What are the criteria for Renin-Angiotensin System (RAS) dysregulation and its management?

Criteria for Renal Artery Stenosis (RAS)

The diagnosis of renal artery stenosis requires both clinical suspicion based on specific criteria AND confirmation with imaging, with Duplex Doppler ultrasound as the first-line test showing a peak systolic velocity >200 cm/s or renal-aortic ratio >3.5 for ≥60% stenosis. 1, 2

Clinical Criteria That Should Trigger RAS Evaluation

The following clinical presentations warrant investigation for RAS:

Age-Related Patterns

• Severe hypertension in patients <35 years old (suggests fibromuscular dysplasia) 2, 3
• New-onset hypertension after age 50 (suggests atherosclerotic disease) 2, 3

Hypertension Characteristics

• Malignant or accelerated hypertension 2
• Refractory hypertension (resistant to multiple medications) 2
• Sudden development or worsening of previously controlled hypertension 2
• Diastolic blood pressure >110 mmHg in young adults 2

Physical Examination Findings

• Abdominal bruit (particularly epigastric or flank) 2, 3

Associated Clinical Features

• Flash pulmonary edema (strongly suggests bilateral RAS) 1, 2, 3
• Medication-induced renal deterioration (worsening renal function after starting ACE inhibitors or ARBs) 3
• Generalized atherosclerotic disease with concurrent hypertension (PAD, coronary disease, carotid disease) 2, 3

Diagnostic Imaging Criteria

First-Line: Duplex Doppler Ultrasound (Class I, Level B)

Primary diagnostic criteria for ≥60% stenosis: 1, 3

• Peak systolic velocity (PSV) ≥200 cm/s (sensitivity 73-91%, specificity 75-96%)
• Renal-aortic ratio (RAR) ≥3.5 (renal artery PSV/aortic PSV) (sensitivity 84-91%, specificity 95-97%)

Secondary supportive criteria: 3

• Acceleration time >70 milliseconds
• Parvus-tardus waveform in intrarenal arteries
• Side-to-side intrarenal resistance index difference ≥0.5 1

Advantages: No contrast required, can be used regardless of renal function, cost-effective 3

Limitations: Operator-dependent, technically limited in obese patients or with overlying bowel gas 1, 3

Alternative Imaging Modalities

CT Angiography: 1, 3

• Sensitivity 64-100%, specificity 92-98%
• Provides excellent anatomic detail including vessel wall calcification
• Caution: Requires iodinated contrast (risk of contrast-induced nephropathy in impaired renal function)

MR Angiography: 1, 3

• Sensitivity 88-94%, specificity 85-100%
• Advantage: No radiation, can assess renal parenchymal blood flow
• Limitation: Overestimates stenosis degree by 26-32%
• Use non-contrast techniques in patients with eGFR <30 mL/min/1.73 m² to avoid nephrogenic systemic fibrosis 2

Catheter angiography: Gold standard for diagnosis, enables hemodynamic pressure measurements 1

Hemodynamic Significance Criteria

Anatomic stenosis thresholds: 2, 3

• Most investigators consider ≥50-60% stenosis significant
• Perfusion pressure typically not reduced until stenosis exceeds 70-75%
• Pressure gradient >20 mmHg across stenosis indicates hemodynamic relevance

The ultimate criterion for true renovascular hypertension is blood pressure reduction after revascularization (angioplasty, stenting, or surgery), not just anatomic stenosis. 2

Epidemiology and Risk Stratification

• >90% of RAS cases are caused by atherosclerosis 1
• Overall prevalence of ≥60% RAS in patients >65 years: 6.8% (men 9.1%, women 5.5%) 1
• In patients with peripheral arterial disease: prevalence ranges 7-42% 1
• 10% of cases are fibromuscular dysplasia (typically middle/distal renal artery in young women) 2

Clinical Presentation Patterns

Unilateral RAS: 1

• Renovascular hypertension (contralateral kidney compensates with increased sodium excretion)
• Preserved overall renal function typically

Bilateral RAS or solitary kidney with RAS: 1

• Higher risk of cardiorenal deterioration
• Flash pulmonary edema
• Progressive renal function impairment
• Difficult to quantify hemodynamic effect of each side 2

Special Considerations

In-stent restenosis surveillance requires higher thresholds: 3

• PSV ≥395 cm/s OR
• RAR ≥5.1 for detecting ≥70% in-stent restenosis

Fibromuscular dysplasia: 2, 3

• Accounts for 10% of cases
• Typically affects younger patients
• Can be reliably graded using continuity equation on ultrasound

Common Pitfalls to Avoid

• Do not rely solely on anatomic stenosis severity; assess clinical context and hemodynamic significance 2, 3
• Bilateral arm blood pressure measurement is mandatory (Class I, Level B) to detect subclavian stenosis that could confound diagnosis 1
• Captopril renography has limited utility (sensitivity 74%, specificity 59% in general practice) and should not be used as primary screening 1
• Avoid gadolinium-based MRA contrast in patients with eGFR <30 mL/min/1.73 m² due to nephrogenic systemic fibrosis risk 2