- Email: [email protected]
Evaluation of the hypertensive infant
Radiol Clin N Am 41 (2003) 931 – 944
Evaluation of the hypertensive infant: a rational approach to diagnosis Christopher G. Roth, MDa, Stephanie E. Spottswood, MDb,*, James C.M. Chan, MDc, Karl S. Roth, MDd a
Department of Radiology, Boston Medical Center, Boston University School of Medicine, 88 East Newton Street, Boston, MA 02118, USA b Department of Radiology, Virginia Commonwealth University Health System, 1250 East Marshall Street, Post Office Box 980615, Richmond, VA 23298 – 0615, USA c Department of Radiology, The Barbara Bush Children’s Hospital, The Maine Medical Center, 22 Bramhall Street, Box 14, Portland, ME 04102, USA d Department of Pediatrics, Creighton University, 2500 California Place, Omaha, NE 69178, USA
The last half of the twentieth century witnessed an explosion of technologic advances, which has revolutionized medical care in particular. One area of medicine in which technologic applications have led to major advances is the field of neonatology. Whereas survival of an infant weighing 750 g in today’s intensive care nursery is hardly unusual, in the early 1960s even the son of President John F. Kennedy was unable to survive at twice that weight. Yet, as with all progress, it has come with a price. For example, the relatively common procedure of umbilical artery catheterization has resulted in an increase in renal artery occlusion. Consequently, renal arterial occlusion has assumed a prominent place on the differential list for renovascular hypertension in infancy [1]. Although numerous authors have raised the level of attention given to detection of hypertension in infancy, consensus on a methodologic approach to etiology has yet to be reached. As noninvasive or minimally invasive imaging techniques continue to improve, it becomes increasingly important to determine which is the most optimal for a given purpose and when in an evaluation it is appropriate. This article reviews and evaluates the pertinent literature
* Corresponding author. E-mail address: [email protected] (S.E. Spottswood).
and uses this analysis to provide the basis for a rational diagnostic approach to infantile hypertension.
Clinical aspects of diagnosis One of the chief deterrents to routine blood pressure measurement in infants has been the irreproducibility of results obtained using the inflatable cuff. This is further complicated by reports that pressure is affected by waking versus sleeping, abdominal palpation, sucking and feeding, position, crying, and agitation [2 – 4]. Normal values for blood pressure in children were defined in the Second Task Force Report from the National Institutes of Health, published in 1987 [5]. Standards were put forth for children under a year and for term infants; the latter have been corroborated by subsequent reports. Less well-defined are normative data for prematurely born infants, although it is generally agreed that normal systolic and diastolic pressures are lower than in term babies and correlate with body weight and chronologic age [6 – 8]. Normal pressures tend to increase from day to day over the first month, further complicating the problem of definition [6 – 8]. In the neonate, precise definition of hypertension remains controversial, with most authors using the criteria of Adleman [9] delineated from a review of
0033-8389/03/$ – see front matter D 2003 Elsevier Inc. All rights reserved. doi:10.1016/S0033-8389(03)00072-1
932
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
the existing literature. These include a reproducible pressure of greater than 90/60 in a term infant and greater than 80/50 in the premature newborn. The Adleman criteria were defined in 1978, however, and subsequent data show much lower normal pressures for very small infants who would not likely have survived in 1978. The definition of hypertension for the preterm baby, according to the Adleman criteria, may be a significant overestimate. By contrast, definition of hypertension in infants younger than 12 months takes into account the difficulty of obtaining reliable diastolic pressures and uses the systolic pressure. A systolic pressure above the 95th percentile for age and height as determined by the 1987 study cited previously [5] taken at least three times defines an abnormality. Gruskin et al [10] have noted that morbidity associated with hypertension increases proportionally with the percentage elevation above the normal in adults; using this as a guide, these workers have defined a hypertensive crisis in a child as one in which the blood pressure exceeds by 30% the agerelated norm. The difficulty in using this approach in the infant younger than 12 months is the imprecision of norms and of measurement of the blood pressure. This is especially true of babies born prematurely, for whom even the norms are practically difficult to establish because of the rapid postnatal changes taking place. Clearly, this area of definition is left to the judgment of the individual physician to resolve on a patient-to-patient basis. Many causes of neonatal hypertension are, by their nature, both curable and life threatening (Box 1). Even such causes as renal artery thrombosis, from which affected infants seem to recover without hypertensive sequelae [11], are intrinsically life threatening and demand diagnosis. It is the authors’ recommendation that any infant with documented hypertension in the first 6 months of life be treated with the respect due any medical and diagnostic emergency. Primary (essential) hypertension has not been well documented to exist in infants and, in any event, must be considered a diagnosis of exclusion. The corollary of this is that the chief causes of infantile hypertension are secondary, of which approximately 70% are renovascular [12,13]. The section that follows discusses a somewhat controversial issue: more sophisticated imaging techniques, which may help to localize subtle abnormalities of arterial circulation in the kidney. Although great care is taken to include discussion of all such methodologies available, advancing technology will undoubtedly create new ones in the future, which require close scrutiny for their usefulness of application in infants.
Box 1. Causes of hypertension in the neonate Renovascular causes Catheter-associated thromboembolic disease Congenital renal artery stenosis Mid-aortic coarctation Renal vein thrombosis Extrinsic renal artery compression (hydronephrosis, hematoma, tumor) Fibromuscular dysplasia Idiopathic arterial calcification Congenital rubella syndrome Renal parenchymal and cystic causes Polycystic kidney disease Multicystic-dysplastic kidney disease Ureteropelvic junction obstruction Unilateral renal hypoplasia Congenital nephrotic syndrome Tuberous sclerosis Acute tubular necrosis Acute cortical necrosis Interstitial nephritis Renal obstruction Miscellaneous causes Neoplasia Neuroblastoma Wilms’ tumor Mesoblastic nephroma Medication Caffeine Dexamethasone Hypercalcemia Vitamin D toxicity Maternal drug addiction (cocaine, heroin) Neurologic Seizures Cardiovascular, pulmonary, and endocrine causes Thoracic aortic coarctation Intracranial hemorrhage Bronchopulmonary dysplasia Pneumothorax Congenital adrenal hyperplasia
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
Radiologic aspects of diagnosis An introduction to renal imaging The goals of imaging are to detect those infants who have renal artery stenosis as the cause of hypertension, to predict curability following intervention, and to identify those patients who have renal parenchymal or structural abnormalities as the cause of their hypertension. The same physiologic and practical considerations that complicate blood pressure measurement in infants also challenge the modalities charged with investigating the cause of hypertension. The imaging modalities that have been used in the evaluation of the hypertensive infant include intravenous urography, renal scintigraphy, ultrasonography, and angiography [14]. CT angiography and MR angiography of the renal arteries have been incorporated into the work-up of the adult hypertensive, but have only anecdotal experience in the infant. Etiologic considerations in imaging Fortunately, the history and physical examination frequently suggest the underlying cause of hypertension in the infant. The potential causes are numerous and the recognized imaging modalities, which are variably invasive, often yield mutually exclusive data. Most cases of hypertension in infants (see Box 1) are caused by renovascular, renal parenchymal, or cystic disease [1]. Renovascular disorders accounted for 48% of neonatal hypertension in a recent study [15]. Catheter-associated thromboembolic disease is the most common offender in this category. The mechanism is believed to be disruption of the vascular endothelium of the umbilical artery following catheter line placement, which initiates thrombus formation. This may propagate directly or embolize to the renal artery causing regions of ischemia or infarction with increased renin release. Other renovascular etiologies include congenital renal artery stenosis, mid-aortic coarctation, renal vein thrombosis, and fibromuscular dysplasia. Finally, extrinsic compression of the renal artery can result from hydronephrosis; tumor; or hematoma (eg, from adrenal hemorrhage) [16]. Renal arteriography is the gold standard for the diagnosis of renovascular disease in the adult. Treatment also may be offered by angiography, because limited data in the older pediatric population have shown that percutaneous transluminal angioplasty can effectively treat renovascular hypertension [17 – 19]. As is discussed, however, angiography is less often performed in the evaluation of neonatal hypertension, most
933
likely because of the technical difficulties and risks of anesthesia. Among renal parenchymal and cystic diseases potentially causing infantile hypertension are polycystic kidney disease (autosomal-recessive far more commonly than autosomal-dominant); unilateral renal hypoplasia; congenital nephrotic syndrome; and acquired conditions, such as acute tubular necrosis, acute cortical necrosis, and interstitial nephritis. Nonparenchymal renal causes of hypertension include ureteropelvic junction obstruction; vesicoureteral junction obstruction; and renal obstruction from other causes, such as calculi, blood clots, or other mass lesion. The nonrenal causes of infantile hypertension (see Box 1) constitute an array of conditions involving different organ systems including endocrine conditions, such as congenital adrenal hyperplasia; pulmonary disorders, such as bronchopulmonary dysplasia and pneumothorax; neoplastic entities, such as Wilms’ tumor and neuroblastoma; neurologic conditions, such as intracranial hypertension and seizures; and miscellaneous causes, such as total parenteral nutrition, hypercalcemia, adrenal hemorrhage, and medications including dexamethasone, adrenergic agents, and others [1]. Most of the nonrenal causes can be suggested by the history, physical examination, and laboratory analysis. Application of imaging to diagnosis of renal parenchymal disease Sonography Because most cases of infantile hypertension are caused by renal abnormalities, a diagnostic approach focused on the kidneys is vital. Renal sonography is typically used as the initial imaging modality in the evaluation of the hypertensive infant because of its convenience, accessibility, noninvasiveness, and lack of radiation exposure. It is highly sensitive in detection of many of the parenchymal diseases of the kidney (see Box 1), and for evaluating anomalies of the renal collecting system. Sonography has replaced the intravenous urogram as the initial imaging modality in the evaluation of infants and small children with hypertension [20]. Sonography is comparable with intravenous urography in the assessment of renal size and hydronephrosis, without the risks of intravenous contrast administration and patient exposure to ionizing radiation. Sonographic evaluation of the kidneys is performed with a combination of gray-scale, color Doppler, and duplex Doppler imaging. Gray-scale imaging depicts a structural rendition of the kidney based on acoustic interfaces (acoustic impedance differences
934
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
between adjacent tissues). Its primary use is for anatomic detail. Color Doppler imaging superimposes a color-coded velocity flow scale, based on the frequency shift of moving tissues, onto the grayscale image. Duplex Doppler imaging provides a spectral trace recording frequency changes over time, reflecting the velocity profile. The Doppler modalities are useful for evaluation of vascular structures. Gray-scale sonography. Gray-scale sonography is initially used to assess the kidneys for any parenchymal or structural abnormality. Coronal, sagittal, and transverse imaging of the kidneys is performed with a high-resolution transducer to simulate a threedimensional view of the renal parenchyma and collecting system. The collecting system is evaluated for hydronephrosis, which can result from ureteropelvic junction obstruction, ureterovesicular junction obstruction, bladder outlet obstruction, or vesicoureteral reflux. Hydronephrosis is easily perceived sonographically as dilatation of the renal collecting system. Hydronephrosis without hydroureter is typical of congenital ureteropelvic junction obstruction; hydronephrosis with hydroureter is apparent with ureterovesicular junction obstruction or vesicoureteral reflux. Renal size is assessed, and any asymmetry in length greater than 5 mm may indicate unilateral renal disease. Normal renal length in a full-term neonate ranges from 4 to 5.5 cm [21]. In the neonate and young infant, the renal parenchyma demonstrates increased cortical echogenicity because the glomeruli occupy a larger volume of the cortex in infants (18%) as compared with older children and adults (8.6%), and 20% of the loops of Henle are located within the cortex rather than within the medulla [22]. Increased numbers of anatomic structures in the cortex create an increased number of interfaces for the ultrasound beam to contact, resulting in increased cortical echogenicity. Additionally, there is a relatively larger volume of medulla in the neonatal kidney than in the adult kidney, with cortico-medullary ratio of 1.64:1 in the neonate and 2.59:1 in the adult [22]. This results in a striking corticomedullary differentiation not seen in older children and adults (Fig. 1). Loss of this corticomedullary differentiation in the neonate reflects diffuse renal disease or congenital dysplasia. Renal cystic diseases are clearly depicted by sonography. Autosomal-recessive polycystic kidney disease characteristically reveals bilaterally enlarged kidneys with diffusely and uniformly increased echogenicity and loss of the normal corticomedullary differentiation. The individual cysts, which actually represent dilated collecting ducts, are too small to be resolved sonographically, but their numerous wall
Fig. 1. Normal renal sonogram of 9-day-old infant with hypertension. Sagittal image of the right kidney demonstrates normal parenchymal echogenicity with good corticomedullary differentiation. Note normal, triangular-shaped, hypoechoic renal pyramids. Duplex Doppler examination was normal.
interfaces produce exceptionally bright kidneys (increased echogenicity) with ultrasound evaluation. Autosomal-dominant polycystic kidney disease, which is less common at this age, exhibits macroscopically visible cysts of varying size. Mesoblastic nephroma, often diagnosed in infancy, and Wilms’ tumor, usually diagnosed in early childhood, manifest sonographically as a mass arising from the kidney. Wilms’ tumor may be accompanied by tumor invasion of the renal vein, which can also be detected sonographically. Hypertension can occur as a result of increased renin production by tumor cells [23]. In the infant with renal artery thrombosis, there is little parenchymal abnormality in the acute phase of vascular obstruction, but with time there is loss of corticomedullary differentiation with diffusely increased echogenicity, and decreased renal size, indicating chronic ischemia. Chronically ischemic or infarcted kidneys appear markedly shrunken and abnormally echogenic (Fig. 2). Renal vein thrombosis likewise exhibits poor corticomedullary differentiation, but the affected kidney is enlarged. Thrombus, usually manifested by intraluminal echogenic material, may be detected in the renal artery or vein, or in the abdominal aorta. Intraluminal thrombus, however, occasionally appears anechoic (without echoes, indistinguishable from the patent blood vessel lumen) and color Doppler imaging is required to demonstrate its presence. Although the presence of echogenic thrombus within the lumen of the aorta or the renal artery is highly suggestive of thrombus, a recent study of
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
Fig. 2. Abnormal renal sonogram in young child with renovascular hypertension. Sagittal sonogram reveals loss of corticomedullary differentiation (compare with Fig. 1) and focal areas of chronic cortical scarring (arrows). Note focal upper pole caliectasis (white arrow).
infantile hypertension has demonstrated no causal relationship between the identification of renal or aortic thrombus and renovascular hypertension [15]. Conversely, many normotensive patients fulfilled gray-scale sonographic criteria for thromboembolism. A prospective study using ultrasound to detect aortic thrombus was positive in 12 of 71 patients in the neonatal intensive care unit; only one of these patients developed hypertension and two normotensive patients subsequently proved to have aortic thrombus did not have sonographically detectable renal artery thrombus [24]. The reported incidence of catheter-associated thromboembolism in infants is highly variable, ranging from 3.5% to 23% in autopsy series to 95% in prospective ultrasound studies [25]. Clearly, it is a common complication, and the presence of echogenic intravascular material associated with systemic hypertension is highly suggestive of renovascular disease; however, earlier reports have demonstrated that grayscale imaging alone does not identify all cases of renovascular hypertension. If the affected renal vessels are beyond first-order branch vessels that cannot be resolved reliably sonographically, and there are no associated morphologic changes in the renal parenchyma, there is no gray-scale sonographic abnormality. It is postulated that small-vessel renal disease can be identified on gray-scale imaging as a dotted corticomedullary junction [26]. Color Doppler imaging. Color Doppler imaging can be used as an adjunct to gray-scale imaging in the detection of intraluminal thrombus, which may be isoechoic to flowing blood. Color Doppler imaging can show absent flow distal to thrombus and the presence of collateral vessels [27]. In addition to
935
renal vascular imaging, the abdominal aorta can be examined from the diaphragm to the bifurcation in the coronal plane, to look for disruption of color flow by thrombus. Color imaging also is useful in distinguishing between anechoic renal hilar vascular structures from a similar-appearing dilated ureter or collecting system. The renal vasculature can be evaluated best sonographically by duplex Doppler imaging. Various quantitative and qualitative measures have been designed to define renovascular disease. The classic duplex Doppler findings in arterial stenosis are an increase in blood flow velocity and spectral broadening. Spectral broadening denotes a widening in the spectrum of detected velocities, which is a manifestation of turbulent flow through a stenotic segment. Because renal blood flow is parabolic and the spectrum is inherently widened, however, spectral broadening is not a valid means of defining turbulent flow in the renal arteries [28]. Other objective measurements have been designed to define sonographically renovascular hypertension. The acceleration index and resistive index have been used to identify renovascular hypertension [28]. The acceleration index is determined by the intersection of a line indicating the upstroke of systole with a line drawn 1 second later perpendicular to the baseline; the height of this line is divided by the ultrasound frequency. The resistive index, a more commonly used measurement, is the ratio of peak diastolic velocity to peak systolic velocity (Fig. 3). Patriquin et al [28] studied 20 children in whom renal artery stenosis was suspected. Doppler tracings from at least three segmental or intralobar arteries were obtained in
Fig. 3. Spectral Doppler image in 1-year-old child with renal artery stenosis. Resistive index (RI) is measured (electronic cursors) as the ratio of the peak diastolic velocity to the peak systolic velocity (RI = 1 [D/S]). In this case 1 (28.8/ 83.5) = 0.66. Note normal Doppler waveform from the renal artery.
936
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
each patient and the acceleration index and resistive index calculated. Both indices were significantly lower in stenotic arteries (the acceleration index to a greater extent), with clear discrimination between normal arteries and those with at least a 75% angiographic stenosis. Normal renal arteries were associated with an acceleration index of 4 to 7; renal arteries with at least 75% stenosis ranged from 0.7 to 2.6. Although used more commonly in practice, the resistive index varied less with renal arterial stenosis with a resistive index of 0.56 or less predicting stenosis with 95% probability [28]. Conversely, a prospective study of hypertensive children aged 12 days to 15 years defined a subset of angiographically proved renovascular hypertensive patients with negative Doppler examinations. The Doppler ultrasound examinations, however, were assessed qualitatively [29]. Specifically, they used pattern recognition of the tardus-parvus phenomenon [30], where pulsus tardus is the slowed, delayed systolic upsweep, and pulsus parvus represents a dampened maximal systolic peak, characteristic of a severe stenosis (Fig. 4). The presence of multiple renal arteries and segmental lesions accounted for most false-negative Doppler examinations. In this series, hypertensive patients with a negative duplex Doppler examination generally had vascular lesions amenable to endovascular or surgical treatment with a high rate of success. It was concluded that for these reasons Doppler sonography may be unreliable in the evaluation of renal artery stenosis. The authors suggested that with a negative Doppler sonogram and a
Fig. 4. Renal sonogram with spectral Doppler image in 1-year-old child with renal artery stenosis demonstrating tardus-parvus phenomenon. Duplex Doppler spectral tracing of the left renal artery reveals delayed and dampened systolic upsweep (arrow) typical of renal artery stenosis (note continuous venous waveform below the line). Compare with normal renal arterial waveform in Fig. 3.
Fig. 5. Renal arteriogram in a 3-year-old patient with uncontrollable hypertension and history of neurofibromatosis. Middle aortic syndrome with renal artery stenosis. Aortic arteriogram reveals marked, long-segment stenosis and irregularity of the aorta extending from the suprarenal region to just above the bifurcation. The right renal artery is occluded at its origin (curved arrow) and the left renal artery (straight arrow) is markedly stenotic. Note also occlusion of the hepatic artery (large arrow). There is marked enlargement of the inferior mesenteric artery and left colic artery (arrowheads), and multiple lumbar arteries. (Courtesy of Jaime Tisnado, Medical College of Virginia, Richmond, VA.)
strong suspicion for renovascular hypertension, selective or superselective arteriography in association with segmental venous renin sampling should be performed because an angiographically demonstrated causal lesion, if treated, most likely results in cure [29]. Angiography is generally deferred in the neonate, however, and medical treatment (often with angiotensin converting enzyme inhibitors [ACEI]) is the mainstay. The aforementioned studies using Doppler ultrasound included very few infants. Technical factors, including the inherent difficulty in obtaining Doppler signal from multiple intrarenal vessels, the long duration of the examination, and the frequent lack of visualization of the proximal renal vasculature because of bowel gas, challenge the implementation
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
of this technique at all, let alone in infants. Multiple additional factors further complicate the application of such techniques in the neonatal ICU, including the use of portable machines; the presence of life support lines and tubes; and the likelihood that the patient is dependent on mechanical ventilation, which renders duplex Doppler sonography virtually impossible (especially in the setting of high-frequency ventilation). Sonography is a versatile modality that offers several parameters for evaluating the hypertensive infant. The implementation of duplex Doppler sonography is limited by operator skill and experience and by the technical difficulties in performing this tech-
937
nique in the intensive care setting. In the persistently hypertensive neonate in which duplex Doppler sonography is not technically feasible, the identification of intraluminal thrombus on gray-scale imaging suggests the diagnosis. The absence of intraluminal thrombus on gray-scale imaging, however, does not exclude renovascular hypertension and further diagnostic investigation should be pursued. Angiography The accuracy of Doppler sonography in the diagnosis of renal artery stenosis has been compared with renal angiography, which is considered the gold
Fig. 6. Technetium (Tc) 99m MAG3 ACEI renogram in a 13-day-old infant with unexplained hypertension. (A, B) Normal baseline study. Posterior images of the kidneys were obtained following the intravenous administration of Tc 99m MAG3 (initial flow images were unremarkable) (A). Note symmetric uptake and excretion of tracer, followed by visualization of the urinary bladder. Normal time-activity curve demonstrates peak renal activity at 3 minutes (normal) and a differential function of 48.8% (left kidney) and 51.2% (right kidney) (B). (C, D) Normal enalaprilat study. Posterior images of the kidneys were obtained following the intravenous administration of enalaprilat, followed by intravenous Tc 99m MAG3 (C). Peak renal activity on the time activity curves is demonstrated at 2 minutes (normal) (D). There is normal differential function: 45% (left kidney) and 55% (right kidney), and no significant renal cortical retention of tracer.
938
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
Fig. 6 (continued ).
standard in the evaluation of renovascular hypertension [14,15,20]. Despite the high incidence of renovascular hypertension in children relative to adults, the use of renal arteriography in children has been limited. The necessity for general anesthesia generally preempts the use of conventional arteriography in infants. Catheter-related vascular injury and radiation exposure are other potential adverse considerations. Although intra-arterial digital subtraction arteriography requires substantially less intravascular contrast material and shortens the duration of the procedure compared with traditional arteriography, resulting in less radiation exposure, it has not substantially increased the use of arteriography in the diagnosis of infantile hypertension. When performed, digital subtraction arteriography images may be compromised by the presence of bowel gas, although both intravenous glucagon and abdominal compression can mitigate this problem [31]. Intravenous digital subtraction arteriography has been attempted as an alternative to arteriography in the evaluation of renovascular hypertension with limited success. Intravenous digital subtraction arteriography requires a higher contrast load and the vessels of interest are frequently not well opacified by this technique. Lesions beyond the first-order branch vessels are not demonstrated by intravenous digital subtraction arteriography and this technique has been
essentially abandoned in the evaluation of the hypertensive infant [20]. The potential benefit of arteriography in the evaluation of the pediatric hypertensive patient is the opportunity for definitive treatment. Percutaneous transluminal angioplasty has been demonstrated to be effective in the adult population and has recently been applied to the pediatric population with success [17,18]. Nonetheless, virtually no data are available regarding the use of percutaneous transluminal angioplasty in infants. The highest rate of success in children has been associated with nonostial, shortsegment main renal arterial lesions; the technical difficulty in traversing ostial lesions, with or without aortic involvement, often precludes successful angioplasty [32]. Most angiographically demonstrated lesions in cases of pediatric hypertension are related to intrinsic vascular disorders, such as fibromuscular dysplasia, neurofibromatosis, and other undifferentiated vasculitides. During arteriography, pharmacologic maneuvers, such as epinephrine infusion, can determine the hemodynamic significance of renal arterial lesions. One of the inherent advantages of angiography is that the main renal artery, and the intrarenal segmental, subsegmental, and any accessory renal arteries are well demonstrated and any of these vessels may be affected
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
939
Fig. 6 (continued ).
in the previously mentioned disorders (Fig. 5). Although these entities do occur in infants, they are not typically the chief diagnostic considerations in this age group, especially in neonatal patients. In infants, the most common underlying abnormality is catheter-related thromboembolism. Aortic and renal arterial thrombus can be demonstrated with contrast aortography and renal arteriography performed by the offending umbilical artery catheter [25]. Many studies have proved the efficacy of arteriography in documenting the presence of thrombus in association with umbilical arterial catheterization. There has been very poor correlation, however, between the presence of thrombus and clinical signs and symptoms. The variably reported incidence of arterial thrombus associated with umbilical artery catheterization is high enough that it may be an incidental finding in some instances. In any event, catheter-associated aortic and renal arterial thrombus has been treated relatively successfully
with medical therapy and not with percutaneous transluminal angioplasty, which argues against the implementation of arteriography [1,15,33]. Because the usual first-line therapy in neonatal renovascular hypertension is ACEI and revascularization is generally not an option, it is more important to identify cases of bilateral renal ischemia and renal ischemia in a solitary kidney in which ACEI therapy is contraindicated. Renal scintigraphy is the least invasive and most reliable means of providing this information. Renal scintigraphy Renal scintigraphy can yield valuable functional data with variable anatomic detail. In the presence of unilateral renal artery stenosis, conventional radionuclide scintigraphy may show evidence of relatively diminished renal perfusion and function of the affected kidney. Because of the autoregulatory mechanism, however, mediated by the renin-angiotensin system,
940
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
Fig. 6 (continued ).
the glomerular filtration rate (GFR) may be maintained at a normal level and the scintigram may be normal. Performing the examination in conjunction with an ACEI greatly increases the sensitivity and specificity of renal scintigraphy for detecting hemodynamically significant renal artery stenosis; the sensitivity and specificity are each approximately 90% [34]. When renal arterial stenosis reaches 60% of the cross-sectional diameter of the artery, the kidney responds by increasing its output of renin, stimulating production of angiotensin II, which augments falling GFR by increasing tone in the efferent arterioles at the cost of generalized vasoconstriction, resulting in systemic hypertension [14]. The administration of an ACEI blocks the production of angiotensin II, which decompensates renal function. An ACEI scintigraphy capitalizes on this physiologic compensation mechanism. A baseline renogram is first performed, which may be normal with a renal arterial stenosis of up to 70% to 80% [14]. Beyond this range, renin-angiotensin compensation may be incomplete and the baseline study may show diminished function. If the kidney has infarcted and there is no residual function, the baseline study results in nonvisualization of the involved kidney.
If the baseline study is normal, the administration of the ACEI eliminates the renin-angiotensin compensation and thereby decreases the renal perfusion commensurate with the degree of stenosis. This translates to a decrease in function in the well-compensated kidney. There is high probability of hemodynamically significant renal artery stenosis when there is (1) marked change in the renogram curve, (2) unilaterally reduced relative uptake of tracer, or (3) unilaterally prolonged renal and parenchymal transit time. In cases of very severe renal artery stenosis (up to 95%) there is no significant change from baseline after ACEI administration with at most minimal residual renal function. When renal arterial stenosis has resulted in complete obstruction, the baseline scintigram may demonstrate some blood pool activity caused by collateral vessels and there is no change after ACEI. Renal scintigraphy for the evaluation of renal artery stenosis can be performed with a choice of ACEI: captopril or enalaprilat. Enalaprilat is administered intravenously, and unlike orally administered captopril, its pharmacologic effect is not dependent on rate of gastrointestinal absorption. ACEIs can cause significant hypotension; blood pressure and heart rate are monitored before and during ACEI administration.
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
The baseline and follow-up ACEI scintigraphy can be performed with either glomerular or tubular radiopharmaceuticals. The original studies performed in pediatric patients used a glomerular agent, Tc 99m diethylenetriamine pentaacetic acid (DTPA) with captopril [35]. Subsequently, Tc 99m mercaptoacetyltriglycine (MAG3), a tubular agent, has been used for ACEI renography. It is preferred over Tc 99m DTPA in patients with elevated serum creatinine, because of its higher renal extraction.
941
The disposition of glomerular agents in the kidney is dependent on the GFR; the rate of accumulation of radiotracer is directly proportional to the GFR. The rate of glomerular agent accumulation can be expressed as the slope of the curve of computergenerated graphs at fixed intervals and differential renal function of each kidney can be derived (Fig. 6). With Tc 99m DTPA, the scintigraphic manifestation of decreased renal function following ACEI administration is decreased extraction and delayed appearance
Fig. 7. Tc 99m MAG3 renogram. Renal artery stenosis in an older child with hypertension. (A) Posterior images of the kidneys were obtained following the intravenous administration of enalaprilat (initial flow images were unremarkable). The early images reveal reduced tracer uptake and function of the relatively smaller right kidney, whereas the normal left kidney reveals normal accumulation and ureteral excretion of tracer. The delayed images demonstrate marked retention of tracer in right kidney (arrow), consistent with hemodynamically significant renal artery stenosis. (B) Normal baseline Tc 99m MAG3 renogram. (Courtesy of Massoud Majd, Children’s National Medical Center, Washington, DC.)
942
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
of the radiotracer in the collecting system. The affected kidney demonstrates relatively decreased uptake. Tubular agents are secreted by the proximal tubules, a function that is maintained in the setting of a falling GFR. As urine production in the ischemic kidney decreases after ACEI administration, the tubular agent accumulates and remains in the cortex because of the fall in urine production. The affected kidney demonstrates parenchymal retention of tracer (Fig. 7). Tc 99m MAG3 has an advantage over Tc 99m DTPA in that the images are of higher resolu-
tion, and measurements of residual cortical activity can be displayed graphically (see Fig. 7). In hypertensive neonates without an umbilical arterial catheter, an abnormal ACEI study indicates renal artery stenosis. A more common cause of hypertension in neonates, however, usually transient, is narrowing of the renal artery because of thrombosis as a complication of the umbilical artery catheter (Fig. 8). The value of ACEI renography in these neonates is to determine whether it is safe to treat them with ACEI therapy.
Fig. 8. Tc 99m MAG3 renogram. Renal artery thrombosis. Neonate who became hypertensive a few days following umbilical artery catheter placement. (A) Initial posterior images obtained following administration of enalaprilat reveal a normal-appearing right kidney, and a smaller, irregularly contoured left kidney, presumably developmental. Delayed images reveal normal excretion from the left kidney, but marked retention of MAG3 in the right kidney (arrow) caused by partial obstruction of the renal artery. Time-activity curves generated from region of interest drawn around the right kidney demonstrate (B) normal preACEI function of the right kidney (pre-captopril) and (C) impaired post-ACEI function (post-enalaprilat). (Courtesy of Massoud Majd, Children’s National Medical Center, Washington, DC.)
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
In addition to its high sensitivity and specificity for hemodynamically significant renal artery stenosis, a major benefit of ACEI renography is that a positive study indicates a high probability that blood pressure is reduced following angiographic intervention [31]. Although this procedure has been performed safely in young children [18], subsequent intervention with percutaneous transluminal angioplasty is an unlikely consideration in the young infant.
Future considerations for imaging diagnosis CT angiography of the renal arteries has had promising results in the detection of renal artery stenosis in the adult population. New developments in CT technology, including spiral CT and multidetector CT, allow volumetric acquisitions during a single breathhold. The volume of acquired data can then be reformatted for display in any plane. Sensitivity and specificity for detection of hemodynamically significant renal artery stenosis in the adult population have been as high as 92% and 83%, respectively [36], and 90% and 97%, respectively [37]. High sensitivity and specificity for this modality may be caused by the ostial location of stenotic lesions seen in adults. Although little data are currently available describing use of CT angiography in infants and children, potential advantages include relative speed of image acquisition (which may obviate need for sedation), and minimal invasiveness, as compared with angiography. Potential disadvantages include inability to breathhold, and limitations in the evaluation of small accessory, segmental, or intrarenal arteries [37], which unfortunately are frequently involved in infants with renal artery stenosis. Additionally, larger doses of intravenous contrast are required with CT angiography than with intra-arterial digital subtraction arteriography [37]. As with CT angiography, little data are available on the use of MR angiography of the renal arteries in infants. Anecdotally, MR angiography has been attempted by one of the authors, in an infant with intractable hypertension, and in an older child with middle aortic syndrome. Limitations were difficulty resolving the small renal arteries, motion artifact during imaging, and the need for sedation for this relatively long study. Obvious advantages include lack of ionizing radiation or intravenous contrast.
Summary This article reviews the literature and describes a methodologic approach to the diagnosis of hyperten-
943
sion in the young infant. The numerous etiologies of hypertension have been discussed and normative blood pressure data for neonates and infants have been provided. Techniques for accurate blood pressure measurement in the intensive care setting and for routine outpatient settings, are discussed. The lengthy discussion of radiologic approach to imaging can be summarized with the following suggested algorithm. Initial screening should be performed with gray-scale sonography, to identify renal parenchymal or collecting system abnormalities, including mass lesions and congenital anomalies. Further imaging with color and duplex Doppler sonography detects renal arterial or aortic thrombosis, and alterations in the arterial waveform caused by intrinsic or extrinsic renal artery narrowing. The major limitation of Doppler sonography is the recognition that disease in accessory renal arteries or in small segmental intrarenal arteries may frequently be undetected. Functional imaging with ACEI renography should follow renal sonography to detect hemodynamically significant renovascular disease (with a sensitivity and specificity of approximately 90%); intravenous enalaprilat is the preferred ACEI. Angiography should be reserved for older children in whom interventional percutaneous angioplasty may be more feasible. A young infant with hypertension caused by renal artery stenosis should be controlled medically until he or she is large enough to undergo angiography and angioplasty successfully. CT angiography and MR angiography, although promising in the adult population, may not adequately resolve the small intrarenal vessels, which are frequently the culprit in renovascular hypertension of infancy.
References [1] Flynn JT. Neonatal hypertension: diagnosis and treatment. Pediatr Nephrol 2000;14:332 – 41. [2] Lee YH, Rosner B, Gould JB, et al. Familial aggregation of blood pressure of newborn infants and their mothers. Pediatrics 1976;58:722 – 9. [3] Sinkin RA, Phillips BL, Adelman RD. Elevation in systemic blood pressure in the neonate during abdominal examination. Pediatrics 1985;76:970 – 2. [4] Moss AJ, Duffie Jr ER, Emmanouilides G. Blood pressure and vasomotor reflexes in the newborn infant. Pediatrics 1963;32:175 – 9. [5] The National Heart, Lung, and Blood Institute (Bethesda, MD). Report of the Second Task Force on Blood Pressure Control in Children. Pediatrics 1987;79:1 – 25. [6] Tan KL. Blood pressure in very low birth weight infants in the first 70 days of life. J Pediatr 1988;112: 266 – 70.
944
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
[7] McGarvey ST, Zinner SH. Blood pressure in infancy. Semin Nephrol 1989;9:260 – 6. [8] Zubrow AB, Hulman S, Kushner H, et al. Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. J Perinatol 1995;15:470 – 9. [9] Adelman RD. Neonatal hypertension. Pediatr Clin North Am 1978;25:99 – 110. [10] Gruskin AB, Lerner GR, Fleischmann LE. Management of acute and primary hypertension in children. In: Murakami K, Kitagawa T, Yabuta K, et al, editors. Recent advances in pediatric nephrology. Amsterdam: Elsevier; 1987. p. 121 – 6. [11] Adelman RD. Long-term follow-up of neonatal renovascular hypertension. Pediatr Nephrol 1987;1:35 – 41. [12] Inglefinger J. Nephrology forum: renovascular hypertension in children. Kidney Int 1993;43:493 – 505. [13] Singh HP, Hurley RM, Myers TF. Neonatal hypertension: incidence and risk factors. Am J Hypertens 1992; 5:51 – 5. [14] Sfakianakis GN, Bourgoignie JJ, Georgiou M, Guerra JJ. Diagnosis of renovascular hypertension with ACE inhibition scintigraphy. Radiol Clin North Am 1993; 31:831 – 48. [15] Chandar JJ, Sfakianakis GN, Zilleruelo GE, Guerra JJ, Georgiou MF, Abithol CL, et al. ACE inhibition scintigraphy in the management of hypertension in children. Pediatr Nephrol 1999;13:493 – 500. [16] Starinsky R, Manor A, Segal M. Non-functioning kidney associated with neonatal adrenal hemorrhage: report of two cases. Pediatr Radiol 1986;16:427 – 9. [17] Tyagi S, Kaul UA, Satsangi DK, Arora R. Percutaneous transluminal angioplasty for renovascular hypertension in children: initial and long-term results. Pediatrics 1997;99:44 – 9. [18] Courtel VC, Soto B, Niaudet P, Gagnadoux MF, Carteret M, Quignodon JF, et al. Percutaneous transluminal angioplasty of renal artery stenosis in children. Pediatr Radiol 1998;28:59 – 63. [19] Stanley P, Hieshima G, Mehringer M. Percutaneous transluminal angioplasty for pediatric renovascular hypertension. Radiology 1984;153:101 – 4. [20] Zerin JM, Hernandez RJ. Renal imaging in children with persistent hypertension. Pediatr Clin North Am 1993; 40:165 – 78. [21] Rosenbaum DM, Korngold E, Teele RL. Sonographic assessment of renal length in normal children. Am J Radiol 1984;142:467 – 9. [22] Hricak H, Slovis TL, Callen CW, et al. Neonatal kidneys: sonographic anatomic correlation. Radiology 1983;147:699 – 702.
[23] Cohen MD. Imaging of children with cancer. St. Louis: Mosby Year Book; 1992. [24] Oppenheimer DA, Carroll BA, Garth KE. Ultrasonic detection of complications following umbilical arterial catheterization in the neonate. Radiology 1982;145: 667 – 72. [25] Ford KT, Teplick SK, Clark RE. Renal artery embolism causing neonatal hypertension. Radiology 1974; 113:169 – 70. [26] Garel LA, Pariente DM, Gubler MC, et al. The dotted cortico-medullary junction: a sonographic indicator of small vessel disease in hypertensive children. Radiology 1984;152:419 – 22. [27] Deeg KH, Wolfel D, Rupprecht TH. Diagnosis of neonatal aortic thrombosis by colour coded Doppler sonography. Pediatr Radiol 1992;2:62 – 3. [28] Patriquin HB, Lafortune M, Jequier J-C, O’Regan S, Garel L, Landriault J, et al. Stenosis of the renal artery: assessment of slowed systole in the downstream circulation with Doppler sonography. Radiology 1992;184: 479 – 85. [29] Garel L, Dubois J, Robitaille P, Russo P, Filiatrault D, Grignon A, et al. Renovascular hypertension in children: curability predicted with negative intrarenal Doppler UAS results. Radiology 1995;195:401 – 5. [30] Kotval PS. Doppler waveform parvus and tardus. J Ultrasound Med 1989;8:435 – 40. [31] Tonkin IL, Stapleton FB, Roy S. Digital subtraction angiography in the evaluation of renal vascular hypertension in children. Pediatrics 1988;81:150 – 7. [32] Mali WP, Puijlaert AJ, Kouwenberg HJ, Klinge J, Donckerwolcke RA, Geijskes BG, et al. Percutaneous transluminal renal angioplasty in children and adolescents. Radiology 1987;165:391 – 4. [33] Caplan MS, Cohn RA, Langman CB, Conway JA, Shkolnik A, Brouillette RT. Favorable outcome of neonatal aortic thrombosis and renovascular hypertension. J Pediatr 1989;115:291 – 5. [34] Taylor AT, Fletcher JW, Nally JV, et al. Procedure for diagnosis of renovascular hypertension. J Nucl Med 1998;39:1297 – 302. [35] Majd M, Potter BM, Guzzetta PC, et al. Effect of captopril on efficacy of renal scintigraphy in detection of renal artery stenosis. J Nucl Med 1983;24:23. [36] Rubin GD, Dake MD, Napel S. Spiral CT of renal artery stenosis: comparison of three-dimensional rendering techniques. Radiology 1994;190:181 – 9. [37] Kim TS, Chung JW, Park JH. Renal artery evaluation: comparison of spiral CT angiography to intra-arterial DSA. J Vasc Interv Radiol 1998;9:553 – 9.
Evaluation of the hypertensive infant: a rational approach to diagnosis Christopher G. Roth, MDa, Stephanie E. Spottswood, MDb,*, James C.M. Chan, MDc, Karl S. Roth, MDd a
Department of Radiology, Boston Medical Center, Boston University School of Medicine, 88 East Newton Street, Boston, MA 02118, USA b Department of Radiology, Virginia Commonwealth University Health System, 1250 East Marshall Street, Post Office Box 980615, Richmond, VA 23298 – 0615, USA c Department of Radiology, The Barbara Bush Children’s Hospital, The Maine Medical Center, 22 Bramhall Street, Box 14, Portland, ME 04102, USA d Department of Pediatrics, Creighton University, 2500 California Place, Omaha, NE 69178, USA
The last half of the twentieth century witnessed an explosion of technologic advances, which has revolutionized medical care in particular. One area of medicine in which technologic applications have led to major advances is the field of neonatology. Whereas survival of an infant weighing 750 g in today’s intensive care nursery is hardly unusual, in the early 1960s even the son of President John F. Kennedy was unable to survive at twice that weight. Yet, as with all progress, it has come with a price. For example, the relatively common procedure of umbilical artery catheterization has resulted in an increase in renal artery occlusion. Consequently, renal arterial occlusion has assumed a prominent place on the differential list for renovascular hypertension in infancy [1]. Although numerous authors have raised the level of attention given to detection of hypertension in infancy, consensus on a methodologic approach to etiology has yet to be reached. As noninvasive or minimally invasive imaging techniques continue to improve, it becomes increasingly important to determine which is the most optimal for a given purpose and when in an evaluation it is appropriate. This article reviews and evaluates the pertinent literature
* Corresponding author. E-mail address: [email protected] (S.E. Spottswood).
and uses this analysis to provide the basis for a rational diagnostic approach to infantile hypertension.
Clinical aspects of diagnosis One of the chief deterrents to routine blood pressure measurement in infants has been the irreproducibility of results obtained using the inflatable cuff. This is further complicated by reports that pressure is affected by waking versus sleeping, abdominal palpation, sucking and feeding, position, crying, and agitation [2 – 4]. Normal values for blood pressure in children were defined in the Second Task Force Report from the National Institutes of Health, published in 1987 [5]. Standards were put forth for children under a year and for term infants; the latter have been corroborated by subsequent reports. Less well-defined are normative data for prematurely born infants, although it is generally agreed that normal systolic and diastolic pressures are lower than in term babies and correlate with body weight and chronologic age [6 – 8]. Normal pressures tend to increase from day to day over the first month, further complicating the problem of definition [6 – 8]. In the neonate, precise definition of hypertension remains controversial, with most authors using the criteria of Adleman [9] delineated from a review of
0033-8389/03/$ – see front matter D 2003 Elsevier Inc. All rights reserved. doi:10.1016/S0033-8389(03)00072-1
932
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
the existing literature. These include a reproducible pressure of greater than 90/60 in a term infant and greater than 80/50 in the premature newborn. The Adleman criteria were defined in 1978, however, and subsequent data show much lower normal pressures for very small infants who would not likely have survived in 1978. The definition of hypertension for the preterm baby, according to the Adleman criteria, may be a significant overestimate. By contrast, definition of hypertension in infants younger than 12 months takes into account the difficulty of obtaining reliable diastolic pressures and uses the systolic pressure. A systolic pressure above the 95th percentile for age and height as determined by the 1987 study cited previously [5] taken at least three times defines an abnormality. Gruskin et al [10] have noted that morbidity associated with hypertension increases proportionally with the percentage elevation above the normal in adults; using this as a guide, these workers have defined a hypertensive crisis in a child as one in which the blood pressure exceeds by 30% the agerelated norm. The difficulty in using this approach in the infant younger than 12 months is the imprecision of norms and of measurement of the blood pressure. This is especially true of babies born prematurely, for whom even the norms are practically difficult to establish because of the rapid postnatal changes taking place. Clearly, this area of definition is left to the judgment of the individual physician to resolve on a patient-to-patient basis. Many causes of neonatal hypertension are, by their nature, both curable and life threatening (Box 1). Even such causes as renal artery thrombosis, from which affected infants seem to recover without hypertensive sequelae [11], are intrinsically life threatening and demand diagnosis. It is the authors’ recommendation that any infant with documented hypertension in the first 6 months of life be treated with the respect due any medical and diagnostic emergency. Primary (essential) hypertension has not been well documented to exist in infants and, in any event, must be considered a diagnosis of exclusion. The corollary of this is that the chief causes of infantile hypertension are secondary, of which approximately 70% are renovascular [12,13]. The section that follows discusses a somewhat controversial issue: more sophisticated imaging techniques, which may help to localize subtle abnormalities of arterial circulation in the kidney. Although great care is taken to include discussion of all such methodologies available, advancing technology will undoubtedly create new ones in the future, which require close scrutiny for their usefulness of application in infants.
Box 1. Causes of hypertension in the neonate Renovascular causes Catheter-associated thromboembolic disease Congenital renal artery stenosis Mid-aortic coarctation Renal vein thrombosis Extrinsic renal artery compression (hydronephrosis, hematoma, tumor) Fibromuscular dysplasia Idiopathic arterial calcification Congenital rubella syndrome Renal parenchymal and cystic causes Polycystic kidney disease Multicystic-dysplastic kidney disease Ureteropelvic junction obstruction Unilateral renal hypoplasia Congenital nephrotic syndrome Tuberous sclerosis Acute tubular necrosis Acute cortical necrosis Interstitial nephritis Renal obstruction Miscellaneous causes Neoplasia Neuroblastoma Wilms’ tumor Mesoblastic nephroma Medication Caffeine Dexamethasone Hypercalcemia Vitamin D toxicity Maternal drug addiction (cocaine, heroin) Neurologic Seizures Cardiovascular, pulmonary, and endocrine causes Thoracic aortic coarctation Intracranial hemorrhage Bronchopulmonary dysplasia Pneumothorax Congenital adrenal hyperplasia
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
Radiologic aspects of diagnosis An introduction to renal imaging The goals of imaging are to detect those infants who have renal artery stenosis as the cause of hypertension, to predict curability following intervention, and to identify those patients who have renal parenchymal or structural abnormalities as the cause of their hypertension. The same physiologic and practical considerations that complicate blood pressure measurement in infants also challenge the modalities charged with investigating the cause of hypertension. The imaging modalities that have been used in the evaluation of the hypertensive infant include intravenous urography, renal scintigraphy, ultrasonography, and angiography [14]. CT angiography and MR angiography of the renal arteries have been incorporated into the work-up of the adult hypertensive, but have only anecdotal experience in the infant. Etiologic considerations in imaging Fortunately, the history and physical examination frequently suggest the underlying cause of hypertension in the infant. The potential causes are numerous and the recognized imaging modalities, which are variably invasive, often yield mutually exclusive data. Most cases of hypertension in infants (see Box 1) are caused by renovascular, renal parenchymal, or cystic disease [1]. Renovascular disorders accounted for 48% of neonatal hypertension in a recent study [15]. Catheter-associated thromboembolic disease is the most common offender in this category. The mechanism is believed to be disruption of the vascular endothelium of the umbilical artery following catheter line placement, which initiates thrombus formation. This may propagate directly or embolize to the renal artery causing regions of ischemia or infarction with increased renin release. Other renovascular etiologies include congenital renal artery stenosis, mid-aortic coarctation, renal vein thrombosis, and fibromuscular dysplasia. Finally, extrinsic compression of the renal artery can result from hydronephrosis; tumor; or hematoma (eg, from adrenal hemorrhage) [16]. Renal arteriography is the gold standard for the diagnosis of renovascular disease in the adult. Treatment also may be offered by angiography, because limited data in the older pediatric population have shown that percutaneous transluminal angioplasty can effectively treat renovascular hypertension [17 – 19]. As is discussed, however, angiography is less often performed in the evaluation of neonatal hypertension, most
933
likely because of the technical difficulties and risks of anesthesia. Among renal parenchymal and cystic diseases potentially causing infantile hypertension are polycystic kidney disease (autosomal-recessive far more commonly than autosomal-dominant); unilateral renal hypoplasia; congenital nephrotic syndrome; and acquired conditions, such as acute tubular necrosis, acute cortical necrosis, and interstitial nephritis. Nonparenchymal renal causes of hypertension include ureteropelvic junction obstruction; vesicoureteral junction obstruction; and renal obstruction from other causes, such as calculi, blood clots, or other mass lesion. The nonrenal causes of infantile hypertension (see Box 1) constitute an array of conditions involving different organ systems including endocrine conditions, such as congenital adrenal hyperplasia; pulmonary disorders, such as bronchopulmonary dysplasia and pneumothorax; neoplastic entities, such as Wilms’ tumor and neuroblastoma; neurologic conditions, such as intracranial hypertension and seizures; and miscellaneous causes, such as total parenteral nutrition, hypercalcemia, adrenal hemorrhage, and medications including dexamethasone, adrenergic agents, and others [1]. Most of the nonrenal causes can be suggested by the history, physical examination, and laboratory analysis. Application of imaging to diagnosis of renal parenchymal disease Sonography Because most cases of infantile hypertension are caused by renal abnormalities, a diagnostic approach focused on the kidneys is vital. Renal sonography is typically used as the initial imaging modality in the evaluation of the hypertensive infant because of its convenience, accessibility, noninvasiveness, and lack of radiation exposure. It is highly sensitive in detection of many of the parenchymal diseases of the kidney (see Box 1), and for evaluating anomalies of the renal collecting system. Sonography has replaced the intravenous urogram as the initial imaging modality in the evaluation of infants and small children with hypertension [20]. Sonography is comparable with intravenous urography in the assessment of renal size and hydronephrosis, without the risks of intravenous contrast administration and patient exposure to ionizing radiation. Sonographic evaluation of the kidneys is performed with a combination of gray-scale, color Doppler, and duplex Doppler imaging. Gray-scale imaging depicts a structural rendition of the kidney based on acoustic interfaces (acoustic impedance differences
934
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
between adjacent tissues). Its primary use is for anatomic detail. Color Doppler imaging superimposes a color-coded velocity flow scale, based on the frequency shift of moving tissues, onto the grayscale image. Duplex Doppler imaging provides a spectral trace recording frequency changes over time, reflecting the velocity profile. The Doppler modalities are useful for evaluation of vascular structures. Gray-scale sonography. Gray-scale sonography is initially used to assess the kidneys for any parenchymal or structural abnormality. Coronal, sagittal, and transverse imaging of the kidneys is performed with a high-resolution transducer to simulate a threedimensional view of the renal parenchyma and collecting system. The collecting system is evaluated for hydronephrosis, which can result from ureteropelvic junction obstruction, ureterovesicular junction obstruction, bladder outlet obstruction, or vesicoureteral reflux. Hydronephrosis is easily perceived sonographically as dilatation of the renal collecting system. Hydronephrosis without hydroureter is typical of congenital ureteropelvic junction obstruction; hydronephrosis with hydroureter is apparent with ureterovesicular junction obstruction or vesicoureteral reflux. Renal size is assessed, and any asymmetry in length greater than 5 mm may indicate unilateral renal disease. Normal renal length in a full-term neonate ranges from 4 to 5.5 cm [21]. In the neonate and young infant, the renal parenchyma demonstrates increased cortical echogenicity because the glomeruli occupy a larger volume of the cortex in infants (18%) as compared with older children and adults (8.6%), and 20% of the loops of Henle are located within the cortex rather than within the medulla [22]. Increased numbers of anatomic structures in the cortex create an increased number of interfaces for the ultrasound beam to contact, resulting in increased cortical echogenicity. Additionally, there is a relatively larger volume of medulla in the neonatal kidney than in the adult kidney, with cortico-medullary ratio of 1.64:1 in the neonate and 2.59:1 in the adult [22]. This results in a striking corticomedullary differentiation not seen in older children and adults (Fig. 1). Loss of this corticomedullary differentiation in the neonate reflects diffuse renal disease or congenital dysplasia. Renal cystic diseases are clearly depicted by sonography. Autosomal-recessive polycystic kidney disease characteristically reveals bilaterally enlarged kidneys with diffusely and uniformly increased echogenicity and loss of the normal corticomedullary differentiation. The individual cysts, which actually represent dilated collecting ducts, are too small to be resolved sonographically, but their numerous wall
Fig. 1. Normal renal sonogram of 9-day-old infant with hypertension. Sagittal image of the right kidney demonstrates normal parenchymal echogenicity with good corticomedullary differentiation. Note normal, triangular-shaped, hypoechoic renal pyramids. Duplex Doppler examination was normal.
interfaces produce exceptionally bright kidneys (increased echogenicity) with ultrasound evaluation. Autosomal-dominant polycystic kidney disease, which is less common at this age, exhibits macroscopically visible cysts of varying size. Mesoblastic nephroma, often diagnosed in infancy, and Wilms’ tumor, usually diagnosed in early childhood, manifest sonographically as a mass arising from the kidney. Wilms’ tumor may be accompanied by tumor invasion of the renal vein, which can also be detected sonographically. Hypertension can occur as a result of increased renin production by tumor cells [23]. In the infant with renal artery thrombosis, there is little parenchymal abnormality in the acute phase of vascular obstruction, but with time there is loss of corticomedullary differentiation with diffusely increased echogenicity, and decreased renal size, indicating chronic ischemia. Chronically ischemic or infarcted kidneys appear markedly shrunken and abnormally echogenic (Fig. 2). Renal vein thrombosis likewise exhibits poor corticomedullary differentiation, but the affected kidney is enlarged. Thrombus, usually manifested by intraluminal echogenic material, may be detected in the renal artery or vein, or in the abdominal aorta. Intraluminal thrombus, however, occasionally appears anechoic (without echoes, indistinguishable from the patent blood vessel lumen) and color Doppler imaging is required to demonstrate its presence. Although the presence of echogenic thrombus within the lumen of the aorta or the renal artery is highly suggestive of thrombus, a recent study of
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
Fig. 2. Abnormal renal sonogram in young child with renovascular hypertension. Sagittal sonogram reveals loss of corticomedullary differentiation (compare with Fig. 1) and focal areas of chronic cortical scarring (arrows). Note focal upper pole caliectasis (white arrow).
infantile hypertension has demonstrated no causal relationship between the identification of renal or aortic thrombus and renovascular hypertension [15]. Conversely, many normotensive patients fulfilled gray-scale sonographic criteria for thromboembolism. A prospective study using ultrasound to detect aortic thrombus was positive in 12 of 71 patients in the neonatal intensive care unit; only one of these patients developed hypertension and two normotensive patients subsequently proved to have aortic thrombus did not have sonographically detectable renal artery thrombus [24]. The reported incidence of catheter-associated thromboembolism in infants is highly variable, ranging from 3.5% to 23% in autopsy series to 95% in prospective ultrasound studies [25]. Clearly, it is a common complication, and the presence of echogenic intravascular material associated with systemic hypertension is highly suggestive of renovascular disease; however, earlier reports have demonstrated that grayscale imaging alone does not identify all cases of renovascular hypertension. If the affected renal vessels are beyond first-order branch vessels that cannot be resolved reliably sonographically, and there are no associated morphologic changes in the renal parenchyma, there is no gray-scale sonographic abnormality. It is postulated that small-vessel renal disease can be identified on gray-scale imaging as a dotted corticomedullary junction [26]. Color Doppler imaging. Color Doppler imaging can be used as an adjunct to gray-scale imaging in the detection of intraluminal thrombus, which may be isoechoic to flowing blood. Color Doppler imaging can show absent flow distal to thrombus and the presence of collateral vessels [27]. In addition to
935
renal vascular imaging, the abdominal aorta can be examined from the diaphragm to the bifurcation in the coronal plane, to look for disruption of color flow by thrombus. Color imaging also is useful in distinguishing between anechoic renal hilar vascular structures from a similar-appearing dilated ureter or collecting system. The renal vasculature can be evaluated best sonographically by duplex Doppler imaging. Various quantitative and qualitative measures have been designed to define renovascular disease. The classic duplex Doppler findings in arterial stenosis are an increase in blood flow velocity and spectral broadening. Spectral broadening denotes a widening in the spectrum of detected velocities, which is a manifestation of turbulent flow through a stenotic segment. Because renal blood flow is parabolic and the spectrum is inherently widened, however, spectral broadening is not a valid means of defining turbulent flow in the renal arteries [28]. Other objective measurements have been designed to define sonographically renovascular hypertension. The acceleration index and resistive index have been used to identify renovascular hypertension [28]. The acceleration index is determined by the intersection of a line indicating the upstroke of systole with a line drawn 1 second later perpendicular to the baseline; the height of this line is divided by the ultrasound frequency. The resistive index, a more commonly used measurement, is the ratio of peak diastolic velocity to peak systolic velocity (Fig. 3). Patriquin et al [28] studied 20 children in whom renal artery stenosis was suspected. Doppler tracings from at least three segmental or intralobar arteries were obtained in
Fig. 3. Spectral Doppler image in 1-year-old child with renal artery stenosis. Resistive index (RI) is measured (electronic cursors) as the ratio of the peak diastolic velocity to the peak systolic velocity (RI = 1 [D/S]). In this case 1 (28.8/ 83.5) = 0.66. Note normal Doppler waveform from the renal artery.
936
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
each patient and the acceleration index and resistive index calculated. Both indices were significantly lower in stenotic arteries (the acceleration index to a greater extent), with clear discrimination between normal arteries and those with at least a 75% angiographic stenosis. Normal renal arteries were associated with an acceleration index of 4 to 7; renal arteries with at least 75% stenosis ranged from 0.7 to 2.6. Although used more commonly in practice, the resistive index varied less with renal arterial stenosis with a resistive index of 0.56 or less predicting stenosis with 95% probability [28]. Conversely, a prospective study of hypertensive children aged 12 days to 15 years defined a subset of angiographically proved renovascular hypertensive patients with negative Doppler examinations. The Doppler ultrasound examinations, however, were assessed qualitatively [29]. Specifically, they used pattern recognition of the tardus-parvus phenomenon [30], where pulsus tardus is the slowed, delayed systolic upsweep, and pulsus parvus represents a dampened maximal systolic peak, characteristic of a severe stenosis (Fig. 4). The presence of multiple renal arteries and segmental lesions accounted for most false-negative Doppler examinations. In this series, hypertensive patients with a negative duplex Doppler examination generally had vascular lesions amenable to endovascular or surgical treatment with a high rate of success. It was concluded that for these reasons Doppler sonography may be unreliable in the evaluation of renal artery stenosis. The authors suggested that with a negative Doppler sonogram and a
Fig. 4. Renal sonogram with spectral Doppler image in 1-year-old child with renal artery stenosis demonstrating tardus-parvus phenomenon. Duplex Doppler spectral tracing of the left renal artery reveals delayed and dampened systolic upsweep (arrow) typical of renal artery stenosis (note continuous venous waveform below the line). Compare with normal renal arterial waveform in Fig. 3.
Fig. 5. Renal arteriogram in a 3-year-old patient with uncontrollable hypertension and history of neurofibromatosis. Middle aortic syndrome with renal artery stenosis. Aortic arteriogram reveals marked, long-segment stenosis and irregularity of the aorta extending from the suprarenal region to just above the bifurcation. The right renal artery is occluded at its origin (curved arrow) and the left renal artery (straight arrow) is markedly stenotic. Note also occlusion of the hepatic artery (large arrow). There is marked enlargement of the inferior mesenteric artery and left colic artery (arrowheads), and multiple lumbar arteries. (Courtesy of Jaime Tisnado, Medical College of Virginia, Richmond, VA.)
strong suspicion for renovascular hypertension, selective or superselective arteriography in association with segmental venous renin sampling should be performed because an angiographically demonstrated causal lesion, if treated, most likely results in cure [29]. Angiography is generally deferred in the neonate, however, and medical treatment (often with angiotensin converting enzyme inhibitors [ACEI]) is the mainstay. The aforementioned studies using Doppler ultrasound included very few infants. Technical factors, including the inherent difficulty in obtaining Doppler signal from multiple intrarenal vessels, the long duration of the examination, and the frequent lack of visualization of the proximal renal vasculature because of bowel gas, challenge the implementation
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
of this technique at all, let alone in infants. Multiple additional factors further complicate the application of such techniques in the neonatal ICU, including the use of portable machines; the presence of life support lines and tubes; and the likelihood that the patient is dependent on mechanical ventilation, which renders duplex Doppler sonography virtually impossible (especially in the setting of high-frequency ventilation). Sonography is a versatile modality that offers several parameters for evaluating the hypertensive infant. The implementation of duplex Doppler sonography is limited by operator skill and experience and by the technical difficulties in performing this tech-
937
nique in the intensive care setting. In the persistently hypertensive neonate in which duplex Doppler sonography is not technically feasible, the identification of intraluminal thrombus on gray-scale imaging suggests the diagnosis. The absence of intraluminal thrombus on gray-scale imaging, however, does not exclude renovascular hypertension and further diagnostic investigation should be pursued. Angiography The accuracy of Doppler sonography in the diagnosis of renal artery stenosis has been compared with renal angiography, which is considered the gold
Fig. 6. Technetium (Tc) 99m MAG3 ACEI renogram in a 13-day-old infant with unexplained hypertension. (A, B) Normal baseline study. Posterior images of the kidneys were obtained following the intravenous administration of Tc 99m MAG3 (initial flow images were unremarkable) (A). Note symmetric uptake and excretion of tracer, followed by visualization of the urinary bladder. Normal time-activity curve demonstrates peak renal activity at 3 minutes (normal) and a differential function of 48.8% (left kidney) and 51.2% (right kidney) (B). (C, D) Normal enalaprilat study. Posterior images of the kidneys were obtained following the intravenous administration of enalaprilat, followed by intravenous Tc 99m MAG3 (C). Peak renal activity on the time activity curves is demonstrated at 2 minutes (normal) (D). There is normal differential function: 45% (left kidney) and 55% (right kidney), and no significant renal cortical retention of tracer.
938
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
Fig. 6 (continued ).
standard in the evaluation of renovascular hypertension [14,15,20]. Despite the high incidence of renovascular hypertension in children relative to adults, the use of renal arteriography in children has been limited. The necessity for general anesthesia generally preempts the use of conventional arteriography in infants. Catheter-related vascular injury and radiation exposure are other potential adverse considerations. Although intra-arterial digital subtraction arteriography requires substantially less intravascular contrast material and shortens the duration of the procedure compared with traditional arteriography, resulting in less radiation exposure, it has not substantially increased the use of arteriography in the diagnosis of infantile hypertension. When performed, digital subtraction arteriography images may be compromised by the presence of bowel gas, although both intravenous glucagon and abdominal compression can mitigate this problem [31]. Intravenous digital subtraction arteriography has been attempted as an alternative to arteriography in the evaluation of renovascular hypertension with limited success. Intravenous digital subtraction arteriography requires a higher contrast load and the vessels of interest are frequently not well opacified by this technique. Lesions beyond the first-order branch vessels are not demonstrated by intravenous digital subtraction arteriography and this technique has been
essentially abandoned in the evaluation of the hypertensive infant [20]. The potential benefit of arteriography in the evaluation of the pediatric hypertensive patient is the opportunity for definitive treatment. Percutaneous transluminal angioplasty has been demonstrated to be effective in the adult population and has recently been applied to the pediatric population with success [17,18]. Nonetheless, virtually no data are available regarding the use of percutaneous transluminal angioplasty in infants. The highest rate of success in children has been associated with nonostial, shortsegment main renal arterial lesions; the technical difficulty in traversing ostial lesions, with or without aortic involvement, often precludes successful angioplasty [32]. Most angiographically demonstrated lesions in cases of pediatric hypertension are related to intrinsic vascular disorders, such as fibromuscular dysplasia, neurofibromatosis, and other undifferentiated vasculitides. During arteriography, pharmacologic maneuvers, such as epinephrine infusion, can determine the hemodynamic significance of renal arterial lesions. One of the inherent advantages of angiography is that the main renal artery, and the intrarenal segmental, subsegmental, and any accessory renal arteries are well demonstrated and any of these vessels may be affected
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
939
Fig. 6 (continued ).
in the previously mentioned disorders (Fig. 5). Although these entities do occur in infants, they are not typically the chief diagnostic considerations in this age group, especially in neonatal patients. In infants, the most common underlying abnormality is catheter-related thromboembolism. Aortic and renal arterial thrombus can be demonstrated with contrast aortography and renal arteriography performed by the offending umbilical artery catheter [25]. Many studies have proved the efficacy of arteriography in documenting the presence of thrombus in association with umbilical arterial catheterization. There has been very poor correlation, however, between the presence of thrombus and clinical signs and symptoms. The variably reported incidence of arterial thrombus associated with umbilical artery catheterization is high enough that it may be an incidental finding in some instances. In any event, catheter-associated aortic and renal arterial thrombus has been treated relatively successfully
with medical therapy and not with percutaneous transluminal angioplasty, which argues against the implementation of arteriography [1,15,33]. Because the usual first-line therapy in neonatal renovascular hypertension is ACEI and revascularization is generally not an option, it is more important to identify cases of bilateral renal ischemia and renal ischemia in a solitary kidney in which ACEI therapy is contraindicated. Renal scintigraphy is the least invasive and most reliable means of providing this information. Renal scintigraphy Renal scintigraphy can yield valuable functional data with variable anatomic detail. In the presence of unilateral renal artery stenosis, conventional radionuclide scintigraphy may show evidence of relatively diminished renal perfusion and function of the affected kidney. Because of the autoregulatory mechanism, however, mediated by the renin-angiotensin system,
940
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
Fig. 6 (continued ).
the glomerular filtration rate (GFR) may be maintained at a normal level and the scintigram may be normal. Performing the examination in conjunction with an ACEI greatly increases the sensitivity and specificity of renal scintigraphy for detecting hemodynamically significant renal artery stenosis; the sensitivity and specificity are each approximately 90% [34]. When renal arterial stenosis reaches 60% of the cross-sectional diameter of the artery, the kidney responds by increasing its output of renin, stimulating production of angiotensin II, which augments falling GFR by increasing tone in the efferent arterioles at the cost of generalized vasoconstriction, resulting in systemic hypertension [14]. The administration of an ACEI blocks the production of angiotensin II, which decompensates renal function. An ACEI scintigraphy capitalizes on this physiologic compensation mechanism. A baseline renogram is first performed, which may be normal with a renal arterial stenosis of up to 70% to 80% [14]. Beyond this range, renin-angiotensin compensation may be incomplete and the baseline study may show diminished function. If the kidney has infarcted and there is no residual function, the baseline study results in nonvisualization of the involved kidney.
If the baseline study is normal, the administration of the ACEI eliminates the renin-angiotensin compensation and thereby decreases the renal perfusion commensurate with the degree of stenosis. This translates to a decrease in function in the well-compensated kidney. There is high probability of hemodynamically significant renal artery stenosis when there is (1) marked change in the renogram curve, (2) unilaterally reduced relative uptake of tracer, or (3) unilaterally prolonged renal and parenchymal transit time. In cases of very severe renal artery stenosis (up to 95%) there is no significant change from baseline after ACEI administration with at most minimal residual renal function. When renal arterial stenosis has resulted in complete obstruction, the baseline scintigram may demonstrate some blood pool activity caused by collateral vessels and there is no change after ACEI. Renal scintigraphy for the evaluation of renal artery stenosis can be performed with a choice of ACEI: captopril or enalaprilat. Enalaprilat is administered intravenously, and unlike orally administered captopril, its pharmacologic effect is not dependent on rate of gastrointestinal absorption. ACEIs can cause significant hypotension; blood pressure and heart rate are monitored before and during ACEI administration.
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
The baseline and follow-up ACEI scintigraphy can be performed with either glomerular or tubular radiopharmaceuticals. The original studies performed in pediatric patients used a glomerular agent, Tc 99m diethylenetriamine pentaacetic acid (DTPA) with captopril [35]. Subsequently, Tc 99m mercaptoacetyltriglycine (MAG3), a tubular agent, has been used for ACEI renography. It is preferred over Tc 99m DTPA in patients with elevated serum creatinine, because of its higher renal extraction.
941
The disposition of glomerular agents in the kidney is dependent on the GFR; the rate of accumulation of radiotracer is directly proportional to the GFR. The rate of glomerular agent accumulation can be expressed as the slope of the curve of computergenerated graphs at fixed intervals and differential renal function of each kidney can be derived (Fig. 6). With Tc 99m DTPA, the scintigraphic manifestation of decreased renal function following ACEI administration is decreased extraction and delayed appearance
Fig. 7. Tc 99m MAG3 renogram. Renal artery stenosis in an older child with hypertension. (A) Posterior images of the kidneys were obtained following the intravenous administration of enalaprilat (initial flow images were unremarkable). The early images reveal reduced tracer uptake and function of the relatively smaller right kidney, whereas the normal left kidney reveals normal accumulation and ureteral excretion of tracer. The delayed images demonstrate marked retention of tracer in right kidney (arrow), consistent with hemodynamically significant renal artery stenosis. (B) Normal baseline Tc 99m MAG3 renogram. (Courtesy of Massoud Majd, Children’s National Medical Center, Washington, DC.)
942
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
of the radiotracer in the collecting system. The affected kidney demonstrates relatively decreased uptake. Tubular agents are secreted by the proximal tubules, a function that is maintained in the setting of a falling GFR. As urine production in the ischemic kidney decreases after ACEI administration, the tubular agent accumulates and remains in the cortex because of the fall in urine production. The affected kidney demonstrates parenchymal retention of tracer (Fig. 7). Tc 99m MAG3 has an advantage over Tc 99m DTPA in that the images are of higher resolu-
tion, and measurements of residual cortical activity can be displayed graphically (see Fig. 7). In hypertensive neonates without an umbilical arterial catheter, an abnormal ACEI study indicates renal artery stenosis. A more common cause of hypertension in neonates, however, usually transient, is narrowing of the renal artery because of thrombosis as a complication of the umbilical artery catheter (Fig. 8). The value of ACEI renography in these neonates is to determine whether it is safe to treat them with ACEI therapy.
Fig. 8. Tc 99m MAG3 renogram. Renal artery thrombosis. Neonate who became hypertensive a few days following umbilical artery catheter placement. (A) Initial posterior images obtained following administration of enalaprilat reveal a normal-appearing right kidney, and a smaller, irregularly contoured left kidney, presumably developmental. Delayed images reveal normal excretion from the left kidney, but marked retention of MAG3 in the right kidney (arrow) caused by partial obstruction of the renal artery. Time-activity curves generated from region of interest drawn around the right kidney demonstrate (B) normal preACEI function of the right kidney (pre-captopril) and (C) impaired post-ACEI function (post-enalaprilat). (Courtesy of Massoud Majd, Children’s National Medical Center, Washington, DC.)
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
In addition to its high sensitivity and specificity for hemodynamically significant renal artery stenosis, a major benefit of ACEI renography is that a positive study indicates a high probability that blood pressure is reduced following angiographic intervention [31]. Although this procedure has been performed safely in young children [18], subsequent intervention with percutaneous transluminal angioplasty is an unlikely consideration in the young infant.
Future considerations for imaging diagnosis CT angiography of the renal arteries has had promising results in the detection of renal artery stenosis in the adult population. New developments in CT technology, including spiral CT and multidetector CT, allow volumetric acquisitions during a single breathhold. The volume of acquired data can then be reformatted for display in any plane. Sensitivity and specificity for detection of hemodynamically significant renal artery stenosis in the adult population have been as high as 92% and 83%, respectively [36], and 90% and 97%, respectively [37]. High sensitivity and specificity for this modality may be caused by the ostial location of stenotic lesions seen in adults. Although little data are currently available describing use of CT angiography in infants and children, potential advantages include relative speed of image acquisition (which may obviate need for sedation), and minimal invasiveness, as compared with angiography. Potential disadvantages include inability to breathhold, and limitations in the evaluation of small accessory, segmental, or intrarenal arteries [37], which unfortunately are frequently involved in infants with renal artery stenosis. Additionally, larger doses of intravenous contrast are required with CT angiography than with intra-arterial digital subtraction arteriography [37]. As with CT angiography, little data are available on the use of MR angiography of the renal arteries in infants. Anecdotally, MR angiography has been attempted by one of the authors, in an infant with intractable hypertension, and in an older child with middle aortic syndrome. Limitations were difficulty resolving the small renal arteries, motion artifact during imaging, and the need for sedation for this relatively long study. Obvious advantages include lack of ionizing radiation or intravenous contrast.
Summary This article reviews the literature and describes a methodologic approach to the diagnosis of hyperten-
943
sion in the young infant. The numerous etiologies of hypertension have been discussed and normative blood pressure data for neonates and infants have been provided. Techniques for accurate blood pressure measurement in the intensive care setting and for routine outpatient settings, are discussed. The lengthy discussion of radiologic approach to imaging can be summarized with the following suggested algorithm. Initial screening should be performed with gray-scale sonography, to identify renal parenchymal or collecting system abnormalities, including mass lesions and congenital anomalies. Further imaging with color and duplex Doppler sonography detects renal arterial or aortic thrombosis, and alterations in the arterial waveform caused by intrinsic or extrinsic renal artery narrowing. The major limitation of Doppler sonography is the recognition that disease in accessory renal arteries or in small segmental intrarenal arteries may frequently be undetected. Functional imaging with ACEI renography should follow renal sonography to detect hemodynamically significant renovascular disease (with a sensitivity and specificity of approximately 90%); intravenous enalaprilat is the preferred ACEI. Angiography should be reserved for older children in whom interventional percutaneous angioplasty may be more feasible. A young infant with hypertension caused by renal artery stenosis should be controlled medically until he or she is large enough to undergo angiography and angioplasty successfully. CT angiography and MR angiography, although promising in the adult population, may not adequately resolve the small intrarenal vessels, which are frequently the culprit in renovascular hypertension of infancy.
References [1] Flynn JT. Neonatal hypertension: diagnosis and treatment. Pediatr Nephrol 2000;14:332 – 41. [2] Lee YH, Rosner B, Gould JB, et al. Familial aggregation of blood pressure of newborn infants and their mothers. Pediatrics 1976;58:722 – 9. [3] Sinkin RA, Phillips BL, Adelman RD. Elevation in systemic blood pressure in the neonate during abdominal examination. Pediatrics 1985;76:970 – 2. [4] Moss AJ, Duffie Jr ER, Emmanouilides G. Blood pressure and vasomotor reflexes in the newborn infant. Pediatrics 1963;32:175 – 9. [5] The National Heart, Lung, and Blood Institute (Bethesda, MD). Report of the Second Task Force on Blood Pressure Control in Children. Pediatrics 1987;79:1 – 25. [6] Tan KL. Blood pressure in very low birth weight infants in the first 70 days of life. J Pediatr 1988;112: 266 – 70.
944
C.G. Roth et al / Radiol Clin N Am 41 (2003) 931–944
[7] McGarvey ST, Zinner SH. Blood pressure in infancy. Semin Nephrol 1989;9:260 – 6. [8] Zubrow AB, Hulman S, Kushner H, et al. Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. J Perinatol 1995;15:470 – 9. [9] Adelman RD. Neonatal hypertension. Pediatr Clin North Am 1978;25:99 – 110. [10] Gruskin AB, Lerner GR, Fleischmann LE. Management of acute and primary hypertension in children. In: Murakami K, Kitagawa T, Yabuta K, et al, editors. Recent advances in pediatric nephrology. Amsterdam: Elsevier; 1987. p. 121 – 6. [11] Adelman RD. Long-term follow-up of neonatal renovascular hypertension. Pediatr Nephrol 1987;1:35 – 41. [12] Inglefinger J. Nephrology forum: renovascular hypertension in children. Kidney Int 1993;43:493 – 505. [13] Singh HP, Hurley RM, Myers TF. Neonatal hypertension: incidence and risk factors. Am J Hypertens 1992; 5:51 – 5. [14] Sfakianakis GN, Bourgoignie JJ, Georgiou M, Guerra JJ. Diagnosis of renovascular hypertension with ACE inhibition scintigraphy. Radiol Clin North Am 1993; 31:831 – 48. [15] Chandar JJ, Sfakianakis GN, Zilleruelo GE, Guerra JJ, Georgiou MF, Abithol CL, et al. ACE inhibition scintigraphy in the management of hypertension in children. Pediatr Nephrol 1999;13:493 – 500. [16] Starinsky R, Manor A, Segal M. Non-functioning kidney associated with neonatal adrenal hemorrhage: report of two cases. Pediatr Radiol 1986;16:427 – 9. [17] Tyagi S, Kaul UA, Satsangi DK, Arora R. Percutaneous transluminal angioplasty for renovascular hypertension in children: initial and long-term results. Pediatrics 1997;99:44 – 9. [18] Courtel VC, Soto B, Niaudet P, Gagnadoux MF, Carteret M, Quignodon JF, et al. Percutaneous transluminal angioplasty of renal artery stenosis in children. Pediatr Radiol 1998;28:59 – 63. [19] Stanley P, Hieshima G, Mehringer M. Percutaneous transluminal angioplasty for pediatric renovascular hypertension. Radiology 1984;153:101 – 4. [20] Zerin JM, Hernandez RJ. Renal imaging in children with persistent hypertension. Pediatr Clin North Am 1993; 40:165 – 78. [21] Rosenbaum DM, Korngold E, Teele RL. Sonographic assessment of renal length in normal children. Am J Radiol 1984;142:467 – 9. [22] Hricak H, Slovis TL, Callen CW, et al. Neonatal kidneys: sonographic anatomic correlation. Radiology 1983;147:699 – 702.
[23] Cohen MD. Imaging of children with cancer. St. Louis: Mosby Year Book; 1992. [24] Oppenheimer DA, Carroll BA, Garth KE. Ultrasonic detection of complications following umbilical arterial catheterization in the neonate. Radiology 1982;145: 667 – 72. [25] Ford KT, Teplick SK, Clark RE. Renal artery embolism causing neonatal hypertension. Radiology 1974; 113:169 – 70. [26] Garel LA, Pariente DM, Gubler MC, et al. The dotted cortico-medullary junction: a sonographic indicator of small vessel disease in hypertensive children. Radiology 1984;152:419 – 22. [27] Deeg KH, Wolfel D, Rupprecht TH. Diagnosis of neonatal aortic thrombosis by colour coded Doppler sonography. Pediatr Radiol 1992;2:62 – 3. [28] Patriquin HB, Lafortune M, Jequier J-C, O’Regan S, Garel L, Landriault J, et al. Stenosis of the renal artery: assessment of slowed systole in the downstream circulation with Doppler sonography. Radiology 1992;184: 479 – 85. [29] Garel L, Dubois J, Robitaille P, Russo P, Filiatrault D, Grignon A, et al. Renovascular hypertension in children: curability predicted with negative intrarenal Doppler UAS results. Radiology 1995;195:401 – 5. [30] Kotval PS. Doppler waveform parvus and tardus. J Ultrasound Med 1989;8:435 – 40. [31] Tonkin IL, Stapleton FB, Roy S. Digital subtraction angiography in the evaluation of renal vascular hypertension in children. Pediatrics 1988;81:150 – 7. [32] Mali WP, Puijlaert AJ, Kouwenberg HJ, Klinge J, Donckerwolcke RA, Geijskes BG, et al. Percutaneous transluminal renal angioplasty in children and adolescents. Radiology 1987;165:391 – 4. [33] Caplan MS, Cohn RA, Langman CB, Conway JA, Shkolnik A, Brouillette RT. Favorable outcome of neonatal aortic thrombosis and renovascular hypertension. J Pediatr 1989;115:291 – 5. [34] Taylor AT, Fletcher JW, Nally JV, et al. Procedure for diagnosis of renovascular hypertension. J Nucl Med 1998;39:1297 – 302. [35] Majd M, Potter BM, Guzzetta PC, et al. Effect of captopril on efficacy of renal scintigraphy in detection of renal artery stenosis. J Nucl Med 1983;24:23. [36] Rubin GD, Dake MD, Napel S. Spiral CT of renal artery stenosis: comparison of three-dimensional rendering techniques. Radiology 1994;190:181 – 9. [37] Kim TS, Chung JW, Park JH. Renal artery evaluation: comparison of spiral CT angiography to intra-arterial DSA. J Vasc Interv Radiol 1998;9:553 – 9.