Basics
Description
Narrowing of 1 or both renal arteries and/or their more distal branches, resulting in decreased perfusion, increased renin release, increased vascular resistance, and systemic hypertension
Epidemiology
- Hypertension in infants and young children is often secondary to some identifiable cause. Of those with secondary hypertension, most have intrinsic renal disease (e.g., renal scarring, dysplasia, chronic nephritis).
- Up to 5% of adults with hypertension have renal artery stenosis (RAS).
- RAS accounts for ~10% of secondary hypertension in children. Its importance clinically is not its frequency but its potential curability.
Risk Factors
- Any condition associated with thromboembolic events (such as a complication of an umbilical artery catheter in newborns)
- Renal trauma including renal artery surgery (e.g., transplantation)
- Extrinsic compression of the renal artery (e.g., Wilms tumor, neuroblastoma, or pheochromocytoma).
General Prevention
Reduce risk factors, such as thromboembolic events, which can lead to renal artery narrowing.
Pathophysiology
Arterial narrowing leads to diminished perfusion of the affected kidney, leading to signals in the juxtaglomerular apparatus, which lead to renin release and results in increased vascular resistance and blood pressure (BP).
Etiology
- Majority are caused by fibromuscular dysplasia (FMD), a noninflammatory vascular disease of unknown etiology.
- Primarily affects females and affects up to 4 in 100 adults
- The renal vasculature is the most common arterial bed affected.
- FMD can concurrently affect other vascular beds including carotid, vertebral, and intracranial vascular beds.
- Arterial narrowing by atheroma is common in adults but rare in children.
Commonly Associated Conditions
- RAS may occur in many other conditions, including congenital anomalies (e.g., renal artery hypoplasia), neurocutaneous disorders (neurofibromatosis [type 1], tuberous sclerosis), vasculitis (Wegener, polyarteritis nodosa, Kawasaki disease, Takayasu arteritis, moyamoya disease), syndromes (Williams, Marfan, Alagille), and infections (e.g., congenital rubella and fungal infection [immunocompromised hosts]).
- Nephrotic syndrome may accompany renal artery stenosis and is probably secondary to it.
- RAS has been associated with multicystic dysplasia in the contralateral kidney.
Diagnosis
History
- Ask about prior BP determinations, family history of hypertension, previous renal disease, symptoms of hypertension, and preexisting conditions associated with renal artery stenosis.
- Signs and symptoms:
- Symptoms of hypertension in infants are not specific and include irritability, poor feeding, and vomiting.
- In children, symptoms include headache, nausea/vomiting, visual disturbance, dizziness, and seizure.
- Many affected children remain asymptomatic and 1/3 of children with RAS are diagnosed incidentally.
Physical Exam
- BP assessment
- Consider RAS in a child with very high BP readings (i.e., at or above the 99th percentile).
- Obtain multiple, manual BP readings using an appropriate-size cuff in the right upper extremity with patient relaxed at baseline heart rate and compare to the BP nomogram for age, sex, and length/height percentile.
- Avoid using automated devices (oscillometers).
- Most accurate readings are obtained with either a mercury column or an aneroid sphygmomanometer.
- Determine the BP in all extremities. A gradient from the upper to lower extremities should prompt evaluation for aortic coarctation or midaortic syndrome.
- Examine the skin for lesions suggestive of vasculitis or neurocutaneous disorder (e.g., cafe au lait macules).
- Assess the child 's facies and habitus for features of associated syndromes.
- View the optic fundi for hypertensive vascular changes.
- Auscultate the lower back and abdomen for the presence of a bruit (suggesting turbulent flow).
- In infancy, signs of heart failure may be present.
Diagnostic Tests & Interpretation
ECG or echocardiogram to assess for left ventricular hypertrophy and function
Lab
- BUN and creatinine to evaluate for renal insufficiency
- Electrolytes to assess possible hyperaldosteronism with hypokalemia and metabolic alkalosis. Hyponatremia may sometimes occur.
- ESR or CRP to screen for vasculitis
Imaging
- The definitive diagnostic test remains the selective renal arteriogram. If the diagnosis is made, angioplasty may be part of the same procedure. Angiography should not be delayed in any child in whom the diagnosis is strongly suspected.
- Renal ultrasound with Doppler to identify a smaller kidney and/or increased resistance to flow is simple and not invasive, but it is neither sensitive nor specific. Length discrepancy of >1 cm in children can increase suspicion for RAS.
- Contrast-enhanced CT or MR angiography also is not completely diagnostic and is not therapeutic.
- Nuclear renal scans using dimercaptosuccinic acid (DMSA) or MAG-3 enhanced with captopril (and more recently angiotensin receptor blockers [ARB]) also are not diagnostic for all children.
- Diagnostic accuracy of various imaging studies including with magnetic resonance angiography (MRA), computed tomography angiography (CTA)
View LargeTechniqueSensitivity (%)Specificity (%)Ultrasound73 " 8571 " 92DMSA with ACE52 " 9363 " 92CTA64 " 9462 " 97MRA64 " 9372 " 97
Diagnostic Procedures/Other
- Avoid excessive investigation in children whose BP is minimally or episodically elevated and therefore in whom the diagnosis of renal artery stenosis is less likely.
- Selective renal vein renin determinations suggest unilateral stenosis if the affected side is 1.5 times the contralateral (normal) side. However, the procedure is invasive and requires catheterization of the femoral vein.
- Random renin determinations have little value and may be misleading. If obtained, renin levels should be interpreted in the context of the urine sodium concentration.
Pathologic Findings
- FMD is a segmental sclerotic process involving smooth muscle hyperplasia of the media layer of the artery. It is unilateral in 75%.
- Stenosis is usually distal in the renal artery, sometimes involving intrarenal branches.
- The stenotic area(s) of the artery may be associated with distal aneurysms.
- In neurofibromatosis, arterial narrowing is at the vessel 's ostium and usually involves the intimal layer.
Differential Diagnosis
- RAS should be suspected and investigated in children with severe, progressive, and/or difficult-to-manage hypertension.
- The differential diagnosis consists of other causes of significant hypertension, including increased intracranial pressure, coarctation of the aorta, midaortic syndrome, rapidly progressive glomerulonephritis, vasculitis, and pheochromocytoma.
Treatment
Treat children who are symptomatic immediately (e.g., severe headaches, seizures, blurred vision, facial palsy).
Medication
- Hypertension accompanying RAS is often difficult to control and may worsen over time. Multiple medications given in high doses are common until the diagnosis is made and angioplasty can be done.
- Because RAS results in increased renin levels, renin-angiotensin blockade with ACE inhibitor therapy (e.g., enalapril, lisinopril) and/or angiotensin receptor blockers (ARBs, e.g., losartan) is often effective. In children where bilateral renal artery stenosis is known or suspected, ACE inhibitor and ARB therapy must be avoided to prevent acute renal failure. 50% of children will have bilateral disease. Renal function should be checked before and after initiation of ACE inhibition or ARB therapy.
- If BP is easy to control on monotherapy, may consider medical management alone rather than angioplasty.
- ²-Blockers, calcium channel blockers, diuretics, and direct vasodilators (e.g., minoxidil, hydralazine) are all possibly effective.
Additional Treatment
General Measures
- If renal artery stenosis is suspected, begin the diagnostic evaluation and pharmacotherapy together.
- If BP is very high, use bed rest until BP is better controlled.
Issues for Referral
- Cardiology follow-up for echo changes, if indicated
- Ophthalmologic follow-up for resolution of vascular changes, if indicated
Surgery/Other Procedures
- Actual surgery on the stenotic renal artery has been replaced by angioplasty, which has been successfully carried out in very young infants. Stents are occasionally used.
- Surgery must sometimes be performed, especially in children with neurofibromatosis where the stenosis is frequently at the renal artery 's ostium.
Inpatient Considerations
Initial Stabilization
- If symptomatic, use potent, rapidly acting medications such as labetalol or nicardipine.
- Be prepared to have difficulty adequately controlling the BP using a single medication.
Admission Criteria
- Children who present with a BP at or above the 99th percentile
- Children who appear to have symptomatic hypertension
- Children with progressive renal insufficiency
Nursing
- Obtain BP levels frequently and carefully.
- Notify MD if high or low limits exceeded.
- Monitor intake of salt, I&O, and weight.
Discharge Criteria
BP in the 90 " 95th percentile
Ongoing Care
Follow-up Recommendations
- The child 's BP must be followed closely, both before and after the angioplasty. Response to angioplasty may be immediate but may require continued antihypertensive therapy at some level for weeks to months.
- Medical therapy should be monitored closely. Until correction, the need for progressively higher doses and/or additional medications is common.
- Disposition
- Close follow-up by the primary care provider, mainly for monitoring BP, and a specialist comfortable with the evaluation and treatment of childhood hypertension.
- Patient and/or family must be familiar with medication, exercise program, and diet.
Patient Monitoring
- Long-term follow-up of the BP is most important. If on no medications, the BP should be checked monthly, preferably somewhere the child is comfortable and the correct cuff is employed. Begin to space visits after 6 months.
- Checking renal growth on serial renal ultrasounds is important (e.g., at 6 months postangioplasty and then yearly). If the child is fully grown, check ultrasound at 6 months.
- Check renal function annually.
Diet
Limit salt intake.
Prognosis
Long-term outcome of percutaneous angioplasty is excellent; most children require no long-term antihypertensive medications. Percutaneous angioplasty is less successful in neurofibromatosis than in other causes of RAS.
Complications
- Rate of restenosis of the renal artery, either ipsilateral or contralateral, is 22 " 39%.
- When renal artery stenosis causes severe hypertension, it may cause encephalopathy, severe headache, seizures, or stroke.
- If untreated, chronic hypertension may cause end-organ damage, including heart and kidney.
- Angiography may lead to contrast-induced renal failure. The procedure may also cause injury to the kidney and/or renal artery.
- Rare cases of subarachnoid hemorrhage secondary to coexisting intracranial aneurysm may occur.
Additional Reading
- Konig K, Gellerman J, Querfeld U, et al. Treatment of severe renal artery stenosis by percutaneous transluminal renal angioplasty and stent implantation: review of the pediatric experience: apropos of two cases. Pediatr Nephrol. 2006;21(5):663 " 671. [View Abstract]
- Olin JW, Gornik HL, Bacharach JM, et al. Fibromuscular dysplasia: state of the science and critical unanswered questions : a scientific statement from the American Heart Association. Circulation. 2014;129(9):1048 " 1078. [View Abstract]
- Rountas C, Vlychou M, Vassiou K, et al. Imaging modalities for renal artery stenosis in suspected renovascular hypertension: prospective intraindividual comparison of color Doppler US, CT angiography, GD-enhanced MR angiography, and digital substraction angiography. Ren Fail. 2007;29(3):295 " 302. [View Abstract]
- Sethna CB, Kaplan BS, Cahill AM, et al. Idiopathic mid-aortic syndrome in children. Pediatr Nephrol. 2008;23(7):1135 " 1142. [View Abstract]
- Shahdadpuri J, Frank R, Gauthier BG, et al. Yield of renal arteriography in the evaluation of pediatric hypertension. Pediatr Nephrol. 2000;14(8 " 9):816 " 819. [View Abstract]
- Spyridopoulos T, Kaziani K, Balanika AP, et al. Ultrasound as a first line screening tool for the detection of renal artery stenosis: a comprehensive review. Med Ultrason. 2010;12(3):228 " 232. [View Abstract]
- Tullus K. Renal artery stenosis: is angiography still the gold standard in 2011? Pediatr Nephrol. 2011;26(6):833 " 837. [View Abstract]
- Vade A, Agrawal R, Lim-Dunham J, et al. Utility of computer tomographic renal angiogram in the management of childhood hypertension. Pediatr Nephrol. 2002;17(9):741 " 744. [View Abstract]
- Zhu G, He F, Gu Y, et al. Angioplasty for pediatric renovascular hypertension: a 13-year experience. Diagn Interv Radiol. 2014;20(3):285 " 292. [View Abstract]
Codes
ICD09
- 440.1 Atherosclerosis of renal artery
- 747.62 Renal vessel anomaly
- 405.91 Unspecified renovascular hypertension
- 447.3 Hyperplasia of renal artery
ICD10
- I70.1 Atherosclerosis of renal artery
- Q27.1 Congenital renal artery stenosis
- I15.0 Renovascular hypertension
- I77.3 Arterial fibromuscular dysplasia
SNOMED
- 302233006 Renal artery stenosis (disorder)
- 271432005 Congenital renal artery stenosis (disorder)
- 73410007 Benign secondary renovascular hypertension (disorder)
- 359553002 Fibromuscular hyperplasia of artery (disorder)
- 289923007 Acquired renal artery stenosis