⚙

Pathophysiology

4

Developmental renal artery narrowing

Congenital renal artery variants, including stenosis, atresia, hypoplasia, or absence, create a small-caliber or absent inflow vessel to the kidney. This structural lesion limits renal perfusion and establishes the anatomic substrate for renovascular hypertension.

endothelial cell link vascular smooth muscle cell link

renal vascular development link ⚠ ABNORMAL

Downstream

Renal hypoperfusion and renovascular hypertension Stenotic or absent renal arterial inflow lowers renal perfusion pressure.

Show evidence (2 references)

PMID:19711640 SUPPORT Human Clinical

"The wide range of renal vascular diseases include congenital renal artery and vein variations, aneurysms, arteriovenous malformations (AVMs), renal artery stenosis, renal vein thrombosis, vasculitis, and traumatic injuries, such as dissection and vascular pedicle injury."

The review places congenital renal artery variation and renal artery stenosis within the renal vascular disease spectrum.

PMID:34461240 SUPPORT Human Clinical

"He was diagnosed with a congenital absence of the right renal artery."

The case report supports congenital renal arterial deficiency as a renal arterial developmental lesion.

Renal hypoperfusion and renovascular hypertension

Reduced perfusion of the affected kidney can activate pressure-sensitive renal endocrine responses and produce secondary systemic hypertension. In children, renal artery stenosis may occur alone or with middle aortic syndrome.

blood pressure regulation link ⚠ ABNORMAL

Downstream

Renin-angiotensin-aldosterone system activation Reduced renal perfusion activates endocrine blood-pressure responses.

Show evidence (2 references)

PMID:29635838 SUPPORT Human Clinical

"BACKGROUND: Renovascular hypertension (RVH) can be caused by renal artery stenosis (RAS) and/or middle aortic syndrome (MAS)."

This pediatric cohort explicitly links renal artery stenosis to renovascular hypertension.

PMID:34461240 SUPPORT Human Clinical

"Renovascular hypertension is a common cause of secondary hypertension."

This supports renovascular hypertension as the blood-pressure consequence of renal arterial disease.

Renin-angiotensin-aldosterone system activation

Reduced renal perfusion from renal artery stenosis activates the renin-angiotensin-aldosterone axis, promoting severe or refractory hypertension and cardiac remodeling in children.

regulation of blood pressure link ↑ INCREASED

Downstream

Left ventricular remodeling from renovascular hypertension Persistent RAAS-driven hypertension increases cardiac afterload and remodeling risk.

Show evidence (1 reference)

PMID:37658875 SUPPORT Human Clinical

"A common cause of RenoVH is renal artery stenosis which acts by reducing blood supply to renal parenchyma and activating the renin-angiotensin-aldosterone axis, often leading to cardiac remodelling."

This directly supports reduced perfusion, RAAS activation, and cardiac remodeling as the central renovascular hypertension mechanism.

Left ventricular remodeling from renovascular hypertension

Severe renovascular hypertension can remodel the pediatric left ventricle and improve after successful intervention.

cardiac muscle hypertrophy link ⚠ ABNORMAL

Show evidence (1 reference)

PMID:37658875 SUPPORT Human Clinical

"Average z-scores improved in interventricular septal thickness in diastole (IVSD), posterior Wall thickness in diastole (PWD) and fractional shortening (FS); left ventricular mass index (LVMI) and relative wall thickness (RWT) also improved."

This supports renovascular hypertension-associated cardiac remodeling and improvement after treatment.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

4

Cardiovascular 2

Renovascular hypertension Hypertension (HP:0000822)

Severity: SEVERE Onset: CHILDHOOD

Show evidence (1 reference)

PMID:34461240 SUPPORT Human Clinical

"The right renal function was recovered, and the blood pressure was well controlled after the Aorta-Right Renal Artery Bypass."

Blood-pressure control after renal artery bypass supports renovascular hypertension as a key manifestation.

Left ventricular hypertrophy Left ventricular hypertrophy (HP:0001712)

Onset: CHILDHOOD

Show evidence (1 reference)

PMID:37658875 SUPPORT Human Clinical

"A common cause of RenoVH is renal artery stenosis which acts by reducing blood supply to renal parenchyma and activating the renin-angiotensin-aldosterone axis, often leading to cardiac remodelling."

This supports cardiac remodeling as a consequence of pediatric renovascular hypertension.

Other 2

Renal artery stenosis Renal artery stenosis (HP:0001920)

Onset: CHILDHOOD

Show evidence (1 reference)

PMID:29635838 SUPPORT Human Clinical

"Vascular involvement ranged from MAS with RAS (20), RAS only (32), and MAS only (1)."

The pediatric series documents renal artery stenosis as a vascular lesion in children with renovascular hypertension.

Kidney atrophy or small kidney Renal hypoplasia (HP:0000089)

Onset: CHILDHOOD

Show evidence (1 reference)

PMID:29483232 PARTIAL Human Clinical

"Morbidity is high in severe cases, with patients at considerable risk for acute events, such as hypertensive encephalopathy, stroke, progressive cardiac and renal dysfunction."

This supports renal morbidity from severe renovascular disease, while the HPO term captures the reviewer-requested small-kidney morphology.

🧬

Genetic Associations

5

NF1 (Syndromic or nonsyndromic renovascular hypertension / midaortic syndrome risk gene)

Show evidence (1 reference)

PMID:34476477 SUPPORT Human Clinical

"Neurofibromatosis type 1 (NF-1) is frequently observed in children with RVH."

This supports NF1 as a major genetic association for pediatric renovascular hypertension.

JAG1 (Monogenic vasculopathy / Alagille-associated midaortic syndrome gene)

Show evidence (1 reference)

PMID:29483232 SUPPORT Human Clinical

"In 15 of 35 (42.9%) families with MAS, whole exome sequencing revealed a mutation in one of the genes previously associated with vascular disease (NF1, JAG1, ELN, GATA6, and RNF213)."

This supports JAG1 among likely causal vascular-disease genes detected in MAS families.

ELN (Monogenic vasculopathy / Williams-associated renovascular disease gene)

Show evidence (1 reference)

PMID:29483232 SUPPORT Human Clinical

"Four families were found to have a likely causal mutation in JAG1, 3 families in ELN, and 1 family each in RNF213 and GATA6 (Figure 1 and Table 1)."

This supports ELN among recurrent monogenic findings in MAS families.

GATA6 (Rare monogenic vasculopathy gene in midaortic syndrome)

Show evidence (1 reference)

PMID:29483232 SUPPORT Human Clinical

"This is the first report of ELN, RNF213, or GATA6 mutations in individuals with MAS."

This supports GATA6 as a rare monogenic finding in MAS.

RNF213 (Rare monogenic vasculopathy gene in midaortic syndrome)

Show evidence (1 reference)

PMID:29483232 SUPPORT Human Clinical

"This is the first report of ELN, RNF213, or GATA6 mutations in individuals with MAS."

This supports RNF213 as a rare monogenic finding in MAS.

💊

Treatments

3

Transcatheter renal artery intervention

Action: endovascular renal artery angioplasty or stenting Ontology label: Therapeutic Procedure NCIT:C49236

Balloon angioplasty and selected stenting may reduce blood pressure burden in pediatric renovascular hypertension when anatomy is suitable.

Show evidence (1 reference)

PMID:29635838 SUPPORT Human Clinical

"Pediatric patients with RVH treated with transcatheter means as the first intervention had significant improvement in BPR, as well as decline in antihypertensive medications and were less likely to suffer major complications."

The pediatric cohort supports transcatheter treatment as a blood-pressure-improving intervention.

Open renal artery reconstruction

Action: open renal artery reconstruction Ontology label: Surgical Procedure NCIT:C15329

Open reconstruction, including aortorenal bypass, endarterectomy, or renal artery replantation, may be used for complex congenital renal arterial disease or refractory renovascular hypertension.

Show evidence (1 reference)

PMID:34461240 SUPPORT Human Clinical

"We advocate open surgery for patients with congenital dysplasia of renal vascular hypertension, in which the most common surgical operations are aortorenal artery bypass, renal artery endarterectomy, and renal artery replantation."

The case report directly lists open surgical reconstruction options for congenital renal vascular hypertension.

Antihypertensive medical therapy

Action: Pharmacotherapy NCIT:C15986

Antihypertensive pharmacotherapy is used before and after intervention to control severe renovascular hypertension. ACE inhibitors and angiotensin receptor blockers require caution or avoidance in bilateral renal artery stenosis or stenosis affecting a solitary kidney because renal perfusion may be angiotensin-II dependent.

Show evidence (2 references)

PMID:26437121 SUPPORT Human Clinical

"Antihypertensive treatment included antihypertensive drugs (100%), percutaneous transluminal angioplasty (92%), renal auto-transplantation (16%), surgical revascularisation (12%) and nephrectomy (12%)."

This pediatric series supports universal use of antihypertensive medication alongside procedural treatment.

PMID:29483232 SUPPORT Human Clinical

"All individuals in whom a likely causal mutation was detected required antihypertensive therapy (Table 1)."

This supports antihypertensive therapy in monogenic pediatric renovascular disease.

{ }

Source YAML

click to show

name: Congenital Renal Artery Stenosis
creation_date: "2026-05-05T15:37:54Z"
updated_date: "2026-05-05T16:34:00Z"
description: >-
  Congenital renal artery stenosis is a developmental renal vascular disorder
  in which renal arterial narrowing, hypoplasia, atresia, or absence reduces
  perfusion to one or both kidneys. The major clinical consequence is pediatric
  renovascular hypertension, and management depends on anatomy, renal function,
  and whether catheter-based or open surgical revascularization is feasible.
category: Congenital
disease_term:
  preferred_term: congenital renal artery stenosis
  term:
    id: MONDO:0019993
    label: congenital renal artery stenosis
parents:
- Vascular disorder
synonyms:
- Congenital RAS
- Congenital renovascular hypertension
- Congenital renal artery hypoplasia
pathophysiology:
- name: Developmental renal artery narrowing
  description: >-
    Congenital renal artery variants, including stenosis, atresia, hypoplasia,
    or absence, create a small-caliber or absent inflow vessel to the kidney.
    This structural lesion limits renal perfusion and establishes the anatomic
    substrate for renovascular hypertension.
  cell_types:
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  - preferred_term: vascular smooth muscle cell
    term:
      id: CL:0000359
      label: vascular associated smooth muscle cell
  biological_processes:
  - preferred_term: renal vascular development
    modifier: ABNORMAL
    term:
      id: GO:0001944
      label: vasculature development
  evidence:
  - reference: PMID:19711640
    reference_title: Imaging of renovascular disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The wide range of renal vascular diseases include congenital renal artery and vein variations, aneurysms, arteriovenous malformations (AVMs), renal artery stenosis, renal vein thrombosis, vasculitis, and traumatic injuries, such as dissection and vascular pedicle injury.
    explanation: The review places congenital renal artery variation and renal artery stenosis within the renal vascular disease spectrum.
  - reference: PMID:34461240
    reference_title: Renal Artery Reconstruction for Refractory Hypertension Caused by Congenital Renal Artery Deficiency.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      He was diagnosed with a congenital absence of the right renal artery.
    explanation: The case report supports congenital renal arterial deficiency as a renal arterial developmental lesion.
  downstream:
  - target: Renal hypoperfusion and renovascular hypertension
    description: Stenotic or absent renal arterial inflow lowers renal perfusion pressure.
- name: Renal hypoperfusion and renovascular hypertension
  description: >-
    Reduced perfusion of the affected kidney can activate pressure-sensitive
    renal endocrine responses and produce secondary systemic hypertension. In
    children, renal artery stenosis may occur alone or with middle aortic
    syndrome.
  biological_processes:
  - preferred_term: blood pressure regulation
    modifier: ABNORMAL
    term:
      id: GO:0008217
      label: regulation of blood pressure
  evidence:
  - reference: PMID:29635838
    reference_title: "Interventions in children with renovascular hypertension: A 27-year retrospective single-center experience."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      BACKGROUND: Renovascular hypertension (RVH) can be caused by renal artery stenosis (RAS) and/or middle aortic syndrome (MAS).
    explanation: This pediatric cohort explicitly links renal artery stenosis to renovascular hypertension.
  - reference: PMID:34461240
    reference_title: Renal Artery Reconstruction for Refractory Hypertension Caused by Congenital Renal Artery Deficiency.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Renovascular hypertension is a common cause of secondary hypertension.
    explanation: This supports renovascular hypertension as the blood-pressure consequence of renal arterial disease.
  downstream:
  - target: Renin-angiotensin-aldosterone system activation
    description: Reduced renal perfusion activates endocrine blood-pressure responses.
- name: Renin-angiotensin-aldosterone system activation
  description: >-
    Reduced renal perfusion from renal artery stenosis activates the
    renin-angiotensin-aldosterone axis, promoting severe or refractory
    hypertension and cardiac remodeling in children.
  biological_processes:
  - preferred_term: regulation of blood pressure
    modifier: INCREASED
    term:
      id: GO:0008217
      label: regulation of blood pressure
  evidence:
  - reference: PMID:37658875
    reference_title: Cardiovascular outcomes improve in children with renovascular hypertension following endovascular and surgical interventions.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A common cause of RenoVH is renal artery stenosis which acts by reducing blood supply to renal parenchyma and activating the renin-angiotensin-aldosterone axis, often leading to cardiac remodelling.
    explanation: This directly supports reduced perfusion, RAAS activation, and cardiac remodeling as the central renovascular hypertension mechanism.
  downstream:
  - target: Left ventricular remodeling from renovascular hypertension
    description: Persistent RAAS-driven hypertension increases cardiac afterload and remodeling risk.
- name: Left ventricular remodeling from renovascular hypertension
  description: Severe renovascular hypertension can remodel the pediatric left ventricle and improve after successful intervention.
  biological_processes:
  - preferred_term: cardiac muscle hypertrophy
    modifier: ABNORMAL
    term:
      id: GO:0003300
      label: cardiac muscle hypertrophy
  evidence:
  - reference: PMID:37658875
    reference_title: Cardiovascular outcomes improve in children with renovascular hypertension following endovascular and surgical interventions.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Average z-scores improved in interventricular septal thickness in diastole (IVSD), posterior Wall thickness in diastole (PWD) and fractional shortening (FS); left ventricular mass index (LVMI) and relative wall thickness (RWT) also improved.
    explanation: This supports renovascular hypertension-associated cardiac remodeling and improvement after treatment.
phenotypes:
- category: Cardiovascular
  name: Renal artery stenosis
  diagnostic: true
  description: Congenital narrowing or deficiency of the renal artery is the defining vascular lesion.
  phenotype_term:
    preferred_term: Renal artery stenosis
    term:
      id: HP:0001920
      label: Renal artery stenosis
    onset:
      onset_category: CHILDHOOD
  evidence:
  - reference: PMID:29635838
    reference_title: "Interventions in children with renovascular hypertension: A 27-year retrospective single-center experience."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vascular involvement ranged from MAS with RAS (20), RAS only (32), and MAS only (1).
    explanation: The pediatric series documents renal artery stenosis as a vascular lesion in children with renovascular hypertension.
- category: Cardiovascular
  name: Renovascular hypertension
  diagnostic: true
  description: Hypertension is the major clinical presentation when renal arterial stenosis reduces kidney perfusion.
  phenotype_term:
    preferred_term: Severe renovascular hypertension
    term:
      id: HP:0000822
      label: Hypertension
    severity: SEVERE
    onset:
      onset_category: CHILDHOOD
  evidence:
  - reference: PMID:34461240
    reference_title: Renal Artery Reconstruction for Refractory Hypertension Caused by Congenital Renal Artery Deficiency.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The right renal function was recovered, and the blood pressure was well controlled after the Aorta-Right Renal Artery Bypass.
    explanation: Blood-pressure control after renal artery bypass supports renovascular hypertension as a key manifestation.
- category: Cardiovascular
  name: Left ventricular hypertrophy
  description: Chronic renovascular hypertension can cause pediatric cardiac remodeling including increased left ventricular mass.
  phenotype_term:
    preferred_term: Left ventricular hypertrophy
    term:
      id: HP:0001712
      label: Left ventricular hypertrophy
    onset:
      onset_category: CHILDHOOD
  evidence:
  - reference: PMID:37658875
    reference_title: Cardiovascular outcomes improve in children with renovascular hypertension following endovascular and surgical interventions.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A common cause of RenoVH is renal artery stenosis which acts by reducing blood supply to renal parenchyma and activating the renin-angiotensin-aldosterone axis, often leading to cardiac remodelling.
    explanation: This supports cardiac remodeling as a consequence of pediatric renovascular hypertension.
- category: Renal
  name: Kidney atrophy or small kidney
  description: Chronic hypoperfusion may leave the affected kidney small or functionally compromised.
  phenotype_term:
    preferred_term: Kidney atrophy or small kidney
    term:
      id: HP:0000089
      label: Renal hypoplasia
    onset:
      onset_category: CHILDHOOD
  evidence:
  - reference: PMID:29483232
    reference_title: Whole exome sequencing identified monogenic causes of midaortic syndrome in a large cohort of patients.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Morbidity is high in severe cases, with patients at considerable risk for acute events, such as hypertensive encephalopathy, stroke, progressive cardiac and renal dysfunction.
    explanation: This supports renal morbidity from severe renovascular disease, while the HPO term captures the reviewer-requested small-kidney morphology.
genetic:
- name: NF1
  association: Syndromic or nonsyndromic renovascular hypertension / midaortic syndrome risk gene
  presence: Positive
  gene_term:
    preferred_term: NF1
    term:
      id: hgnc:7765
      label: NF1
  notes: NF1 is the best-supported monogenic association in pediatric renovascular hypertension and midaortic syndrome cohorts.
  evidence:
  - reference: PMID:34476477
    reference_title: Molecular genetic evaluation of pediatric renovascular hypertension due to renal artery stenosis and abdominal aortic coarctation in neurofibromatosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Neurofibromatosis type 1 (NF-1) is frequently observed in children with RVH.
    explanation: This supports NF1 as a major genetic association for pediatric renovascular hypertension.
- name: JAG1
  association: Monogenic vasculopathy / Alagille-associated midaortic syndrome gene
  presence: Positive
  gene_term:
    preferred_term: JAG1
    term:
      id: hgnc:6188
      label: JAG1
  evidence:
  - reference: PMID:29483232
    reference_title: Whole exome sequencing identified monogenic causes of midaortic syndrome in a large cohort of patients.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In 15 of 35 (42.9%) families with MAS, whole exome sequencing revealed a mutation in one of the genes previously associated with vascular disease (NF1, JAG1, ELN, GATA6, and RNF213).
    explanation: This supports JAG1 among likely causal vascular-disease genes detected in MAS families.
- name: ELN
  association: Monogenic vasculopathy / Williams-associated renovascular disease gene
  presence: Positive
  gene_term:
    preferred_term: ELN
    term:
      id: hgnc:3327
      label: ELN
  evidence:
  - reference: PMID:29483232
    reference_title: Whole exome sequencing identified monogenic causes of midaortic syndrome in a large cohort of patients.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Four families were found to have a likely causal mutation in JAG1, 3 families in ELN, and 1 family each in RNF213 and GATA6 (Figure 1 and Table 1).
    explanation: This supports ELN among recurrent monogenic findings in MAS families.
- name: GATA6
  association: Rare monogenic vasculopathy gene in midaortic syndrome
  presence: Positive
  gene_term:
    preferred_term: GATA6
    term:
      id: hgnc:4174
      label: GATA6
  evidence:
  - reference: PMID:29483232
    reference_title: Whole exome sequencing identified monogenic causes of midaortic syndrome in a large cohort of patients.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This is the first report of ELN, RNF213, or GATA6 mutations in individuals with MAS.
    explanation: This supports GATA6 as a rare monogenic finding in MAS.
- name: RNF213
  association: Rare monogenic vasculopathy gene in midaortic syndrome
  presence: Positive
  gene_term:
    preferred_term: RNF213
    term:
      id: hgnc:14539
      label: RNF213
  evidence:
  - reference: PMID:29483232
    reference_title: Whole exome sequencing identified monogenic causes of midaortic syndrome in a large cohort of patients.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This is the first report of ELN, RNF213, or GATA6 mutations in individuals with MAS.
    explanation: This supports RNF213 as a rare monogenic finding in MAS.
diagnosis:
- name: Renal vascular imaging
  description: >-
    Doppler ultrasound, CT angiography, MR angiography, catheter angiography, and
    functional renal assessment are used to define renal artery anatomy, lesion
    length, kidney perfusion, and candidacy for revascularization.
  diagnosis_term:
    preferred_term: computed tomography angiography
    term:
      id: MAXO:0000571
      label: computed tomography procedure
  results: Imaging demonstrates congenital renal artery narrowing, hypoplasia, atresia, absence, or related renovascular lesions.
  evidence:
  - reference: PMID:19711640
    reference_title: Imaging of renovascular disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Because renal artery stenosis is an important vascular abnormality encountered in clinical practice, imaging of this entity will be emphasized.
    explanation: The review supports renal vascular imaging as central to evaluating renal artery stenosis.
treatments:
- name: Transcatheter renal artery intervention
  description: >-
    Balloon angioplasty and selected stenting may reduce blood pressure burden
    in pediatric renovascular hypertension when anatomy is suitable.
  treatment_term:
    preferred_term: endovascular renal artery angioplasty or stenting
    term:
      id: NCIT:C49236
      label: Therapeutic Procedure
  evidence:
  - reference: PMID:29635838
    reference_title: "Interventions in children with renovascular hypertension: A 27-year retrospective single-center experience."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pediatric patients with RVH treated with transcatheter means as the first intervention had significant improvement in BPR, as well as decline in antihypertensive medications and were less likely to suffer major complications.
    explanation: The pediatric cohort supports transcatheter treatment as a blood-pressure-improving intervention.
- name: Open renal artery reconstruction
  description: >-
    Open reconstruction, including aortorenal bypass, endarterectomy, or renal
    artery replantation, may be used for complex congenital renal arterial
    disease or refractory renovascular hypertension.
  treatment_term:
    preferred_term: open renal artery reconstruction
    term:
      id: NCIT:C15329
      label: Surgical Procedure
  evidence:
  - reference: PMID:34461240
    reference_title: Renal Artery Reconstruction for Refractory Hypertension Caused by Congenital Renal Artery Deficiency.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We advocate open surgery for patients with congenital dysplasia of renal vascular hypertension, in which the most common surgical operations are aortorenal artery bypass, renal artery endarterectomy, and renal artery replantation.
    explanation: The case report directly lists open surgical reconstruction options for congenital renal vascular hypertension.
- name: Antihypertensive medical therapy
  description: >-
    Antihypertensive pharmacotherapy is used before and after intervention to
    control severe renovascular hypertension. ACE inhibitors and angiotensin
    receptor blockers require caution or avoidance in bilateral renal artery
    stenosis or stenosis affecting a solitary kidney because renal perfusion may
    be angiotensin-II dependent.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:26437121
    reference_title: Associated extrarenal vascular diseases may complicate the treatment and outcome of renovascular hypertension.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Antihypertensive treatment included antihypertensive drugs (100%), percutaneous transluminal angioplasty (92%), renal auto-transplantation (16%), surgical revascularisation (12%) and nephrectomy (12%).
    explanation: This pediatric series supports universal use of antihypertensive medication alongside procedural treatment.
  - reference: PMID:29483232
    reference_title: Whole exome sequencing identified monogenic causes of midaortic syndrome in a large cohort of patients.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All individuals in whom a likely causal mutation was detected required antihypertensive therapy (Table 1).
    explanation: This supports antihypertensive therapy in monogenic pediatric renovascular disease.
review_notes: >-
  The reviewer-suggested HP:0004970 for severe hypertension was not used because
  the local HPO term cache labels HP:0004970 as "Ascending tubular aorta
  aneurysm"; the page instead keeps HP:0000822 with severity SEVERE and the more
  specific preferred term "Severe renovascular hypertension." Proteinuria and
  headache were not added because the fetched, validator-backed caches did not
  provide disorder-specific quotable support for those manifestations.

📚

References & Deep Research

Deep Research

1

Falcon ▸

Disease Characteristics Research Template

Edison Scientific Literature 29 citations 2026-05-05T11:55:45.009515

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

Disease Name: Congenital Renal Artery Stenosis
MONDO ID: (if available)
Category: Congenital

Research Objectives

Please provide a comprehensive research report on Congenital Renal Artery Stenosis covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

What is the disease? Provide a concise overview.
What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
What are the common synonyms and alternative names?
Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
Risk Factors:

Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Genetic risk factors (causal variants, susceptibility loci, modifier genes)
Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
Protective Factors:

Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Genetic protective factors (protective variants, modifier alleles)
Environmental protective factors (diet, lifestyle, exposures that reduce risk)
Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Pathogenic Variants:
Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
Variant type/class (missense, frameshift, nonsense, splice-site, structural)
Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
Functional consequences (loss of function, gain of function, dominant negative)
Modifier Genes: Genes that modify disease severity or expression
Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

Search first: CDC databases, WHO, PubMed, NHANES
Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

Search first: PubMed, Gene Ontology, Reactome
Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Molecular Profiling (if available):
Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
Advanced Technologies (if applicable):
Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

Organ Level:
Primary organs directly affected
Secondary organ involvement (complications, secondary effects)
Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Tissue and Cell Level:
Specific tissue types affected (epithelial, connective, muscle, nervous)
Specific cell populations targeted (with Cell Ontology terms)

Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Subcellular Level:
Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Localization:
Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

Onset:
Typical age of onset (congenital, pediatric, adult, geriatric)
Onset pattern (acute, subacute, chronic, insidious)

Search first: OMIM, Orphanet, HPO, PubMed
Progression:
Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
Progression rate (rapid, slow, variable)
Disease course pattern (episodic, relapsing-remitting, progressive, stable)
Disease duration (self-limited, chronic lifelong)

Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Patterns:
Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

Epidemiology:
Prevalence (cases per 100,000 at given time)
Incidence (new cases per 100,000 per year)

Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
For Genetic Etiology:
Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
Population Demographics:
Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
Geographic distribution of specific variants
Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

Clinical Tests:
Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
Genetic Testing:

Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
Overview of recommended genetic testing approach
Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
FISH > Search first: ClinVar, cytogenetics databases, PubMed
Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
Omics-Based Diagnostics (if applicable):
RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
Clinical Criteria:
Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
Screening:
Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

Survival and Mortality:
Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
Morbidity and Function:
Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
Disease Course:
Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
Prediction:
Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

Pharmacotherapy:
Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
Advanced Therapeutics:
Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
Surgical and Interventional:
Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
Supportive and Rehabilitative:
Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
Experimental:
Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
Treatment Outcomes:
Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
Treatment Strategy:
Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

Prevention Levels:
Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
Immunization: Vaccine strategies (if applicable)

Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Screening and Early Detection:
Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
Behavioral Interventions: Lifestyle modifications to reduce risk

Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Counseling: Genetic counseling (risk assessment, family planning guidance)

Search first: NSGC resources, ACMG guidelines, GeneReviews
Public Health:
Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
Prophylaxis: Preventive medications or procedures

Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

Taxonomy: Species affected (with NCBI Taxon identifiers)

Search first: NCBI Taxonomy
Breed: Specific breeds affected (with VBO identifiers if applicable)

Search first: VBO (Vertebrate Breed Ontology)
Gene: Orthologous genes in other species (with NCBI Gene IDs)

Search first: NCBI Gene
Natural Disease:
Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
Comparative Biology:
Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
Transmission (if applicable):
Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

Model Types:
Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
Genetic Models:
Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
Model Characteristics:
Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
Applications:
Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
Resources:
Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

Cite primary literature (PMID preferred) for all mechanistic and clinical claims
Prioritize recent reviews and landmark papers
Include direct quotes from abstracts where possible to support key statements
Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Comprehensive Disease Characteristics Report: Congenital Renal Artery Stenosis (CRAS)

Executive summary

Congenital/pediatric renal artery stenosis (RAS) is a narrowing of the renal artery(ies) present from birth or developing in childhood, often manifesting as renovascular hypertension (RVH). The central pathophysiologic concept is reduced renal perfusion, which activates the renin–angiotensin–aldosterone system (RAAS) and drives severe or refractory hypertension, with risk of end-organ injury (kidney atrophy/CKD, cardiac remodeling/heart failure, cerebrovascular complications). In modern pediatric practice, digital subtraction angiography (catheter angiography) remains the diagnostic gold standard, while percutaneous transluminal renal angioplasty (PTRA) is a common first-line revascularization strategy in appropriately selected children; outcomes vary by etiology, and restenosis/reintervention is frequent in complex arteriopathies and mid-aortic syndrome (MAS). (goyal2023pediatricrenovascularhypertension pages 1-2, persu2021beyondatherosclerosisand pages 4-5, pytlos2024renalarterystenosis pages 12-14, redhead2024cardiovascularoutcomesimprove pages 1-2)

Evidence quick reference (curated)

Domain	Key finding	Value / statistic	Population / context	Citation
Disease term / definition	Pediatric renal artery stenosis (RAS)	Narrowing of the renal arteries	Children with renovascular disease/hypertension	(pytlos2024renalarterystenosis pages 1-2)
Disease term / definition	Mid-aortic syndrome (MAS)	Stenosis of the abdominal aorta with branch involvement (“abdominal coarctation”)	Pediatric MAS often coexists with renal artery disease	(pytlos2024renalarterystenosis pages 1-2)
Epidemiology	Pediatric arterial hypertension prevalence	~4%	General pediatric population	(pytlos2024renalarterystenosis pages 1-2)
Epidemiology	Renovascular disease among secondary pediatric hypertension	5–10%	Childhood secondary hypertension	(pytlos2024renalarterystenosis pages 1-2, peco‐antic2016associatedextrarenalvascular pages 4-5)
Epidemiology	RVH among pediatric hypertension	Up to 10%	Pediatric hypertension overall	(goyal2023pediatricrenovascularhypertension pages 1-2)
Epidemiology	RVH among secondary pediatric hypertension etiologies	Close to one-fourth	Secondary causes of childhood hypertension	(goyal2023pediatricrenovascularhypertension pages 1-2)
Epidemiology	Incidence of pediatric RVH/RAS	1.9 per million children/year	25 cases over 13 years in hospitals serving ~1 million children	(peco‐antic2016associatedextrarenalvascular pages 4-5)
Epidemiology	MAS among aortic stenosis/coarctation cases	0.5–2%	Rare pediatric vascular disorder	(pytlos2024renalarterystenosis pages 1-2)
Epidemiology	Children with RVH who also have renal-artery plus mid-aortic narrowing	20–48%	Pediatric renovascular hypertension cohorts	(pytlos2024renalarterystenosis pages 1-2)
Etiology	Isolated/congenital developmental lesions	Congenital hypoplasia/deficiency and focal congenital stenosis described	Rare, often grouped with non-inflammatory pediatric RAS	(pytlos2024renalarterystenosis pages 1-2, goyal2023pediatricrenovascularhypertension pages 1-2)
Etiology	Fibromuscular dysplasia (FMD)	Major contributor to pediatric RAS in North America/Europe	Generalized non-inflammatory arteriopathy; commonest cause in developed settings	(pytlos2024renalarterystenosis pages 2-4, goyal2023pediatricrenovascularhypertension pages 1-2)
Etiology	Neurofibromatosis type 1 (NF1)	12% of one pediatric RVH/RAS cohort; 17.1% of MAS families had NF1 mutations	Syndromic/monogenic pediatric renovascular disease	(peco‐antic2016associatedextrarenalvascular pages 4-5, warejko2018wholeexomesequencing pages 3-5)
Etiology	Williams syndrome / ELN / del(7q11.23)	Prevalence ~1 in 10,000; ELN/Williams deletions in 3/35 MAS families (8.6%)	Syndromic vascular stenosis with renal artery involvement	(persu2021beyondatherosclerosisand pages 4-5, warejko2018wholeexomesequencing pages 3-5)
Etiology	Alagille syndrome / JAG1	JAG1 in 4/35 MAS families (11.4%)	Syndromic MAS/RAS; often progressive vasculopathy	(warejko2018wholeexomesequencing pages 3-5, persu2021beyondatherosclerosisand pages 4-5)
Etiology	Takayasu arteritis	Cause of pediatric RAS in some regional series: 73–89%; incidence 1–2/million/year in Europe/North America	Inflammatory large-vessel cause; more common in Asian/African settings	(pytlos2024renalarterystenosis pages 2-4, goyal2023pediatricrenovascularhypertension pages 1-2)
Etiology	Monogenic contribution to MAS	~43% of 35 families	Whole-exome sequencing in pediatric MAS	(warejko2018wholeexomesequencing pages 5-6, warejko2018wholeexomesequencing pages 1-2)
Pathophysiology	Renin–angiotensin–aldosterone system activation	Central mechanism of renovascular hypertension	Renal hypoperfusion from stenosis drives renin-dependent hypertension	(goyal2023pediatricrenovascularhypertension pages 1-2, peco‐antic2016associatedextrarenalvascular pages 4-5)
Diagnostics	Duplex Doppler ultrasound findings	Tardus-parvus waveform, decreased peak systolic velocity; absent intrarenal flow in occlusion	Noninvasive screening/triage in pediatric RAS	(persu2021beyondatherosclerosisand pages 11-12)
Diagnostics	Cross-sectional angiography	CTA/MRA used; no single screening test is sufficient	Defines anatomy, extent, and associated lesions	(goyal2023pediatricrenovascularhypertension pages 1-2, persu2021beyondatherosclerosisand pages 4-5)
Diagnostics	Gold-standard test	Digital subtraction / catheter-based angiography	Definitive diagnosis or formal exclusion of RAS in children	(goyal2023pediatricrenovascularhypertension pages 1-2, persu2021beyondatherosclerosisand pages 4-5, persu2021beyondatherosclerosisand pages 11-12)
Treatment / safety	RAAS blockade contraindication	ACEi/ARB absolutely contraindicated	Bilateral RAS or RAS in a solitary kidney due to risk of acute renal failure/volume overload/pulmonary edema	(pytlos2024renalarterystenosis pages 12-14)
Treatment / outcomes	PTRA overall cure rate	36%	Pediatric RAS series summarized in 2024 review	(pytlos2024renalarterystenosis pages 12-14)
Treatment / outcomes	PTRA BP improvement beyond cure	Additional 32% improved	Pediatric RAS series summarized in 2024 review	(pytlos2024renalarterystenosis pages 12-14)
Treatment / outcomes	Etiology-specific response to intervention	>50% idiopathic RAS; 36% FMD; 80% Takayasu; 71% NF1	Pediatric endovascular outcomes by cause	(pytlos2024renalarterystenosis pages 12-14)
Treatment / outcomes	Restenosis after PTA	Up to 44%	Pediatric focal stenotic lesions/syndromic disease	(persu2021beyondatherosclerosisand pages 4-5)
Treatment / outcomes	Restenosis after stent placement	35.5–37%	Pediatric stenting reserved for recoil/occlusion/early recurrence	(pytlos2024renalarterystenosis pages 12-14)
Treatment / outcomes	BP control after endovascular ± surgical intervention	54.4% achieved BP control; 21.3% discontinued all antihypertensives; 45.9% reduced medications	152 children in longitudinal observational study	(redhead2024cardiovascularoutcomesimprove pages 9-10)
Treatment / outcomes	MAS angioplasty burden	Angioplasty occurrence ~28%; reintervention up to 67% at 5 years	Pediatric MAS has lower durability than focal RAS	(pytlos2024renalarterystenosis pages 12-14)

Table: This table condenses the most actionable facts for congenital/pediatric renal artery stenosis and related renovascular hypertension, including definitions, epidemiology, etiologies, diagnostics, and treatment outcomes. It is useful as a quick-reference evidence summary with context-specific statistics and supporting citation IDs.

1. Disease information

1.1 Definition and overview

Pediatric renal artery stenosis (RAS) is defined as narrowing of the renal arteries and is an important cause of pediatric renovascular hypertension. (pytlos2024renalarterystenosis pages 1-2)
Middle aortic syndrome (MAS) (also called abdominal aortic coarctation / abdominal coarctation) is defined as stenosis of the abdominal aorta with involvement of renal/visceral branches and is a key congenital/pediatric context in which RAS occurs. (pytlos2024renalarterystenosis pages 1-2)

1.2 Key identifiers (OMIM/Orphanet/ICD/MeSH/MONDO)

Limitation of current tool-retrieved corpus: authoritative ontology identifiers (MONDO ID, MeSH descriptor/ID, ICD-10/ICD-11 codes, Orphanet, OMIM) specific to “congenital renal artery stenosis” were not directly retrievable from the available full-text evidence captured in this run. This report therefore provides evidence-based clinical definitions and syndromic genetic identifiers at the gene/syndrome level (e.g., NF1, ELN/Williams-Beuren, JAG1/Alagille), but cannot reliably populate a MONDO/MeSH/ICD mapping without additional database-specific retrieval. (pytlos2024renalarterystenosis pages 1-2, warejko2018wholeexomesequencing pages 3-5, coleman2022moleculargeneticevaluation pages 1-2)

1.3 Synonyms and alternative names (commonly used)

Common overlapping terms used in the literature include: * Renovascular hypertension (RVH) in children (clinical syndrome of hypertension due to renovascular lesions) (goyal2023pediatricrenovascularhypertension pages 1-2) * Renal artery stenosis (RAS) (pytlos2024renalarterystenosis pages 1-2) * Mid-aortic syndrome (MAS) / abdominal aortic coarctation (pytlos2024renalarterystenosis pages 1-2)

1.4 Evidence source type (patient-level vs aggregated)

Most evidence for pediatric/congenital RAS is derived from: * Observational cohorts/series (e.g., 152-child longitudinal cohort with echo follow-up after interventions) (redhead2024cardiovascularoutcomesimprove pages 1-2) * Retrospective pediatric series (e.g., 25 cases over 13 years in a defined pediatric catchment) (peco‐antic2016associatedextrarenalvascular pages 4-5) * Systematic/structured reviews synthesizing pediatric RAS/MAS data (pytlos2024renalarterystenosis pages 1-2, pytlos2024renalarterystenosis pages 12-14) * Genomic cohort studies (e.g., WES in MAS families; NF1-focused molecular profiling of stenotic arteries) (warejko2018wholeexomesequencing pages 1-2, coleman2022moleculargeneticevaluation pages 1-2)

2. Etiology

2.1 Disease causal factors (current understanding)

Pediatric/congenital RAS is etiologically heterogeneous and can be classified into: * Non-inflammatory arteriopathies: particularly fibromuscular dysplasia (FMD), described as a major contributor to pediatric RAS in North America/Europe. (pytlos2024renalarterystenosis pages 2-4) * Inflammatory large-vessel vasculitis: notably Takayasu arteritis, which is regionally prevalent in some pediatric series. (goyal2023pediatricrenovascularhypertension pages 1-2, pytlos2024renalarterystenosis pages 2-4) * Syndromic/genetic causes: especially neurofibromatosis type 1 (NF1), Williams–Beuren syndrome (WBS; ELN region deletion), and Alagille syndrome (JAG1/NOTCH pathway). (persu2021beyondatherosclerosisand pages 4-5, warejko2018wholeexomesequencing pages 3-5) * Anatomic distribution phenotypes: focal stenosis vs multifocal disease; MAS is a congenital or acquired narrowing of the abdominal aorta often involving renal arteries. (goyal2023pediatricrenovascularhypertension pages 1-2, pytlos2024renalarterystenosis pages 1-2)

2.2 Risk factors

Genetic/syndromic risk factors (monogenic contributors): * MAS has a high monogenic yield by whole-exome sequencing (WES): likely causal dominant mutations were found in 15/35 families (≈42.9%), involving NF1, JAG1, ELN, GATA6, RNF213. (warejko2018wholeexomesequencing pages 1-2) * In the same MAS cohort, the most frequent gene was NF1 (6/35 families; 17.1%), followed by JAG1 (4/35; 11.4%) and ELN (3/35; 8.6%). (warejko2018wholeexomesequencing pages 3-5)

Clinical epidemiologic risk context: * In one pediatric RVH/RAS cohort, NF1 accounted for 12% of cases. (peco‐antic2016associatedextrarenalvascular pages 4-5)

Population/region-dependent etiologic spectrum: * A 2023 pediatric interventional radiology review notes that FMD is commonly reported in developed countries, whereas Takayasu arteritis is more common in parts of Asia/Africa. (goyal2023pediatricrenovascularhypertension pages 1-2)

2.3 Protective factors

No specific protective genetic variants or environmental protective factors for congenital/pediatric RAS were identified in the retrieved evidence set.

2.4 Gene–environment interactions

No gene–environment interaction studies specific to congenital/pediatric RAS were identified in the retrieved evidence set.

3. Phenotypes

3.1 Core clinical phenotype spectrum

Pediatric RAS/RVH may be clinically silent and detected only by blood pressure measurement; a pediatric cohort reported ~1/3 asymptomatic despite severe hypertension, highlighting the importance of screening/measurement rather than symptom-driven diagnosis. (peco‐antic2016associatedextrarenalvascular pages 4-5, goyal2023pediatricrenovascularhypertension pages 1-2)

Key phenotype mappings to HPO terms are provided below.

Phenotype / finding	Type	Suggested HPO term	HPO ID	Typical onset	Frequency / notes	Key citation(s)
Severe hypertension	Clinical sign	Severe systemic arterial hypertension	HP:0004970	Childhood	Core presentation of pediatric renovascular hypertension; may be clinically silent, with elevated BP as the sole manifestation in some children; about one-third of children in one cohort were asymptomatic despite severe hypertension	(goyal2023pediatricrenovascularhypertension pages 1-2, peco‐antic2016associatedextrarenalvascular pages 4-5)
Headache	Symptom	Headache	HP:0002315	Childhood	Common symptom of severe hypertension; pediatric NF1-associated RAS case presented with long-standing headache	(goyal2023pediatricrenovascularhypertension pages 1-2)
Abdominal bruit	Clinical sign	Abdominal bruit	HP:0031881	Childhood	Supportive bedside clue in renovascular disease; highlighted in pediatric/syndromic RVH discussions	(persu2021beyondatherosclerosisand pages 1-2)
Left ventricular hypertrophy / cardiac remodeling	Imaging / cardiac phenotype	Left ventricular hypertrophy	HP:0001712	Childhood	Cardiac remodeling occurs secondary to RAAS-driven hypertension; in a 152-patient cohort, IVSD, PWD, LVMI, RWT and FS improved after intervention; 6 children presented in heart failure	(redhead2024cardiovascularoutcomesimprove pages 1-2, redhead2024cardiovascularoutcomesimprove pages 9-10)
Heart failure	Clinical complication	Congestive heart failure	HP:0001635	Childhood	Uncommon but important severe presentation; 6/152 children in the 2024 longitudinal cohort presented in heart failure	(redhead2024cardiovascularoutcomesimprove pages 1-2)
Kidney atrophy / small kidney	Imaging finding	Small kidney	HP:0000089	Childhood	Reflects chronic renal hypoperfusion; may accompany unilateral stenosis/hypoplasia and progressive disease	(persu2021beyondatherosclerosisand pages 4-5, persu2021beyondatherosclerosisand pages 11-12)
Decreased glomerular filtration rate	Laboratory abnormality	Decreased glomerular filtration rate	HP:0012213	Childhood	Reported especially in progressive syndromic disease such as Alagille-associated renovascular disease	(persu2021beyondatherosclerosisand pages 4-5)
Proteinuria	Laboratory abnormality	Proteinuria	HP:0000093	Childhood	Can accompany RAAS activation and hyponatremic hypertensive syndrome in severe renovascular hypertension	(peco‐antic2016associatedextrarenalvascular pages 4-5)
Hyponatremic hypertensive syndrome	Laboratory / clinical syndrome	Hyponatremia; Polyuria; Proteinuria	HP:0002902; HP:0000103; HP:0000093	Childhood	Severe RAAS activation may produce hyponatremic hypertensive syndrome with polyuria, electrolyte loss, and proteinuria	(peco‐antic2016associatedextrarenalvascular pages 4-5)
Bilateral renal artery stenosis	Imaging / vascular phenotype	Bilateral renal artery stenosis	HP:0012723	Childhood / congenital	Reported in 24–78% of pediatric series; bilateral disease is clinically important because ACEi/ARB therapy is contraindicated in bilateral RAS or solitary-kidney RAS	(goyal2023pediatricrenovascularhypertension pages 1-2, pytlos2024renalarterystenosis pages 12-14)
Midaortic syndrome / abdominal aortic coarctation	Imaging / vascular phenotype	Abdominal aortic coarctation	HP:0002626	Congenital / childhood	MAS is a rare but important cause of severe childhood hypertension; 20–48% of children with renovascular hypertension may have combined renal-artery and mid-aortic narrowing	(pytlos2024renalarterystenosis pages 1-2, pytlos2024renalarterystenosis pages 2-4)
Weak femoral pulses / upper-lower extremity BP gradient	Clinical sign	Decreased femoral pulse; Systolic blood pressure difference between upper and lower limbs	HP:0030971; HP:0033279	Childhood	Suggestive of midaortic syndrome; described with weak femoral pulses and BP gradient between upper and lower extremities	(persu2021beyondatherosclerosisand pages 4-5)
Tardus-parvus intrarenal waveform / reduced peak systolic velocity	Imaging finding	Abnormal renal artery Doppler ultrasound	HP:0034059	Childhood	Characteristic Doppler clue to hemodynamically significant stenosis; complete occlusion may show absent intrarenal flow	(persu2021beyondatherosclerosisand pages 11-12)
Absence of symptoms despite severe disease	Clinical course	Asymptomatic hypertension	HP:0000007	Childhood	About one-third of children in one cohort remained asymptomatic despite severe hypertension, underscoring screening importance	(peco‐antic2016associatedextrarenalvascular pages 4-5)

Table: This table maps major pediatric/congenital renal artery stenosis and renovascular hypertension findings to suggested HPO terms, with onset and frequency notes where reported. It is useful for knowledge-base curation of phenotype annotations and evidence-backed clinical features.

3.2 Frequency/severity/progression (selected quantitative data)

Bilateral RAS is common in pediatric series (24–78% reported). (goyal2023pediatricrenovascularhypertension pages 1-2)
Pediatric RVH can cause cardiac remodeling; in a 152-patient cohort, 6 children presented in heart failure, and multiple echocardiographic indices improved following intervention. (redhead2024cardiovascularoutcomesimprove pages 1-2)

3.3 Quality of life impact

Direct patient-reported outcome measures (e.g., PedsQL, PROMIS) were not identified in the retrieved sources. Indirectly, severe hypertension and need for repeated procedures/medications imply substantial burden. (pytlos2024renalarterystenosis pages 12-14, redhead2024cardiovascularoutcomesimprove pages 1-2)

4. Genetic / molecular information

4.1 Causal genes and syndromes (strongly supported)

NF1 (neurofibromatosis type 1) * In a prospective cohort of 102 pediatric RVH patients with RAS ± abdominal aortic coarctation, 13 (12.5%) had clinical NF1. (coleman2022moleculargeneticevaluation pages 1-2)

JAG1 (Alagille syndrome) * JAG1 truncating variants were identified in multiple families with syndromic MAS in WES-based studies. (warejko2018wholeexomesequencing pages 5-6, warejko2018wholeexomesequencing pages 1-2)

ELN region (Williams–Beuren syndrome; 7q11.23 deletion) * WES/CNV analysis in MAS families identified ELN/Williams-related deletions in a subset (3/35 families). (warejko2018wholeexomesequencing pages 3-5, warejko2018wholeexomesequencing pages 1-2)

Additional monogenic genes reported in MAS WES cohorts * GATA6 and RNF213 were each identified in single MAS families in the WES study. (warejko2018wholeexomesequencing pages 1-2)

4.2 Pathogenic variants (examples, where available in evidence)

The MAS WES study reported a range of NF1 variant types (missense, splice-site, frameshift, truncating) and provided specific examples (e.g., c.1166A>G p.H389R; c.1260+5G>A; c.3457_3460del p.L1153Mfs*4). (warejko2018wholeexomesequencing pages 3-5)

4.3 Molecular mechanisms (authoritative mechanistic evidence)

NF1 vasculopathy (human lesion ‘omics’ + histology): * Human stenotic renal arteries in NF1 show a consistent remodeling pattern (intimal thickening, disrupted internal elastic lamina, medial thinning) and transcriptomic evidence of NF1 haploinsufficiency and inflammatory/proliferative signaling: approximately 5-fold reduction in NF1 expression, MAPK pathway activation, and increased MCP1. (coleman2022moleculargeneticevaluation pages 1-2) * Immunostaining demonstrated markedly increased pERK1 (Ras–MAPK pathway activity) in NF1 stenotic artery tissue. (coleman2022moleculargeneticevaluation pages 8-9)

Causal chain (NF1 example): germline NF1 variant → neurofibromin haploinsufficiency → Ras–MAPK activation + MCP1/CCR2-mediated monocyte recruitment and vascular smooth muscle proliferative responses → neointimal hyperplasia and arterial remodeling → renal hypoperfusion → RAAS activation → severe hypertension and downstream end-organ injury. (coleman2022moleculargeneticevaluation pages 8-9, redhead2024cardiovascularoutcomesimprove pages 1-2)

4.4 Epigenetics, modifier genes, and molecular profiling beyond NF1

No disease-specific epigenetic studies or multi-omics signatures (beyond NF1 arterial RNA-Seq in the retrieved corpus) were identified.

5. Environmental information

Congenital RAS is primarily developmental/genetic/structural in the retrieved sources. Environmental contributors (toxins, lifestyle) and infectious agents were not identified as primary causes in the retrieved evidence set.

6. Mechanism / pathophysiology

6.1 RAAS-driven renovascular hypertension

A central mechanistic statement supported in the pediatric literature is that renal artery stenosis reduces renal perfusion, activates the RAAS axis, and can drive severe hypertension and cardiac remodeling. (redhead2024cardiovascularoutcomesimprove pages 1-2, goyal2023pediatricrenovascularhypertension pages 1-2)

6.2 Suggested ontology mappings

GO Biological Process (suggested): * renin secretion / renin-angiotensin system regulation * regulation of systemic arterial blood pressure * vascular smooth muscle cell proliferation * inflammatory cell chemotaxis (monocyte chemotaxis)

Cell Ontology (CL) (suggested): * vascular smooth muscle cell * endothelial cell * monocyte / macrophage (CCR2+ inflammatory monocyte subset conceptually relevant)

These are suggested based on the described mechanisms (RAAS activation; VSMC proliferation; MCP1/CCR2 monocyte infiltration) rather than explicitly enumerated ontology IDs in the retrieved papers. (coleman2022moleculargeneticevaluation pages 8-9, redhead2024cardiovascularoutcomesimprove pages 1-2)

7. Anatomical structures affected

Organ/system level: * Kidney (renal parenchyma ischemia, atrophy) and renal arteries (primary lesion). (pytlos2024renalarterystenosis pages 1-2, persu2021beyondatherosclerosisand pages 11-12) * Cardiovascular system (hypertension-related cardiac remodeling; sometimes heart failure). (redhead2024cardiovascularoutcomesimprove pages 1-2) * Aorta and branch vessels in MAS (abdominal aorta, renal and visceral branch ostia). (pytlos2024renalarterystenosis pages 1-2)

UBERON suggestions (non-exhaustive): kidney; renal artery; abdominal aorta; heart left ventricle.

Lateralization: * Both unilateral and bilateral disease occurs; bilateral stenosis can be common. (goyal2023pediatricrenovascularhypertension pages 1-2)

8. Temporal development

Onset: congenital/childhood (by definition), often detected during childhood BP screening or workup for severe hypertension. (goyal2023pediatricrenovascularhypertension pages 1-2, pytlos2024renalarterystenosis pages 1-2)
Progression: etiology-dependent; syndromic arteriopathies (e.g., NF1) can be progressive with recurrence/restenosis after intervention. (persu2021beyondatherosclerosisand pages 4-5)

9. Inheritance and population

9.1 Epidemiology (quantitative data available)

Childhood arterial hypertension prevalence: ~4%. (pytlos2024renalarterystenosis pages 1-2)
Renovascular disease contribution: 5–10% of secondary pediatric hypertension. (pytlos2024renalarterystenosis pages 1-2, peco‐antic2016associatedextrarenalvascular pages 4-5)
Incidence estimate (regional cohort): 25 pediatric RVH/RAS cases over 13 years in hospitals serving ~1 million children → ~1.9 per million children/year. (peco‐antic2016associatedextrarenalvascular pages 4-5)
MAS rarity: ~0.5–2% of aortic stenosis cases; among pediatric RVH cohorts, 20–48% may have combined renal artery plus mid-aortic narrowing. (pytlos2024renalarterystenosis pages 1-2)

9.2 Inheritance patterns (genetic etiologies)

MAS WES findings support primarily autosomal dominant monogenic contributors (e.g., NF1, JAG1, ELN), with variable expressivity and syndromic vs isolated presentations. (warejko2018wholeexomesequencing pages 3-5, warejko2018wholeexomesequencing pages 1-2)
NF1 variants in the NF1-RVH cohort were often novel; de novo variants were reported as common (about half in that cohort per extracted summary). (coleman2022moleculargeneticevaluation pages 7-8)

10. Diagnostics

10.1 Imaging and diagnostic strategy

No single screening test is uniformly accurate for pediatric RVH; noninvasive imaging (ultrasound/CTA/MRA) is used for screening and anatomical definition. (goyal2023pediatricrenovascularhypertension pages 1-2, persu2021beyondatherosclerosisand pages 4-5)
Digital subtraction/catheter angiography is repeatedly emphasized as the diagnostic gold standard for pediatric RVH/RAS and for definitive exclusion/confirmation. (goyal2023pediatricrenovascularhypertension pages 1-2, persu2021beyondatherosclerosisand pages 4-5, persu2021beyondatherosclerosisand pages 11-12)
Duplex Doppler ultrasound clues include tardus–parvus waveforms and changes in peak systolic velocity; complete occlusion can show absent intrarenal flow. (persu2021beyondatherosclerosisand pages 11-12)

10.2 Differential diagnosis (etiologic breadth)

Differential includes non-inflammatory arteriopathies (FMD), vasculitis (Takayasu), syndromic vascular disease (NF1, WBS, Alagille), thromboembolism/catheter-related injury, extrinsic compression, trauma/radiation, and MAS. (pytlos2024renalarterystenosis pages 2-4, pytlos2024renalarterystenosis pages 1-2)

10.3 Genetic testing

For syndromic/diffuse disease and MAS phenotypes, reviews recommend evaluation for extrarenal involvement and referral for genetic evaluation/testing. (pytlos2024renalarterystenosis pages 2-4)

11. Outcome / prognosis

11.1 Blood pressure and cardiovascular outcomes after intervention

A 2024 longitudinal pediatric cohort (152 children with RVH undergoing ≥1 endovascular intervention, some with surgery) reported: * BP control achieved in 54.4% post-intervention * 45.9% reduced antihypertensive medications * 21.3% discontinued all antihypertensive therapy * Improvement in multiple echocardiographic parameters consistent with reversal/improvement of cardiac remodeling. (redhead2024cardiovascularoutcomesimprove pages 1-2)

11.2 Restenosis and reintervention

Restenosis after PTA has been reported in up to 44%. (persu2021beyondatherosclerosisand pages 4-5)
For pediatric stenting (reserved indications), restenosis rates in summarized series were ~35.5–37%. (pytlos2024renalarterystenosis pages 12-14)
In MAS, reintervention burden is high (reintervention up to 67% at 5 years in summarized data). (pytlos2024renalarterystenosis pages 12-14)

12. Treatment

12.1 Medical therapy

Children often require multi-drug antihypertensive therapy; however, medical therapy alone may be insufficient for durable BP control in anatomic lesions. (pytlos2024renalarterystenosis pages 1-2, pytlos2024renalarterystenosis pages 12-14)

Critical safety constraint (RAAS blockade): * ACE inhibitors/ARBs are absolutely contraindicated in bilateral RAS or RAS in a solitary kidney due to risk of acute renal failure/volume overload/pulmonary edema. (pytlos2024renalarterystenosis pages 12-14)

12.2 Endovascular and surgical interventions (real-world implementation)

Angioplasty (PTRA) is commonly described as the treatment of choice in selected pediatric patients; surgery is reserved for complex anatomy or failed endovascular approaches. (goyal2023pediatricrenovascularhypertension pages 1-2, persu2021beyondatherosclerosisand pages 4-5)

Effectiveness (quantitative): * In a 2024 pediatric review synthesis, PTRA showed an overall cure rate of 36% and BP improvement in an additional 32%, with etiology-specific differences (e.g., higher success in Takayasu arteritis and NF1 than FMD in the summarized series). (pytlos2024renalarterystenosis pages 12-14)

12.3 MAXO (Medical Action Ontology) suggestions

Percutaneous transluminal angioplasty
Vascular stent placement
Surgical vascular reconstruction / bypass
Antihypertensive drug therapy
Aspirin antiplatelet therapy / peri-procedural anticoagulation

These MAXO actions are suggested based on interventions described in pediatric reviews and cohorts. (goyal2023pediatricrenovascularhypertension pages 1-2, pytlos2024renalarterystenosis pages 12-14, redhead2024cardiovascularoutcomesimprove pages 1-2)

12.4 Trials

No pediatric congenital RAS-specific interventional clinical trials with extractable NCT identifiers were identified via the clinical trials search in this run.

13. Prevention

Primary prevention is generally not applicable for congenital developmental lesions. Secondary/tertiary prevention in practice consists of: * routine pediatric BP measurement to avoid delayed diagnosis (given frequent asymptomatic presentation) (peco‐antic2016associatedextrarenalvascular pages 4-5) * early imaging workup when RVH is suspected (goyal2023pediatricrenovascularhypertension pages 1-2) * long-term surveillance for recurrence/restenosis in progressive syndromic vasculopathies (e.g., NF1) (persu2021beyondatherosclerosisand pages 4-5)

14. Other species / natural disease

No naturally occurring veterinary analogs or cross-species epidemiology were identified in the retrieved evidence set.

15. Model organisms

Mechanistic support for NF1 arteriopathy includes mouse model evidence implicating monocyte/macrophage lineage Nf1 haploinsufficiency, CCR2/MCP1-mediated inflammatory recruitment, and neointimal hyperplasia (as summarized within the NF1 molecular study). (coleman2022moleculargeneticevaluation pages 8-9)

Recent developments and “latest research” emphasis (2023–2024)

Key 2023–2024 contributions in the retrieved set include: * A 2023 pediatric interventional radiology perspective emphasizing that pediatric RVH is often silent, angiography remains gold standard, and angioplasty is a key therapy within multidisciplinary care. Publication date: Aug 2023. URL: https://doi.org/10.1055/s-0043-1772496 (goyal2023pediatricrenovascularhypertension pages 1-2) * A 2024 pediatric cohort demonstrating measurable improvement in cardiac remodeling and medication reduction after endovascular ± surgical intervention, with 54.4% BP control. Publication date: Sep 2024 (online earlier per DOI record). URL: https://doi.org/10.1007/s00467-023-06123-5 (redhead2024cardiovascularoutcomesimprove pages 1-2) * A 2024 pediatric review summarizing endovascular outcomes (cure/improvement rates, restenosis after stents, and RAAS blockade contraindications in bilateral/solitary kidney RAS). Publication date: Nov 2024. URL: https://doi.org/10.3390/jcm13226778 (pytlos2024renalarterystenosis pages 12-14)

Notes on PMID availability

Several high-value sources in this run are available with DOI and journal metadata, but PMIDs were not provided in the extracted evidence snippets; therefore, PMID-based citation is not guaranteed here. URLs/DOIs and publication months/years are included where available.

References (URLs in evidence)

Pytlos J, et al. Journal of Clinical Medicine (Nov 2024). https://doi.org/10.3390/jcm13226778 (pytlos2024renalarterystenosis pages 1-2, pytlos2024renalarterystenosis pages 12-14)
Redhead ECG, et al. Pediatric Nephrology (Sep 2024). https://doi.org/10.1007/s00467-023-06123-5 (redhead2024cardiovascularoutcomesimprove pages 1-2)
Goyal K, et al. Indian J Radiol Imaging (Aug 2023). https://doi.org/10.1055/s-0043-1772496 (goyal2023pediatricrenovascularhypertension pages 1-2)
Coleman DM, et al. Human Molecular Genetics (Sep 2022). https://doi.org/10.1093/hmg/ddab241 (coleman2022moleculargeneticevaluation pages 1-2, coleman2022moleculargeneticevaluation pages 8-9)
Warejko JK, et al. Hypertension (Apr 2018). https://doi.org/10.1161/HYPERTENSIONAHA.117.10296 (warejko2018wholeexomesequencing pages 3-5, warejko2018wholeexomesequencing pages 1-2)
Persu A, et al. Hypertension (Oct 2021). https://doi.org/10.1161/hypertensionaha.121.17004 (persu2021beyondatherosclerosisand pages 4-5, persu2021beyondatherosclerosisand pages 11-12)
Peco-Antić A, et al. Acta Paediatrica (2016). https://doi.org/10.1111/apa.13229 (peco‐antic2016associatedextrarenalvascular pages 4-5)

References

(goyal2023pediatricrenovascularhypertension pages 1-2): Kanav Goyal, Taruna Yadav, Pawan Kumar Garg, Pushpinder Khera, Sarbesh Tiwari, and Rengarajan Rajagopal. Pediatric renovascular hypertension: a pediatric interventional radiologist's perspective. Indian Journal of Radiology and Imaging, 33:508-513, Aug 2023. URL: https://doi.org/10.1055/s-0043-1772496, doi:10.1055/s-0043-1772496. This article has 2 citations.
(persu2021beyondatherosclerosisand pages 4-5): Alexandre Persu, Caitriona Canning, Aleksander Prejbisz, Piotr Dobrowolski, Laurence Amar, Constantina Chrysochou, Jacek Kądziela, Mieczysław Litwin, Daan van Twist, Patricia Van der Niepen, Gregoire Wuerzner, Peter de Leeuw, Michel Azizi, Magda Januszewicz, and Andrzej Januszewicz. Beyond atherosclerosis and fibromuscular dysplasia: rare causes of renovascular hypertension. Hypertension, 78:898-911, Oct 2021. URL: https://doi.org/10.1161/hypertensionaha.121.17004, doi:10.1161/hypertensionaha.121.17004. This article has 41 citations and is from a domain leading peer-reviewed journal.
(pytlos2024renalarterystenosis pages 12-14): Jakub Pytlos, Aneta Michalczewska, Piotr Majcher, Mariusz Furmanek, and Piotr Skrzypczyk. Renal artery stenosis and mid-aortic syndrome in children—a review. Journal of Clinical Medicine, 13:6778, Nov 2024. URL: https://doi.org/10.3390/jcm13226778, doi:10.3390/jcm13226778. This article has 6 citations.
(redhead2024cardiovascularoutcomesimprove pages 1-2): Emily C. G. Redhead, Alicia Paessler, Zainab Arslan, Premal Patel, Kishore Minhas, Colin Forman, Paolo Hollis, Sebastiano Lava, Florin Ionescu, Devi Manuel, Samiran Ray, Nicos Kessaris, Alessandro Giardini, Vineetha Ratnamma, Nadine Dobby, Kjell Tullus, Jacob Simmonds, and Jelena Stojanovic. Cardiovascular outcomes improve in children with renovascular hypertension following endovascular and surgical interventions. Pediatric Nephrology (Berlin, Germany), 39:521-530, Sep 2024. URL: https://doi.org/10.1007/s00467-023-06123-5, doi:10.1007/s00467-023-06123-5. This article has 5 citations.
(pytlos2024renalarterystenosis pages 1-2): Jakub Pytlos, Aneta Michalczewska, Piotr Majcher, Mariusz Furmanek, and Piotr Skrzypczyk. Renal artery stenosis and mid-aortic syndrome in children—a review. Journal of Clinical Medicine, 13:6778, Nov 2024. URL: https://doi.org/10.3390/jcm13226778, doi:10.3390/jcm13226778. This article has 6 citations.
(peco‐antic2016associatedextrarenalvascular pages 4-5): Amira Peco‐Antić, Nataša Stajić, Zoran Krstić, Radovan Bogdanović, Gordana Miloševski‐Lomić, Milan Đukić, and Dušan Paripović. Associated extrarenal vascular diseases may complicate the treatment and outcome of renovascular hypertension. Acta Paediatrica, Jan 2016. URL: https://doi.org/10.1111/apa.13229, doi:10.1111/apa.13229. This article has 10 citations and is from a peer-reviewed journal.
(pytlos2024renalarterystenosis pages 2-4): Jakub Pytlos, Aneta Michalczewska, Piotr Majcher, Mariusz Furmanek, and Piotr Skrzypczyk. Renal artery stenosis and mid-aortic syndrome in children—a review. Journal of Clinical Medicine, 13:6778, Nov 2024. URL: https://doi.org/10.3390/jcm13226778, doi:10.3390/jcm13226778. This article has 6 citations.
(warejko2018wholeexomesequencing pages 3-5): Jillian K. Warejko, Markus Schueler, Asaf Vivante, Weizhen Tan, Ankana Daga, Jennifer A. Lawson, Daniela A. Braun, Shirlee Shril, Kassaundra Amann, Michael J.G. Somers, Nancy M. Rodig, Michelle A. Baum, Ghaleb Daouk, Avram Z. Traum, Heung Bae Kim, Khashayar Vakili, Diego Porras, James Lock, Michael J. Rivkin, Gulraiz Chaudry, Leslie B. Smoot, Michael N. Singh, Edward R. Smith, Shrikant M. Mane, Richard P. Lifton, Deborah R. Stein, Michael A. Ferguson, and Friedhelm Hildebrandt. Whole exome sequencing reveals a monogenic cause of disease in ≈43% of 35 families with midaortic syndrome. Hypertension, 71:691–699, Apr 2018. URL: https://doi.org/10.1161/hypertensionaha.117.10296, doi:10.1161/hypertensionaha.117.10296. This article has 35 citations and is from a domain leading peer-reviewed journal.
(warejko2018wholeexomesequencing pages 5-6): Jillian K. Warejko, Markus Schueler, Asaf Vivante, Weizhen Tan, Ankana Daga, Jennifer A. Lawson, Daniela A. Braun, Shirlee Shril, Kassaundra Amann, Michael J.G. Somers, Nancy M. Rodig, Michelle A. Baum, Ghaleb Daouk, Avram Z. Traum, Heung Bae Kim, Khashayar Vakili, Diego Porras, James Lock, Michael J. Rivkin, Gulraiz Chaudry, Leslie B. Smoot, Michael N. Singh, Edward R. Smith, Shrikant M. Mane, Richard P. Lifton, Deborah R. Stein, Michael A. Ferguson, and Friedhelm Hildebrandt. Whole exome sequencing reveals a monogenic cause of disease in ≈43% of 35 families with midaortic syndrome. Hypertension, 71:691–699, Apr 2018. URL: https://doi.org/10.1161/hypertensionaha.117.10296, doi:10.1161/hypertensionaha.117.10296. This article has 35 citations and is from a domain leading peer-reviewed journal.
(warejko2018wholeexomesequencing pages 1-2): Jillian K. Warejko, Markus Schueler, Asaf Vivante, Weizhen Tan, Ankana Daga, Jennifer A. Lawson, Daniela A. Braun, Shirlee Shril, Kassaundra Amann, Michael J.G. Somers, Nancy M. Rodig, Michelle A. Baum, Ghaleb Daouk, Avram Z. Traum, Heung Bae Kim, Khashayar Vakili, Diego Porras, James Lock, Michael J. Rivkin, Gulraiz Chaudry, Leslie B. Smoot, Michael N. Singh, Edward R. Smith, Shrikant M. Mane, Richard P. Lifton, Deborah R. Stein, Michael A. Ferguson, and Friedhelm Hildebrandt. Whole exome sequencing reveals a monogenic cause of disease in ≈43% of 35 families with midaortic syndrome. Hypertension, 71:691–699, Apr 2018. URL: https://doi.org/10.1161/hypertensionaha.117.10296, doi:10.1161/hypertensionaha.117.10296. This article has 35 citations and is from a domain leading peer-reviewed journal.
(persu2021beyondatherosclerosisand pages 11-12): Alexandre Persu, Caitriona Canning, Aleksander Prejbisz, Piotr Dobrowolski, Laurence Amar, Constantina Chrysochou, Jacek Kądziela, Mieczysław Litwin, Daan van Twist, Patricia Van der Niepen, Gregoire Wuerzner, Peter de Leeuw, Michel Azizi, Magda Januszewicz, and Andrzej Januszewicz. Beyond atherosclerosis and fibromuscular dysplasia: rare causes of renovascular hypertension. Hypertension, 78:898-911, Oct 2021. URL: https://doi.org/10.1161/hypertensionaha.121.17004, doi:10.1161/hypertensionaha.121.17004. This article has 41 citations and is from a domain leading peer-reviewed journal.
(redhead2024cardiovascularoutcomesimprove pages 9-10): Emily C. G. Redhead, Alicia Paessler, Zainab Arslan, Premal Patel, Kishore Minhas, Colin Forman, Paolo Hollis, Sebastiano Lava, Florin Ionescu, Devi Manuel, Samiran Ray, Nicos Kessaris, Alessandro Giardini, Vineetha Ratnamma, Nadine Dobby, Kjell Tullus, Jacob Simmonds, and Jelena Stojanovic. Cardiovascular outcomes improve in children with renovascular hypertension following endovascular and surgical interventions. Pediatric Nephrology (Berlin, Germany), 39:521-530, Sep 2024. URL: https://doi.org/10.1007/s00467-023-06123-5, doi:10.1007/s00467-023-06123-5. This article has 5 citations.
(coleman2022moleculargeneticevaluation pages 1-2): Dawn M Coleman, Yu Wang, Min-Lee Yang, Kristina L Hunker, Isabelle Birt, Ingrid L Bergin, Jun Z Li, James C Stanley, and Santhi K Ganesh. Molecular genetic evaluation of pediatric renovascular hypertension due to renal artery stenosis and abdominal aortic coarctation in neurofibromatosis type 1. Human molecular genetics, 31:334-346, Sep 2022. URL: https://doi.org/10.1093/hmg/ddab241, doi:10.1093/hmg/ddab241. This article has 8 citations and is from a domain leading peer-reviewed journal.
(persu2021beyondatherosclerosisand pages 1-2): Alexandre Persu, Caitriona Canning, Aleksander Prejbisz, Piotr Dobrowolski, Laurence Amar, Constantina Chrysochou, Jacek Kądziela, Mieczysław Litwin, Daan van Twist, Patricia Van der Niepen, Gregoire Wuerzner, Peter de Leeuw, Michel Azizi, Magda Januszewicz, and Andrzej Januszewicz. Beyond atherosclerosis and fibromuscular dysplasia: rare causes of renovascular hypertension. Hypertension, 78:898-911, Oct 2021. URL: https://doi.org/10.1161/hypertensionaha.121.17004, doi:10.1161/hypertensionaha.121.17004. This article has 41 citations and is from a domain leading peer-reviewed journal.
(coleman2022moleculargeneticevaluation pages 8-9): Dawn M Coleman, Yu Wang, Min-Lee Yang, Kristina L Hunker, Isabelle Birt, Ingrid L Bergin, Jun Z Li, James C Stanley, and Santhi K Ganesh. Molecular genetic evaluation of pediatric renovascular hypertension due to renal artery stenosis and abdominal aortic coarctation in neurofibromatosis type 1. Human molecular genetics, 31:334-346, Sep 2022. URL: https://doi.org/10.1093/hmg/ddab241, doi:10.1093/hmg/ddab241. This article has 8 citations and is from a domain leading peer-reviewed journal.
(coleman2022moleculargeneticevaluation pages 7-8): Dawn M Coleman, Yu Wang, Min-Lee Yang, Kristina L Hunker, Isabelle Birt, Ingrid L Bergin, Jun Z Li, James C Stanley, and Santhi K Ganesh. Molecular genetic evaluation of pediatric renovascular hypertension due to renal artery stenosis and abdominal aortic coarctation in neurofibromatosis type 1. Human molecular genetics, 31:334-346, Sep 2022. URL: https://doi.org/10.1093/hmg/ddab241, doi:10.1093/hmg/ddab241. This article has 8 citations and is from a domain leading peer-reviewed journal.

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OpenScientist Report

Pathophysiology

Pathograph

Phenotypes

Genetic Associations

Treatments

Source YAML

References & Deep Research

Deep Research

Disease Characteristics Research Template

Target Disease

Research Objectives

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic/Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome/Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Citation Requirements

Output Format

Comprehensive Disease Characteristics Report: Congenital Renal Artery Stenosis (CRAS)

Executive summary

Evidence quick reference (curated)

1. Disease information

1.1 Definition and overview

1.2 Key identifiers (OMIM/Orphanet/ICD/MeSH/MONDO)

1.3 Synonyms and alternative names (commonly used)

1.4 Evidence source type (patient-level vs aggregated)

2. Etiology

2.1 Disease causal factors (current understanding)

2.2 Risk factors

2.3 Protective factors

2.4 Gene–environment interactions

3. Phenotypes

3.1 Core clinical phenotype spectrum

3.2 Frequency/severity/progression (selected quantitative data)

3.3 Quality of life impact

4. Genetic / molecular information

4.1 Causal genes and syndromes (strongly supported)

4.2 Pathogenic variants (examples, where available in evidence)

4.3 Molecular mechanisms (authoritative mechanistic evidence)

4.4 Epigenetics, modifier genes, and molecular profiling beyond NF1

5. Environmental information

6. Mechanism / pathophysiology

6.1 RAAS-driven renovascular hypertension

6.2 Suggested ontology mappings

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

9.1 Epidemiology (quantitative data available)

9.2 Inheritance patterns (genetic etiologies)

10. Diagnostics

10.1 Imaging and diagnostic strategy

10.2 Differential diagnosis (etiologic breadth)

10.3 Genetic testing

11. Outcome / prognosis

11.1 Blood pressure and cardiovascular outcomes after intervention

11.2 Restenosis and reintervention

12. Treatment

12.1 Medical therapy

12.2 Endovascular and surgical interventions (real-world implementation)

12.3 MAXO (Medical Action Ontology) suggestions

12.4 Trials

13. Prevention

14. Other species / natural disease

15. Model organisms

Recent developments and “latest research” emphasis (2023–2024)

Notes on PMID availability

References (URLs in evidence)