Urinary kallikrein excretion has been reported to be decreased in patients with essential hypertension and elevated in patients with primary aldosteronism as a reflection of mineralocorticoid activity. Low renin essential hypertension (LREH) has been postulated to result from excess production of an unknown mineralocorticoid(s). Urinary kallikrein excretion was compared in outpatients with essential hypertension, mineralocorticoid hypertension (primary aldosteronism and 17α-hydroxylase deficiency), and in normal subjects of the same race. No significant difference in urinary kallikrein excretion of patients with LREH vs. normal renin essential hypertension (NREH) was found for either black (4.1 ± 0.4 vs. 4.8 ± 0.5 esterase units (EU)/24 h, mean ± SE, for 27 LREH and 38 NREH, respectively) or white patients (12.2 ± 2.3 vs. 11.7 ± 1.4 EU/24 h for 13 LREH and 25 NREH, respectively). Urinary kallikrein was decreased in black vs. white hypertensive patients and normal subjects. However, in patients with normal renal function (creatinine clearance ≥ 80 ml/min) urinary kallikrein was not significantly decreased in either black hypertensive vs. black normal subjects (4.3 ± 0.3 vs. 5.4 ± 0.6 EU/24 h) or in white hypertensive vs. white normal subjects (11.9 ± 1.2 vs. 8.4 ± 0.9 EU/24 h). In contrast, hypertensive patients with mild renal insufficiency (creatinine clearance of 41.8 ± 78.5 ml/min) had reduced (P<0.05) urinary kallikrein (3.3 EU/24 h with creatinine clearance of 63.6 ± 2.0 for 24 black patients and 4.2 ± 0.7 EU/24 h with creatinine clearance of 67.0 ± 3.5 for 6 white patients). These results suggest that a reduction in urinary kallikrein excretion rate is an early accompaniment of hypertensive renal injury. Urinary kallikrein excretion in response to a 6-d 10-meq sodium diet and a 3-d Florinef (0.5 mg b.i.d.) administration was compared in hypertensive patients with normal renal function vs. race and age-matched normal subjects. Stimulation of urinary kallikrein excretion by Florinef was equal in black and white normal subjects vs. hypertensive patients (black normals = 12.3 ± 2.7 [n = 9], NREH = 11.7 ± 1.8 [n = 10], LREH = 10.9 ± 1.5 [n = 12]; white normals = 21.2 ± 2.9 [n = 11], essential hypertension = 20.9 ± 3.2 [10 NREH, 5 LREH]). Stimulation of urinary kallikrein excretion with low sodium diet was decreased (P < 0.05) only in black LREH (black normals = 11.2 ± 2.4 [n = 10], NREH = 10.1 ± 2.7 [n = 10], LREH = 7.4 ± 1.1 [n = 13]; white normals = 19.1 ± 2.7 [n = 13], essential hypertension = 17.5 ± 2.3 [nine NREH, four LREH]). However, during low sodium diet, black patients with LREH had evidence for less sodium depletion as manifested by a decreased rise in urinary aldosterone excretion (16.3 ± 2.7 vs. 33.3 ± 6.4 μg/24 h for black normals) and a failure to achieve metabolic balance in 11/13 patients. Thus, the lesser kallikrein stimulation appeared to result from these two factors. Black and white hypertensives with creatinine clearance <80 ml/min had little increase in urinary kallikrein excretion with Florinef or low sodium diet. 5 of 12 patients with primary aldosteronism or 17α-hydroxylase deficiency did not have an elevated urinary kallikrein excretion rate. Mild renal insufficiency may have contributed to this finding in two of these five patients. Nevertheless, this finding illustrates a limitation to the use of urinary kallikrein excretion rate as an index of mineralocorticoid activity. However, it appears that the majority of patients with LREH have no evidence for excess production of an unknown mineralocorticoid. The failure to find a decrease in urinary kallikrein excretion in racially matched patients with essential hypertension and normal renal function questions the postulate of a role of the kallikrein-kinin system in the initiation of essential hypertension.
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