Fibromuscular dysplasia was first reported as a disease by Ledbetter et al. in 1938, and the term “fibromuscular hyperplasia or fibroplasia” was used in the early stages of the disease. FMD is now defined as an idiopathic, segmental, noninflammatory, nonatherosclerotic vascular disease that primarily affects small and medium-sized arteries, leading to arterial stenosis and aneurysms. Although the prevalence of renal artery FMD is still unknown, evidence suggests that there is a significant delay between the detection of symptoms and the final diagnosis of renal artery FMD, and because most health care providers are unfamiliar with renal artery FMD, treatment of renal artery FMD is often not the most appropriate treatment, leading to decreased quality of life and the development of potentially serious sequelae, such as refractory hypertension, aneurysm rupture, or arterial entrapment. The clinical presentation varies from asymptomatic to one that resembles systemic vasculitis, often leading to an incorrect diagnosis. Epidemiology Renal artery FMD predominantly affects women aged 15-50 years and is four times more common in women than in men FMD is also seen in infants, children and the elderly. FMD has even been reported to be a common cause of secondary hypertension in the elderly. In Europe and the United States, about 10% of renal vascular hypertension is caused by FMD, but no statistics are available in China. The prevalence of symptomatic FMD is estimated to be about 0.4%, while asymptomatic FMD may affect up to 5% of adult women. Pathogenesis The pathogenesis of FMD is unclear, and it has been tentatively determined that FMD is associated with environmental factors and may have a genetic predisposition. Various hypotheses have been proposed, including mechanical, hormonal, and genetic. Smoking and a history of hypertension have been associated with an increased risk of the disease. Genetic factors may play an important role in the development and progression of FMD. The higher prevalence of the disease in first-degree relatives of patients with renal artery FMD compared to normal subjects suggests that renal artery FMD may be an inherited disease. Several societies in Europe and the United States are currently collaborating in an attempt to find genetic markers for renal artery FMD. Staging OW Kincaid et al. first proposed the staging of renal artery FMD in 1968, and in 1971 Harrison and McCormack proposed a landmark staging of FMD, which identified three staging categories based on the vessel wall involved in FMD: intimal FMD, mesenteric FMD, and epicardial FMD, and has been used to date. With the further understanding of FMD, some scholars have summarized the renal artery FMD staging and its characteristics as follows: Classification Incidence Pathology Imaging manifestations Mesenteric dysplasia Mesenteric fibrous hyperplasia 75C80% Alternating thinning or thickening of the lesion area with fibrous myeloplasia, containing collagen, some areas may be accompanied by loss of elastic intima. They are usually found in the middle and distal renal arteries, with “bead-like” changes, and the diameter of the “beads” is larger than the normal arterial diameter. A few patients have aneurysm formation. Perimembranous fibrous hyperplasia 10C15% Massive collagen deposition in the outer part of the mids (at the junction of the mids and the outer membrane), forming a homogeneous ring of elastic tissue. Focal stenosis of the artery (occasionally multiple stenoses) with “beads” smaller in diameter than normal arteries. Intimal hyperplasia 1C2% Smooth muscle cell hyperplasia only without fibrous hyperplasia Focal smooth concentric stenosis (similar to intimal FMD) Intimal fibrous tissue hyperplasia <10%< span=""> Rounded or eccentric collagen deposits in the intima, with irregular arrangement of interstitial cells in a loose stroma of subintimal connective tissue. No lipid or inflammatory component. Fragmented or overlapping endoelastic membranes. Smooth long stenosis or focal banded stenosis Hyperplasia of fibrous tissue of the epithelium <1%< span=""> Dense collagen replaces fibrous tissue of the epithelium and may extend into the surrounding tissue. Highly confined tubular stenosis It is important to note that the pathologic subtypes of FMD are not mutually exclusive, and a variety of stenoses can be identified on imaging in the same patient, with early studies showing that in up to 2/3 of cases, more than one layer of the diseased artery is often involved. With interventional procedures replacing surgical treatment, histotyping has been less frequently reported. A recent paper dealing with histopathology showed similar age distribution and patient gender, location of the lesion as in previous reports, and the finding that mesenteric dysplasia crosses over with other types. The clinical manifestations of FMD can range from asymptomatic to systemic disease (similar to necrotizing vasculitis). fmd occurs primarily in the renal and internal carotid arteries, but can occur in any vascular bed of the body. Symptoms vary depending on the segment, degree of stenosis, and type of lesion involved. The incidence in each vascular bed is shown in the following table: Involved arteries Frequency (%) Renal artery Bilateral 60C75 35 Cerebral vessels (carotid artery, vertebral artery) Combined intracranial aneurysm 25-30 7-50 Multiple vessels 28 Remaining vessels (iliac artery, superficial femoral artery, N artery, tibiofibular artery, mesenteric artery, hepatic artery, splenic artery, coronary artery, subclavian artery, brachial artery, etc.) Data not available Table 2 Prevalence of FMD in each vascular bed Renal artery FMD often occurs in young women and mainly presents as sudden refractory hypertension, accounting for approximately 10% of renal vascular hypertension. Right-sided is more common than left-sided, and about 35% of lesions are bilateral. Sometimes a systolic or diastolic murmur can be heard in the epigastrium or lumbar region. Sometimes the murmur may be the only symptom, but it lacks sensitivity and specificity for the diagnosis of renal artery FMD. When arterial entrapment or renal artery infarction is present it may manifest as low back pain, hematuria and acute hypertension. Patients may have hypokalemia due to renal artery stenosis leading to activation of the renin angiotensin (RAAS) system, resulting in secondary aldosteronism. Studies have shown that patients with unilateral renal artery FMD have significantly reduced cortical thickness and kidney length, but rarely develop renal insufficiency. Therefore, they do not show increased creatinine as in atherosclerotic renal artery stenosis. The natural course of renal artery FMD has been described in several studies, which have shown that complications of renal artery FMD include aneurysm formation, arterial coarctation, renal artery occlusion (mainly due to coarctation), and renal infarction. It is generally accepted that renal artery mesenteric disease is stable and has a good prognosis, while intimal or epicardial disease may progress and is associated with progressive decline in renal function. The dose and type of hypertensive drugs do not correlate significantly with whether the renal artery progresses. In patients with renal artery FMD, renal insufficiency rarely occurs, although renal cortical atrophy can be as high as 63%. Although the prognosis for patients with renal artery FMD is generally good, aneurysm and entrapment are often considered complications of renal artery FMD, which can lead to serious consequences. Because FMD is a systemic disease (involving multiple vessels in about 28% of patients), spontaneous carotid artery entrapment is a common cause of stroke in young and middle-aged adults, and is associated with carotid artery FMD in about 15% of cases. Therefore, early diagnosis of FMD is particularly important. Diagnostic clues FMD mainly affects women aged 15-50 years. The following clues suggest renal artery stenosis due to FMD: (1) hypertension at age of onset less than 30 years (Evidence class I, category B) (2) recent persistent worsening of previously well-controlled blood pressure (Evidence class I, category C) (3) malignant or recalcitrant hypertension in young adults (Evidence class I, category C) (4) azotemia following angiotensinase inhibitor (ACEI) or angiotensin receptor blocker ( (5) Unexplained renal atrophy or bilateral renal size difference of 37.5 px or more (Evidence Class I B) (6) Sudden onset of unexplained pulmonary edema (especially with azotemia) (Evidence Class I B) (7) Class II evidence of ①Unexplained heart failure or angina ②Systolic or diastolic murmur in the upper abdomen or back Imaging DUS is a good screening test for FMD of the renal arteries. dUS is the least expensive of the imaging tests and can detect proximal as well as mid and distal flow velocities that are accelerated and provide disease-related information on the location and extent of stenosis, kidney size and obstruction. The test does not require patients to adjust antihypertensive medications or use potentially toxic contrast agents. The disadvantages of DUS are that it is less sensitive in diagnosing paranephric artery stenosis; it is time-consuming, highly dependent on the skill level of the examiner, and highly influenced by the patient’s condition (e.g., obesity and intestinal gas). In our country, where the use of ultrasound is quite popular, there is some difficulty in diagnosing FMD in a short time. CTA plays an increasing role in the diagnosis and follow-up of renal artery FMD, with good sensitivity and specificity. CTA is commonly used in patients in whom DUS cannot be adequately visualized (such as obesity or excessive abdominal gas). The application of multi-row spiral CT can improve the resolution of CTA images. Compared to MRA, CTA has the advantages of high spatial resolution; no flow-through effect, which prevents overestimation of arterial stenosis; and the ability to visualize calcified tissue and metallic stents (e.g., endovascular stents and stent grafts). The disadvantages are the ionizing radiation and the need to apply potentially nephrotoxic iodine-containing contrast agents. This limits its use in patients with renal insufficiency. MRA is slightly less accurate than CTA for the evaluation of renal artery FMD, but can be used in patients with renal insufficiency and can also show arterial wall thickness for the identification of polyarteritis. Enhanced MRA with gadolinium as the contrast agent can improve image quality, reduce development time, and reduce motion artifacts due to patient activity, which can improve its sensitivity and specificity. It has been reported to have a sensitivity of 97% (95% CI: 83%, 100%) and specificity of 93% (95% CI: 66%, 100%) for the diagnosis of renal aortic FMD. The disadvantage is that it is difficult to distinguish the branch vascular lesions of the renal arteries and there are false positive cases in practice. Recently, Prchal et al. concluded that MRA increases the risk of systemic sclerosis of nephrogenic origin and therefore cannot be used in patients with a glomerular filtration rate (GFR) < 30 mL/(min/1. 73 m2 ). In addition, MRA should not be used in patients with metallic grafts (e.g., mechanical heart valves, cerebral aneurysm clips, pacemakers) and is contraindicated in patients with claustrophobic syndrome. DSA Despite the advantages of each of these examinations, transcatheter angiography remains the most accurate method for diagnosing FMD. DSA not only shows the condition of the renal aorta, but also accurately demonstrates aneurysm formation and branch vessel anatomy with a spatial resolution of 0.2-0.3 mm and allows multi-angle projection. The disadvantage is that although progression of renal artery FMD occurs in up to 37% of patients with renal artery FMD, it is often difficult to evaluate the progression of the lesion based on imaging alone, especially in patients with mesenteric FMD, where it is difficult to determine whether new stenoses are forming due to the presence of multiple constrictions and dilatations, and visual estimates of the degree of stenosis vary greatly between examiners, making it difficult to accurately measure the degree of arterial stenosis and give a quantitative evaluation. It is very difficult to distinguish FMD from arteritis by imaging alone, and other indicators must be combined. However, about 15% of the lesions in renal artery FMD do not have the characteristic "bead-like" appearance, and they often exist in multiple forms, and various types may coexist (Figure 1). FMD should be differentiated from the following diseases: atherosclerotic renal artery stenosis (ARAS), multiple aortitis (Takayasu's arteritis), Ehlers' artery stenosis, and other arterial diseases. arteritis, EhlersCDanlos syndrome (vascular type), Alport's syndrome, pheochromocytoma, and Marfan's syndrome. Marfan's syndrome. Drug therapy is the first line of treatment for secondary hypertension due to renal artery FMD and should follow hypertension guidelines. Available drugs are ACEI, ARB, calcium channel blockers, beta-blockers, etc. In contrast, percutaneous transluminal angioplasty (PTA) may be the first-line treatment of choice for younger patients with new-onset hypertension due to FMD because of the high likelihood of curing the hypertension. Other treatments including antiplatelet and lipid-lowering therapy are currently based mainly on the experience with coronary PTA and may be beneficial to reduce complication formation or restenosis after PTA. Due to the lack of clinical trials comparing the efficacy of pharmacological treatment with revascularization for hypertension due to FMD, the need for aggressive intervention in asymptomatic FMD remains inconclusive. Reconstruction should be considered in cases of ≥50% (or 60%) diameter stenosis with: (1) recent hypertension (even if the blood pressure is well controlled by medication); (2) intractable hypertension; (3) intolerance to antihypertensive medication; (4) poor compliance making blood pressure difficult to control; and (5) ischemia resulting in a reduction in the size of the affected kidney. PTA has now replaced surgical treatment as the treatment of choice for patients with indications because PTA is less expensive, less invasive, has a shorter recovery time, can be performed on an outpatient basis and has a lower mortality rate associated with surgery; more importantly, if intervention is unsuccessful, surgical treatment can still be performed. Due to improvements in the design of guidewires, catheters, and balloons, as well as improvements in the skill level of the medical staff, angioplasty can be performed even in complex renal artery lesions, and angioplasty has the same effect on main and branch renal artery stenoses. 5.Progress Since the study of FMD requires a large amount of case data, The FMD Society of America has been established to raise public awareness of FMD and to raise funds for an international FMD registry. Seven FMD registries have been established in the United States and one in Europe. Existing research is focused on unraveling the pathophysiological mechanisms of FMD, finding susceptibility genes for FMD, more accurately assessing the risk of FMD, and improving the diagnosis and quantification of renal artery FMD. Therapeutically studies will involve the use of distal protection devices at the time of intervention to prevent distal embolization. A registry and uniform follow-up model should be used after PTA treatment of patients to clearly determine the prognostic impact of FMD type, involved arteries, etc. on hypertension, etc.