- Email: [email protected]
Renal artery stenosis in children
Clinical Radiology (1991) 44, 376-382
Renal Artery Stenosis in Children L. R O B I N S O N , W_ G E D R O Y C , J. R E I D Y and H. M. S A X T O N
Department o f Diagnostic Radiology, Guy's Hospital, London In a large paediatric renal unit over the last 14 years, 19 children (I0 male and 9 female, aged I week to 16 years, mean 7 years) with renal arterystenosis (RAS) were evaluated. Transplant RAS cases were not included. All 19 children were hypertensive. In I0 this was an incidental finding. Based on clinical findings and arteriography, the causes of RAS included a middle aortic syndrome (MAS) (n=5), neurofibromatosis ( n = 3 ) , William's syndrome ( n = 3 ) , fibromuscular hyperplasia (FMH) (n = 4), idiopathic RAS (n = 2) and isolated branch artery stenosis (n = 2). Previous studies have suggested F M H is the commonest cause of RAS in the paediatric population. In our study the largest subgroup are MAS/William's syndrome children, in whom the angiographic appearances were indistinguishable. Where possible, management, both surgical and radiological, and eventual outcomes have been described. Robinson, L., Gedroyc, W., Reidy, J. & Saxton, H.M. (1991). Clinical Radiology 44, 376382. Renal Artery Stenosis in Children
Renal artery stenosis (RAS) is a relatively uncommon cause of hypertension in a hospital-based paediatric practice. In selected groups of hypertensive children who have undergone angiography RAS has been found in 420% of children (Stanley et al., 1984) with a greater frequency in younger patients (Lawson et al., 1977). As it is a potentially correctable condition that can damage renal function it is important not to overlook the diagnosis. There is a greater range of causes of RAS in children than in adults: they include fibromuscular hyperplasia ( F M H ) (Makker and Moorthy, 1979), neurofibromatosis (NF) (Greene et al., 1974), William's syndrome, Takayasu's arteritis, a n d an entity known as the middle aortic syndrome (MAS) (Sen et al., 1963; Lewis et al., 1988). This study describes the clinical and radiological findings in 19 cases of RAS in children presenting to a large paediatric unit over the last 14 years. Where possible the treatment, management and long-term outcome are described. P A T I E N T S AND M E T H O D S F r o m 1974 to 1988 19 children with RAS (10 male and 9 female; age 1 week to 16 years, mean 7 years) were examined at our hospital. Patients with transplant RAS were excluded. A retrospective review of the case notes and radiological findings of these children was made. Abdominal aortography via a percutaneous femoral puncture was obtained in all patients. Rapid sequence imaging using cut film and/or digital subtraction angiography (DSA) was performed with obliques/laterals and selective renal artery catherization as required. Follow-up arteriograms were obtained in five patients (range of follow up 1-10 years). Three patients also had arch aortography. Patients were categorized using a combination of clinical and arteriographic findings into the various causes of renal artery stenosis described below. N F was a clinical diagnosis with classical skin and skeletal changes. Similarly children with William's syndrome showed the Correspondence to: Dr L. Robinson, Radiology Department, Guy's Hospital, London SE1 9RT.
typical clinical and biochemical features with elfin faces, mental retardation and hypercalcaemia in infancy (Chesney, 1987). The F M H subgroup was based on the angiographic findings of this condition (Goncharenko et al., 1981) but if these were not seen or if there was an isolated main/branch artery stenosis, the term 'idiopathic' was used in cases with no associated clinical anomaly. The MAS group was defined by the arteriographic findings of tubular stenosis of the abdominal aorta in the absence of any clinical or biochemical evidence of arteritis. If there was fever, rash, arthritis, myalgia and an elevated ESR with additional aortic narrowing, Takayasu's arteritis would be suggested. RESULTS All children were hypertensive but in 10 this was an incidental finding at an otherwise routine clinical examination. Clinical manifestations included cardiac failure (n = 2), signs and symptoms of malignant hypertension (n = 1), polydipsia and vomiting (n = 1), epistaxis (n = 1), and swollen eyelids and hands (n = 1). In three patients the full presenting clinical details were not available. Based on the above criteria the causes of RAS in our 19 children were as follows: % MAS William's syndrome FMH NF Idiopathic RAS Isolated branch stenosis
5 3 4 3 2 2
26 16 21 16 10.5 10.5
No cases of Takayasu's arteritis were found. Middle Aortic Syndrome and William's Syndrome
The three children with William's syndrome had angiographic appearances indistinguishable from those of the five MAS patients who formed the largest subgroup. The ESR was normal in six of the eight patients and not measured in the other two. One child in the MAS group had multiple congenital anomalies. N o child had
377
RENAL ARTERY STENOSIS IN CHILDREN
(,) (b)
(c)
(d)
Fig. I - Male patient aged 6 years with MAS. (a) There is severe stenosis of the abdominal aorta and stenoses of both the origin of the coeliac (black arrow) and SMA. (b) There is an enlarged collateral from the I M A (open arrow). (c), (d). The same patient aged 16 (digital angiogram). There has been no significant change in appearance. The stenoses involving the proximal two of the three left renal arteries at their origins (open arrows) and the moderate stenosis to the origin of the single right renal artery (closed arrow) are more clearly seen (d).
clinical evidence of an arteritis. The radiological findings of these eight patients are summarized below. All eight patients had smooth segmental narrowing of the abdominal aorta over a variable distance (Figs 1, 2 and 3). In five patients this narrowing affected the suprarenal aorta (Figs 1-3). All eight patients had involvement of renal arteries - in seven this was bilateral. Five patients also had involvement of superior mesenteric
(SMA) and coeliac arteries (Figs 1-3). No inferior mesenteric artery (IMA) abnormality was seen. Only one patient had an iliac stenosis and this child additionally had abnormal vertebral arteries on an arch aortogram with bilateral stenoses. An angiogram 1 year later showed some progression of the iliac lesions. One other child with very severe disease had a repeat study 11 years later which showed no exidence of progression (Fig. 1). One other
378
CLINICAL RADIOLOGY
Fig. 3 Male aged 13 years with William's syndrome. The appearances are indistinguishable from the MAS example in Fig 2. There is narrowing of the abdominal aorta. The origin of both renal arteries are stenosed with post-stenotic dilatation (arrows). There is also severe stenosis to the origins of both the coeliac and S M A vessels (arrowed) with collateral formation from the I M A and enlarged intercostals.
Fig. 2 - F e m a l e patient aged 6 years with MAS. Note the severe narrowing of the abdominal aorta. The coliac artery and S M A have not filled. There is enlargement of intercostal arteries and collaterals from the I M A (white arrow). There is also stenosis of the origin of both renal arteries with post-stenotie dilatation (open arrows).
child in this group had an arch angiogram which was normal. Percutaneous transluminal angioplasty (PTA) was not attempted in any of these eight patients in view of the very extensive nature of the abnormalities, reasonably adequate medical management and because previous authors have reported no long term success (Messina et al., 1986). Two children (one MAS, one William's syndrome) had major reconstructive surgery. The child with MAS (aged 7) had a thoracic aorta to aortic bifurcation bypass graft with bilateral autotransplantation of both kidneys. Fifteen months later this child is well and off all medication. The child with William's syndrome (aged 13) underwent left renal autotransplantation and right iliorenal saphenous vein bypass graft but died of gram negative sepsis and bleeding 5 days post-operatively. The other six children were considered not suitable for surgery either because of the extent of their lesions or the fact that the medical treatment ~of their hypertension had been reasonably successful.
Fibromuscular Hyperplasia Classical findings of the irregular 'beaded' appearance of F M H (Makker and Moorthy, 1979) were seen in four patients, and in all cases this was unilateral. Two patients
(50%) had additional branch artery stenosis (Fig. 4). Normal aorta and mesenteric vessels were seen in all patients. P T A was attempted and successfully performed in two patients (aged 3 and 6 years). In both there was a good post-angioplasty result followed by an immediate clinical improvement with reduction in bloodpressure and drug therapy. One patient had a repeat angiogram 10 months later with no evidence of restenosis of the main arterial lesion (Fig. 4b) although some small branch renal stenoses were still evident. The other two children presented before P T A was available. One child (aged 14 years) had a saphenous vein bypass graft and remains well and off treatment 9 years following surgery. The fourth child (aged 7 months) had a nephrectomy but died due to a post-operative arrhythmia.
Neurofibromatosis Three children had clinically evident NF. The renal artery stenoses were bilateral in two patients with typical smooth ostial narrowings. In addition two patients had abdominal aortic coarctation (Fig. 5), associated in one case with narrowing of the origins of the superior mesenteric and coeliac arteries. One child in this group had the right kidney autotransplanted to the right iliac fossa (with the renal artery grafted to the internal iliac artery and the renal vein to the c o m m o n iliac vein) and initially d i d well, no longer needing medication. After 3 years, however, a D M S A scan showed the transplant to have only 12% function. One child has been managed medically. One child had bilateral angioplasty procedures attempted on two different occasions. Each time the stenoses proved resistant to dilatation with no angiographic or clinical improvement (Fig. 5b). Bilateral saphenous vein grafts were subsequently performed to revascularize both renal arteries.
379
RENAL ARTERY STENOSIS IN CHILDREN
(a)
(a)
(b) Fig 5 Male aged 5 years with NF. (a) Typical smooth ostial narrowings are seen in both renal arteries. Abdominal coarctation is also noted (arrow). The opacity seen in the left upper quadrant was a
tablet in the stomach. (b) Same child following angioplasty to left renal artery. Although this was technically successful, the stenosis proved resistant to dilatation with no angiographic improvement (arrow). One renal artery s u b s e q u e n t l y occluded and the kidney was lost b u t 4 years later a severe stenosis had developed at the distal g r a f t - r e n a l artery anastomosis of the other kidney. This was treated by angioplasty with a good radiological and clinical response.
Idiopathic RAS Plus Isolated Branch Artery Lesions
(b) Fig. 4 - Female aged 5 years with FMH. (a) The main renal artery shows two areas of narrowing in its mid portion with slight dilatation in between (double arrow). Within the kidney there are a number of areas
ofstenosis or occlusion (singlearrows). (b) Same child 10 months after a successful angioplasty. Smallbranch renal stenoses are still evident. The main renal artery appears normal.
T w o children had unilateral R A S b u t w i t h o u t the appearance of F M H or other diagnostic clinical features. Extensive periureteric collaterals were seen in one patient_ The other patient h a d a long severe t u b u l a r stenosis extending to the r e n a l h i l u m (Fig. 6) with multiple b r a n c h stenoses. I n a d d i t i o n there was some moderate distal aortic arch c o a r c t a t i o n with d i l a t a t i o n of the ascending aorta. I n b o t h these chilidren the a b d o m i n a l aorta and mesenteric vessels were n o r m a l .
380
CLINICAL RADIOLOGY
Fig. 6 - Male aged 3 m o n t h s with idiopathic RAS. There is a long tubular stenosis of the left renal artery extending to the renal hilum (arrow).
PTA was attempted in one of these children (aged 14) but the 'waisting' of the balloon could not be abolished despite multiple high pressure dilatations and there was no clinical improvement. Autotransplantation was then undertaken but the kidney infarcted one day postoperatively. The Other child aged 3 months died of unrelated causes shortly after his angiogram. Two patients showed branch stenoses in the absence of main renal artery lesions. In one patient this was bilateral. Abdominal vasculature was otherwise normal in both patients. In one patient at the initial study aortography appeared normal (Fig. 7a). As a subsequent D M S A (Fig. 7b) showed a focal abnormality, selective magnification renal arteriography was performed which showed a focal branch stenosis and an ischaemic segment of kidney (Fig. 7c)_ This patient was treated by nephrectomy which cured her severe hypertension. The other patient was lost to follow up.
DISCUSSION Renovascular hypertension in children is rare but the lack of specific signs and symptoms in over 50% of our patients presenting incidentally emphasizes the need to measure the blood pressure in all children routinely as part of a clinical examination. It is well documented that the I V U has limited value for diagnosing RAS in the hypertensive children (Lawson et al., 1977; Stringer et al., 1984; Watson et al., 1984) and now has no role. However, imaging with nuclear medicine and ultrasound should be performed in view of the possibility of renal parenchymal lesions causing hypertension. Angiography is recommended for all patients in whom a non-vascular cause for the hypertension has not been established, or in children" with hypertension that is unexpected and progressive or difficult to control. Angiography in experienced hands is a very low risk procedure, particularly in recent years with the introduction of smaller catheters, non-ionic contrast and digital angiography. Flush techniques will detect renal artery stenoses in the majority of patients but we believe that selective examinations to show main intrarenal arteries
must be performed if the main arteries appear normal so that branch stenoses are not missed. This was emphasized in one of our patients where a significant branch lesion was missed initially on a flush aortogram (Fig. 7). We also believe that lateral views should be performed to evaluate the origins of the mesenteric vessels if renal artery pathology is seen because involvement of these vessels is c o m m o n in MAS, William's syndrome (62_5% in our study), N F (33% in our study) and rarely in FMH. Angiography also has an importat role after surgery in evaluating the patient with a clinical change or deterioration in renal function. Stanley (1984) classified RAS histologically and Mall et al. (1987) suggest classification by location and length of the stenosis. We feel that classification relating to underlying etiology as established by clinicoradiological criteria is more useful because it can give a guide to appropriate treatment and possibly to eventual outcome_ Stanley (1984) in his paper on renal vascular disease and renovascular hypertension in children claims F M H and its variants are the commonest cause ofrenovascular hypertension in children, accounting for 95% of patients, whereas in our large series the MAS/William's syndrome patients predominate (combined total 42%), compared with F M H accounting for 21%. There has been some debate in the literature as to the exact nature of MAS, with Berkman and Lande (1989) suggesting that it is a variant of Takayasu's arteritis. The distinction is important clinically as anti-inflammatory drugs may be useful in some patients with Takayasu's arteritis_ Classically Takayasu's arteritis occurs in oriental adolescent females with signs of an arteritis with an elevated ESR, malaise, fever, pain and night sweats (Lupi-Herrera et al., 1977). Pulmonary artery involvement is seen in up to 50% of patients. 'Skipped' areas of aortic involvement, aneurysms and narrowings alternating with normal segments are characteristic of Takayasu's arteritis (Lande, 1976). In MAS the patients are younger, there is no evidence of an acute arteritis and there is no clinical evidence to suggest pulmonary artery disease. Additionally in MAS the disease appears to arrest at puberty, compared with Takayasu's arteritis which is progressive (Meranze and O'Neill~ 1989). Histologic examination of involved regions of Takayasu's arteritis will show inflammatory change, a finding not seen in patients with the midaortic syndrome (Lewis et al., 1988). The differences are sufficient to make us feel that it is a separate entity. N F can be either inherited or sporadic but hypertension can be caused by lesions other than RAS, such as phaeochromocytoma. Renal P T A in adults is now an established technique for treatment of m a n y forms of RAS (Martin et al., 198 l; Mahler et al., 1982). The procedure is more difficult in children with smaller vessels but selected paediatric groups show a good response with this technique (Mathias et al., 1981; Stanley et al., 1984), particularly the cases of F M H which as in adults showed an excellent response to PTA. RAS secondary to N F is rare and usually caused not by a neurofibroma but by intimal fibrosis or proliferation of fibrous tissue. Small peripheral renal arteries are often stenosed because of small vessel dysplasia (Greene et al., 1974). Lesions caused by N F can be readily crossed for attempted PTA but the stenoses are resistant to inflation of the balloon (Lund et al., 1984; Miller et al., 1985).
RENAL ARTERY STENOSISIN CHILDREN
381
(b) (a)
(~) Fig. 7 - Female patient aged 15 years with isolated branch artery stenosis. (a) 'Normal' flush aortogram. (b) The DMSA scan shows a focal defect at the right upper pole. (e) A repeat angiography with selective catheterization confirms a focal branch stenosis with collateraI formation (arrow) and a focal defect on the nephrogram corresponding to the DMSA abnormality and delayed emptying of the distal vessels_
R e s p o n s e to P T A is similarly p o o r in M A S (Lewis et al., 1988), W i l l i a m ' s s y n d r o m e a n d T a k a y a s u ' s arteritis, p r e s u m a b l y because o f the progressive w i d e s p r e a d n a t u r e o f these diseases. P T A m a y h o w e v e r have a role in those p a t i e n t s w h o have u n d e r g o n e surgical b y p a s s p r o c e d u r e s a n d p r e s e n t with s u b s e q u e n t stenoses at surgical sites, as was seen in one o f o u r cases o f N F . In the series r e p o r t e d by Lewis et al. (1988) the m a i n s t a y o f t r e a t m e n t for M A S has been c o m p l e x b y p a s s surgery b u t it is n o t clear w h a t the precise i n d i c a t i o n s for surgery were a n d surgery is n o t always feasible in this g r o u p o f p a t i e n t s ( G u p t a , 1979). The m o r t a l i t y rate in
these cases can be high due to the extensive vessel i n v o l v e m e n t a n d the difficulties in finding an a p p r o p r i a t e graft. M o s t o f o u r p a t i e n t s (75%) have d o n e well on medical t r e a t m e n t alone with g o o d g r o w t h a n d preservation o f renal function. O u r c u r r e n t a p p r o a c h when dealing with M A S is to r e c o m m e n d that surgery only be considered as second line t r e a t m e n t after a d e q u a t e medical t r e a t m e n t has failed.
Acknowledgements.We thank Ms Bernadette Maloney for typing the manuscript.
382
CLINICAL RADIOLOGY
REFERENCES
Berkmen, YM & Lande, A (1989). Letter. Radiology, 170, 571. Chesney, R (1987), Idiopathic hypercalcaemia. In Nelson Textbook of Pediatrics 13th edn., eds Behrman, RE & Vaughn, VC, p. 1381. WB Saunders, Philadelphia. Goncharenko, V, Gerlock AJ, Jr, Shaft, MI & Hollifield JW (1981). Progression of renal artery fibromuscular dysplasia in 42 patients as seen on angiography. Radiology, 139, 45 51. Greene, JF, Fitzwater, J & Burgess, J (1974). Arterial lesions associated with neurofibromatosis. American Journal of Clinical Pathology, 62, 481-487. aortic syndrome. Thorax, 34, 470-478. Lande, A (1976). Takayasu's arteritis and congenital coarctation of the descending and abdominal aorta: a critical review. American Journal of Radiology, 127, 227 233. Lawson, JD, Buerth, R, Foster, JH & Dean, RH (1977). Diagnosis and management of renovascular hypertension in childhood. Archives of Surgery, 112, 1307 1316. Lewis III, VD, Meranze, SG, McLean, GK, O'Neille JA, Berkowitz, HD & Burke, DR (1988). The midaortic syndrome: diagnosis and management. Radiology, 167, I 11-113. Lund, G, Sinaiko, A, Castaneda-Zuniga, W, Cragg, A, Salomonwitz, E & Amplatz, K (1984). PTA for treatment of RAS in children. European Journal of Radiology, 4, 254 257. Lupi-Herrera, E, Sanchez-Torres, G, Marchushamer, J, Mispireta, J, Horwitz, S & Vela, JE (1977). Takayasu's arteritis: clinical study of 107 cases. American Heart Journal, 93, 94 102. Mahler, F, Probst, P, Haertel, M, Weidmann, P & Krneta, A (1982). Lasting improvement of renovascular hypertension by transluminal dilation of atherosclerotic and non-atherosclerotic RAS. A follow up study. Circulation, 65, 611 617. Makker, SO & Moorthy, B (1979). Fibromuscular dysplasia of renal arteries: an important cause of renovascular hypertension in chil-
dren. European Journal of Radiology, 4, 254 257. Mali, WP, Puijlaert, CB, Kowwenberg, J, Klinge, J, Donckerwolcke, R, Geijskes, Bet al. (1987). Percutaneous transluminal angioplasty in children and adolescenets. Radiology, 165, 391 394. Martin, EC, Mattern, RF, Baer, L, Fankuchen, E & Casarella, WJ (1981). Renal angioplasty for hypertension: predictive factors for longterm success. American Journal of Radiology, 137, 921 924. Mathlas, K, Struck, E, Schindera, F. & Urbanyi, B (1981). Percutaneous treatment of renovascular hypertension. Paediatric Radiology, II, 154 156. Meranze, SG & O'NeilL JA (1989). Letter. Radiology, 170, 572. Messina, LM, Goldstone, J, Ferrell, LD, Reilley, LM, Ehrenfeld, WK & Stoney, RJ (1986). Middle aortic syndrome: effectiveness and durability of complex arterial rcvascularization techniques. Annals of Surgery, 204, 331 337. Miller, G, Ford, K, Braun, S, Newman, G, Moore, A, Malone, R et al. (1985). Percutaneous transluminal angloplasty vs surgery for renovascular hypertension. American Journal of Radiology, 144, 447450. Sen, PK, Kinare, SG, Engineer, SD & Parulkar, GB (1963). The middle aortic syndrome. British Heart Journal, 25, 610-618. Stanley, JC (1984), Renavascular disease and renovascular hypertension in children. Urologic Clinies of North America, II, 451 463. Stanley, P, Hieschima, G & Mehringer, M (1984), Percutaneous transluminal angioplasty for paediatric renovascular hypertension. Radiology, 153, 101 104. Stringer, DA, de Bruyn, R, Dillon, MJ & Gordon, I (1984). Comparison of aortography, renal vein renin sampling, radionuclide scans, ultrasound and the IVU in the investigation of childhood renovascular hypertension. British Journal of Radiology, 57, 111 121. Watson, AR, Balfe, J & Hardy, B (1984). Renovascular hypertension in children. A changing perspective in management. Journal of Paediatries, 106, 366-372.
Renal Artery Stenosis in Children L. R O B I N S O N , W_ G E D R O Y C , J. R E I D Y and H. M. S A X T O N
Department o f Diagnostic Radiology, Guy's Hospital, London In a large paediatric renal unit over the last 14 years, 19 children (I0 male and 9 female, aged I week to 16 years, mean 7 years) with renal arterystenosis (RAS) were evaluated. Transplant RAS cases were not included. All 19 children were hypertensive. In I0 this was an incidental finding. Based on clinical findings and arteriography, the causes of RAS included a middle aortic syndrome (MAS) (n=5), neurofibromatosis ( n = 3 ) , William's syndrome ( n = 3 ) , fibromuscular hyperplasia (FMH) (n = 4), idiopathic RAS (n = 2) and isolated branch artery stenosis (n = 2). Previous studies have suggested F M H is the commonest cause of RAS in the paediatric population. In our study the largest subgroup are MAS/William's syndrome children, in whom the angiographic appearances were indistinguishable. Where possible, management, both surgical and radiological, and eventual outcomes have been described. Robinson, L., Gedroyc, W., Reidy, J. & Saxton, H.M. (1991). Clinical Radiology 44, 376382. Renal Artery Stenosis in Children
Renal artery stenosis (RAS) is a relatively uncommon cause of hypertension in a hospital-based paediatric practice. In selected groups of hypertensive children who have undergone angiography RAS has been found in 420% of children (Stanley et al., 1984) with a greater frequency in younger patients (Lawson et al., 1977). As it is a potentially correctable condition that can damage renal function it is important not to overlook the diagnosis. There is a greater range of causes of RAS in children than in adults: they include fibromuscular hyperplasia ( F M H ) (Makker and Moorthy, 1979), neurofibromatosis (NF) (Greene et al., 1974), William's syndrome, Takayasu's arteritis, a n d an entity known as the middle aortic syndrome (MAS) (Sen et al., 1963; Lewis et al., 1988). This study describes the clinical and radiological findings in 19 cases of RAS in children presenting to a large paediatric unit over the last 14 years. Where possible the treatment, management and long-term outcome are described. P A T I E N T S AND M E T H O D S F r o m 1974 to 1988 19 children with RAS (10 male and 9 female; age 1 week to 16 years, mean 7 years) were examined at our hospital. Patients with transplant RAS were excluded. A retrospective review of the case notes and radiological findings of these children was made. Abdominal aortography via a percutaneous femoral puncture was obtained in all patients. Rapid sequence imaging using cut film and/or digital subtraction angiography (DSA) was performed with obliques/laterals and selective renal artery catherization as required. Follow-up arteriograms were obtained in five patients (range of follow up 1-10 years). Three patients also had arch aortography. Patients were categorized using a combination of clinical and arteriographic findings into the various causes of renal artery stenosis described below. N F was a clinical diagnosis with classical skin and skeletal changes. Similarly children with William's syndrome showed the Correspondence to: Dr L. Robinson, Radiology Department, Guy's Hospital, London SE1 9RT.
typical clinical and biochemical features with elfin faces, mental retardation and hypercalcaemia in infancy (Chesney, 1987). The F M H subgroup was based on the angiographic findings of this condition (Goncharenko et al., 1981) but if these were not seen or if there was an isolated main/branch artery stenosis, the term 'idiopathic' was used in cases with no associated clinical anomaly. The MAS group was defined by the arteriographic findings of tubular stenosis of the abdominal aorta in the absence of any clinical or biochemical evidence of arteritis. If there was fever, rash, arthritis, myalgia and an elevated ESR with additional aortic narrowing, Takayasu's arteritis would be suggested. RESULTS All children were hypertensive but in 10 this was an incidental finding at an otherwise routine clinical examination. Clinical manifestations included cardiac failure (n = 2), signs and symptoms of malignant hypertension (n = 1), polydipsia and vomiting (n = 1), epistaxis (n = 1), and swollen eyelids and hands (n = 1). In three patients the full presenting clinical details were not available. Based on the above criteria the causes of RAS in our 19 children were as follows: % MAS William's syndrome FMH NF Idiopathic RAS Isolated branch stenosis
5 3 4 3 2 2
26 16 21 16 10.5 10.5
No cases of Takayasu's arteritis were found. Middle Aortic Syndrome and William's Syndrome
The three children with William's syndrome had angiographic appearances indistinguishable from those of the five MAS patients who formed the largest subgroup. The ESR was normal in six of the eight patients and not measured in the other two. One child in the MAS group had multiple congenital anomalies. N o child had
377
RENAL ARTERY STENOSIS IN CHILDREN
(,) (b)
(c)
(d)
Fig. I - Male patient aged 6 years with MAS. (a) There is severe stenosis of the abdominal aorta and stenoses of both the origin of the coeliac (black arrow) and SMA. (b) There is an enlarged collateral from the I M A (open arrow). (c), (d). The same patient aged 16 (digital angiogram). There has been no significant change in appearance. The stenoses involving the proximal two of the three left renal arteries at their origins (open arrows) and the moderate stenosis to the origin of the single right renal artery (closed arrow) are more clearly seen (d).
clinical evidence of an arteritis. The radiological findings of these eight patients are summarized below. All eight patients had smooth segmental narrowing of the abdominal aorta over a variable distance (Figs 1, 2 and 3). In five patients this narrowing affected the suprarenal aorta (Figs 1-3). All eight patients had involvement of renal arteries - in seven this was bilateral. Five patients also had involvement of superior mesenteric
(SMA) and coeliac arteries (Figs 1-3). No inferior mesenteric artery (IMA) abnormality was seen. Only one patient had an iliac stenosis and this child additionally had abnormal vertebral arteries on an arch aortogram with bilateral stenoses. An angiogram 1 year later showed some progression of the iliac lesions. One other child with very severe disease had a repeat study 11 years later which showed no exidence of progression (Fig. 1). One other
378
CLINICAL RADIOLOGY
Fig. 3 Male aged 13 years with William's syndrome. The appearances are indistinguishable from the MAS example in Fig 2. There is narrowing of the abdominal aorta. The origin of both renal arteries are stenosed with post-stenotic dilatation (arrows). There is also severe stenosis to the origins of both the coeliac and S M A vessels (arrowed) with collateral formation from the I M A and enlarged intercostals.
Fig. 2 - F e m a l e patient aged 6 years with MAS. Note the severe narrowing of the abdominal aorta. The coliac artery and S M A have not filled. There is enlargement of intercostal arteries and collaterals from the I M A (white arrow). There is also stenosis of the origin of both renal arteries with post-stenotie dilatation (open arrows).
child in this group had an arch angiogram which was normal. Percutaneous transluminal angioplasty (PTA) was not attempted in any of these eight patients in view of the very extensive nature of the abnormalities, reasonably adequate medical management and because previous authors have reported no long term success (Messina et al., 1986). Two children (one MAS, one William's syndrome) had major reconstructive surgery. The child with MAS (aged 7) had a thoracic aorta to aortic bifurcation bypass graft with bilateral autotransplantation of both kidneys. Fifteen months later this child is well and off all medication. The child with William's syndrome (aged 13) underwent left renal autotransplantation and right iliorenal saphenous vein bypass graft but died of gram negative sepsis and bleeding 5 days post-operatively. The other six children were considered not suitable for surgery either because of the extent of their lesions or the fact that the medical treatment ~of their hypertension had been reasonably successful.
Fibromuscular Hyperplasia Classical findings of the irregular 'beaded' appearance of F M H (Makker and Moorthy, 1979) were seen in four patients, and in all cases this was unilateral. Two patients
(50%) had additional branch artery stenosis (Fig. 4). Normal aorta and mesenteric vessels were seen in all patients. P T A was attempted and successfully performed in two patients (aged 3 and 6 years). In both there was a good post-angioplasty result followed by an immediate clinical improvement with reduction in bloodpressure and drug therapy. One patient had a repeat angiogram 10 months later with no evidence of restenosis of the main arterial lesion (Fig. 4b) although some small branch renal stenoses were still evident. The other two children presented before P T A was available. One child (aged 14 years) had a saphenous vein bypass graft and remains well and off treatment 9 years following surgery. The fourth child (aged 7 months) had a nephrectomy but died due to a post-operative arrhythmia.
Neurofibromatosis Three children had clinically evident NF. The renal artery stenoses were bilateral in two patients with typical smooth ostial narrowings. In addition two patients had abdominal aortic coarctation (Fig. 5), associated in one case with narrowing of the origins of the superior mesenteric and coeliac arteries. One child in this group had the right kidney autotransplanted to the right iliac fossa (with the renal artery grafted to the internal iliac artery and the renal vein to the c o m m o n iliac vein) and initially d i d well, no longer needing medication. After 3 years, however, a D M S A scan showed the transplant to have only 12% function. One child has been managed medically. One child had bilateral angioplasty procedures attempted on two different occasions. Each time the stenoses proved resistant to dilatation with no angiographic or clinical improvement (Fig. 5b). Bilateral saphenous vein grafts were subsequently performed to revascularize both renal arteries.
379
RENAL ARTERY STENOSIS IN CHILDREN
(a)
(a)
(b) Fig 5 Male aged 5 years with NF. (a) Typical smooth ostial narrowings are seen in both renal arteries. Abdominal coarctation is also noted (arrow). The opacity seen in the left upper quadrant was a
tablet in the stomach. (b) Same child following angioplasty to left renal artery. Although this was technically successful, the stenosis proved resistant to dilatation with no angiographic improvement (arrow). One renal artery s u b s e q u e n t l y occluded and the kidney was lost b u t 4 years later a severe stenosis had developed at the distal g r a f t - r e n a l artery anastomosis of the other kidney. This was treated by angioplasty with a good radiological and clinical response.
Idiopathic RAS Plus Isolated Branch Artery Lesions
(b) Fig. 4 - Female aged 5 years with FMH. (a) The main renal artery shows two areas of narrowing in its mid portion with slight dilatation in between (double arrow). Within the kidney there are a number of areas
ofstenosis or occlusion (singlearrows). (b) Same child 10 months after a successful angioplasty. Smallbranch renal stenoses are still evident. The main renal artery appears normal.
T w o children had unilateral R A S b u t w i t h o u t the appearance of F M H or other diagnostic clinical features. Extensive periureteric collaterals were seen in one patient_ The other patient h a d a long severe t u b u l a r stenosis extending to the r e n a l h i l u m (Fig. 6) with multiple b r a n c h stenoses. I n a d d i t i o n there was some moderate distal aortic arch c o a r c t a t i o n with d i l a t a t i o n of the ascending aorta. I n b o t h these chilidren the a b d o m i n a l aorta and mesenteric vessels were n o r m a l .
380
CLINICAL RADIOLOGY
Fig. 6 - Male aged 3 m o n t h s with idiopathic RAS. There is a long tubular stenosis of the left renal artery extending to the renal hilum (arrow).
PTA was attempted in one of these children (aged 14) but the 'waisting' of the balloon could not be abolished despite multiple high pressure dilatations and there was no clinical improvement. Autotransplantation was then undertaken but the kidney infarcted one day postoperatively. The Other child aged 3 months died of unrelated causes shortly after his angiogram. Two patients showed branch stenoses in the absence of main renal artery lesions. In one patient this was bilateral. Abdominal vasculature was otherwise normal in both patients. In one patient at the initial study aortography appeared normal (Fig. 7a). As a subsequent D M S A (Fig. 7b) showed a focal abnormality, selective magnification renal arteriography was performed which showed a focal branch stenosis and an ischaemic segment of kidney (Fig. 7c)_ This patient was treated by nephrectomy which cured her severe hypertension. The other patient was lost to follow up.
DISCUSSION Renovascular hypertension in children is rare but the lack of specific signs and symptoms in over 50% of our patients presenting incidentally emphasizes the need to measure the blood pressure in all children routinely as part of a clinical examination. It is well documented that the I V U has limited value for diagnosing RAS in the hypertensive children (Lawson et al., 1977; Stringer et al., 1984; Watson et al., 1984) and now has no role. However, imaging with nuclear medicine and ultrasound should be performed in view of the possibility of renal parenchymal lesions causing hypertension. Angiography is recommended for all patients in whom a non-vascular cause for the hypertension has not been established, or in children" with hypertension that is unexpected and progressive or difficult to control. Angiography in experienced hands is a very low risk procedure, particularly in recent years with the introduction of smaller catheters, non-ionic contrast and digital angiography. Flush techniques will detect renal artery stenoses in the majority of patients but we believe that selective examinations to show main intrarenal arteries
must be performed if the main arteries appear normal so that branch stenoses are not missed. This was emphasized in one of our patients where a significant branch lesion was missed initially on a flush aortogram (Fig. 7). We also believe that lateral views should be performed to evaluate the origins of the mesenteric vessels if renal artery pathology is seen because involvement of these vessels is c o m m o n in MAS, William's syndrome (62_5% in our study), N F (33% in our study) and rarely in FMH. Angiography also has an importat role after surgery in evaluating the patient with a clinical change or deterioration in renal function. Stanley (1984) classified RAS histologically and Mall et al. (1987) suggest classification by location and length of the stenosis. We feel that classification relating to underlying etiology as established by clinicoradiological criteria is more useful because it can give a guide to appropriate treatment and possibly to eventual outcome_ Stanley (1984) in his paper on renal vascular disease and renovascular hypertension in children claims F M H and its variants are the commonest cause ofrenovascular hypertension in children, accounting for 95% of patients, whereas in our large series the MAS/William's syndrome patients predominate (combined total 42%), compared with F M H accounting for 21%. There has been some debate in the literature as to the exact nature of MAS, with Berkman and Lande (1989) suggesting that it is a variant of Takayasu's arteritis. The distinction is important clinically as anti-inflammatory drugs may be useful in some patients with Takayasu's arteritis_ Classically Takayasu's arteritis occurs in oriental adolescent females with signs of an arteritis with an elevated ESR, malaise, fever, pain and night sweats (Lupi-Herrera et al., 1977). Pulmonary artery involvement is seen in up to 50% of patients. 'Skipped' areas of aortic involvement, aneurysms and narrowings alternating with normal segments are characteristic of Takayasu's arteritis (Lande, 1976). In MAS the patients are younger, there is no evidence of an acute arteritis and there is no clinical evidence to suggest pulmonary artery disease. Additionally in MAS the disease appears to arrest at puberty, compared with Takayasu's arteritis which is progressive (Meranze and O'Neill~ 1989). Histologic examination of involved regions of Takayasu's arteritis will show inflammatory change, a finding not seen in patients with the midaortic syndrome (Lewis et al., 1988). The differences are sufficient to make us feel that it is a separate entity. N F can be either inherited or sporadic but hypertension can be caused by lesions other than RAS, such as phaeochromocytoma. Renal P T A in adults is now an established technique for treatment of m a n y forms of RAS (Martin et al., 198 l; Mahler et al., 1982). The procedure is more difficult in children with smaller vessels but selected paediatric groups show a good response with this technique (Mathias et al., 1981; Stanley et al., 1984), particularly the cases of F M H which as in adults showed an excellent response to PTA. RAS secondary to N F is rare and usually caused not by a neurofibroma but by intimal fibrosis or proliferation of fibrous tissue. Small peripheral renal arteries are often stenosed because of small vessel dysplasia (Greene et al., 1974). Lesions caused by N F can be readily crossed for attempted PTA but the stenoses are resistant to inflation of the balloon (Lund et al., 1984; Miller et al., 1985).
RENAL ARTERY STENOSISIN CHILDREN
381
(b) (a)
(~) Fig. 7 - Female patient aged 15 years with isolated branch artery stenosis. (a) 'Normal' flush aortogram. (b) The DMSA scan shows a focal defect at the right upper pole. (e) A repeat angiography with selective catheterization confirms a focal branch stenosis with collateraI formation (arrow) and a focal defect on the nephrogram corresponding to the DMSA abnormality and delayed emptying of the distal vessels_
R e s p o n s e to P T A is similarly p o o r in M A S (Lewis et al., 1988), W i l l i a m ' s s y n d r o m e a n d T a k a y a s u ' s arteritis, p r e s u m a b l y because o f the progressive w i d e s p r e a d n a t u r e o f these diseases. P T A m a y h o w e v e r have a role in those p a t i e n t s w h o have u n d e r g o n e surgical b y p a s s p r o c e d u r e s a n d p r e s e n t with s u b s e q u e n t stenoses at surgical sites, as was seen in one o f o u r cases o f N F . In the series r e p o r t e d by Lewis et al. (1988) the m a i n s t a y o f t r e a t m e n t for M A S has been c o m p l e x b y p a s s surgery b u t it is n o t clear w h a t the precise i n d i c a t i o n s for surgery were a n d surgery is n o t always feasible in this g r o u p o f p a t i e n t s ( G u p t a , 1979). The m o r t a l i t y rate in
these cases can be high due to the extensive vessel i n v o l v e m e n t a n d the difficulties in finding an a p p r o p r i a t e graft. M o s t o f o u r p a t i e n t s (75%) have d o n e well on medical t r e a t m e n t alone with g o o d g r o w t h a n d preservation o f renal function. O u r c u r r e n t a p p r o a c h when dealing with M A S is to r e c o m m e n d that surgery only be considered as second line t r e a t m e n t after a d e q u a t e medical t r e a t m e n t has failed.
Acknowledgements.We thank Ms Bernadette Maloney for typing the manuscript.
382
CLINICAL RADIOLOGY
REFERENCES
Berkmen, YM & Lande, A (1989). Letter. Radiology, 170, 571. Chesney, R (1987), Idiopathic hypercalcaemia. In Nelson Textbook of Pediatrics 13th edn., eds Behrman, RE & Vaughn, VC, p. 1381. WB Saunders, Philadelphia. Goncharenko, V, Gerlock AJ, Jr, Shaft, MI & Hollifield JW (1981). Progression of renal artery fibromuscular dysplasia in 42 patients as seen on angiography. Radiology, 139, 45 51. Greene, JF, Fitzwater, J & Burgess, J (1974). Arterial lesions associated with neurofibromatosis. American Journal of Clinical Pathology, 62, 481-487. aortic syndrome. Thorax, 34, 470-478. Lande, A (1976). Takayasu's arteritis and congenital coarctation of the descending and abdominal aorta: a critical review. American Journal of Radiology, 127, 227 233. Lawson, JD, Buerth, R, Foster, JH & Dean, RH (1977). Diagnosis and management of renovascular hypertension in childhood. Archives of Surgery, 112, 1307 1316. Lewis III, VD, Meranze, SG, McLean, GK, O'Neille JA, Berkowitz, HD & Burke, DR (1988). The midaortic syndrome: diagnosis and management. Radiology, 167, I 11-113. Lund, G, Sinaiko, A, Castaneda-Zuniga, W, Cragg, A, Salomonwitz, E & Amplatz, K (1984). PTA for treatment of RAS in children. European Journal of Radiology, 4, 254 257. Lupi-Herrera, E, Sanchez-Torres, G, Marchushamer, J, Mispireta, J, Horwitz, S & Vela, JE (1977). Takayasu's arteritis: clinical study of 107 cases. American Heart Journal, 93, 94 102. Mahler, F, Probst, P, Haertel, M, Weidmann, P & Krneta, A (1982). Lasting improvement of renovascular hypertension by transluminal dilation of atherosclerotic and non-atherosclerotic RAS. A follow up study. Circulation, 65, 611 617. Makker, SO & Moorthy, B (1979). Fibromuscular dysplasia of renal arteries: an important cause of renovascular hypertension in chil-
dren. European Journal of Radiology, 4, 254 257. Mali, WP, Puijlaert, CB, Kowwenberg, J, Klinge, J, Donckerwolcke, R, Geijskes, Bet al. (1987). Percutaneous transluminal angioplasty in children and adolescenets. Radiology, 165, 391 394. Martin, EC, Mattern, RF, Baer, L, Fankuchen, E & Casarella, WJ (1981). Renal angioplasty for hypertension: predictive factors for longterm success. American Journal of Radiology, 137, 921 924. Mathlas, K, Struck, E, Schindera, F. & Urbanyi, B (1981). Percutaneous treatment of renovascular hypertension. Paediatric Radiology, II, 154 156. Meranze, SG & O'NeilL JA (1989). Letter. Radiology, 170, 572. Messina, LM, Goldstone, J, Ferrell, LD, Reilley, LM, Ehrenfeld, WK & Stoney, RJ (1986). Middle aortic syndrome: effectiveness and durability of complex arterial rcvascularization techniques. Annals of Surgery, 204, 331 337. Miller, G, Ford, K, Braun, S, Newman, G, Moore, A, Malone, R et al. (1985). Percutaneous transluminal angloplasty vs surgery for renovascular hypertension. American Journal of Radiology, 144, 447450. Sen, PK, Kinare, SG, Engineer, SD & Parulkar, GB (1963). The middle aortic syndrome. British Heart Journal, 25, 610-618. Stanley, JC (1984), Renavascular disease and renovascular hypertension in children. Urologic Clinies of North America, II, 451 463. Stanley, P, Hieschima, G & Mehringer, M (1984), Percutaneous transluminal angioplasty for paediatric renovascular hypertension. Radiology, 153, 101 104. Stringer, DA, de Bruyn, R, Dillon, MJ & Gordon, I (1984). Comparison of aortography, renal vein renin sampling, radionuclide scans, ultrasound and the IVU in the investigation of childhood renovascular hypertension. British Journal of Radiology, 57, 111 121. Watson, AR, Balfe, J & Hardy, B (1984). Renovascular hypertension in children. A changing perspective in management. Journal of Paediatries, 106, 366-372.