ro-42-5892 and Albuminuria

Remikiren is an orally active renin inhibitor with established antihypertensive efficacy. As a single dose it induces renal vasodilatation, suggesting specific renal actions. Data on the renal effects of continued treatment by renin inhibition are not available, either in subjects with normal, or in subjects with impaired renal function.. The effect of 8 days of treatment with remikiren 600 mg o.i.d. on blood pressure, renal haemodynamics, and proteinuria was studied in 14 hypertensive patients with normal or impaired renal function.The study was conducted on an ambulatory in-hospital basis and was designed in a single-blind, longitudinal order.. Remikiren induced a significant peak fall in mean arterial pressure of 11.2+/-0.8%, with corresponding trough values of -6+/-0.8%. This fall was somewhat more pronounced in the patients with renal function impairment (-13.3 vs -9.6%; P<0.01). Glomerular filtration rate remained stable, whereas effective renal plasma flow increased from 301+/-35 to 330+/-36 ml/min/1.73 m(2) (P<0.05). Filtration fraction and renal vascular resistance fell by 10+/-2% and 15+/-2% respectively (both P<0.01). Remikiren induced a cumulated sodium loss of -82+/-22 mmol and a positive potassium balance of 49+/-9 mmol (both P<0.01). During remikiren, proteinuria fell by 27% (range -18 to -38%; P<0.01) in the patients with overt proteinuria at onset (n=6). In the remainder of the patients albuminuria fell by 20% (range -1 to -61%, P<0.05). No side-effects were observed.. Continued treatment with remikiren induced a sustained fall in blood pressure, renal vasodilatation, negative sodium balance, and a reduction in glomerular protein leakage. These data are consistent with a renoprotective potential of renin inhibition.

Topics: Adult; Aged; Albuminuria; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Imidazoles; Kidney; Kidney Glomerulus; Longitudinal Studies; Middle Aged; Proteinuria; Renal Circulation; Renin; Single-Blind Method; Sodium; Vascular Resistance; Vasodilation

Remikiren is an orally available renin inhibitor with an established blood pressure-lowering effect in patients with essential hypertension. No data are available on the renal effects of remikiren in humans. We therefore studied the effects of a single oral administration of remikiren on blood pressure and renal function in 16 patients with essential hypertension on a restricted dietary sodium intake. Remikiren induced a peak fall in mean arterial pressure of 8.5 +/- 0.8%. The glomerular filtration rate (GFR) remained stable, whereas the effective renal-plasma flow rose by 11.3 +/- 1.4%. As a consequence, the filtration fraction and the renal vascular resistance fell by 11.7 +/- 1.2% and 17.6 +/- 1.3%, respectively. These systemic and renal hemodynamic changes were more pronounced in individuals with a higher initial immunoreactive renin. Remikiren induced a significant rise in the fractional excretion of sodium [0.38% (0.24-0.52) to 0.50% (0.31-0.76)] and lithium [28.7% (25.0-32.4) to 33.2% (27-39.4)]. Moreover, remikiren induced a decrease in urinary albumin excretion [497 (268-815) to 252 (114-389) micrograms/h]. In patients with essential hypertension, a single oral dose of remikiren can induce a renal vasodilation, without affecting the GFR and despite a significant decrease in blood pressure. This systemic and renal hemodynamic response is more pronounced in case of a more activated renin-angiotensin system.

Topics: Administration, Oral; Adult; Aged; Albuminuria; Antihypertensive Agents; Blood Pressure; Cross-Over Studies; Diet, Sodium-Restricted; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Hypertension; Imidazoles; Kidney; Male; Middle Aged; Renal Circulation; Renin; Renin-Angiotensin System; Sodium; Vascular Resistance; Vasodilation