Therapeutic use of the natriuretic peptide ularitide in acute renal failure

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.