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Renal Imaging in Children with Persistent Hypertension
CHILDHOOD HYPERTENSION
0031-3955/93 $0.00
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RENAL IMAGING IN CHILDREN WITH PERSISTENT HYPERTENSION J.
Michael Zerin, MD, and Ramiro
J.
Hernandez, MD
Because persistent hypertension in children is frequently secondary to an identifiable underlying disorder (often renal or renovascular), any child with well-documented persistent hypertension (i.e., blood pressure measurements over the 90th percentile for age obtained on three or more separate occasions over a 6- to 12-month period) merits careful medical evaluation. 15,28,39,43 The role that imaging plays in the evaluation of the hypertensive child depends largely on the results of thorough historical, physical, and laboratory examinations. 28, 35, 41, 43 There is no single imaging approach applicable to all children. How aggressively one searches for an underlying renal parenchymal or renovascular disorder must instead be individualized in each child. Several factors can be used to guide the aggressiveness of the approach to imaging in these children, however. 28, 41-43 The severity of the elevation of the child's blood pressure is an important consideration. A more aggressive approach to imaging is appropriate in children with more severely elevated blood pressure (especially when there is elevation of the diastolic pressure) because of the risk of the child becoming symptomatic or suffering secondary endorgan complications (e.g., cardiovascular, renal, and neurologic). The presence of symptoms or signs of hypertensive crisis or secondary complications indicates the need for emergent investigation. The indications for medical therapy and the effectiveness and risks (both immediate and long-term) of such therapy must be carefully considered. The reliability of patient compliance is also a consideration. From the Department of Radiology, Section of Pediatric Radiology, University of Michigan Hospitals, Ann Arbor, Michigan
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Lifelong medical therapy for hypertension carries the potential for complications that must be balanced against the possible hazards, discomfort, and expense of the proposed imaging procedures. An aggressive approach to imaging can be quite expensive and also carries some risk of morbidity. For example, although serious contrast reactions and other complications are uncommon during selective renal arteriography, they do occur. As a result, invasive imaging. procedures cannot be routinely justified, especially in children with borderline or mild asymptomatic hypertension not requiring medical therapy in whom the probability of discovering a curable disorder is low. Assessment of the pretest probability of discovering a treatable cause for that child's hypertension is crucial. As a rule of thumb, the younger the child and the more severe the elevation of the blood pressure, the greater the probability that imaging studies will reveal an underlying abnormality. 7, 28, 35, 41, 43 The imaging evaluation can be tailored considerably in children in whom findings on physical examination (e.g., discrepant blood pressures in the upper and lower extremities in coarctation of the aorta), family history (e.g., polycystic kidney disease), or laboratory examination (e.g., elevated urinary catecholamine excretion in pheochromocytoma) are strongly suggestive of a specific cause for their hypertension or the child is known to have a disorder that can be associated with hypertension (e.g., renal artery stenosis in a child with neurofibromatosis). With this in mind, an approach to renal imaging is presented in which children with hypertension are divided into three groups: (1) healthy children with borderline or mild asymptomatic hypertension in whom the suspicion of underlying renal parenchymal or renovascular disease is low; (2) children in whom a renal parenchymal disorder (e.g., chronic pyelonephritis) is suspected based on clinical evaluation and screening imaging studies; and (3) imaging children in whom a renovascular disorder (e.g., renal artery stenosis) is suspected based on clinical evaluation and screening imaging studies.
CHILDREN WITH MILD, ASYMPTOMATIC HYPERTENSION
In many children with borderline or mild hypertension, the abnormal blood pressure measurements are detected during routine physical examinations, and there are no other related abnormal findings. 28, 31, 39, 43 In fact, this group includes a large number of children. 31 Because hypertension in children is often secondary to renal parenchymal disease (usually chronic atrophic pyelonephritis or glomerulonephritis),17, 28, 35, 39, 42, 43 noninvasive imaging of the upper urinary tract is frequently requested. The yield of positive examinations is low, however, especially if there is a family history of essential hypertension, if the child is overweight, or if the child is an adolescent. 18, 25, 31, 43, 53, 54 As
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a result, there is considerable controversy regarding the cost effectiveness of routinely performing screening imaging studies of the upper urinary tract in children with borderline or mild hypertension. 28 , 31, 39, 42, 43,54 Certainly, in asymptomatic children who do undergo screening imaging studies, further imaging is generally not indicated unless an abnormality is detected. Traditionally, the intravenous urogram (IVU) has been the examination of choice. 6, 11, 17, 28, 39, 41-43, 51 Cortical scarring (Fig. 1) and hydronephrosis are detectable at IVU, and the renal sizes can be measured and compared with norms for age or body size (i.e., height and weight).8, 24, 32 Renal masses, whether cystic or solid, are usually detectable if they are large enough or located so that they deform the collecting system or alter the cortical contours of the kidney.9 Renal function also can be assessed in a qualitative fashion. Functional changes attributable to significant renal artery stenosis are uncommon, however. 7, 22, 26, 33, 42 More recently, many institutions, including University of Michigan Hospitals, have begun using renal ultrasound (US) to replace IVU in screening the upper urinary tract in children with mild hypertension. US is comparable to IVU in the assessment of renal size and hydronephrosis. 12, 21, 24, 34, 45 Because of its greater anatomic resolution, US is more reliable than IVU in the detection and evaluation of cystic and solid renal mass lesions,9, 23, 49 although it is probably somewhat less sensitive than IVU for the detection of small, focal cortical scars (Fig. 2).12,34 One major advantage of US in comparison with IVU is that US
Figure 1. This 10-year-old girl with reflux nephropathy 'p~esented with sever~ sympto~atic hypertension (blood pressure 190/120). Serum creatinine was normal. Unne contained trace protein and 5 to 7 red blood cells with no casts. She had no documented history of urinary tract infection. Intravenous pyelogram (20 minutes after injection) showed an atrophic right kidney (RK) with severe parenchymal scarring (arrowheads), consistent with reflux nephropathy. The left kidney (LK) appeared normal. Right grade 2 vesicoureteral reflux was later demonstrated at cystography.
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Figure 2. This 10-year-old girl with reflux nephropathy presented with severe hypertension and a history of recurrent urinary tract infection. Urinalysis was normal. Renal sonography (coronal view) revealed a large, focal scar (arrowhead) in the lateral aspect of the upper pole of the left kidney (long axis marked by cross-hairs). The left kidney otherwise appeared normal. Severe left vesicoureteral reflux was demonstrated at cystography. F = echogenic renal sinus fat, R = echo lucent renal parenchyma.
involves no ionizing radiation and does not require administration of intravenous contrast. Overall, the two examinations are reported to be equally sensitive in screening for renal parenchymal disease. 12, 34 CHILDREN BELIEVED TO HAVE RENAL PARENCHYMAL DISEASE
The largest group of children with secondary hypertension have underlying renal parenchymal disease (Table 1).17, 28, 35, 39, 42, 43 On occasion, the child has a known disorder that can be associated with renal disease (e.g., chronic glomerulonephritis in systemic lupus) or has been previously diagnosed to have chronic renal disease (e.g., renal dysplasia secondary to severe posterior urethral valves). Family history can be suggestive in other children (e.g., polycystic kidney disease). Occasionally, however, screening laboratory and imaging studies reveal previously unsuspected renal abnormalities. Reflux nephropathy (i.e., chronic atrophic pyelonephritis) (Figs. 1 and 2) and chronic glomerulonephritis are the most frequent causes of hypertension secondary to renal parenchymal disease in childhood. 17, 28, 35, 39, 42, 43 Renal dysplasia, congenital obstructive uropathy, and renal cystic disorders are less common. Global or segmental renal "hypoplasia" (Ask-Upmark kidney) also has been described as a cause of hypertension; however, in most cases this probably represents renal
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Table 1. RENAL PARENCHYMAL DISORDERS ASSOCIATED WITH PERSISTENT HYPERTENSION IN CHILDHOOD
Common* Reflux nephropathy (chronic atrophic pyelonephritis) Chronic glomerulonephritis Renal dysplasia Renal transplant complications
Uncommon* Obstructive uropathy (congenital or acquired) Renal cystic disease Polycystic kidney disease (recessive or dominant) Medullary cystic disease Ouvenile nephronophthisis) Multicystic dysplastic kidney Renal compression (Page kidney) Renal "hypoplasia" (segmental or global)t Renal tumor Renal vein thrombosis Other chronic medical renal disease 'Common or uncommon as causes of hypertension during childhood. tin most cases, renal "hypoplasia" probably represents severe, early reflux nephropathy.2.3o
parenchymal destruction secondary to severe reflux nephropathy early in life rather than being a truly congenital or developmental disorder of nephrogenesis. 2 , 30 Hypertension also can develop secondary to prior renal trauma with renal compression (i.e., Page kidney)38,48 or renal ischemia and infarction. Tumors of the kidneys (i.e., Wilms tumor) are rarely associated with hypertension,l1 although these are usually detected on physical examination as a palpable mass rather than being discovered incidentally during the evaluation of a child with the isolated finding of hypertension. The approach to the imaging evaluation in each child depends on the specific abnormality that is suspected. Multiple modalities including US, IVU, voiding cystourethrography, and functional renal imaging with radionuclide diuretic renography (DTPA) and renal cortical scintigraphy (DMSA) are frequently necessary for complete anatomic and functional delineation of many abnormalities. Consultation and close cooperation with both the pediatric radiologist and pediatric nuclear medicine specialist are important in order to optimize the evaluation in each child. Imaging-assisted percutaneous renal biopsy can be useful in selected children with glomerulonephritis or nephrotic syndrome. Whereas the fluoroscopically monitored procedure requires opacification of the intrarenal collecting system with intravenously administered contrast medium, sonographically monitored biopsy avoids the risks of intravenous contrast (which can be heightened in the context of diminished renal function) and also does not involve exposure to radiation. Computed tomography is rarely indicated, except in selected cases in which a tumor of the kidneyll or adrenal glands is suspected. CT also can be useful in children with persistent posttraumatic perinephric
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collections38,48 (i.e., Page kidney) and in exceptional cases of polycystic or multicystic renal disorders in which coexistent tumor is suspected. 3 Nonobstructive hydronephrosis and focal cortical scarring (chronic atrophic pyelonephritis) are the imaging hallmarks of reflux nephropathy (Figs. 1 and 2).9 With moderate to severe reflux early in life there also can be a global injury to renal growth, with diffuse parenchymal thinning resulting in the appearance of a small or "hypoplastic" kidney.2, 30 There mayor may not be a documented history of recurrent urinary infection, and vesicoureteral reflux is not always seen in older children because scarring represents permanent destruction of renal parenchyma that does not improve after reflux resolves. 44 Although spatial resolution is poorer with renal cortical scintigraphy than with either IVU or US, it is the most sensitive and precise test for quantifying segmental functional and anatomic defects in the renal parenchyma in chronic pyelonephritis and renal infarction. In some patients with severe reflux nephropathy, the kidneys can be uniformly small and echogenic at US with reduced function at IVU and scintigraphy and cannot be distinguished from the appearance seen in other forms of severe, end-stage renal disease (Fig. 3) such as chronic glomerulonephritis, interstitial nephritis, renal vein thrombosis, or renal dysplasia. 9 , 49 Systemic manifestations of vasculitis or other immune-mediated disease would point toward the diagnosis of glomerulonephritis, al-
Figure 3. This 9-year-old girl with end-stage renal disease (probably due to reflux
nephropathy) presented with severe hypertension and renal failure. Both kidneys were small and diffusely echogenic. The right kidney (K and arrowheads) is diffusely more echogenic (i.e., white) than the liver (L). Corticomedullary differentiation is absent, and the renal pyramids and central renal sinus fat cannot be distinguished from the renal cortex (compare with Fig. 2). Although bilateral grade 2 vesicoureteral reflux was demonstrated at cystography, both the sonographic appearance and subsequent renal biopsy were nonspecific and consistent with severe, end-stage renal disease.
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though biopsy may be required for histologic diagnosis. Renal dysplasia48, 50 is usually related to congenital obstrUctive uropathy. A combination of US (or IVU), cystourethrography, and renal functional imaging is usually required for complete anatomic and functional diagnosis. In children with renal atrophy secondary to chronic ischemia (e.g., renal artery stenosis) or renal vein thrombosis, the kidneys are reduced in size, although they are usually smooth in contour and can appear architecturally normal or abnormally echogenic at US. 50 Function can be either normal or reduced. Thromboembolic occlusion of the main renal artery or, more commonly, multiple smaller intrarenal branches with multisegmental renal parenchymal ischemia and infarction can occur in children with renal artery stenosis or congenital heart disease and in neonates with umbilical artery catheters. With acute thromboembolic occlusion of the main renal artery, the kidney becomes abnormally echogenic at US, although it usually remains normal in size. Later on, the kidney decreases in size as it atrophies. 50 With peripheral obstruction (e.g., in the newborn with an umbilical artery catheter), the sonographic and functional changes are dependent on the severity and extent of the resulting parenchymal infarction. When US and urography are normal (often the case acutely), the defects in perfusion can be demonstrated with greatest sensitivity at renal cortical scintigraphy (using DMSA) when clinically indicated. In the cystic renal disorders20, 23, 49 the kidneys are usually enlarged. Although large macrocysts are usually not seen in autosomal recessive ("infantile-type") polycystic kidney disease, smaller cysts can sometimes be resolved with high-resolution US equipment. 20, 23 The kidneys appear uniformly (and often severely) enlarged and echogenic at US because of reflection of the sound waves at the interfaces between innumerable microcysts, and the normal corticomedullary differentiation is lost. Autosomal dominant ("adult-type") polycystic kidney disease also can present in childhood,20, 23 although hypertension is rarely encountered in these patients before adulthood. In infants,' the appearance at US may simulate that of autosomal recessive disease. Increasing numbers of cortical macrocysts appear over time and result in progressive renal enlargement. Uremic medullary cystic disease (juvenile nephronophthisis) is a rare inherited disorder that can also present in childhood with hypertension. 20, 23, 50 Early in the course of the disease the kidneys can be normal in size, although they are generally echogenic with loss of the normal corticomedullary differentiation. Variable numbers of cysts are also usually visible in the medulla and at the corticomedullary junction. As renal fibrosis advances (often with marked acceleration of the hypertension) the kidneys gradually decrease in size and become increasingly echogenic as in other forms of end-stage medical renal disease. 23,49 Hypertension has been reported in children with cystic renal dysplasia (including multicystic kidneys), although this association is probably quite rare. 29 Multicystic dysplastic kidneys are usually large early in life because of the volume of fluid within the cysts. 2, 23, 50 As the cyst fluid is absorbed over time, the
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kidney becomes undetectable at imaging, or only a small, echogenic remnant of dysplastic renal tissue remains visible. 49 CHILDREN BELIEVED TO HAVE RENOVASCULAR DISEASE
Whether or not to pursue the diagnosis of renal artery stenosis remains one of the most vexing problems in the evaluation of the child with hypertension. Selective renal arteriography is the accepted standard for the radiographic evaluation of children with renovascular hypertension7, 16, 26, 27, 33, 51; however, it is invasive, involves radiation, and requires that intravascular contrast material be administered. Although many children with renovascular disease do not present with severe and uncontrollable hypertension,28, 33, 43 most children with mild, asymptomatic hypertension and possibly even some children with medically controllable hypertension need not be submitted to the risks of renal arteriography. The decision to pursue a "complete" evaluation for renovascular disease (i.e., including selective renal arteriography) can usually be individualized based on (1) the severity of the hypertension and presence of symptoms; (2) the indications for and response to medical therapy; (3) the clinical presentation (e.g., a bruit over the flank or history of neurofibromatosis); (4) the results of noninvasive studies (if any are performed); and (5) the likelihood of a satisfactory patient response to therapy and compliance with follow-up.29, 30, 43 Certainly, young children and all children with unexplained hypertension that is severe or poorly controlled should be completely evaluated. 28, 33, 39, 41-43
NONINVASIVE IMAGING STUDIES
A number of noninvasive imaging studies, including IVU,ll, 17, 28, 39, 41-43,51 Doppler renal US,5, 10, 19. 26, SO, 52 intravenous digital subtraction angiography (IVDSA),13, 14, 22, 26 and renal scintigraphy, 26, 40 have been used to screen children with hypertension for underlying renovascular disease. All of these modalities yield excessive numbers of false-negative results, however. This is especially true if the stenosis is mild, symmetrical, or peripheral. As a result, noninvasive imaging frequently does not alter the indications for angiography in children with suspected renovascular hypertension. At IVU, unilateral delay in excretion of contrast by a kidney that is smaller than its contralateral mate is the classical finding in moderate to severe renal artery stenosis. 6, 9, 28, 33 Diminished concentration of the contrast material by the affected kidney also can result in decreased opacity of the collecting system on that side. Notching of the renal pelvis and proximal ureter by distended collateral vessels is an uncommon but important observation. Unfortunately, 35% to 40% of children
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with hypertension with significant renal parenchymal or renovascular disease have no abnormality detected at IVU,7, 28, 33, 41, 42 Furthermore, the "hypertensive urogram," in which sequential tomographic images of the kidneys are rapidly obtained early in the study, offers no diagnostic advantages over the conventional IVU. 9, 14, 26, 28 Intravenous digital subtraction angiography has been used for screening hypertensive patients for renal artery stenosis. 13, 14,22,26,27 The main advantage of IVDSA over conventional angiography is that IVDSA can be performed after peripheral, intravenous injection of contrast material and does not require arterial catheterization. The volume of contrast material that is required is significantly greater than with conventional renal arteriography, however, which may pose a problem for patients with diminished renal function or cardiac disease. Furthermore, despite early enthusiasm for this technique, the sensitivity of IVDSA is significantly limited by its relatively poor spatial resolution, especially in evaluating smaller vessels. Although atherosclerotic lesions of the main renal arteries are detected in adults with reasonable sensitivity, 13, 14 IVDSA is significantly less sensitive in detecting stenoses secondary to fibromuscular dysplasia,27 the most common cause of renal artery stenosis in childhood. 33 In addition, stenotic lesions of the intrarenal, segmental, or subsegmental arteries (common in children with fibromuscular dysplasia)16 and accessory renal arteries (approximately 15%-20% of stenoses) are rarely detected with IVDSA.26, 27 As a result, renal IVDSA is no longer used in our department for screening patients with hypertension. In many institutions, renal US has replaced IVU in screening because it provides anatomic information equivalent or superior to IVU.12, 34 Standard US imaging provides no direct information regarding renal function or the patency of the renal vessels, however. The use of pulsed-Doppler US technology for screening patients with suspected renovascular hypertension is based on the theory that the increase in velocity and turbulence of blood flow within stenotic vessels might be detectable. Attempts to use Doppler US to investigate renovascular disease in children and adults with hypertension have met with variable success, however.6, 10, 19,26,52 Some investigators have found increased velocity of flow within the main renal artery and dampening of the pulse amplitude in the intrarenal arteries with spectral broadening to be sensitive Doppler findings of angiographically significant renal artery stenosis. Others have not been able to reproduce these results, however, instead finding the examination to be extremely time-consuming and of no predictive value in screening patients with hypertension for renovascular disease. The most consistent success with this technique has been in patients with renal allografts. 19, 52 As a result, Doppler US does not currently have a routine role in the screening evaluation of children with suspected renovascular hypertension, although it is possible that this may change with future research.
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SELECTIVE RENAL ARTERIOGRAPHY
Selective renal arteriography (with aortography) is highly sensitive and specific and remains the standard for the diagnosis of hemodynamically significant renal artery stenosis (Figs. 4 and 5),7,16,26,27,33,51 When properly performed with subtracted magnification views in multiple projections, the location, severity, and extent of significant stenoses of the main renal arteries can be detected, as can lesions involving the intrarenal, segmental, and subsegmental arteries as well as any accessory renal arteries (present in approximately 15%-20% of the population). The cause of the stenosis can also usually be determined based upon the angiographic appearance. Pharmacologic maneuvers (e.g., instillation of epinephrine into the renal artery to increase detection of capsular collateral vessels) can be performed to determine the hemodynamic significance of a stenotic lesion that is discovered during selective catheterization of the affected renal artery. Renal vein renin sampling is also used to predict the response to revascularization,
Figure 4. This 4.5-year-old girl with renal artery stenosis presented with severe hypertension and headaches. Results of renal sonography were normal. Renal arteriography was requested. During selective injection of the left renal artery, a severe, focal stenosis at the origin of an upper pole lobar artery was demonstrated (open arrow). There is also more subtle, irregular narrowing of the main renal artery (arrowheads), consistent with fibromuscular dysplasia. A notchlike defect in the upper pole of the kidney represents a parenchymal infarct (arrow).
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Figure 5. This 12·year·old girl with renal artery stenosis and neurofibromatosis developed severe hypertension (diastolic pressures from 130 to 145 mm Hg). Severe stenosis of the aortic ostium of the right renal artery (arrows) with diffuse narrowing of the remainder of the main right renal artery (arrowheads) was demonstrated during renal arteriography. A = aorta.
although the reliability of this method has not been entirely satisfactory. 1, 26, 37, 46, 51 Fibromuscular dysplasia is the most frequent cause of renal artery stenosis in children, accounting for more than 90% of cases (Table 2),7, 16, 28 At angiography, fibromuscular dysplasia typically produces an irregular, beaded appearance with narrowing of the mid and distal portions of the main renal arteries in the renal hilum. The intrarenal segmental and subsegmental arteries also can be affected (Fig, 4). With increasing numbers of successful pediatric renal transplants, renal transplant artery stenosis also is being encountered. Renal artery Table 2. RENOVASCULAR DISORDERS ASSOCIATED WITH HYPERTENSION IN CHILDHOOD
Renal artery stenosis Fibromuscular dysplasia Renal transplant artery stenosis Posttraumatic Vasculitis Neurofibromatosis Williams syndrome Abdominal aortic developmental abnormalities Thromboembolic disease Umbilical artery catheterization (neonates) Congenital heart disease Renal vein thrombosis
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stenosis in transplants occurs almost exclusively in patients with cadaver transplants and is usually related to chronic allograft rejection. 3 Both the main renal artery and the intrarenal segmental vessels can be involved. Renal artery stenosis also can be seen in neurofibromatosis (Fig. 5), Williams syndrome and vasculitis and can be associated with thoracic and abdominal aortic developmental anomalies with coarctation. Rarely, renovascular hypertension results from extrinsic compression of the renal pedicle by extra-renal tumor or adenopathy in the renal hilum or by intrinsic tumors of the kidney (e.g., Wilms tumor). Mass lesions can usually be detected at US, although computed tomography generally provides superior delineation of tumor extent and radiologic stage. Atherosclerotic disease, by far the most common cause of renal artery stenosis in adults, is rarely encountered in children. PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY
Percutaneous transluminal angioplasty (PTA) is being used with increasing frequency in the nonsurgical management of intrinsic renal artery stenosis in children3, 36, 51 and has dramatically reduced the need for renal autotransplantation. A balloon catheter is placed percutaneously into one of the femoral arteries and is advanced until it straddles the stenotic segment of the vessel. The balloon is then inflated, resulting in mechanical dilatation of the stenosis. The rate of success with this procedure varies depending on the location and length of the stenotic segment and is most often successful in patients with fibromuscular dysplasia who have short lesions in the mid and distal main renal arteries and in patients with renal transplant artery stenosis. Dilatation is less often successful in patients with lesions involving the aortic orifice of the renal artery (most patients with neurofibromatosis and those with abdominal aortic developmental anomalies). PTA is also frequently not technically feasible in patients with stenoses of smaller intrarenal segmental arteries. PTA is of no value in patients with peripheral thromboembolic disease with segmental renal ischemia and in those with extrinsic compression of the renal pedicle. Normalization of blood pressure frequently occurs after technically successful PTA, although this is not always the case. Successful treatment of restenosis with repeat PTA has been reported in children.
References 1. Alroomi LG, Murphy AV, Nelson CS, et al: Renal vein renin measurement and
arteriography in the investigation and management of severe childhood hypertension. Clin Chim Acta 150:103, 1985 2. Arant BS Jr, Sotelo-Avila C, Bernstein J: Segmental "hypoplasia" of the kidney (AskUpmark). J Pediatr 95:931, 1979 3. Barth MO, Gagnadoux MF, Mareschal JL, et al: Angioplasty of renal transplant artery stenosis in children. Pediatr Radiol 19:383, 1989
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4. Berger PE, Munschauer RW, Kuhn JP: Computed tomography and ultrasound of renal and perirenal diseases in infants and children. Pediatr Radiol 9:91, 1980 5. Berland LL, Koslin DB, Routh WD, et al: Renal artery stenosis: Prospective evaluation of diagnosis with color duplex US compared with angiography: Work in progress. Radiology 174:421, 1990 6. Bookstein JJ, Abrams HL, Buenger RE, et al: Radiologic aspects of renovascular hypertension. Part 2. The role of urography in unilateral renovascular disease. JAMA 1220:1225, 1972 7. Clayman AS, Bookstein JJ: The role of renal angiography in pediatric hypertension. Radiology lO8:lO7, 1973 8. Currarino G, Williams B, Dana K: Kidney length correlated with age: Normal values in children. Radiology 150:703, 1984 9. Currarino G: The genitourinary tract. In Silverman FN, Frederic N, Kuhn JP, et al (eds): Essentials of Caffey's Pediatric X-ray Diagnosis. Chicago, Year Book Medical Publishers, 1990, p. 653 10. Desberg AL, Paushter DM, Lammert GK, et al: Renal artery stenosis: Evaluation with color Doppler flow imaging. Radiology 177:749, 1990 11. Diament MI, Stanley P, Boechat MI, et al: Pediatric hypertension: An approach to imaging. Pediatr Radiol 16:461, 1986 12. Diament MI, Takasugi J, Kangarloo H: Hydronephrosis in childhood: Reliability of ultrasound screening. Pediatr Radiol 14:31, 1984 l3. Dunnick NR, Svetkey LP, Cohan RH, et al: Intravenous digital subtraction angiography: Use in screening for renovascular hypertension. Radiology 171:219, 1989 14. Dunnick NR, Ford KK, Johnson A, et al: Digital intravenous subtraction angiography for investigating renovascular hypertension: Comparison with hypertensive urography. South Med J 78:690, 1985 15. Fixler DE, Kautz JA, Dana K: Systolic blood pressure differences among pediatric epidemiological studies. Hypertension 2(suppl 1):3, 1980 16. Fry WI, Ernst CB, Stanley JC, et al: Renovascular hypertension in the pediatric patient. Arch Surg lO7:692, 1973 17. Gill DG, Mendes da Costa B, Cameron JS, et al: Analysis of 100 children with severe and persistent hypertension. Arch Dis Child 51:951, 1976 18. Gillum RF, Prineas RJ, Sopko G, et al: Elevated blood pressure in school children: Prevalence, persistence, and hemodynamics: The Minneapolis Children's Blood Pressure study. Am Heart J lO5:316, 1983 19. Grenier N, Douws C, Morel D, et al: Detection of vascular complications in renal allografts with color Doppler flow imaging. Radiology 178:217, 1991 20. Grossman H, Rosenberg ER, Bowie JD, et al: Sonographic diagnosis of renal cystic diseases. AJR Am J Roentgenol 140:81, 1983 21. Han B, Babcock DS: Sonographic measurements and appearance of normal kidneys in children. AJR Am J Roentgenol 145:511, 1985 22. Havey RI, Krumlovsky F, del Greco F, et al: Screening for renovascular hypertension: Is renal digital-subtraction angiography the preferred non-invasive test? JAMA 254:388, 1985 23. Hayden CK Jr, Swischuk LE, Smith TH, et al: Renal cystic disease in childhood. Radiographics 6:97, 1986 24. Hederstrom E, Forsberg L: Accuracy of repeated kidney size estimation by ultrasonography and urography in children. Acta Radiol (Stockh) 26:603, 1985 25. Heyden S, Bartel AG, Hames CG, et al: Elevated blood pressure levels in adolescents, Evans County, Georgia. JAMA 209:1683, 1969 26. Hillman BJ: Imaging advances in the diagnosis of renovascular hypertension. AJR Am J Roentgenol 153:5, 1989 27. Illescas FF, Braun SD, Cohan RH, et al: Fibromuscular dysplasia of renal arteries: Comparison of intravenous digital subtraction angiography. Canadian Association of Radiologists Journal 39:167, 1988 28. Ingelfinger JR: Pediatric Hypertension. Philadelphia, WB Saunders, 1982 29. Javadpour N, Chelouhy E, Moncada L: Hypertension in a child caused by a multicystic kidney. J Urol lO4:918, 1970 30. Johnston JH, Mix LW: The Ask-Upmark kidney: A form of ascending pyelonephritis? Br J Urol 48:393, 1976
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31. Julius S: Clinical and physiological significance of borderline hypertension at youth. Pediatr Clin North Am 25:35, 1978 32. Klare B, Geiselhardt B, Wesch H, et al: Radiological kidney size in childhood. Pediatr Radiol 9:153, 1980 33. Korobkin M, Perloff DL, Palubinskas AJ: Renal arteriography in the evaluation of unexplained hypertension in children and adolescents. J Pediatr 88:388, 1976 34. Leonidas JC, McCauley RGK, Klauber Gc, et al: Sonography as a substitute for excretory urography in children with urinary tract infection. AJR Am J Roentgenol 144:815, 1985 35. Londe S: Causes of hypertension in the young. Pediatr Clin North Am 25:55, 1978 36. Mali WPTM, Puiljaert CBA, Kouwenberg HJ, et al: Percutaneous transluminal renal angioplasty in children and adolescents. Radiology 165:391, 1987 37. Marks LS, Maxwell MH: Renal vein renin: Value and limitations in the prediction of operative results. Urol Clin North Am 2:311, 1975 38. Marshall WH Jr, Castellino RA: Hypertension produced by constricting capsular renal lesions. Radiology 101:561, 1971 39. Pruitt AW: Systemic Hypertension. In Behrman RE, Vaughan VC III, Nelson WE, et al (eds): Nelson Textbook of Pediatrics, ed 13. Philadelphia, WB Saunders, 1987, p 1027 40. Ramirez G, Savader S, Farber S, et al: Low-dose captopril scintigraphy in the evaluation of renovascular hypertension. Clin Nucl Med 15:480, 1990 41. Rance CP, Arbus GS, Balfe JW, et al: Persistent systemic hypertension in infants and children. Pediatr Clin North Am 21:801, 1974 42. Robson AM: Special diagnostic studies for the detection of renal and renovascular forms of hypertension. Pediatr Clin North Am 25:83, 1978 43. Rocchini AP: Childhood hypertension: Etiology, diagnosis, and treatment. Pediatr Clin North Am 31:1259, 1984 44. Rolleston GL, Shannon SJ, Utley WLF: Relationship of infantile vesicoureteral reflux to renal damage. BMJ 1:460, 1970 45. Rosenbaum DM, Korngold E, Teele RL: Sonographic assessment of renal length in normal children. AJR Am J RoentgenoI142:467, 1984 46. Roubidoux MA, Dunnick NR, Klotman PE, et al: Renal vein renins: Inability to predict response to revascularization in patients with hypertension. Radiology 178:819, 1991 47. Sanders RC, Nussbaum AR, Solez K: Renal dysplasia: Sonographic findings. Radiology 167:623, 1988 48. Scott PL, Yune HY, Feinberger MH: Page kidney: An unusual cause of hypertension. Radiology 119:547, 1976 49. Siegel MJ: Urinary tract. In Siegel MJ (ed): Pediatric Sonography. New York, Raven Press, 1991, p 257 50. Snider JF, Hunter DW, Moradian GP, et al: Transplant renal artery stenosis: Evaluation with duplex sonography. Radiology 172:1027, 1989 51. Stanley P, Hieshima G, Mehringer M: Percutaneous transluminal angioplasty for pediatric renovascular hypertension. Radiology 153:101, 1984 52. Stringer DA, deBruyn R, Dillon MJ, et al: Comparison of aortography, renal vein renin sampling, radionuclide scans, ultrasound, and the IVU in the investigation of childhood renovascular hypertension. Br J Radiol 57:111, 1984 53. Stringer DA, O'Halpin D, Liu P, et al: Duplex Dopper sonography for renal artery stenosis in the post-transplant pediatric patient. Pediatr Radiol 19:187, 1989 54. Voors AW, Webber LS, Berenson GS: Epidemiology of essential hypertension in youth: Implications for clinical practice. Pediatr Clin North Am 25:15, 1978 55. Voors AW, Webber LS, Frerichs RR, et al: Body height and body mass as determinants of basal blood pressure in children: The Bogalusa heart study. Am J Epidemiol 106:101, 1977
Address reprint requests to J. Michael Zerin, MD Section of Pediatric Radiology C.S. Mott Children's Hospital University of Michigan Hospitals Ann Arbor, MI48109-0252
0031-3955/93 $0.00
+ .20
RENAL IMAGING IN CHILDREN WITH PERSISTENT HYPERTENSION J.
Michael Zerin, MD, and Ramiro
J.
Hernandez, MD
Because persistent hypertension in children is frequently secondary to an identifiable underlying disorder (often renal or renovascular), any child with well-documented persistent hypertension (i.e., blood pressure measurements over the 90th percentile for age obtained on three or more separate occasions over a 6- to 12-month period) merits careful medical evaluation. 15,28,39,43 The role that imaging plays in the evaluation of the hypertensive child depends largely on the results of thorough historical, physical, and laboratory examinations. 28, 35, 41, 43 There is no single imaging approach applicable to all children. How aggressively one searches for an underlying renal parenchymal or renovascular disorder must instead be individualized in each child. Several factors can be used to guide the aggressiveness of the approach to imaging in these children, however. 28, 41-43 The severity of the elevation of the child's blood pressure is an important consideration. A more aggressive approach to imaging is appropriate in children with more severely elevated blood pressure (especially when there is elevation of the diastolic pressure) because of the risk of the child becoming symptomatic or suffering secondary endorgan complications (e.g., cardiovascular, renal, and neurologic). The presence of symptoms or signs of hypertensive crisis or secondary complications indicates the need for emergent investigation. The indications for medical therapy and the effectiveness and risks (both immediate and long-term) of such therapy must be carefully considered. The reliability of patient compliance is also a consideration. From the Department of Radiology, Section of Pediatric Radiology, University of Michigan Hospitals, Ann Arbor, Michigan
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Lifelong medical therapy for hypertension carries the potential for complications that must be balanced against the possible hazards, discomfort, and expense of the proposed imaging procedures. An aggressive approach to imaging can be quite expensive and also carries some risk of morbidity. For example, although serious contrast reactions and other complications are uncommon during selective renal arteriography, they do occur. As a result, invasive imaging. procedures cannot be routinely justified, especially in children with borderline or mild asymptomatic hypertension not requiring medical therapy in whom the probability of discovering a curable disorder is low. Assessment of the pretest probability of discovering a treatable cause for that child's hypertension is crucial. As a rule of thumb, the younger the child and the more severe the elevation of the blood pressure, the greater the probability that imaging studies will reveal an underlying abnormality. 7, 28, 35, 41, 43 The imaging evaluation can be tailored considerably in children in whom findings on physical examination (e.g., discrepant blood pressures in the upper and lower extremities in coarctation of the aorta), family history (e.g., polycystic kidney disease), or laboratory examination (e.g., elevated urinary catecholamine excretion in pheochromocytoma) are strongly suggestive of a specific cause for their hypertension or the child is known to have a disorder that can be associated with hypertension (e.g., renal artery stenosis in a child with neurofibromatosis). With this in mind, an approach to renal imaging is presented in which children with hypertension are divided into three groups: (1) healthy children with borderline or mild asymptomatic hypertension in whom the suspicion of underlying renal parenchymal or renovascular disease is low; (2) children in whom a renal parenchymal disorder (e.g., chronic pyelonephritis) is suspected based on clinical evaluation and screening imaging studies; and (3) imaging children in whom a renovascular disorder (e.g., renal artery stenosis) is suspected based on clinical evaluation and screening imaging studies.
CHILDREN WITH MILD, ASYMPTOMATIC HYPERTENSION
In many children with borderline or mild hypertension, the abnormal blood pressure measurements are detected during routine physical examinations, and there are no other related abnormal findings. 28, 31, 39, 43 In fact, this group includes a large number of children. 31 Because hypertension in children is often secondary to renal parenchymal disease (usually chronic atrophic pyelonephritis or glomerulonephritis),17, 28, 35, 39, 42, 43 noninvasive imaging of the upper urinary tract is frequently requested. The yield of positive examinations is low, however, especially if there is a family history of essential hypertension, if the child is overweight, or if the child is an adolescent. 18, 25, 31, 43, 53, 54 As
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a result, there is considerable controversy regarding the cost effectiveness of routinely performing screening imaging studies of the upper urinary tract in children with borderline or mild hypertension. 28 , 31, 39, 42, 43,54 Certainly, in asymptomatic children who do undergo screening imaging studies, further imaging is generally not indicated unless an abnormality is detected. Traditionally, the intravenous urogram (IVU) has been the examination of choice. 6, 11, 17, 28, 39, 41-43, 51 Cortical scarring (Fig. 1) and hydronephrosis are detectable at IVU, and the renal sizes can be measured and compared with norms for age or body size (i.e., height and weight).8, 24, 32 Renal masses, whether cystic or solid, are usually detectable if they are large enough or located so that they deform the collecting system or alter the cortical contours of the kidney.9 Renal function also can be assessed in a qualitative fashion. Functional changes attributable to significant renal artery stenosis are uncommon, however. 7, 22, 26, 33, 42 More recently, many institutions, including University of Michigan Hospitals, have begun using renal ultrasound (US) to replace IVU in screening the upper urinary tract in children with mild hypertension. US is comparable to IVU in the assessment of renal size and hydronephrosis. 12, 21, 24, 34, 45 Because of its greater anatomic resolution, US is more reliable than IVU in the detection and evaluation of cystic and solid renal mass lesions,9, 23, 49 although it is probably somewhat less sensitive than IVU for the detection of small, focal cortical scars (Fig. 2).12,34 One major advantage of US in comparison with IVU is that US
Figure 1. This 10-year-old girl with reflux nephropathy 'p~esented with sever~ sympto~atic hypertension (blood pressure 190/120). Serum creatinine was normal. Unne contained trace protein and 5 to 7 red blood cells with no casts. She had no documented history of urinary tract infection. Intravenous pyelogram (20 minutes after injection) showed an atrophic right kidney (RK) with severe parenchymal scarring (arrowheads), consistent with reflux nephropathy. The left kidney (LK) appeared normal. Right grade 2 vesicoureteral reflux was later demonstrated at cystography.
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Figure 2. This 10-year-old girl with reflux nephropathy presented with severe hypertension and a history of recurrent urinary tract infection. Urinalysis was normal. Renal sonography (coronal view) revealed a large, focal scar (arrowhead) in the lateral aspect of the upper pole of the left kidney (long axis marked by cross-hairs). The left kidney otherwise appeared normal. Severe left vesicoureteral reflux was demonstrated at cystography. F = echogenic renal sinus fat, R = echo lucent renal parenchyma.
involves no ionizing radiation and does not require administration of intravenous contrast. Overall, the two examinations are reported to be equally sensitive in screening for renal parenchymal disease. 12, 34 CHILDREN BELIEVED TO HAVE RENAL PARENCHYMAL DISEASE
The largest group of children with secondary hypertension have underlying renal parenchymal disease (Table 1).17, 28, 35, 39, 42, 43 On occasion, the child has a known disorder that can be associated with renal disease (e.g., chronic glomerulonephritis in systemic lupus) or has been previously diagnosed to have chronic renal disease (e.g., renal dysplasia secondary to severe posterior urethral valves). Family history can be suggestive in other children (e.g., polycystic kidney disease). Occasionally, however, screening laboratory and imaging studies reveal previously unsuspected renal abnormalities. Reflux nephropathy (i.e., chronic atrophic pyelonephritis) (Figs. 1 and 2) and chronic glomerulonephritis are the most frequent causes of hypertension secondary to renal parenchymal disease in childhood. 17, 28, 35, 39, 42, 43 Renal dysplasia, congenital obstructive uropathy, and renal cystic disorders are less common. Global or segmental renal "hypoplasia" (Ask-Upmark kidney) also has been described as a cause of hypertension; however, in most cases this probably represents renal
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Table 1. RENAL PARENCHYMAL DISORDERS ASSOCIATED WITH PERSISTENT HYPERTENSION IN CHILDHOOD
Common* Reflux nephropathy (chronic atrophic pyelonephritis) Chronic glomerulonephritis Renal dysplasia Renal transplant complications
Uncommon* Obstructive uropathy (congenital or acquired) Renal cystic disease Polycystic kidney disease (recessive or dominant) Medullary cystic disease Ouvenile nephronophthisis) Multicystic dysplastic kidney Renal compression (Page kidney) Renal "hypoplasia" (segmental or global)t Renal tumor Renal vein thrombosis Other chronic medical renal disease 'Common or uncommon as causes of hypertension during childhood. tin most cases, renal "hypoplasia" probably represents severe, early reflux nephropathy.2.3o
parenchymal destruction secondary to severe reflux nephropathy early in life rather than being a truly congenital or developmental disorder of nephrogenesis. 2 , 30 Hypertension also can develop secondary to prior renal trauma with renal compression (i.e., Page kidney)38,48 or renal ischemia and infarction. Tumors of the kidneys (i.e., Wilms tumor) are rarely associated with hypertension,l1 although these are usually detected on physical examination as a palpable mass rather than being discovered incidentally during the evaluation of a child with the isolated finding of hypertension. The approach to the imaging evaluation in each child depends on the specific abnormality that is suspected. Multiple modalities including US, IVU, voiding cystourethrography, and functional renal imaging with radionuclide diuretic renography (DTPA) and renal cortical scintigraphy (DMSA) are frequently necessary for complete anatomic and functional delineation of many abnormalities. Consultation and close cooperation with both the pediatric radiologist and pediatric nuclear medicine specialist are important in order to optimize the evaluation in each child. Imaging-assisted percutaneous renal biopsy can be useful in selected children with glomerulonephritis or nephrotic syndrome. Whereas the fluoroscopically monitored procedure requires opacification of the intrarenal collecting system with intravenously administered contrast medium, sonographically monitored biopsy avoids the risks of intravenous contrast (which can be heightened in the context of diminished renal function) and also does not involve exposure to radiation. Computed tomography is rarely indicated, except in selected cases in which a tumor of the kidneyll or adrenal glands is suspected. CT also can be useful in children with persistent posttraumatic perinephric
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collections38,48 (i.e., Page kidney) and in exceptional cases of polycystic or multicystic renal disorders in which coexistent tumor is suspected. 3 Nonobstructive hydronephrosis and focal cortical scarring (chronic atrophic pyelonephritis) are the imaging hallmarks of reflux nephropathy (Figs. 1 and 2).9 With moderate to severe reflux early in life there also can be a global injury to renal growth, with diffuse parenchymal thinning resulting in the appearance of a small or "hypoplastic" kidney.2, 30 There mayor may not be a documented history of recurrent urinary infection, and vesicoureteral reflux is not always seen in older children because scarring represents permanent destruction of renal parenchyma that does not improve after reflux resolves. 44 Although spatial resolution is poorer with renal cortical scintigraphy than with either IVU or US, it is the most sensitive and precise test for quantifying segmental functional and anatomic defects in the renal parenchyma in chronic pyelonephritis and renal infarction. In some patients with severe reflux nephropathy, the kidneys can be uniformly small and echogenic at US with reduced function at IVU and scintigraphy and cannot be distinguished from the appearance seen in other forms of severe, end-stage renal disease (Fig. 3) such as chronic glomerulonephritis, interstitial nephritis, renal vein thrombosis, or renal dysplasia. 9 , 49 Systemic manifestations of vasculitis or other immune-mediated disease would point toward the diagnosis of glomerulonephritis, al-
Figure 3. This 9-year-old girl with end-stage renal disease (probably due to reflux
nephropathy) presented with severe hypertension and renal failure. Both kidneys were small and diffusely echogenic. The right kidney (K and arrowheads) is diffusely more echogenic (i.e., white) than the liver (L). Corticomedullary differentiation is absent, and the renal pyramids and central renal sinus fat cannot be distinguished from the renal cortex (compare with Fig. 2). Although bilateral grade 2 vesicoureteral reflux was demonstrated at cystography, both the sonographic appearance and subsequent renal biopsy were nonspecific and consistent with severe, end-stage renal disease.
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though biopsy may be required for histologic diagnosis. Renal dysplasia48, 50 is usually related to congenital obstrUctive uropathy. A combination of US (or IVU), cystourethrography, and renal functional imaging is usually required for complete anatomic and functional diagnosis. In children with renal atrophy secondary to chronic ischemia (e.g., renal artery stenosis) or renal vein thrombosis, the kidneys are reduced in size, although they are usually smooth in contour and can appear architecturally normal or abnormally echogenic at US. 50 Function can be either normal or reduced. Thromboembolic occlusion of the main renal artery or, more commonly, multiple smaller intrarenal branches with multisegmental renal parenchymal ischemia and infarction can occur in children with renal artery stenosis or congenital heart disease and in neonates with umbilical artery catheters. With acute thromboembolic occlusion of the main renal artery, the kidney becomes abnormally echogenic at US, although it usually remains normal in size. Later on, the kidney decreases in size as it atrophies. 50 With peripheral obstruction (e.g., in the newborn with an umbilical artery catheter), the sonographic and functional changes are dependent on the severity and extent of the resulting parenchymal infarction. When US and urography are normal (often the case acutely), the defects in perfusion can be demonstrated with greatest sensitivity at renal cortical scintigraphy (using DMSA) when clinically indicated. In the cystic renal disorders20, 23, 49 the kidneys are usually enlarged. Although large macrocysts are usually not seen in autosomal recessive ("infantile-type") polycystic kidney disease, smaller cysts can sometimes be resolved with high-resolution US equipment. 20, 23 The kidneys appear uniformly (and often severely) enlarged and echogenic at US because of reflection of the sound waves at the interfaces between innumerable microcysts, and the normal corticomedullary differentiation is lost. Autosomal dominant ("adult-type") polycystic kidney disease also can present in childhood,20, 23 although hypertension is rarely encountered in these patients before adulthood. In infants,' the appearance at US may simulate that of autosomal recessive disease. Increasing numbers of cortical macrocysts appear over time and result in progressive renal enlargement. Uremic medullary cystic disease (juvenile nephronophthisis) is a rare inherited disorder that can also present in childhood with hypertension. 20, 23, 50 Early in the course of the disease the kidneys can be normal in size, although they are generally echogenic with loss of the normal corticomedullary differentiation. Variable numbers of cysts are also usually visible in the medulla and at the corticomedullary junction. As renal fibrosis advances (often with marked acceleration of the hypertension) the kidneys gradually decrease in size and become increasingly echogenic as in other forms of end-stage medical renal disease. 23,49 Hypertension has been reported in children with cystic renal dysplasia (including multicystic kidneys), although this association is probably quite rare. 29 Multicystic dysplastic kidneys are usually large early in life because of the volume of fluid within the cysts. 2, 23, 50 As the cyst fluid is absorbed over time, the
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kidney becomes undetectable at imaging, or only a small, echogenic remnant of dysplastic renal tissue remains visible. 49 CHILDREN BELIEVED TO HAVE RENOVASCULAR DISEASE
Whether or not to pursue the diagnosis of renal artery stenosis remains one of the most vexing problems in the evaluation of the child with hypertension. Selective renal arteriography is the accepted standard for the radiographic evaluation of children with renovascular hypertension7, 16, 26, 27, 33, 51; however, it is invasive, involves radiation, and requires that intravascular contrast material be administered. Although many children with renovascular disease do not present with severe and uncontrollable hypertension,28, 33, 43 most children with mild, asymptomatic hypertension and possibly even some children with medically controllable hypertension need not be submitted to the risks of renal arteriography. The decision to pursue a "complete" evaluation for renovascular disease (i.e., including selective renal arteriography) can usually be individualized based on (1) the severity of the hypertension and presence of symptoms; (2) the indications for and response to medical therapy; (3) the clinical presentation (e.g., a bruit over the flank or history of neurofibromatosis); (4) the results of noninvasive studies (if any are performed); and (5) the likelihood of a satisfactory patient response to therapy and compliance with follow-up.29, 30, 43 Certainly, young children and all children with unexplained hypertension that is severe or poorly controlled should be completely evaluated. 28, 33, 39, 41-43
NONINVASIVE IMAGING STUDIES
A number of noninvasive imaging studies, including IVU,ll, 17, 28, 39, 41-43,51 Doppler renal US,5, 10, 19. 26, SO, 52 intravenous digital subtraction angiography (IVDSA),13, 14, 22, 26 and renal scintigraphy, 26, 40 have been used to screen children with hypertension for underlying renovascular disease. All of these modalities yield excessive numbers of false-negative results, however. This is especially true if the stenosis is mild, symmetrical, or peripheral. As a result, noninvasive imaging frequently does not alter the indications for angiography in children with suspected renovascular hypertension. At IVU, unilateral delay in excretion of contrast by a kidney that is smaller than its contralateral mate is the classical finding in moderate to severe renal artery stenosis. 6, 9, 28, 33 Diminished concentration of the contrast material by the affected kidney also can result in decreased opacity of the collecting system on that side. Notching of the renal pelvis and proximal ureter by distended collateral vessels is an uncommon but important observation. Unfortunately, 35% to 40% of children
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with hypertension with significant renal parenchymal or renovascular disease have no abnormality detected at IVU,7, 28, 33, 41, 42 Furthermore, the "hypertensive urogram," in which sequential tomographic images of the kidneys are rapidly obtained early in the study, offers no diagnostic advantages over the conventional IVU. 9, 14, 26, 28 Intravenous digital subtraction angiography has been used for screening hypertensive patients for renal artery stenosis. 13, 14,22,26,27 The main advantage of IVDSA over conventional angiography is that IVDSA can be performed after peripheral, intravenous injection of contrast material and does not require arterial catheterization. The volume of contrast material that is required is significantly greater than with conventional renal arteriography, however, which may pose a problem for patients with diminished renal function or cardiac disease. Furthermore, despite early enthusiasm for this technique, the sensitivity of IVDSA is significantly limited by its relatively poor spatial resolution, especially in evaluating smaller vessels. Although atherosclerotic lesions of the main renal arteries are detected in adults with reasonable sensitivity, 13, 14 IVDSA is significantly less sensitive in detecting stenoses secondary to fibromuscular dysplasia,27 the most common cause of renal artery stenosis in childhood. 33 In addition, stenotic lesions of the intrarenal, segmental, or subsegmental arteries (common in children with fibromuscular dysplasia)16 and accessory renal arteries (approximately 15%-20% of stenoses) are rarely detected with IVDSA.26, 27 As a result, renal IVDSA is no longer used in our department for screening patients with hypertension. In many institutions, renal US has replaced IVU in screening because it provides anatomic information equivalent or superior to IVU.12, 34 Standard US imaging provides no direct information regarding renal function or the patency of the renal vessels, however. The use of pulsed-Doppler US technology for screening patients with suspected renovascular hypertension is based on the theory that the increase in velocity and turbulence of blood flow within stenotic vessels might be detectable. Attempts to use Doppler US to investigate renovascular disease in children and adults with hypertension have met with variable success, however.6, 10, 19,26,52 Some investigators have found increased velocity of flow within the main renal artery and dampening of the pulse amplitude in the intrarenal arteries with spectral broadening to be sensitive Doppler findings of angiographically significant renal artery stenosis. Others have not been able to reproduce these results, however, instead finding the examination to be extremely time-consuming and of no predictive value in screening patients with hypertension for renovascular disease. The most consistent success with this technique has been in patients with renal allografts. 19, 52 As a result, Doppler US does not currently have a routine role in the screening evaluation of children with suspected renovascular hypertension, although it is possible that this may change with future research.
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SELECTIVE RENAL ARTERIOGRAPHY
Selective renal arteriography (with aortography) is highly sensitive and specific and remains the standard for the diagnosis of hemodynamically significant renal artery stenosis (Figs. 4 and 5),7,16,26,27,33,51 When properly performed with subtracted magnification views in multiple projections, the location, severity, and extent of significant stenoses of the main renal arteries can be detected, as can lesions involving the intrarenal, segmental, and subsegmental arteries as well as any accessory renal arteries (present in approximately 15%-20% of the population). The cause of the stenosis can also usually be determined based upon the angiographic appearance. Pharmacologic maneuvers (e.g., instillation of epinephrine into the renal artery to increase detection of capsular collateral vessels) can be performed to determine the hemodynamic significance of a stenotic lesion that is discovered during selective catheterization of the affected renal artery. Renal vein renin sampling is also used to predict the response to revascularization,
Figure 4. This 4.5-year-old girl with renal artery stenosis presented with severe hypertension and headaches. Results of renal sonography were normal. Renal arteriography was requested. During selective injection of the left renal artery, a severe, focal stenosis at the origin of an upper pole lobar artery was demonstrated (open arrow). There is also more subtle, irregular narrowing of the main renal artery (arrowheads), consistent with fibromuscular dysplasia. A notchlike defect in the upper pole of the kidney represents a parenchymal infarct (arrow).
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Figure 5. This 12·year·old girl with renal artery stenosis and neurofibromatosis developed severe hypertension (diastolic pressures from 130 to 145 mm Hg). Severe stenosis of the aortic ostium of the right renal artery (arrows) with diffuse narrowing of the remainder of the main right renal artery (arrowheads) was demonstrated during renal arteriography. A = aorta.
although the reliability of this method has not been entirely satisfactory. 1, 26, 37, 46, 51 Fibromuscular dysplasia is the most frequent cause of renal artery stenosis in children, accounting for more than 90% of cases (Table 2),7, 16, 28 At angiography, fibromuscular dysplasia typically produces an irregular, beaded appearance with narrowing of the mid and distal portions of the main renal arteries in the renal hilum. The intrarenal segmental and subsegmental arteries also can be affected (Fig, 4). With increasing numbers of successful pediatric renal transplants, renal transplant artery stenosis also is being encountered. Renal artery Table 2. RENOVASCULAR DISORDERS ASSOCIATED WITH HYPERTENSION IN CHILDHOOD
Renal artery stenosis Fibromuscular dysplasia Renal transplant artery stenosis Posttraumatic Vasculitis Neurofibromatosis Williams syndrome Abdominal aortic developmental abnormalities Thromboembolic disease Umbilical artery catheterization (neonates) Congenital heart disease Renal vein thrombosis
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stenosis in transplants occurs almost exclusively in patients with cadaver transplants and is usually related to chronic allograft rejection. 3 Both the main renal artery and the intrarenal segmental vessels can be involved. Renal artery stenosis also can be seen in neurofibromatosis (Fig. 5), Williams syndrome and vasculitis and can be associated with thoracic and abdominal aortic developmental anomalies with coarctation. Rarely, renovascular hypertension results from extrinsic compression of the renal pedicle by extra-renal tumor or adenopathy in the renal hilum or by intrinsic tumors of the kidney (e.g., Wilms tumor). Mass lesions can usually be detected at US, although computed tomography generally provides superior delineation of tumor extent and radiologic stage. Atherosclerotic disease, by far the most common cause of renal artery stenosis in adults, is rarely encountered in children. PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY
Percutaneous transluminal angioplasty (PTA) is being used with increasing frequency in the nonsurgical management of intrinsic renal artery stenosis in children3, 36, 51 and has dramatically reduced the need for renal autotransplantation. A balloon catheter is placed percutaneously into one of the femoral arteries and is advanced until it straddles the stenotic segment of the vessel. The balloon is then inflated, resulting in mechanical dilatation of the stenosis. The rate of success with this procedure varies depending on the location and length of the stenotic segment and is most often successful in patients with fibromuscular dysplasia who have short lesions in the mid and distal main renal arteries and in patients with renal transplant artery stenosis. Dilatation is less often successful in patients with lesions involving the aortic orifice of the renal artery (most patients with neurofibromatosis and those with abdominal aortic developmental anomalies). PTA is also frequently not technically feasible in patients with stenoses of smaller intrarenal segmental arteries. PTA is of no value in patients with peripheral thromboembolic disease with segmental renal ischemia and in those with extrinsic compression of the renal pedicle. Normalization of blood pressure frequently occurs after technically successful PTA, although this is not always the case. Successful treatment of restenosis with repeat PTA has been reported in children.
References 1. Alroomi LG, Murphy AV, Nelson CS, et al: Renal vein renin measurement and
arteriography in the investigation and management of severe childhood hypertension. Clin Chim Acta 150:103, 1985 2. Arant BS Jr, Sotelo-Avila C, Bernstein J: Segmental "hypoplasia" of the kidney (AskUpmark). J Pediatr 95:931, 1979 3. Barth MO, Gagnadoux MF, Mareschal JL, et al: Angioplasty of renal transplant artery stenosis in children. Pediatr Radiol 19:383, 1989
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