CI: 0.48-0.77), 0.85 (95% CI: 0.76-0.94) and 0.96 (95% CI: 0.92-1.00), respectively. In addition, the cut-off levels were 9.30 ng/mg (sensitivity 65.4%, specificity 55.0%), 12.32 ng/mg (sensitivity 55.8%, specificity 65.0%) and 17.44 ng/mg (sensitivity 44.2%, specificity 70.0%), respectively, for distinguishing normoalbuminuric type 2 diabetes from healthy controls.
  
  
  CONCLUSIONS
  The authors propose that angiotensinogen could be one of the potential urinary biomarkers for diagnosis in established diabetic nephropathy. It appeared even before the significant albuminuria in diabetic nephropathy. It might be useful as an early biomarker of activation of the renin-angiotensin system in diabetic nephropathy.
authors: Division of Nephrology, Department of Medicine , Phramongkutklao Hospital and College of Medicine , Bangkok 10400 , Thailand.
authors: Bancha
authors: B
authors: Satirapoj
authors: Division of Nephrology, Department of Medicine , Phramongkutklao Hospital and College of Medicine , Bangkok 10400 , Thailand.
authors: Nuttawut
authors: N
authors: Siritaweesuk
authors: Division of Nephrology, Department of Medicine , Phramongkutklao Hospital and College of Medicine , Bangkok 10400 , Thailand.
authors: Ouppatham
authors: O
authors: Supasyndh
keywords: biomarker; diabetic nephropathy; renin–angiotensin–aldosterone system; urinary angiotensinogen