Urodilatin
Evidence: CEvidence: DGrade C — Applies to native Urodilatin's own direct human physiology evidence: multiple small, controlled, acute-dose intravenous/bolus administration studies in healthy volunteers and congestive-heart-failure patients (PMID 2146885, PMID 10070128, PMID 1333960, PMID 1832983), consistently showing real renal natriuretic/diuretic effects, generally more potent per microgram than circulating ANP, with cardiovascular (blood-pressure) effects only at higher doses. This is genuine direct human evidence, not merely mechanistic, but it consists of small, acute, short-duration dosing studies, not a therapeutic-outcome or larger RCT programme for native, non-manufactured Urodilatin itself. This grade does NOT extend to or from the existing ANP page (Grade C, independently assigned) despite the shared NPPA precursor, and does NOT absorb the Ularitide clinical-development programme's outcome..
Grade D — Ularitide clinical-development programme.
Ularitide is, per every source reviewed across three stages of this project's research, an exact-sequence manufactured/synthetic form of Urodilatin — not a sequence-modified analogue. Its clinical-development programme includes a large, well-conducted Phase III RCT (TRUE-AHF, PMID 28402745, N=2,157) that showed favorable short-term hemodynamic effects but a clearly NEGATIVE primary long-term cardiovascular-mortality endpoint (HR 1.03, P=0.75) and no improvement in the prespecified clinical composite endpoint. Ularitide has NO FDA or other regulatory approval as a result. This 'D' reflects a real, large, methodologically sound trial programme that nonetheless produced a clear negative pivotal result and no approval — distinct from, and deliberately graded lower than, this project's precedent for an approved-but-mixed-outcome related programme (e.g., BNP/Nesiritide's 'B', where Nesiritide IS an approved, currently marketed product despite its own pivotal trial's negative primary efficacy result). This related-programme grade must NEVER be used to inflate or replace native Urodilatin's own 'C' grade for endogenous renal physiology claims, and native Urodilatin's grade must never be used to imply Ularitide/TRUE-AHF succeeded.
Renal / Fluid-Balance Signaling
Evidence Snapshot
What this grade covers
Applies to native Urodilatin's own direct human physiology evidence: multiple small, controlled, acute-dose intravenous/bolus administration studies in healthy volunteers and congestive-heart-failure patients (PMID 2146885, PMID 10070128, PMID 1333960, PMID 1832983), consistently showing real renal natriuretic/diuretic effects, generally more potent per microgram than circulating ANP, with cardiovascular (blood-pressure) effects only at higher doses. This is genuine direct human evidence, not merely mechanistic, but it consists of small, acute, short-duration dosing studies, not a therapeutic-outcome or larger RCT programme for native, non-manufactured Urodilatin itself. This grade does NOT extend to or from the existing ANP page (Grade C, independently assigned) despite the shared NPPA precursor, and does NOT absorb the Ularitide clinical-development programme's outcome.
Regulatory Context
Native Urodilatin has no approved therapeutic status; it is an endogenous renal peptide. Ularitide, its exact-sequence manufactured investigational form, was tested in Phase III trials (TRUE-AHF) but never received FDA or other major regulatory approval, and its clinical-development history is presented here as investigational-only, not as an approved-drug regulatory status.
Research Takeaway
Urodilatin is a 32-amino-acid peptide, ANP(95-126), processed from the same proANP (NPPA) precursor as circulating ANP but cleaved by a distinct protease localized to the renal distal tubule/collecting duct, producing a molecule with a 4-residue N-terminal extension and materially different pharmacology from circulating ANP.
See all 7 evidence claims →Quick Summary
Urodilatin is a 32-amino-acid kidney-derived natriuretic peptide, distinct from circulating ANP despite sharing the same gene precursor, with genuine but modest direct human evidence for renal natriuretic/diuretic effects. Its exact-sequence manufactured form, Ularitide, was tested in a large Phase III trial (TRUE-AHF) that showed favorable short-term hemodynamics but no long-term cardiovascular-mortality benefit — a negative pivotal result that is central to this molecule's evidence picture and explains why it was never approved as a drug.
Mechanism & Research Overview
Urodilatin is a 32-amino-acid kidney-derived natriuretic peptide, distinct from circulating ANP despite sharing the same gene precursor, with genuine but modest direct human evidence for renal natriuretic/diuretic effects. Its exact-sequence manufactured form, Ularitide, was tested in a large Phase III trial (TRUE-AHF) that showed favorable short-term hemodynamics but no long-term cardiovascular-mortality benefit — a negative pivotal result that is central to this molecule's evidence picture and explains why it was never approved as a drug.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Urodilatin is a 32-amino-acid peptide, ANP(95-126), processed from the same proANP (NPPA) precursor as circulating ANP but cleaved by a distinct protease localized to the renal distal tubule/collecting duct, producing a molecule with a 4-residue N-terminal extension and materially different pharmacology from circulating ANP.
Sources: Isolation and structural analysis of 'Urodilatin', a new peptide of the cardiodilatin-(ANP)-family, extracted from human urine; Urodilatin: a newly described member of the ANP family
Supported
Intravenously administered Urodilatin produces dose-dependent natriuretic/diuretic renal effects in controlled human studies, generally more potent per microgram than equivalent doses of circulating ANP, with blood-pressure-lowering effects emerging only at higher doses.
Sources: Urodilatin, a natriuretic factor from kidneys, can modify renal and cardiovascular function in men; Cardiovascular, endocrine, and renal effects of urodilatin in normal humans
Supported
Bolus Urodilatin injection produces measurable hemodynamic and renal effects in patients with congestive heart failure, a disease population distinct from the healthy-volunteer studies underlying claim uro-c2.
Supported
Ularitide, the exact-sequence synthetic/manufactured form of Urodilatin used in clinical development, has no FDA or other regulatory approval; its pivotal Phase III trial (TRUE-AHF) did not demonstrate a long-term cardiovascular-mortality benefit.
Sources: Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure (TRUE-AHF); Rationale for and design of the TRUE-AHF trial: the effects of ularitide on the short-term clinical course and long-term mortality of patients with acute heart failure
Supported
TRUE-AHF's favorable short-term hemodynamic findings must not be presented as evidence that Ularitide/Urodilatin improves acute-heart-failure outcomes; the trial's own primary mortality and clinical-composite endpoints were both negative.
Sources: Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure (TRUE-AHF)
Supported
Ularitide's exact-sequence relationship to native Urodilatin does not mean TRUE-AHF's negative clinical-trial result reflects a failure of endogenous native Urodilatin physiology, nor does native Urodilatin's own positive small-study physiology evidence imply Ularitide would succeed in a larger trial — these are evaluated and graded separately.
Supported
The manufacturing route by which ularitide has been produced for clinical use (recombinant expression versus solid-phase chemical synthesis) is described inconsistently across sources found in this review and is not conclusively resolved; this does not change its confirmed exact-sequence identity relative to native Urodilatin.
Sources: NCATS Inxight Drugs: Ularitide Substance Record; US Patent 5,449,751: Cardiodilatin fragment, process for preparing same and use thereof
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
Must be described as a lack of demonstrated long-term benefit, not reframed as a physiologic safety event — TRUE-AHF did not identify a major new safety signal, it failed on efficacy.Safety Consideration
Blood-pressure-lowering effects observed at higher urodilatin doses in controlled physiology studies; clinically relevant in any future dosing context.Safety Consideration
Ularitide has never received FDA or other major regulatory approval; no dosing or safety profile should be presented as if for an approved drug.Safety Consideration
Direct human evidence for native Urodilatin itself is real but limited to small, acute, short-duration dosing studies, not a large or long-term human evidence base.
Research Areas Being Studied
Research areas discussed on this page reflect the Renal / Fluid-Balance Signaling category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure (TRUE-AHF) (2017):
- Urodilatin, a natriuretic factor from kidneys, can modify renal and cardiovascular function in men (1990):
- Isolation and structural analysis of 'Urodilatin', a new peptide of the cardiodilatin-(ANP)-family, extracted from human urine (1988):
- Cardiovascular, endocrine, and renal effects of urodilatin in normal humans ():
- Haemodynamic and renal effects of urodilatin bolus injections in patients with congestive heart failure ():
- Urodilatin, a kidney-derived natriuretic factor, is excreted with a circadian rhythm and is stimulated by saline infusion in man ():
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure (TRUE-AHF) | 2017 | N=2,157 patients with acute heart failure; double-blind RCT, continuous IV ularitide 15 ng/kg/min vs placebo for 48 hours | Ularitide produced favorable short-term hemodynamic effects without reducing cardiac troponin. PRIMARY LONG-TERM RESULT NEGATIVE: cardiovascular mortality 21.7% (ularitide) vs 21.0% (placebo), HR 1.03 (95% CI 0.85-1.25), P=0.75 — statistically indistinguishable from no effect. The clinical composite endpoint was also not improved. | Genuine negative/null Phase III mortality trial; must not be presented as evidence that Urodilatin/Ularitide improves acute heart failure outcomes. | |
| Urodilatin, a natriuretic factor from kidneys, can modify renal and cardiovascular function in men | 1990 | N=8 healthy subjects; dose-response 25/50/100 mcg IV urodilatin vs. ANF-(99-126) 50 mcg vs. placebo | Urodilatin's renal (diuretic/natriuretic) effects were more potent per microgram than circulating ANF-(99-126); cardiovascular (blood-pressure-lowering) effect emerged only at the highest dose; plasma renin/aldosterone/catecholamines were unchanged. | ||
| Isolation and structural analysis of 'Urodilatin', a new peptide of the cardiodilatin-(ANP)-family, extracted from human urine | 1988 | Original isolation and structural characterization of Urodilatin, a 32-amino-acid peptide, ANP(95-126), extracted from human urine. | |||
| Cardiovascular, endocrine, and renal effects of urodilatin in normal humans | Healthy human volunteers | Direct human evidence of urodilatin's cardiovascular, endocrine, and renal effects, corroborating a natriuretic/diuretic action distinct from circulating ANP. | |||
| Haemodynamic and renal effects of urodilatin bolus injections in patients with congestive heart failure | Patients with congestive heart failure (disease population, not healthy volunteers) | Bolus urodilatin injection produced measurable hemodynamic and renal effects in patients with congestive heart failure. | |||
| Urodilatin, a kidney-derived natriuretic factor, is excreted with a circadian rhythm and is stimulated by saline infusion in man | Urinary Urodilatin excretion follows a circadian rhythm and is stimulated by saline infusion in humans. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| NCATS Inxight Drugs: Ularitide Substance Record | Confirms Ularitide shares the identical 32-amino-acid ANP(95-126) sequence with native Urodilatin; describes Ularitide as 'a recombinant form of urodilatin.' | No source link available | |||
| US Patent 5,449,751: Cardiodilatin fragment, process for preparing same and use thereof | States that urodilatin 'has been completely synthetically prepared by means of the solid phase synthesis method according to Merrifield using BOC amino acids' — manufacturing-route context only, not a clinical or identity-authority source. | No source link available |
Review Articles / Secondary Sources
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Rationale for and design of the TRUE-AHF trial: the effects of ularitide on the short-term clinical course and long-term mortality of patients with acute heart failure | 2017 | Design/rationale paper for the TRUE-AHF trial. | |||
| [Urodilatin. Use of a new peptide in intensive care] | 1995 | German-language discussion of Urodilatin's clinical use in intensive-care settings. | |||
| Urodilatin: a newly described member of the ANP family | 1989 | Review of Urodilatin as a distinct member of the ANP peptide family, distinguishing it from circulating ANP. | |||
| The renal urodilatin system: clinical implications | Review-level discussion of the renal urodilatin system and its clinical implications, used as discovery/context-tier evidence. |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published physiology and clinical-trial research about Urodilatin and its investigational manufactured form Ularitide and does not provide medical advice, an individualized treatment recommendation, or dosing instructions.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated .
Follow research updates for Urodilatin
Get notified in your MitoCore account when this profile is updated, a new study is added, or its evidence grade changes.
Get updates when new studies or safety notes are added for this peptide.
Get educational updates on new studies, evidence-grade changes, and safety notes. Educational content only — not medical advice.