Renal effects of ularitide in patients with decompensated heart failure

• Published in: The American heart journal Vol. 155; no. 6; pp. 1012.e1 - 1012.e8
• Main Authors: Lüss, Hartmut, Mitrovic, Veselin, Seferovic, Petar M., Simeunovic, Dejan, Ristić, Arsen D., Moiseyev, Valentin S., Forssmann, Wolf-Georg, Hamdy, Ahmed M., Meyer, Markus
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.06.2008; Elsevier; Elsevier Limited
• Subjects: Aged; Atrial Natriuretic Factor - pharmacology; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Creatinine - blood; Diuretics - pharmacology; Double-Blind Method; Drug dosages; Female; Fluids; Glomerular Filtration Rate; Heart; Heart failure; Heart Failure - drug therapy; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Infusions, Intravenous; Kidney - drug effects; Male; Medical sciences; Middle Aged; Patients; Peptide Fragments - pharmacology; Pulmonary arteries; Severity of Illness Index; Human; Heart failure; Heart disease; Cardiovascular disease; Circulatory system; Cardiology; Ularitide; Kidney
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2008.02.011

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. In SIRIUS II, a double-blind phase II trial, 221 patients hospitalized for DHF (with dyspnea at rest or minimal activity, cardiac index ≤2.5 L/min per square meter, and pulmonary artery wedge pressure ≥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. 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. 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.