Urodilatin

Cardiovascular / Renal

Also known as: Ularitide, ANP(95-126)

Natriuretic PeptidesResearch phase: Phase 3 (ularitide, failed primary endpoint)Regulatory: Not approved. Ularitide failed Phase 3 TRUE-AHF trial.

Mechanism

Urodilatin is the kidney's own version of ANP that promotes sodium and water excretion. Its synthetic form, ularitide, was tested in Phase 3 trials for acute heart failure.

Technical detail

Urodilatin (ANP 95-126) is a 32-amino acid natriuretic peptide processed from proANP in distal tubular cells, differing from ANP by a 4-amino acid N-terminal extension conferring resistance to neutral endopeptidase. It acts locally on collecting duct NPR-A receptors to promote natriuresis and diuresis. The synthetic form ularitide completed Phase 3 (TRUE-AHF) for acute heart failure but failed the primary endpoint.

Evidence

  • Haemodynamic and clinical effects of ularitide in decompensated heart failure

    Mitrovic V et al. (2006) — European Heart Journal — PMID: 17074775

    In a randomized placebo-controlled phase II trial of 221 patients with decompensated heart failure, intravenous ularitide lowered pulmonary capillary wedge pressure and improved dyspnea, with dose-related hypotension but no early creatinine signal through day 3.

    moderate
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