Section 9 -

Renovascular Hypertension Donna J. Lager, M.D. Matthew Lewin, M.D.

Case 8: Renovascular Hypertension A 58-year old woman was admitted with uncontrolled hypertension and was found to have a small atrophic right kidney with an elevated renin level. Serum creatinine was 0.9 mg/dl. Renovascular hypertension is defined as high blood pressure secondary to renal artery stenosis. Any process that narrows the main renal artery can lead to renovascular hypertension. The diagnosis depends on the fall in blood pressure after the stenosis has been corrected. The most common cause in adults, particularly men, is atherosclerosis, while fibromuscular dysplasia, which accounts for approximately 10-30% of cases, affects young patients. Other less common causes of renal artery stenosis include dissecting aneurysms of the aorta and renal arteries, arteriovenous malformations or fistulae, Takayasu aortitis, coarctation of the aorta, renal artery thrombosis, compression of the renal artery by tumor, neurofibromatosis, intimal tears due to trauma and radiation injury. Atherosclerosis Atherosclerotic renal artery stenosis is usually located in the proximal portion of the renal artery, with the stenosis present at the ostium of the renal artery in approximately half the cases. Bilateral disease occurs in 30-60% of cases. The involved renal artery is narrowed by eccentric plaque which is composed of amorphous material, cell debris and foam cells, the overlying intima is thickened and the smooth muscle cells in the media may become rarefied with increased medial and adventitial fibrosis. Calcifications may occur and these lesions may be complicated by local thrombosis, hemorrhage and dissection. Fibromuscular Dysplasia (FMD) Fibromuscular dysplasia is a non-inflammatory, non-atherosclerotic condition that is more frequent in younger individuals and women, and affects small and medium-sized vessels. Renal artery FMD is most common (60-75%) followed by the cervicocranial arteries (25-30%), visceral arteries (9%) and the arteries in the extremities (5%). At least two vascular beds are involved in up to 28% of patients. A uniform classification system of renal artery FMD still in use today, was proposed in 1971 and is also applicable to extrarenal arterial involvement. Three main types are identified according to the dominant arterial wall layer involved. Intimal fibroplasia Medial FMD Medial fibroplasia Perimedial fibroplasia Medial hyperplasia Adventitial (periadventitial) fibroplasias Intimal fibroplasia: Intimal fibroplasia accounts for less than 10% of all FMD lesions and is characterized by circumferential or eccentric deposition of collagen in the intima without a lipid or inflammatory component. The internal elastic lamina is identifiable, but may be fragmented or duplicated. Medial fibroplasia: Medial fibroplasia is the most common form of FMD found in 75-80% of all cases. Microscopically this form is characterized by alternating areas of thinned media and thickened fibromuscular ridges, forming the classic "string of beads" radiographically. Typically the beading is larger than the normal caliber of the artery, and is located in the middle to distal portion of the artery. Perimedial fibroplasia: Perimedial fibroplasia, more common in young girls, accounts for 10-15% of all lesions, and is characterized by a homogenous collar of elastic tissue at the junction of the media and the adventitia. This lesion causes focal stenosis of the renal artery and occasionally multiple lesions are observed, however the "beads" are less numerous than in medial fibroplasias and are smaller in diameter than the renal artery. Medial hyperplasia: Medial hyperplasia accounts for only 1-2% of arterial stenoses and appears as a concentric, smooth stenosis on angiogram. It may be indistinguishable radiographically from intimal fibroplasia. The stenosis is produced from hyperplasia of the smooth muscle without fibrosis, medial disruption or aneurysm formation. Adventitial fibroplasia: Adventitial fibroplasia is rare (<1%), and is characterized by replacement of the fibrous tissue of the adventitia with dense collagen. It may extend into the surrounding tissue, but the other arterial layers and elastic lamina remain intact. Clinical Presentation and Diagnosis: The cause of FMD is unknown, however genetic factors may play a role in the development of FMD since it is more common among first-degree relatives of patients with FMD of the renal arteries and among patients with the angiotensin-converting enzyme allele, ACE-I. Cigaratte smoking and a history of hypertension are associated with an increased risk of FMD. Fibromuscular dysplasia of the renal arteries tends to affect women between 15 and 50 years of age and in most cases, the patients are asymptomatic, with FMD discovered incidentally for other reasons. The Ehlers-Danlos syndrome, type IV, has been associated with FMD and the syndrome is suspected in patients with multiple aneurysms and typical radiographic findings of FMD. There are isolated reports of FMD occurring in associated with Marfan's syndrome, Alport's syndrome, pheochromocytoma and Takayasu's arteritis. It may be difficult to distinguish FMD from vasculitis; however the finding of elevated markers of an inflammatory process, anemia and a positive ANCA antibody is more suggestive of vasculitis. Morphologic Findings in Renovascular Hypertension: In renovascular hypertension, particularly in younger patients, there is diffuse atrophy of proximal tubules which become smaller in diameter and are lined by cuboidal cells, often with more cleared cytoplasm. This type of atrophy is usually not accompanied by interstitial fibrosis, and the glomeruli appear normal. The cleared cytoplasm of the tubular epithelial cells and their resemblance to the zona fasciculate of the adrenal gland, led to the descriptive term, "endocrine kidney". In older individuals with renovascular hypertension, there may be widespread tubular atrophy, interstitial fibrosis and glomerulosclerosis. References: Tisher CC, Brenner BM. (eds) Renal Pathology with Clinical and Functional Correlations, 2nd Edition, JB Lippincott, Co, 1994. Daniels SR, Loggie JMH, McEnery PT, Towbin RB. Clinical Spectrum of Intrinsic Renovascular Hypertension in Children. Pediatrics 80(5):698-704, 1987. Harrison EG, McCormack LJ. Pathologic classification of renal arterial disease in renovascular hypertension. Mayo Clin Proc 46:161-167, 1971. Fenves AZ, Ram CVS. Fibromuscular Dysplasia of the Renal Arteries. Curr Hyper Reports 1:546-549, 1999. Begelman SM, Olin JW. Fibromuscular dysplasia. Curr Op Rheum 12:41-47, 2000. Slovut DP, Olin JW. Fibromuscular Dyplasia. NEJM 350:1862-1871, 2004.