Narrowing of one or both renal arteries → obstruction of renal blood flow → ischemia → renin release and activation of the renin-angiotensin-aldosterone system → hyperreninemic hyperaldosteronism (increased renin → increased angiotensin → increased aldosterone) → increased sodium retention and peripheral vascular resistance → renovascular hypertension (secondary hypertension)
Prolonged renal hypoperfusion → chronic stimulation of the juxtaglomerular apparatus to secrete renin → hyperplasia of the juxtaglomerular apparatus
No improvement in renal blood flow → ischemic renal injury → renal insufficiency and progressive renal atrophy (unilateral or bilateral depending on laterality of RAS)
Clinical features
History:
Resistant HTN (uncontrolled on ≥3 anti-hypertensives, including a diuretic).
Abrupt-onset severe HTN (onset <30 yo or >55 yo). c
Recurrent flash pulmonary edema (unexplained, with normal LV systolic function).
Worsening of renal function (rise in serum Cr >30%) after initiating an ACEi or ARB.
Physical Examination:
Abdominal systolic-diastolic bruit (high-specificity, heard lateral to the epigastrium/umbilicus).
Unilateral atrophic kidney (found incidentally on imaging).
Diagnostics
Initial Screen (First Test): Renal duplex Doppler U/S (measures peak systolic velocities and renal-aortic ratio >3.5). Non-invasive, safe, but highly operator-dependent.
CT angiography (CTA): High resolution; contraindicated in renal insufficiency (risk of contrast-induced AKI).
Magnetic Resonance Angiography (MRA): High resolution; contraindicated in severe renal failure (risk of nephrogenic systemic fibrosis [NSF] with gadolinium-based contrast when GFR <30).
Confirmatory / Gold Standard (Best Test): Invasive catheter-based Renal Angiography. Typically reserved for patients undergoing concurrent revascularization.
Key Labs:
Secondary hyperaldosteronism: Elevated renin (PRA) and elevated aldosterone.
Aldosterone-to-Renin Ratio (ARR) < 20 (rules out primary hyperaldosteronism).
BMP: Hypokalemia (due to aldosterone-mediated K+ wasting), elevated Cr.
Treatment
Medical Therapy (First-line for AS-RAS):
ACEi (e.g., Lisinopril) or ARB (e.g., Losartan): Block the RAAS to control HTN. c
Contraindication: Bilateral RAS or unilateral RAS in a solitary kidney. RAAS blockade dilates the efferent arteriole, reducing intraglomerular pressure and triggering acute decline in GFR.
Aspirin, high-intensity statin, and smoking cessation to manage underlying atherosclerosis.
FMD: PTRA without stenting is the definitive treatment of choice (often curative in young patients).
AS-RAS: PTRA with stenting is reserved for refractory cases (recurrent flash pulmonary edema, progressive CKD/declining GFR, or HTN refractory to optimal medical therapy).