Maximum renal responses to renin inhibition in healthy study participants: VTP-27999 versus aliskiren

Background: Renin inhibition with aliskiren induced the largest increases in renal plasma flow (RPF) in salt-depleted healthy volunteers of all renin–angiotensin system (RAS) blockers. However, given its side-effects at doses higher than 300 mg, no maximum effect of renin inhibition could be established. We hypothesized that VTP-27999, a novel renin inhibitor without major side-effects at high doses, would allow us to establish this. Methods and results: The effects of escalating VTP-27999 doses (75–600 mg) on RPF, glomerular filtration rate (GFR), and plasma RAS components were compared with those of 300 mg aliskiren in 22 normal volunteers on a low-sodium diet. VTP-27999 dose-dependently increased RPF and GFR; its effects on both parameters at 600 mg (increases of 18 ± 4 and 20 ± 4%, respectively) were equivalent to those at 300 mg, indicating that a maximum had been reached. The effects of 300 mg aliskiren (increases of 13 ± 5 and 8 ± 6%, respectively; P 
Source: Journal of Hypertension - Category: Cardiology Tags: ORIGINAL PAPERS: Kidney Source Type: research