Renal effects of ularitide in patients with decompensated heart failure.
BACKGROUND
Renal function frequently deteriorates in decompensated heart failure (DHF) patients, and one determinant is reduced renal blood flow. This may, in part, result from low cardiac output (CO), reduced mean arterial pressure (MAP), and venous congestion. The combined impact of both venous congestion (elevated right atrial pressure [RAP]) and low MAP are reflected by a reduced pressure gradient MAP-RAP. This study investigated the renal effects of ularitide, a synthetic version of the renal natriuretic peptide urodilatin in DHF patients.


METHODS
In SIRIUS II, a double-blind phase II trial, 221 patients hospitalized for DHF (with dyspnea at rest or minimal activity, cardiac index <or=2.5 L/min per square meter, and pulmonary artery wedge pressure >or=18 mm Hg) were randomized to a single 24-hour infusion of ularitide (7.5, 15, or 30 ng/kg per minute) or placebo added to standard therapy.


RESULTS
Estimated glomerular filtration rate, serum creatinine, creatinine clearance, and blood urea nitrogen (BUN) were not impaired by ularitide throughout infusion and during a 2-day follow-up period. At 24 hours, 15 ng/kg per minute ularitide reduced BUN levels (-4.07 +/- 12.30 vs -0.20 +/- 7.50 for placebo, P < .05). Ularitide at 15 and 30 ng/kg per minute rapidly elevated CO with sustained effects. Although 15 ng/kg per minute ularitide preserved the pressure gradient MAP-RAP, 30 ng/kg per minute ularitide reduced MAP-RAP by -7.8 +/- 10.6 mm Hg vs -2.4 +/- 9.8 mm Hg for placebo (P < .01, at 6 hours). A strong inverse correlation between MAP-RAP and BUN levels (Corr = -0.50579, P = .00015) was observed with 15 ng/kg per minute ularitide.


CONCLUSIONS
Single 24-hour infusions of ularitide at 15 ng/kg per minute preserved short-term renal function in DHF patients possibly by both elevating CO and maintaining the MAP-RAP pressure gradient.
Cardiopep Pharma GmbH, Hannover, Germany. hartmut.luess@web.de
Hartmut
H
Lüss
Veselin
V
Mitrovic
Petar M
PM
Seferovic
Dejan
D
Simeunovic
Arsen D
AD
Ristić
Valentin S
VS
Moiseyev
Wolf-Georg
WG
Forssmann
Ahmed M
AM
Hamdy
Markus
M
Meyer
D000368:Aged; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004232:Diuretics / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology; D012720:Severity of Illness Index
D004232:Diuretics; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D003404:Creatinine