Anaritide
Also known as: anaritide acetate, ANP 4-28, ANP‑1‑28, ANP(1-28), Atrial natriuretic peptide (1‑28), atrial natriuretic peptide analog, Auriculin, C‑ANP, M-1475
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Summary
Anaritide is a synthetic 25‑amino‑acid analogue of atrial natriuretic peptide (ANP) belonging to the natriuretic peptide family. It has been studied as a potential therapy for conditions involving fluid overload and renal dysfunction, such as acute tubular necrosis, oliguric acute renal failure, cirrhosis‑related ascites, and radiocontrast‑induced nephropathy. While some reviews cite regulatory approval for acute decompensated heart failure, the compound is generally listed as investigational.
Mechanism of Action
Anaritide mimics endogenous ANP by binding to the natriuretic peptide receptor‑A (NPR‑A), a membrane‑bound guanylyl cyclase. Activation of NPR‑A raises intracellular cyclic GMP, leading to vasodilation of afferent renal arterioles, constriction of efferent arterioles, increased glomerular filtration rate, natriuresis, and diuresis. The cGMP cascade also reduces sympathetic tone and inhibits renin‑angiotensin‑aldosterone activity, contributing to blood‑pressure lowering effects.
What the Research Shows
Clinical investigations have produced mixed results. A 504‑patient trial in acute tubular necrosis showed no overall improvement in dialysis‑free survival, but a subgroup with oliguria experienced a higher survival rate (27% vs 8%). A separate 222‑patient study in oliguric acute renal failure found a non‑significant trend toward better dialysis‑free survival and a marked drop in systolic blood pressure. In cirrhotic patients, anaritide increased urine output and sodium excretion but caused dose‑dependent hypotension, limiting its utility. A trial of 247 patients at risk for radiocontrast‑induced nephropathy found no reduction in incidence. Reviews note its exploration for decompensated heart failure, but recent data question efficacy and safety.
Reported Benefits
Evidence demonstrates that anaritide can produce natriuresis and diuresis, raising urine flow and sodium excretion in cirrhosis and experimental settings. In oliguria‑predominant acute renal failure, modest improvements in dialysis‑free survival have been observed, suggesting a potential benefit in selected renal‑failure subpopulations. The peptide also lowers arterial pressure via cGMP‑mediated vasodilation.
Limitations of the Evidence
Overall trial outcomes have been neutral or negative, with benefits confined to narrow subgroups (e.g., oliguria). Larger studies have not confirmed reductions in dialysis need or mortality. Blood‑pressure lowering can be excessive, especially at higher infusion rates, limiting tolerability. The lack of effect in radiocontrast nephropathy and mixed renal‑failure results highlight uncertain clinical value.
Safety Considerations
The most consistent adverse effect is dose‑related hypotension; several studies reported systolic pressures falling below 90 mm Hg, particularly at infusion rates ≥0.06 µg/kg/min. In oliguric renal‑failure trials, blood‑pressure drops were significantly greater than with placebo. No major organ toxicity was reported, but the hypotensive response may worsen outcomes in patients without oliguria, underscoring the need for careful monitoring.
How It Is Administered
Anaritide is administered as an intravenous infusion, with study doses ranging from 0.015 to 0.300 µg/kg/min over 2‑24 hours. Subcutaneous delivery has also been explored, though most clinical data involve IV infusion. The peptide is supplied as a sterile solution suitable for infusion.
Routes of Administration
Goals & Uses
- Inhibition of RAASNeurohormonal ModulationModerate
- Vasodilation / blood pressure reductionCardiovascularModerate
- Acute decompensated heart failureCardiovascularModerate
- Natriuresis and diuresisFluid/electrolyte ManagementModerate
- Acute heart failure managementCardiovascularLow
- Treatment of acute renal failureRenal ProtectionLow
- Hypertensive renal diseaseRenalLow
- Hypertensive crisisCardiovascularLow
- Renal sodium excretionRenalModerate
Contraindications
- Hypersensitivity to anaritide or ANP analogsImmunologicHigh
- Cardiogenic shockCardiovascularHigh
- PregnancyPopulationModeratePotential fetal risk or insufficient safety data
- Recent myocardial infarction (<30 days)CardiovascularModerate
- HypotensionCardiovascularHigh
- Severe hypotensionCardiovascularHigh
Adverse Effects
- Electrolyte imbalance (e.g., hyponatremia)MetabolicUncommon
- Injection site reactionsLocalUncommon
- HeadacheNeurologicCommonPain in the head or upper neck
- Electrolyte disturbancesMetabolicUncommon
- HypotensionCardiovascularCommonLow blood pressure
- FlushingVascularUncommonWarmth and redness of the skin
- NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
- DizzinessNeurologicUncommonFeeling faint, lightheaded, or unsteady
Drug Interactions
- Loop diureticsLow
- Other vasodilators (e.g., nitroglycerin)Moderate
- ACE inhibitors or ARBsLow
- NSAIDsLowMay increase renal risk in susceptible patients
- ACE inhibitorsModerate
- AntihypertensivesModerateMay potentiate hypotensive effects in some contexts
- DiureticsModerateMay worsen dehydration or electrolyte imbalance
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patientsAgeRelative
- ElderlyAgeRelative
- Severe hypotension or hemodynamic instabilityCardiovascularAbsolute
- Renal impairment (eGFR <30 mL/min)RenalRelative
Regulatory Status
- European UnionInvestigationalNo EMA marketing authorization; limited clinical development.
- United StatesInvestigationalNever received FDA approval; studied in Phase II trials.
- United KingdomInvestigationalNot licensed; used only in research settings.
Studied in Phase I/II trials; development discontinued; not approved in any major jurisdiction.
Evidence & Sources
- Journal ArticleModerateHayek S, Nemer M2011-01-01T00:00:00.000000Z
- Journal ArticleModerateAllgren RL, et al.1997-01-01T00:00:00.000000Z
- Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study GroupJournal ArticleModerateLewis J, et al.2000-01-01T00:00:00.000000Z
- Journal ArticleModerateFried T, et al.1990-01-01T00:00:00.000000Z
- Journal ArticleModerateKurnik BR, et al.1998-01-01T00:00:00.000000Z
- Journal ArticleModeratePotter LR, et al.2009-01-01T00:00:00.000000Z
Frequently Asked Questions
What condition has anaritide shown the most promise for?
Small benefits have been noted in patients with oliguria‑dominant acute renal failure, where dialysis‑free survival was higher than with placebo. However, the evidence is limited to subgroup analyses and not yet definitive.
Why is hypotension a concern with anaritide?
Anaritide activates NPR‑A, increasing cGMP and causing vasodilation. Clinical trials reported dose‑dependent drops in systolic blood pressure, sometimes below 90 mm Hg, which can limit its use, especially in patients without oliguria.
Is anaritide approved for any medical use?
Some reviews state that anaritide has been approved for acute decompensated heart failure, but the compound is generally listed as investigational, and its regulatory status varies across sources.
Can anaritide prevent kidney injury from contrast agents?
A randomized trial in patients with chronic renal impairment found no reduction in the incidence of radiocontrast‑induced nephropathy compared with placebo, indicating no proven preventive benefit.
How is anaritide given to patients?
In clinical studies the peptide is delivered intravenously as a continuous infusion, typically for 2 to 24 hours, with doses measured in micrograms per kilogram per minute. Subcutaneous administration has also been studied.
What is Anaritide?
Anaritide is a synthetic 25‑amino‑acid analogue of atrial natriuretic peptide (ANP) belonging to the natriuretic peptide family. It has been studied as a potential therapy for conditions involving fluid overload and renal dysfunction, such as acute tubular necrosis, oliguric acute renal failure, cirrhosis‑related ascites, and radiocontrast‑induced nephropathy. While some reviews cite regulatory approval for acute decompensated heart failure, the compound is generally listed as investigational.
What is Anaritide used for?
Anaritide is educationally associated with: Inhibition of RAAS, Vasodilation / blood pressure reduction, Acute decompensated heart failure, Natriuresis and diuresis, Acute heart failure management, Treatment of acute renal failure, Hypertensive renal disease, Hypertensive crisis, Renal sodium excretion. Educational only — not medical advice.
How is Anaritide administered?
Recorded routes of administration: Intravenous, Subcutaneous.
What are the potential side effects of Anaritide?
Reported adverse effects include: Electrolyte imbalance (e.g., hyponatremia), Injection site reactions, Headache, Electrolyte disturbances, Hypotension, Flushing, Nausea, Dizziness. This list is not exhaustive — consult a qualified clinician.
Who should avoid Anaritide?
Recorded contraindications: Hypersensitivity to anaritide or ANP analogs, Cardiogenic shock, Pregnancy, Recent myocardial infarction (<30 days), Hypotension, Severe hypotension. Consult a qualified clinician before use.