An estimated 2% to 4% of children have clinically significant hypertension. Primary, or essential, hypertension is relatively uncommon in children. Approximately 90% of hypertensive children less than 10 years of age have a secondary form. Eighty percent of secondary hypertension in the pediatric age group is related to renal disease. The most common underlying pathology is a parenchymal disease of the kidneys, such as glomerulonephritis, nephritis, or reflux nephropathy. Only 20% of renal hypertension in children is due to abnormalities of the large renal arteries. There are also various endocrinological conditions that can cause hypertension, including corticosteroid medications, pheochromocytoma, adrenal adenoma, adrenocortical carcinoma, adrenogenital syndrome, and primary aldosteronism (Table 52-1).¹

The frequencies of the different causes of childhood hypertension vary somewhat with age. The most common etiologies of hypertension in neonates are renal artery thrombosis, renal artery stenosis, renal anomalies, coarctation of the aorta, and bronchopulmonary dysplasia. Approximately 70% of infants with hypertension have narrowing or occlusion of a major renal artery. In neonates, the typical mechanism is embolization or extension of thrombus from the abdominal aorta precipitated by umbilical artery catheterization. In young children, the most common causes of hypertension are renal parenchymal disease, renal artery stenosis, and coarctation of the aorta. Renal parenchymal disease and renal artery stenosis are the most common causes of hypertension in older children. Teenagers may develop hypertension due to renal parenchymal diseases or obesity.

Individuals with essential hypertension frequently begin to develop elevation of blood pressure during childhood. Although end-organ complications of essential hypertension are uncommon in children, left ventricular hypertrophy and retinal microangiopathy are potential early findings. Studies utilizing sonography have shown subclinical increased intima–media thickness, decreased elasticity, and increased diameter in the carotid arteries of hypertensive children.² Early findings of arterial damage also can occur in children with obesity, dyslipidemia, and homocystinemia. Essential hypertension is rare in infants.

The term renovascular hypertension indicates renin-mediated elevation of blood pressure in association with a stenotic lesion in the main renal artery or a branch artery. The renal artery stenosis causes diminished renal perfusion pressure that is detected by the juxtaglomerular apparatus in the afferent arterioles. The juxtaglomerular apparatus releases the proteolytic enzyme renin, which converts angiotensin to angiotensin I. Angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II, which is a potent vasoconstrictor and stimulant for release of aldosterone by the adrenal glands. The released aldosterone promotes retention of sodium and water. Elevation of systemic blood pressure occurs by way of increased vascular tone and increased intravascular volume. Increase in systemic blood pressure and constriction of postglomerular arterioles under the effect of angiotensin II serve to maintain renal perfusion pressure and glomerular filtration. Potential clinical findings in the patient with renovascular hypertension include an abdominal or flank bruit, unexplained azotemia, and sudden onset of refractory hypertension. Many of the causes of renovascular hypertension are amenable to correction (Table 52-2).³

Fibrous dysplasia (fibromuscular dysplasia) is the most common cause of renal artery stenosis and renovascular hypertension in children beyond the neonatal age group. Other conditions that are sometimes associated with renal artery stenosis include neurofibromatosis type 1, Williams syndrome, arteritis, coarctation, middle aortic syndrome, and extrinsic renal artery compression.

Typically, the initial imaging technique for the evaluation of a child with suspected renovascular disease is sonography. The examination should include careful evaluation of the renal parenchyma for signs of medical renal disease. Asymmetry of the kidneys is an important sign of potential renovascular disease, as the affected kidney is often small and may have manifestations of scarring. Sonography also serves to exclude urinary tract obstruction or a renal or other retroperitoneal mass. Only rarely does ultrasound allow direct visualization of a stenotic lesion in a renal artery. The sonographic evaluation of a hypertensive child should include careful evaluation of the abdominal aorta.

Doppler evaluation is an essential component in the sonographic workup of a patient with suspected renovascular disease. A peak velocity in the renal artery of greater than 100 cm/s is suggestive of renal artery stenosis. A renal artery-to-aorta peak systolic velocity ratio of greater than 3.5 is a strong indicator for the presence of renal artery stenosis. Distal to the stenosis, the systolic peak of the renal artery waveform often appears flattened. An acceleration time of greater than 0.07 seconds in this portion of the vessel is associated with renal artery stenosis. The tardusparvus pattern occurs distal to a severe stenosis (e.g., in the arcuate arteries); this refers to slow systolic acceleration and diminished peak systolic velocity. With severe stenosis, the systolic peak disappears and the waveform distal to the lesion is monophasic (Figure 52-1). Diastolic flow in the renal artery is sometimes elevated. The sensitivity of Doppler sonography for the diagnosis of renal artery hypertension in children is unknown. False-negative examinations can occur with mild stenosis, stenosis involving 1 or more intrarenal arteries, and stenosis of an accessory renal artery.^4–7

Renal scintigraphy in conjunction with the use of an ACE inhibitor, such as captopril or enalaprilat, can be helpful for the diagnosis of renovascular hypertension and for determining the functional significance of a known renal artery stenosis. There are various specific protocols for this examination, but most involve renal imaging without and with ACE administration. The examination can be performed either with ^99mTc-mercaptoacetyltriglycine (MAG₃), which is cleared by tubular secretion, or with ^99mTc-diethylenetriaminepentaacetic acid (DTPA), which is excreted by glomerular filtration. Scintigraphy performed during ACE inhibitor therapy shows diminished glomerular filtration and tubular secretion in the affected kidney or the affected portion of the kidney. This is due to diminished perfusion pressure distal to a hemodynamically significant renal artery stenosis; the ACE inhibitor blocks compensatory efferent arteriolar vasoconstriction in the glomeruli.

Depending on the technique and the radiopharmaceutical utilized, the potential scintigraphic findings in the kidney served by a stenotic artery include: (1) diminished/delayed renal perfusion during the flow phase, (2) a small kidney, (3) diminished/delayed initial parenchymal uptake, and (4) retention of tracer in the cortex. Evaluations utilizing MAG₃ demonstrate prolongation of cortical transit, due to poor tubular washout. Alteration in the initial uptake is usually the predominant finding with DTPA imaging, as clearance of this agent is entirely by glomerular filtration. A comparative study in the absence of antihypertensive therapy has a more normal appearance, as the physiological events initiated by renin and ACE serve to counteract the local renal sequelae of arterial stenosis. The sensitivity of this technique for the detection of renovascular hypertension is 85% to 90% and specificity is greater than 90%. False-negative examinations can occur with bilateral renal artery stenosis or markedly compromised renal function.^8–10

CT of patients with suspected renovascular hypertension provides excellent depiction of parenchymal renal abnormalities, such as scarring. Helical contrast-enhanced CT of the kidneys with 3D reformatted images of the renal vasculature can often demonstrate stenotic lesions of the renal artery. The volume rendering 3D technique provides higher specificity for the diagnosis of renal artery stenosis than does maximum intensity projection. In general, renal arterial diameter narrowing of greater than 50% is hemodynamically significant.^11,12

As with CT, MR studies provide cross-sectional and 3D depiction of renal parenchymal anatomy and renal vascular anatomy. Technically adequate MR angiography effectively demonstrates clinically significant renal artery lesions in most patients. Imaging with IV gadolinium administration increases the sensitivity of this technique. With contrast-enhanced MR renography, the cortical-to-aortic peak enhancement ratio is diminished with renal artery stenosis and the cortical-to-aortic time delay is increased.¹³ MR renography can also be utilized in a similar manner as scintigraphy to assess changes in renal function (i.e., filtration and tubular secretion) during treatment with an ACE.¹⁴

The gold standard technique for the detection of renal artery stenosis is transcatheter angiography and renal vein renin sampling. Arteriography allows accurate detection and characterization of lesions of the main renal arteries and intrarenal branches (Figure 52-2). Angioplasty is generally indicated for any technically amenable renal artery stenosis in a child with hypertension. It is effective in treating stenoses due to fibrous dysplasia, which is the most common cause of pediatric renovascular disease.

Renal vein renin sampling is useful for selected patients to confirm lateralization of renovascular hypertension. This involves transcatheter collection of blood samples from the renal veins and the infrarenal and suprarenal portions of the inferior vena cava. When there is evidence of focal renal disease, branch renal vein sampling may be beneficial. When renovascular hypertension is due to unilateral kidney disease, there is elevation of blood renin activity in the underperfused kidney and suppression of renin excretion from the normal kidney. The usual standard for clinically significant lateralization is an ipsilateral:contralateral renal vein renin ratio of 1.5 or greater. Substantial lateralization does not occur when there is bilateral renal artery disease or hypertension due to aortic disease. Well-formed collateral vessels in a patient with unilateral disease can quantitatively diminish lateralization.

Fibrous Dysplasia

Renal vascular stenosis due to fibrous dysplasia (fibromuscular dysplasia; fibromuscular fibroplasia) results from abnormal overgrowth of fibrous tissue or muscular tissue in the arterial wall. Classification of fibromuscular dysplasia is based on the predominantly affected layers of the arterial wall. Fibrous dysplasia is a congenital vascular dysplasia, with maldevelopment of the fibrous, muscular, and elastic tissues of the artery. Occasionally, there is concomitant involvement of vessels remote to the kidney, such as the great vessels of the aortic arch, extremity arteries, and visceral arteries. Fibrous dysplasia of the renal arteries tends to respond well to balloon angioplasty. Fibrous dysplasia is more common in females.^15–17

Intimal fibroplasia is the most common cause of renal artery stenosis in children. There is concentric subintimal accumulation of collagen, involving the internal elastic membrane. The resultant stenosis usually appears smooth on angiographic studies (Figure 52-3). This stenosis may be band-like, tubular, or funnel shaped (Figure 52-4). Typically, the narrowing is located in the mid to distal aspect of the renal artery; occasionally a branch vessel is involved. The narrowing tends to be progressive with time. Secondary dissection or thrombosis can occur.

Medial fibroplasia is the most common cause of nonatherosclerotic renal artery stenosis in adults, but is rare in children. Replacement of smooth muscle by collagen within the media forms thick ridges. These alternate with zones of vessel dilation due to focal thinning of the internal elastic membrane, thereby producing a classic “string of beads” appearance on angiographic studies. Most often, involvement predominates in the distal two-thirds of the main renal artery and its branches. The “aneurysms” between the stenotic bands are usually greater in caliber than the normal renal artery. Prominent collateral circulation is usually lacking.

Perimedial fibroplasia occurs almost exclusively in girls older than 10 years of age. There is bilateral involvement in approximately 15% of cases. There is collagen infiltration into the outer layer of the media over a variable length of the renal artery. The thickness of the collagen varies along the involved segment. The typical angiographic appearance of perimedial fibroplasia is severe beaded narrowing over a relatively long segment of the renal artery. In contradistinction to medial fibroplasia, the segments between stenoses do not exceed the normal renal artery luminal diameter.

Medial hyperplasia is an uncommon form of fibrous dysplasia, in which there is concentric hyperplastic medial smooth muscle and fibrous tissue. There are 1 or more areas of short, smooth narrowing. Aneurysm formation is lacking. This form of fibrous dysplasia predominantly affects teenagers and young to middle-aged adult males.

Adventitial dysplasia is a rare form of fibrous dysplasia in which a collagenous infiltrate surrounds the adventitia. This results in tubular or discrete focal stenoses, usually involving the distal main renal arteries or the major branch vessels.

Neurofibromatosis

Hypertension occurs in approximately 1% of patients with neurofibromatosis type 1. The causes of hypertension in these patients include renal artery stenosis, coarctation of aorta, and pheochromocytoma. Renal artery stenosis is by far the most common etiology, particularly in children. The usual mechanism of renal artery stenosis in these patients is proliferation of neural tissue in the arterial wall and perivascular nodular proliferations. A mesodermal dysplasia of small intrarenal vessels can also occur. More than 50% of renal artery stenoses in patients with neurofibromatosis type 1 are ostial.¹⁸

The diagnostic imaging features of renal artery stenosis due to neurofibromatous vasculopathy are similar to those of intimal fibroplasia. However, aortic narrowing often accompanies visceral artery stenoses in these patients. Percutaneous transluminal angioplasty is relatively ineffectual for the treatment of renal artery stenosis in patients with neurofibromatosis type 1, particularly when the stenosis is ostial; medical and surgical options offer the best long-term results. Angioplasty is reasonably effective for treating postsurgical stenoses in these patients, however.^19,20

Middle Aortic Syndrome

Middle aortic syndrome (midaortic dysplastic syndrome) is a progressive vascular disorder that involves the midthoracic through abdominal segments of the aorta, usually accompanied by narrowing of major visceral branches, including the renal arteries. Hypertension is usually present. Imaging studies demonstrate diffuse narrowing of the thoracoabdominal segment of the aorta and the major branch vessels (Figure 52-5). There is usually a smooth, tapered appearance of the aorta, with disproportionate narrowing of the infrarenal portion. Renal artery involvement typically occurs as long stenoses. If there is severe renal artery narrowing, collateral flow to the kidneys usually is from ureteral, adrenal, and gonadal arteries that fill from lower intercostal arteries. Because there is no active inflammation with middle aortic syndrome, there is no abnormal vessel wall enhancement on CT and MR. The great vessels of the thorax are not involved in patients with middle aortic syndrome. There is additional discussion of middle aortic syndrome in Chapter 12.^21,22