Renal artery stenosis is caused by a narrowing of one or both arteries that supply blood to the kidneys. The most common cause, by a wide margin, is atherosclerosis, the same plaque buildup that narrows arteries elsewhere in the body. The second most common cause is a structural abnormality of the artery wall called fibromuscular dysplasia. Together, these two conditions account for the vast majority of cases, though rarer causes exist.
Atherosclerosis: The Leading Cause
Atherosclerosis is responsible for most cases of renal artery stenosis. It develops the same way it does in the heart or legs: fats, cholesterol, and other substances gradually accumulate inside the artery wall, forming plaques. Over time, these plaques harden and thicken, physically narrowing the channel through which blood flows. In the renal arteries, plaques tend to form near the opening where the artery branches off the aorta, the body’s largest blood vessel.
The process begins when fatty particles in the blood penetrate the artery’s inner lining at points of mechanical stress. Several factors accelerate this damage: high cholesterol, high blood pressure, smoking, diabetes, elevated levels of an amino acid called homocysteine, and possibly viral infection or immune-related injury. Once the lining is disrupted, the body’s inflammatory response kicks in, and plaque accumulates layer by layer over years or decades. As the buildup grows, blood flow to the kidney drops. A stenosis is considered hemodynamically significant, meaning it meaningfully restricts flow, when the artery loses more than 70% of its opening.
Because atherosclerosis is a systemic disease, people with renal artery stenosis from this cause often have plaque buildup in other arteries too. This is why the risk factors mirror those for heart disease and stroke: older age, high blood pressure, high cholesterol, diabetes, obesity, smoking, sedentary lifestyle, and a family history of early cardiovascular disease.
Fibromuscular Dysplasia
Fibromuscular dysplasia (FMD) is the second most common cause. Unlike atherosclerosis, it has nothing to do with cholesterol or plaque. Instead, the cells in the artery wall itself grow abnormally, creating areas of thickening that squeeze the channel. On imaging, the affected artery often shows a distinctive “string of beads” pattern: alternating segments of narrowing (from fibrous webs in the wall) and small bulges where the artery dilates just past each tight spot. The beads are typically larger than the normal diameter of the artery.
FMD overwhelmingly affects women. In the largest U.S. registry of FMD patients, 91% were female, with an average age at diagnosis of about 52. That said, it has been diagnosed across the full lifespan, from children as young as 5 to adults in their 80s. The cause of FMD is not fully understood, but it appears to involve a combination of genetic predisposition, hormonal factors, and possibly mechanical stress on the artery wall. It tends to affect the middle and far portions of the renal artery, in contrast to atherosclerosis, which clusters near the artery’s origin.
How Narrowing Triggers a Hormonal Chain Reaction
Whatever the underlying cause, the consequences of a narrowed renal artery follow the same path. When blood flow to a kidney drops, the kidney interprets this as a sign of low blood pressure throughout the body. It responds by releasing an enzyme called renin into the bloodstream. This sets off a cascade that the body normally uses to raise blood pressure during emergencies, but in this case, the trigger never goes away.
Renin breaks apart a protein made by the liver, producing a hormone fragment called angiotensin I. That fragment is inactive on its own. But when it reaches the lungs and kidneys, another enzyme clips it into angiotensin II, which is extremely potent. Angiotensin II causes small arteries throughout the body to constrict, immediately raising blood pressure. It also signals the adrenal glands to release aldosterone and prompts the brain to release a hormone that tells the kidneys to hold onto water. Aldosterone makes the kidneys retain sodium, which pulls even more water into the bloodstream, raising blood volume and pressure further.
The result is persistent high blood pressure that can be difficult to control with standard medications. This is one of the hallmark signs that raises suspicion for renal artery stenosis in the first place: blood pressure that stays stubbornly elevated despite multiple drugs, or that develops suddenly in someone who had normal readings before.
Rare and Less Common Causes
Beyond atherosclerosis and FMD, a handful of other conditions can narrow the renal arteries, though together they account for a very small fraction of cases.
Vasculitis
Inflammation of the blood vessel walls, known as vasculitis, can cause thickening and scarring that narrows or even blocks the renal artery. This accounts for fewer than 1% of all cases. Specific types of vasculitis linked to renal artery narrowing include Takayasu arteritis, which typically affects younger women and targets the aorta and its major branches, and polyarteritis nodosa, which attacks medium-sized arteries throughout the body.
Genetic Conditions
Certain inherited disorders can alter how blood vessel walls develop, leading to stenosis in childhood or early adulthood. Neurofibromatosis type 1 (NF1) causes a blood vessel abnormality that can produce renal artery narrowing. People with NF1 make up a notable proportion of all patients diagnosed with non-atherosclerotic renal artery stenosis. The exact frequency of this vascular involvement is still unknown, but it is an established complication of the condition. Williams syndrome, another genetic disorder, can also affect the renal arteries through abnormal development of the vessel wall.
External Compression
In rare situations, something outside the artery physically presses on it. Reported causes include an enlarged diaphragmatic crus (a muscular band where the diaphragm attaches to the spine), congenital fibrous bands, and, very rarely, nearby tumors. These cases tend to surface in younger patients or in people who have high blood pressure with no traditional vascular risk factors. A clue to this type of stenosis is that compression can change with breathing: the artery may be pinched during exhalation and released during inhalation. Diagnosis often requires dynamic imaging that captures the artery in both phases of the breathing cycle.
Who Is Most at Risk
The risk profile depends entirely on which type of stenosis is involved. For atherosclerotic renal artery stenosis, the risk factors are the same ones that promote plaque buildup anywhere in the body: aging, high blood pressure, high cholesterol, diabetes, obesity, smoking, physical inactivity, and family history of cardiovascular disease. Smoking is particularly notable because it both damages artery linings and accelerates plaque progression. These cases are most common in people over 50, particularly those who already have signs of vascular disease elsewhere.
For fibromuscular dysplasia, the risk profile looks completely different. Being female is the strongest demographic association. FMD can appear at any age but is most often diagnosed around the early 50s. Its precise triggers remain unclear, and it can develop in people with no cardiovascular risk factors at all. The genetic and vascular conditions that cause stenosis in younger patients each carry their own distinct risk profiles, but they are uncommon enough that screening is typically reserved for people already diagnosed with those underlying conditions.