Background: We previously reported that kidney and urinary angiotensinogen levels were significantly increased before the development of diabetic nephropathy in diabetic rats. To address this system in humans, we have developed an enzyme-linked immunosorbent assay for human angiotensinogen and reported that urinary excretion of angiotensinogen levels is enhanced in patients with chronic kidney disease, including patients with type 2 diabetes. On the basis of these findings, this study was performed to demonstrate that urinary angiotensinogen levels increased before the onset of microalbuminuria and that urinary angiotensinogen can be an early biomarker of intrarenal renin-angiotensin system status in normoalbuminuric patients with type 1 diabetes compared with age- and sex-matched control subjects.
Methods: The study included 28 patients with type 1 diabetes and 21 control subjects. No subject received renin-angiotensin system blockades. Random spot urine samples as well as blood samples were obtained and analyzed.
Results: Urinary albumin:creatinine ratio or urinary protein:creatinine ratio did not increase in patients compared with control subjects, suggesting that these patients were in their premicroalbuminuric phase of diabetic nephropathy. However, the urinary angiotensinogen:creatinine ratio was significantly higher in patients than in control subjects (12.1 +/- 3.2 microg/g versus 4.2 +/- 0.7 microg/g). Importantly, an increase in plasma angiotensinogen levels was not observed (26.3 +/- 1.3 microg/mL versus 29.5 +/- 3.3 microg/mL).
Conclusions: Thus, in patients, an increase in urinary angiotensinogen levels is observed, and this increase is precedent to an increase in urinary albumin levels, suggesting that urinary angiotensinogen may function as an early marker of diabetic nephropathy.