Renovascular Disease

Renal Artery Stenosis: Causes and Pathophysiology

Two Main Causes of RAS

Atherosclerotic RAS (80–90%): The most common cause, typically in elderly patients with widespread atherosclerotic disease. The stenosis is characteristically an ostial lesion (within 1 cm of the aortic origin), representing an extension of aortic atherosclerotic plaque into the renal artery orifice. Usually bilateral (40–50% of patients with significant stenosis have bilateral disease). Associated with significant PAD, aortic atherosclerosis, and coronary disease. The plaque consists of lipid-rich atheroma similar to aortic/coronary plaques, with risk of rupture, thrombosis, and distal embolisation.

Fibromuscular Dysplasia (FMD) (10–15%): A non-atherosclerotic, non-inflammatory arterial disease affecting the renal artery media and causing alternating stenoses and aneurysmal dilatations, producing the classic “string of beads” appearance on angiography. FMD predominantly affects young to middle-aged women (peak incidence 15–50 years, female-to-male ratio ~4:1). Bilateral in ~30% of cases. FMD also commonly affects the carotid and vertebral arteries. The pathophysiology is unclear; dysplasia of the muscular media predisposes to progressive stenosis. FMD is associated with dissection risk.

Pathophysiology: The RAAS Activation Cascade

Renal artery stenosis reduces blood pressure in the renal vessels distal to the stenosis. The juxtaglomerular apparatus (specialised cells in the afferent arteriole wall) senses this reduced renal perfusion pressure and responds by releasing renin. Renin cleaves angiotensinogen to form angiotensin I. Angiotensin-converting enzyme (ACE) in the lungs converts angiotensin I to angiotensin II. Angiotensin II is a powerful vasoconstrictor and stimulates aldosterone secretion (promoting sodium and water retention). The result is hypertension and sodium retention, expanding intravascular volume. The mechanism is particularly important for understanding RAS pathophysiology: the affected kidney relies on angiotensin II to maintain glomerular filtration pressure by causing efferent arteriolar vasoconstriction. When ACE inhibitors or ARBs are used, angiotensin II is reduced, efferent arteriolar vasodilation occurs, and glomerular filtration pressure falls. If the stenosis is severe (reducing renal perfusion already), blocking angiotensin II may drop renal perfusion pressure below the threshold needed for filtration, causing acute renal function deterioration. This is why careful monitoring of creatinine is necessary when starting ACE inhibitors in patients with unilateral RAS.

Differences Between Atherosclerotic and FMD