Pediatric Renovascular Hypertension: Diagnosis and Management

Abstract

Pediatric renovascular hypertension (RVH) is a significant cause of secondary hypertension in children, often resulting from renal artery stenosis (RAS) due to nonatherosclerotic etiologies such as fibromuscular dysplasia (FMD), mid aortic syndrome (MAS), and syndromic conditions like neurofibromatosis type 1 (NF-1). Early diagnosis is critical to prevent long-term complications, including renal dysfunction and cardiovascular disease. Diagnostic evaluation begins with ultrasound, which, despite its limitations, remains the first-line modality. Advanced imaging techniques such as CT angiography (CTA), MR angiography (MRA), and digital subtraction angiography (DSA) provide detailed vascular assessment, with DSA considered the gold standard. Adjunctive tools like intravascular pressure measurements, intravascular imaging, and renal vein renin sampling supplement DSA. Management should have multidisciplinary consensus and is tailored to the individual patient. Pharmacological therapy is seldom sufficient and percutaneous transluminal angioplasty is effective in many cases. Stent placement and surgical interventions are reserved for refractory or complex cases. Chemical ablation in select cases and emerging therapies such as renal denervation offer additional options. This review outlines the current diagnostic and therapeutic approaches to pediatric RVH, emphasizing the importance of personalized care and the role of specialist pediatric centers, with experience in managing RVH, in optimizing outcomes.

Hypertension in Childhood

Hypertension in childhood arises from a complex interplay of genetic, environmental, and physiological factors, with causes broadly categorized into primary (essential) and secondary types.

The criterion for diagnosing pediatric hypertension is based on the distribution of blood pressure among healthy children and adolescents determined by gender, age, and height. The 90th and 95th percentiles of the normal distributions are often set as reference ranges for high normal blood pressure and hypertension, respectively. ¹

Primary hypertension is increasingly common in adolescents in the Western world and is associated with modifiable lifestyle factors such as dietary habits, obesity, and sedentary lifestyle. Children with hypertension are more likely to be overweight, and the prevalence of hypertension in this cohort can reach up to 40%. ^{2 3} Children of hypertensive parents, through genetic predisposition, are also at higher risk, although environmental factors such as diet and exercise modulate this risk. ²

Secondary hypertension, caused by an underlying medical condition, is more prevalent in younger children. Underlying conditions can include renal parenchymal disease, renovascular disease, endocrine disorders, hormone secreting neuroendocrine tumors such as pheochromocytoma and paraganglioma, and the side effects of several medications such as corticosteroids.

The etiology of secondary hypertension in children varies by age, with renovascular hypertension (RVH) being the most common cause in younger children (42%) and renal parenchymal disease more common in older children (77%). ⁴ Both the conditions activate the renin-angiotensin-aldosterone system (RAAS). In RVH, renal hypoperfusion results in increased renal production of the hormone renin, which triggers a cascade resulting in angiotensin II production causing increased blood pressure through systemic vasoconstriction and aldosterone-mediated sodium retention and volume expansion. ^{3 5}

Renal artery stenosis (RAS) is the most common cause of RVH. While atherosclerotic disease is the commonest cause of RAS in adulthood, it is nonatherosclerotic RAS that is more prevalent in childhood. Etiologies include fibromuscular dysplasia (FMD), a noninflammatory vasculopathy which can present with a range of findings ranging from “string of beads” to vascular kinking, ⁶ the sequela of vasculitides such as Takayasu arteritis, mid aortic syndrome (MAS), developmental narrowing of the abdominal aorta, renal arteries, and mesenteric arteries, or due to underlying genetic conditions such as neurofibromatosis type 1 (NF-1) and Williams syndrome. ⁵ Syndrome-related RVH is often severe and progressive, highlighting the need for blood pressure screening in this cohort. ⁷

RVH is a challenging diagnosis in infancy and young children and the delay in diagnosis can lead to prolonged symptomatology, reduced renal growth, or the loss of renal size in the kidney involved. ⁸ RVH should be suspected clinically in children with hypertension, hypertension refractory to medical management, and when associated with positive examination findings such as abdominal bruits. Clinical suspicion of RVH should prompt swift imaging investigations and intervention to prevent long-term complications of uncontrolled hypertension including progressive renal dysfunction and cardiovascular disease.

Diagnosis

Diagnostic evaluation of pediatric hypertension includes noninvasive imaging with ultrasound, radionuclide imaging, and CT or MR angiography. Catheter-based angiography, with adjunct endovascular techniques, remains the gold standard investigation for suspected RVH as it is able to detect subtle or distal lesions. ⁹

Ultrasound

Ultrasound is universally the first-line imaging modality when RVH is suspected and can detect RVH in both indirect and direct ways. However, its accuracy depends on the operator's experience and patient compliance.

The presence of abnormal intrarenal arterial waveforms demonstrating a prolonged systolic upstroke and reduced peak systolic amplitude, the “parvus et tardus” waveform, is indictive of an arterial stenosis. The presence of this waveform does not locate the stenosis but only tells us that it is upstream of the point at which the waveform is sampled. It has been shown to be a reliable parameter in pediatric patients. ^{10 11} The presence of bilateral parvus et tardus waveforms suggests either bilateral RAS or disease further upstream in the aorta. Renal size asymmetry, with a size discrepancy of >1 cm between the right and left kidney, is a soft sign of hypoperfusion of the smaller kidney and, when coupled with an abnormal intrarenal waveform, further supports the presence of RAS in that kidney ( Figs. 1 and 2 ).

Fig. 1.

A 7-year-old with hypertension. ( A ) Grayscale ultrasound showing that both kidneys are normal in shape and there is preserved corticomedullary differentiation. However, there is a size discrepancy between the kidneys. The left kidney measures 8.98 cm, which is above the 95th centile for the age, and the right kidney measures 6.01 cm, which is below the 50th centile for the age. ( B ) Pulsed wave Doppler assessment of the right main renal artery demonstrating slightly delayed systolic upstroke with dampening of the waveform in keeping with a parvus at tardus waveform. ( C ) A dimercaptosuccinic acid (DMSA) scan showing that the left kidney exhibits good uptake of tracer and is functionally larger than the right kidney, which itself shows reasonable uptake of tracer. The left kidney contributes 75% to total renal function and the right kidney 25% to total renal function. ( D ) Selective catheter angiogram of the right renal artery confirms the presence of a severe ostial stenosis with post-stenotic dilatation of the distal right renal artery. ( E ) The right renal artery narrowing was crossed with a guidewire and angioplasty performed with a 3.5-mm angioplasty balloon. A subtle residual waist is seen with the angioplasty balloon inflated. ( F ) Completion angiogram showing much improved appearances of the right renal artery origin with brisk contrast flow to the right kidney. ( G ) A DMSA performed 1 year following the initial angioplasty showing that both the kidneys demonstrate good uptake of tracer, and the right kidney remains functionally smaller than the left. However, the right kidney has gained a significant amount of parenchymal function in comparison to the pre-angioplasty DMSA study. The differential function now measured 56% from the left kidney and 44% from the right kidney. ( H ) At the second catheter angiogram, a selective angiogram of the right renal artery shows a persisting mild ostial stenosis with post-stenotic dilatation of the distal right main renal artery. Angioplasty of this ostial narrowing was performed using a 4-mm, high-pressure angioplasty balloon. ( I ) Completion angiogram, with the right renal artery guidewire still in situ, showing markedly improved appearances with improved caliber of the right renal artery origin and brisk flow to the right kidney. ( J ) An ultrasound following the second angioplasty demonstrating interval growth of the right kidney which now measures 8.1 cm in bipolar diameter and which is above the 50th centile for the age. ( K ) Pulsed wave Doppler assessment of the right main renal artery demonstrating a swift systolic upstroke and normal waveform.

Fig. 2.

A 13-year-old with incidentally detected hypertension requiring two anti-hypertensives. ( A ) Pulsed wave Doppler ultrasound of intrarenal arteries in the right kidney showing “parvus et tardus” waveform. ( B ) Dimercaptosuccinic acid (DMSA) showed reduced tracer uptake in the left kidney with 75% of the function on the left and 25% on the right. ( C ) Coronal CT maximal intensity projection showing the left kidney is significantly smaller than the left. ( D ) Axial oblique image showing the right renal artery is small with proximal stenosis. ( E ) Right renal artery angiography showing proximal main right renal artery stenosis with intrarenal and capsular collaterals arising from a pre-stenotic branch. A tight stenosis in an intrarenal branch supplying the lower pole is also seen; this was not noted on CT. ( F ) Angioplasty of the intrarenal lower pole branch with 2.25 mm × 15 mm monorail balloon and then ( G ) angioplasty of the main renal artery with a 4 mm × 20 mm monorail balloon. ( H ) Completion right renal artery angiography showing improvement in luminal caliber at both stenosis with marked improvement of renal perfusion, particularly at the lower pole.

Direct assessment of the main renal arteries with pulsed-wave Doppler ultrasound can be used to facilitate dynamic assessment of flow. Peak systolic velocity (PSV) >180 to 200 cm/s, acceleration time >80 ms, a renal–aortic ratio (RAR) >2.3 to 3.5, resistive index (RI) <0.5, or difference in RI >0.05 between kidneys indicate stenosis. However, this is technically challenging in infants due to noncompliance and the small vessel size. ¹⁰ Furthermore, main renal and intrarenal branch artery flow parameters should be interpreted with caution in children as they are affected by hemodynamic differences related to hydration state and age. ¹¹ For example, high velocities in neonates are to be expected as they have higher resistance to flow in the immature renal vascular beds. ¹²

In older children who are compliant, and because of the increased vessel size, direct assessment of the diameter of the abdominal aorta and the renal arteries is possible on grayscale ultrasound in order to diagnose MAS and RAS.

Ultrasound has several limitations when RVH is suspected. Small accessory, segmental, and intrarenal branch arteries may be missed, leading to false negatives. ¹³ Doppler ultrasound has a reported sensitivity of 63 to 90% and specificity of 68 to 95% for detecting aortic or main RAS in children compared to CT, MR, or catheter angiography as reference standards. ^{10 11} Therefore a negative ultrasound does not exclude RAS and further imaging is warranted where clinical suspicion of RVH persists. ¹⁰

Contrast-enhanced ultrasound (CEUS), although not routinely utilized in this setting, is an emerging imaging modality where the intravenous administration of microbubble contrast can be used to identify perfusion defects in RAS and has a role in documenting improved perfusion following angioplasty. ¹⁴

Radionuclide Imaging

Dimercaptosuccinic acid (DMSA) scintigraphy is not a primary diagnostic tool for identifying RAS but serves as a supportive modality in the broader diagnostic workup by assessing split renal function and detecting ischemic damage ( Figs. 1 and 2 ).

Reduced split function or focal areas of photopenia in a kidney, in isolation, are not highly sensitive for detecting RAS but reduced split function in a kidney, with supportive ultrasound findings, is. It should also be noted that equal split function during the diagnostic workup of RVH may be a false negative if there is bilateral RAS or MAS and the kidneys may, in fact, be equally poorly functioning. These factors limit the sensitivity of DMSA in detecting vascular stenoses when compared to catheter angiography. ¹⁵

DMSA may be considered a more useful marker following intervention in evaluating treatment outcomes. For example, a poorly functioning kidney on DMSA pre-angioplasty which then demonstrates normalized function post-angioplasty is a reliable marker of improved renal perfusion following intervention. ¹⁶ In a review of children with RVH with abnormal DMSA scans, post-angioplasty DMSA scans were used to qualify cure, improvement, and no change following intervention, suggesting its utility in monitoring response after intervention. ¹⁷ DMSA can also be used to determine function in a kidney that is not amenable to percutaneous intervention and/or surgical revascularization. When a kidney contributes less than 10% function consideration should be given to nephrectomy/ACE-mediated infarction (so-called “medical nephrectomy”).

DMSA pre- and post-angiotensin-converting enzyme inhibitor (ACEi) administration has been considered a potential method of localizing RAS in children as the administration of the drug impairs renal autoregulation, which can accentuate renal ischemia and worsen the split function. However, results are inconsistent in children, with reported sensitivities of 59 to 73% and specificities of 68 to 88%, limiting its role as a diagnostic tool for this purpose. ^{9 18}

CT and MR Imaging

Computed tomography angiography (CTA) and magnetic resonance angiography (MRA), depending on institutional preference, are widely used in the evaluation of suspected RVH in children. CTA, with carefully optimized contrast and radiation dose parameters, has better spatial resolution and is less susceptible to artefact than MRA and can be performed without sedation or anesthesia. CTA has been shown to have marginally improved sensitivity, 88 to 90 versus 80%, and specificity, 81 to 89.7 versus 63%, when compared to MRA ^{19 20 21} and is generally considered superior at detecting vascular lesions in the main renal arteries or first-order branches that MRA may overlook. ²² As MR technology improves, with rapid time-resolved acquisition of volumetric images, at high temporal and spatial resolution, the sensitivity of MRA may advance. Furthermore, it may be possible to evaluate dynamic renal perfusion and identify ischemic areas of renal perfusion regardless of whether a stenotic vessel can be accurately depicted or not. ²³ Sensitivity of CT for detection of RAS, particularly intrarenal branch stenoses, is likely to improve with the newest generation of photon counting CT scanners. Although not yet evaluated for pediatric renal arteries, initial studies show it has potential for superior image quality and visualization of abdominal artery branches in adults ²⁴ ( Fig. 2 ).

Besides diagnosis, CTA and MRA can be an invaluable in planning endovascular intervention, for example, to identify the origin of accessory renal arteries or to evaluate the angle of take-off of a renal artery, which can influence the direction of approach, e.g., femoral versus axillary.

The limitations of both CTA and MRA are that, although they may depict aortic or main renal artery anatomy, studies have shown that they can miss main renal artery or intrarenal branch stenoses when compared to subsequent interrogation by catheter angiogram. ^{15 19} Therefore, a negative CTA or MRA, but a strong clinical and/or ultrasound suspicion of RVH, does not remove the need to advance to catheter angiography.

Angiography

Digital subtraction angiography (DSA) is consistently identified as the gold standard for diagnosing vascular lesions in children with RVH. ^{15 16 17}

Pediatric DSA is performed under general anesthesia. Ultrasound-guided arterial access is essential, given the increased complication rate in children. ²⁵ Although femoral access is the mainstay of aortic and renal angiography in children, there are cases when axillary access may need to be considered given the acute angle of take-off of the renal arteries in young children, particularly when subsequent intervention is anticipated. Radial and brachial access are generally avoided due to the small vessel size in young children, but trans-radial access can likely be safely used in adolescents. ²⁶ A general principle is to use the smallest sized vascular sheath possible to mitigate the risk of sheath-related complications and the use of low-profile radial sheaths in the femoral and axillary arteries are favored. In general, a 4-French sheath is safe and adequate even in infants. To further mitigate the risk of sheath and catheter-related thrombosis, a fluid bag can be attached to the side arm of the sheath so that there is constant infusion of saline around it. Furthermore, intraprocedural systemic heparinization, with pre- and post-ACT measurements, is advocated to prevent thrombosis in children <10 to 15 kg. ²⁵

If CTA or MRA has not been performed as part of the diagnostic workup, a rotational pump angiogram is a sensible first step in order to obtain a three-dimensional overview of the aortic and renal artery anatomy. This is particularly useful to delineate the origin of the renal arteries and identify the presence of accessory renal arteries without having to first catheterize them and risk catheter-related spasm. Spasm is a significant problem in children as their vessels are highly spasmogenic, and once present, can be difficult to differentiate from a true stenosis, even after the intra-arterial administration of 1 to 3 microgram/kg aliquots of glyceryl trinitrate. If a CTA or MRA has already been performed, a rotational pump angiogram may not be required and a two-dimensional single or biplane aortogram may suffice. Contrast volume and injection rate parameters for pump aortography are determined by the patient's weight and the vessel being injected. ²⁷

Selective renal angiograms, typically performed in two views, can then be undertaken using a 4-French guide catheter, the choice of which should be tailored to the morphology of the renal artery origin. In cases of peripheral intrarenal branch stenoses it may be necessary to undertake superselective microcatheter angiography using a tri-axial catheter technique. If so, a second flush bag should be placed onto the guide catheter using a rotating hemostatic valve.

Ventilation should be suspended for all image acquisition to mitigate respiratory artefact, and this should be discussed with the anesthetist beforehand to ensure paralysis is possible throughout the procedure.

Contrast nephropathy/toxicity is a rare occurrence but careful consideration should be given to the total contrast dose administered in children. The total contrast volume used should be <5 mL/kg in neonates and 6 to 8 mL/kg beyond the neonatal period. ²⁵ In complex interventions, the anticipated contrast dose may exceed these values and the operator may consider diluting the contrast or converting to carbon dioxide angiography in order to continue the procedure safely. ²⁸

DSA offers superior spatial and temporal resolution compared to noninvasive imaging and is uniquely capable of detecting accessory, distal, and intrarenal branch stenoses, including those missed by CTA or MRA. ^{16 17 19} DSA has been shown to identify 28% of vascular stenoses in children with RVH that were not seen on any noninvasive imaging modality. ²² Therefore, the presence of poorly controlled hypertension on two or more anti-hypertensive agents or one agent at high dose, with no other identifiable cause, and even in the presence of normal noninvasive imaging studies, can be considered an indication to proceed to DSA. ^{9 16} At the authors' institutions consideration is given to angiography.

Besides identifying the presence of vascular lesions, DSA also enables simultaneous planning and therapeutic interventions for the management of those vascular lesions. Despite its invasive nature, when performed at an experienced specialist center, the complication rate in children is low ¹⁶ ( Figs. 1 and 2 ).

Intravascular Pressure Measurements

Intravascular pressure measurements are a useful adjunct during DSA, particularly to assess the hemodynamic significance of questionable arterial lesions and can help determine whether or not a lesion is contributing to hypertension. Their use confers functional assessment and complements other intravascular imaging techniques like intravascular ultrasound (IVUS), which provide structural detail. Intravascular pressure measurements can be taken with a catheter; however, the authors prefer to use a 0.014″ wireless physiology wire, which can cross stenoses with ease compared with a 4-French catheter.

Intravascular pressure measurements are particularly relevant when visual findings alone are inconclusive. ¹⁶ For example, a commonly encountered scenario seen in patients with Williams syndrome–associated RVH is a slender, gracile, abdominal aorta without a focal stenosis as well as bilateral RAS. If there is a gradual suprarenal aortic gradient, one can infer this “lesion” is constitutional and does not represent an aorta that should be intervened upon. Although there are no established pressure gradient criteria, the authors regard an abrupt mean arterial pressure gradient of 10 mmHg across the abdominal aorta or renal artery as pathological and an indication for intervention.

Adult literature suggests that a post-angioplasty trans-lesional pressure gradient of ≤10 mmHg or reduced by >80% promotes a high success rate in RVH. ²⁹ However, this is not validated in children and the use of intravascular pressure measurements to quantify improvement following angioplasty should be interpreted with caution as pediatric RAS is typically a disease of the intimal and medial fibrosis and thus relies on remodeling of the vessel wall and immediate improvement in the trans-lesional gradient may not be evident. ³⁰ A worsening pressure gradient, however, may be indicative of an iatrogenic insult that requires further intervention.

Intravascular Imaging

IVUS, although not yet validated in children, is a high-resolution intravascular imaging technique that can be incorporated into the imaging strategy when undertaking DSA. IVUS offers detailed visualization beyond the vessel lumen and may help assess vessel wall thickness, the presence of intimal or medial calcification, and evaluate the outcomes of angioplasty or stenting. IVUS can also identify complications not easily appreciated on DSA, such as dissection which may require repeat angioplasty or emergent stenting. In the latter case, IVUS is then additionally useful to assist in appropriate stent sizing and assess stent apposition. ^{16 17} For pediatric renal arteries, the authors use coronary IVUS catheters which are monorail and lower profile than those typically used for imaging adult veins.

Renal Vein Renin Sampling

Renal vein renin sampling can be used in pediatric RVH to help localize the source of renin-driven hypertension when angiographic findings are indeterminate. This is useful in cases with bilateral or intrarenal abnormalities. ¹⁶ Another scenario where it may be helpful is when no abnormality is detected on DSA but a focally elevated renin value warrants review of the angiographic images and there have been cases of subtle intrarenal stenosis which have only been detected on retrospective review of the imaging alongside the results of the renal vein renin sampling.

Renal vein renin sampling is performed using a transfemoral transvenous approach. Using an appropriately sized guide catheter venous samples are collected from the inferior vena cava, the right main renal vein, and the left main renal vein. A microcatheter technique can then be used to obtain intrarenal venous samples from the upper, mid, and lower pole tributaries in both kidneys.

The samples take some time to process so renal vein renin sampling has no role in real-time decision-making about whether to proceed to endovascular intervention. However, once available, a renin ratio >1.5 between the renal veins is considered significant, while a ratio <1.3 between the contralateral renal vein and the inferior vena cava is abnormal and supports a diagnosis of RAS.

Management

Although medical management with pharmacological agents is the first-line treatment, RVH is often refractory to medical management and necessitates intervention. Angioplasty is effective in pediatric RVH, particularly in FMD, whereas stent insertion is largely avoided. Surgery is reserved for cases of resistant hypertension or progressive renal dysfunction, where endovascular intervention has failed, with techniques tailored to minimize ischemia and accommodate growth. ⁵ The management of pediatric RVH must be personalized through a multidisciplinary approach, and the tailored use of pharmacological, endovascular, and surgical interventions allow for favorable outcomes in the vast majority of patients. ³¹

Pharmacological Management

Drug therapy for pediatric RVH often involves polypharmacy. ACEi and angiotensin receptor blockers (ARBs) are generally avoided in bilateral disease due to the risk of renal impairment, especially in bilateral disease. In fact, an abrupt fall in glomerular filtration rate (GFR) is often seen after the administration of ACEi and ARBs, and this can be a diagnostic clue when RVH is not already suspected. ³² Medical therapy alone rarely cures RVH but an optimal pharmacological regimen should be initiated prior to endovascular intervention.

Following intervention, low-dose Aspirin is added to reduce recurrence, by reducing the rates of platelet aggregation, possibly reducing inflammatory neointimal hyperplasia and improving vascular remodeling at site of angioplasty. ³³ There is no consensus on dose but 1 mg/kg/day for 3 to 6 months has been proposed. ³⁴ For patients who are likely to require repeated interventions, the authors advocate keeping the patient on Aspirin for the duration of their interventions.

Angioplasty

Angioplasty is the most common endovascular intervention for managing RVH in children, particularly when blood pressure is inadequately controlled with medications or there are adverse effects from prolonged polypharmacy. The primary goal of angioplasty is to improve renal perfusion and growth, preserve renal function, remove or reduce the number of antihypertensive agents the patient is on, reduce the risk of end-stage organ damage such as cardiac dysfunction, and, when cure is not possible, delay the need for surgery until after puberty. ¹⁷

Once a vascular stenosis has been identified on RAS, the lesion is crossed with a guidewire and angioplasty performed with a low-profile balloon. Due to the paucity of kit designed for the small sizes in pediatric intervention, ³⁵ the authors' preference is to use 0.014″ guidewires and coronary mono-rail balloons for small renal arteries ( Figs. 1 and 2 ). In the case of MAS with a suprarenal, flow-limiting, aortic stenosis, the aorta can be treated by angioplasty as well as the diseased renal arteries. The aorta is treated first with safety wires placed in the superior mesenteric artery (SMA) and bilateral renal arteries to mitigate the risk of iatrogenic occlusion of the artery origins. Celiac axis and SMA origin stenoses are often encountered in MAS but they are seldom intervened upon because of adequate collateral flow to those vascular territories from the hypertrophied arc of Riolan. ³⁶

Semi-compliant and non-compliant/high pressure balloon angioplasty is effective across a range of vessel sizes and severities of stenosis. Cutting balloon angioplasty is reserved for recalcitrant or complex stenoses as it confers a higher risk of dissection or aneurysm, and its use should be carefully considered ^{17 37 38} but there is evidence that, in experienced hands, cutting balloon angioplasty is well tolerated and effective. ³⁹

Reported outcomes following angioplasty vary. Cure, normotension without medication, has been reported in 18 to 60% of cases and improvement, blood pressure control with medication, has been reported in 17 to 65% of cases. Short-segment stenosis with minimal residual narrowing post-procedure is associated with better outcomes. Restenosis occurs in 17 to 41% of cases, but repeat angioplasty is generally safe and effective. ¹⁷ Besides improved blood pressure control, angioplasty has also been demonstrated to confer long-term preservation of renal function, as reflected by an increase in affected kidney size and improved GFR. ⁴⁰ Although less favorable, there is also evidence to suggest that patients with total main renal artery or branch occlusion are suitable for endovascular intervention as technical success in recanalization has been demonstrated. ⁴¹ Improvement in cardiac outcomes after angioplasty has been demonstrated by way of echocardiogram changes in which almost half of patients demonstrate improvement in abnormal echocardiographic parameters. ⁴²

The outcome of angioplasty for RAS in children has been found to be influenced by numerous factors including patient's age and the etiology of RVH. The location of the stenosis, with ostial stenosis having a less favorable outcome compared to non-ostial stenosis, and the length of the stenosis, with stenoses <10 mm showing a more favorable outcome, are also important. ^{37 43}

Although patients and their families should be counseled about potential complications, such as vascular dissection and transection, angioplasty remains a safe and effective first-line treatment for pediatric RVH with a low major complication rate. ⁴⁴ Despite this, efforts should be made to plan for all possible outcomes and angioplasty in children should be discouraged in centers where pediatric vascular surgery and intensive care unit provisions are not available.

Stent Insertion

Angioplasty alone, without stent insertion, is preferred in children due to the limitation of vessel growth, and hence its luminal diameter, once a stent is placed, the increased restenosis rates, and the increased rate of reintervention required following stent placement. There is evidence that restenosis rates after stenting are significantly higher than after angioplasty alone at 35.5% versus 17.4%, respectively. ^{38 45}

Where angioplasty alone has been unsuccessful in managing a vascular stenosis, consideration should be given to surgical options rather than stent insertion as the presence of a stent in the renal artery can preclude future surgical options as resecting the stented portion of the renal artery can limit the length of native renal artery available for successful surgical reimplantation or auto-transplant and necessitate a graft to extend the length of the artery, which itself confers additional future complexity. Furthermore, an inappropriately placed stent, for example, with its proximal end protruding into the abdominal aorta or distal end protruding into a branch vessel, can have poor outcomes creating an aortic stenosis where there previously wasn't one or further reduced renal perfusion, increasing future surgical complexity.

Nonetheless, stent insertion may be considered in specific scenarios such as in cases of recalcitrant stenosis, significant elastic recoil, iatrogenic dissection, or renal artery rupture and management of surgical complications such as anastomotic stricutres. ¹⁷

A specific example where stent insertion may also be considered is in severe MAS where angioplasty alone is only a temporizing measure until a definitive surgical intervention can be performed, which is generally deferred until the patient has reached full growth potential. In cases of severe refractory hypertension with evidence of end-organ failure despite repeated angioplasty, stent insertion across the diseased segment of the abdominal aorta avoiding the origins of the renal arteries (type I suprarenal MAS) can be performed to provide blood pressure control and allow growth until surgery can be safely considered. ⁴⁶

When required, balloon-expandable stents are favored as they allow some degree of future dilation to accommodate growth of the patient. ⁴⁷ In cases of severe MAS or following iatrogenic rupture of the aorta or renal artery following angioplasty, a covered stent is favored. As previously discussed, there is no such stent designed specifically for use in the abdominal aorta or renal arteries of children. The authors generally use peripheral stent graft systems for small aortas and coronary stents in the renal arteries. Although drug-eluting and bioabsorbable stents have been reported in pediatric cases, their use remains non-routine due to insufficient supporting data. ^{48 49}

Chemical Ablation

In the case of a peripheral intrarenal branch stenosis where angioplasty is not technically possible, superselective ethanol injection can be considered to ablate that segment of renal parenchyma by inducing an irreversible endothelial injury, leading to tissue infarction. In doing so, the goal is to ablate the part of the kidney that is driving excess renin production and improve blood pressure control. ¹⁷ This targeted infarction reduces hypertension while preserving more renal tissue compared to nephrectomy or partial nephrectomy. ⁵⁰

Ablation with ethanol requires careful patient selection and superselective microcathertization of the diseased branch vessel to avoid non-target embolization. Furthermore, this technique should be avoided in proximal, first- or second-order branch stenosis as the potential volume of kidney ablated is not justified, not to mention the volume of ethanol that would be required to achieve an ablation of this magnitude.

Importantly, coil embolization proximal to an intrarenal branch stenosis should not be performed. Proximal embolization will inevitably lead to the formation of intrarenal collateral vessels to preserve blood flow to that segment of devascularized kidney, and this perpetuates the renal ischemia and hypertension. Ethanol, by contrast, does not occlude the vessel but ensures ablation of the targeted vascular territory driving renin production. ⁹

Renal Denervation

Endovascular renal denervation is a promising adjunctive therapy for treating RVH where conventional endovascular interventions have failed and is designed to disrupt renal sympathetic nerve activity to lower blood pressure. It involves delivering energy, either low-dose radiofrequency or focused ultrasound energy, to the adventitia of the renal arteries, where the sympathetic nerves are located, in order to thermally ablate afferent and efferent renal nerves. ⁵¹ Second-generation systems, including multielectrode catheters and ultrasound-based devices, have improved procedural consistency and efficacy. ⁵²

The RADIANCE II trial has demonstrated, in adult patients, that renal denervation causes a significant reduction in daytime ambulatory systolic blood pressure at 2 months of up to −7.9 mmHg, with the effect consistent across the 24-hour cycle and across subgroups, and with no major adverse events reported. ⁵³ However, studies are required in pediatric cohorts before it can be considered an established therapy in clinical practice.

Surgery

Surgery plays an important role when repeated endovascular interventions have been unsuccessful, or are not feasible, in treating complex or refractory vascular lesions in MAS or RAS. Despite higher complication rates compared to angioplasty (15% vs. 6%), surgery has been shown to elicit higher rates of cure (54% vs. 36%). ¹⁷

Surgical interventions include renal artery reimplantation, aorto-renal bypass, and renal auto-transplantation. Depending on institutional preference, surgery tends to be deferred until adolescence due to the technical challenges of operating in small children and the potential for growth-related complications. In fact, a main RAS detected in infancy and which is amenable to auto-transplant, may be deferred for many years in favor of repeat angioplasty in order to allow the patient to grow and improve the risk profile of surgery.

Although some surgeons caution that prior angioplasty may complicate surgical dissection due to fibrosis, ^{17 50} once of a suitable size, successful surgery is possible even after multiple and repeated endovascular treatments. ⁵⁴ The use of three-dimensionally printed vascular models, which the interventional radiologist can assist with, can significantly improve surgical planning, reduce anesthesia time, and enhance patient and family understanding. ⁵⁴

Surgical nephrectomy can be considered in unilateral RAS and has been shown to be effective in curing the hypertension driven by the poorly functioning kidney. ⁵⁵ However, nephrectomy is reserved for cases where surgery needs to be undertaken in younger age groups, and where it is felt that surgical revascularization is not technically feasible, or when the patient's condition does not allow for the prolonged operative time required for these incredibly complex surgeries.

Conclusion

Pediatric RVH represents a complex and multifaceted clinical challenge, requiring early recognition and a nuanced, multidisciplinary approach. The condition is most commonly caused by nonatherosclerotic RAS, with causes ranging from FMD to MAS to syndromic and inflammatory conditions. Accurate diagnosis is paramount and relies on a tiered imaging strategy. Although ultrasound remains the first-line modality, its limitations necessitate the use of advanced imaging techniques such as CTA, MRA, and ultimately DSA, which remains the gold standard for detecting subtle or distal vascular lesions that are often missed on noninvasive imaging.

Management of RVH is equally complex and must be personalized. Optimum pharmacological therapy is essential but often insufficient alone. Angioplasty is the cornerstone of endovascular treatment, offering high rates of blood pressure control and renal function preservation. Stent placement is generally avoided due to growth limitations and the increased risk of restenosis and reintervention rates but may be necessary in very select cases. Surgical revascularization is reserved for refractory cases or when endovascular approaches fail. Emerging techniques such as renal denervation provide promising adjuncts, though further pediatric-specific data are needed.

Ultimately, successful outcomes in pediatric RVH depend on timely diagnosis, expert imaging interpretation, and access to interventional and surgical expertise at specialized centers. A tailored, patient-centered approach, supported by multidisciplinary collaboration between nephrology, interventional radiology, and vascular surgery, is essential to optimize both short- and long-term outcomes in this complex patient population.