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.