The role of urinary kininogen in the regulation of kinin generation

The kallikrein-kininogen-kinin system has been postulated to play a role in the regulation of blood pressure and modulation of renal salt and water transport. The activity of this system has usually been determined by measurements of urinary kallikrein excretion. However, urinary kallikrein rarely correlates with simultaneously measured urinary kinins. To further evaluate the factors influencing urinary kinin excretion, we evaluated the role of urinary kininogen in this system. Urines were analyzed from normal subjects and individuals with untreated essential hypertension and end-stage renal disease. Intact urinary kininogen was significantly correlated with urinary kinins in normal subjects (r = 0.65, P = 0.003) and essential hypertensives (r = 0.52, P = 0.026). In both essential hypertension and end-stage renal disease, urinary kinins were significantly decreased (8.00 +/- 1.93, 0.90 +/- 0.18, P less than 0.05, respectively) compared to controls (23.73 +/- 5.20). In essential hypertensives, the reduction in urinary kinins was paralleled by a reduction in intact kininogen with a normal excretion of kallikrein. In end-stage renal disease, the reduction in kinins was paralleled by a reduction in kallikrein with a normal excretion of intact kininogen. This data suggests that kininogen may be an important determinant of urinary kinin excretion in various disease states.