Background
Ularitide is a member of the natriuretic peptide family. This hormone exhib
its an N-terminal extension by four amino acids compared with atrial natriu
retic peptide. Ularitide was shown to exert strong diuretic and natriuretic
effects when infused intravenously. Its main action sites are the glomerul
um, inducing preglomerular vasodilation and postglomerular vasoconstriction
and thereby elevating the glomerular filtration rate, and the tubular syst
em inhibiting Na+-reabsorption. In initial uncontrolled clinical trials, th
is peptide was shown to have beneficial effects in patients suffering from
oliguric acute renal failure.
Methods
We conducted a double-blind, placebo-controlled, multicenter, dose-finding
trial recruiting 176 patients randomized into 4 different Ularitide doses g
roups (U5, U20, U40, and U80 ng/kg/min) and a placebo group (U0). Ularitide
/placebo infusion was performed for 5 days with half the originally infused
close on day 5. The primary objective of the study was to test various dos
es of Ularitide in patients suffering from oliguric acute renal failure to
avoid mechanical venal replacement therapy during the first 12 hours.
Findings
The results indicate that Ularitide does not reduce the incidence of mechan
ical venal replacement therapy compared with placebo-treated patients durin
g the first 12 h of treatment (U0: 36 (20), U5: 35 (11), U20: 36 (9), U40:
28 (8), U80: 41 (12), (% (n) (p = 0.87)). Diuresis increased in the Ulariti
de-treated groups and the placebo group after onset of infusion and did not
show any significant difference in the first 12 h collection period (U0: 5
76 U5: 514 U20: 500 U40: 360, U80: 158 ML/12h (Median). (p = 0.16)).
Interpretation
In summary, the incidence of mechanical renal replacement therapy in critic
ally ill patients suffering from oliguric acute renal failure could not be
altered positively by Ularitide administration according to our protocol. F
urther prospective clinical trials are needed to answer the question whethe
r a different patient collective or a prophylactic administration of Ularit
ide are more promising approaches in the clinical setting of oliguric acute
renal failure.