Renal and systemic effects of continued treatment with renin inhibitor remikiren in hypertensive patients with normal and impaired renal function

Abstract

Background. 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. Methods. 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. Results. 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 somewehat 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 m2 (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. Conclusions. 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.