A Definite Role for the Kallikrein-Kinin System in the Renal Hemodynamic Response to an Oral Protein Load during the Aging Process

Abstract

The effect of aging on the physiologic responses of renal plasma flow (RPF) and glomerular filtration rate to an acute oral protein load (renal reserve) is a poorly understood process. In this study of 37 healthy human volunteers, distributed among three groups (group 1: n = 13, age range 20–39 years; group 2: n = 13, age range 40–59 years; group 3: n = 11, age range 60–68 years), we evaluated the influence of age on some of the vasoactive systems such as plasma renin activity, urinary kallikrein, plasmatic prokallikrein, plasmatic kallikrein, and plasmatic kininogen on RPF and creatinine clearance (Ccr) in response to an acute oral protein load (1 g/kg body weight). The aging process diminished but did not cease the increments in RPF (group 1: 539.6 vs. 658.9 ml/min/1.73 m², p < 0.001; group 2: 509.0 vs. 570.7 ml/min/ 1.73 m², p < 0.001; group 3: 453.9 vs. 506.0 ml/min/ 1.73 m², p < 0.001) and Ccr (group 1: 139.7 vs. 166.5 ml/ min/1.73 m², p < 0.001; group 2: 126.6 vs. 142.2 ml/min/1.73 m², p < 0.001; group 3: 112.6 vs. 121.4 ml/min/ 1.73 m², p < 0.01) after a protein overload. The plasma renin activity did not change after a meat meal. On the other hand, all parameters regarding the kinin system changed significantly in the direction of increased bradykinin formation, despite aging (urinary kallikrein – group 1: 0.25 vs. 0.44 mU/ml, p < 0.005; group 2: 0.25 vs. 0.41 mU/ml, p < 0.005; group 3: 0.33 vs. 0.47 mU/ml, p < 0.005/plasmatic kininogen – group 1: 1.3 vs. 0.9 µg LBK/ml, p < 0.005; group 2: 1.1 vs. 0.7 µg LBK/ml, p < 0.005; group 3: 0.8 vs. 0.7 µg LBK/ml, p < 0.005). These findings indicate that: (1) the aging process narrows but does not cease the increment range in Ccr and RPF after acute oral protein ingestion; (2) increased bradykinin formation plays a definite role in the acute renal vasodilatory response, and (3) contrary to previous clinical studies, our results suggest that the renal reserve is progressively and significantly reduced during the aging process.