Renal Artery Stenosis An important cause of hypertension

Renal Artery Stenosis: An important cause of hypertension Dr Claire Hathorn Sp. R, RHSC Edinburgh 11 th May 2010

Presentation • 3 year old girl • Well • Minor intercurrent illness – A&E • BP 144/91

History & Examination • Asymptomatic • PMH – Eczema, viral induced wheeze • FH – nil of note • Normal examination • Height and weight on 97 th centile

Initial Investigations • BP 120 -140 / 90 -100 mm. Hg • • • Urinalysis negative FBC, U&Es, LFTs, coagulation 4 limb BP ECG Renal USS & dopplers • ALL NORMAL

Further Investigations • • • Renin Aldosterone Cortisol PTH ACTH Complement C 3 C 4 ANA 2. 6 136 192 34 12 560 1. 01 0. 18 neg • Urine catecholamines N • Urine cortisol 11. 9 • Urine prot: creat ratio 39 (slightly raised) • Urine MC&S negative

Radiology • Echo – normal • DMSA – divided function 50% • MR Angiogram – slight irregularity of superior surface of right renal artery, felt unlikely to represent stenosis. No evidence of duplex. Conclusion: normal.

DMSA

MR Angiogram

Specialist Opinions • Cardiology: – No clinical evidence of coarctation – No LVH on Echo • Ophthalmology – Examination normal – No hypertensive retinopathy • No cause or complication of hypertension

Impression & Management • Blood pressure not well-controlled on 3 drugs – Atenolol 20 mg bd – Amlodipine 2. 5 mg od – Doxazosin 0. 5 mg od • Renovascular disease most likely diagnosis • Referred formal angiography at Great Ormond Street Hospital

Angiography • Critical stenosis of left upper pole branch of main renal artery • Normal right renal arteries • Angioplasty performed • Atenolol & Doxazosin stopped • Aspirin started

Progress • Remained hypertensive 1 month postangioplasty: 120/61 • Amlodipine continued • Doxazosin restarted • 3 months post-angioplasty, BP well-controlled: 50 -75 th centile

Discussion

Renovascular Hypertension • • Aetiology Clinical Features Investigations Management

Renovascular Hypertension • 5 -10% of all childhood hypertension • Amenable to potentially curative treatment • Causes & management different to adults

Aetiology in Children • Fibromuscular dysplasia – most common in UK • • Syndromes: Neurofibromatosis, Williams, Marfan Vasculitides: Takayasu, Kawasaki Extrinsic compression: Wilm’s, Neuroblastoma Other: Renal transplant, trauma, radiation

Clinical Spectrum • Bilateral disease in 53 -78% • Intrarenal disease in 44% • Intrarenal & main artery stenosis in 31% • Most children without co-morbidities have single focal branch artery stenosis Tullus et al. Renovascular hypertension in children. Lancet. 2008; 371: 1453 -1463

Anatomic distribution of renal artery stenosis in children: implications for imaging • • • Cinncinnati Children’s Hospital, 1993 -2005 24 stenoses identified in 21 children, R=L 12 male, mean age 9 yrs 3 mths (30 mths – 18 yrs) No co-morbidities 90% children had a single stenosis 75% lesions located in branch / accessory arteries Vo et al. Pediatric Radiology 2006; 36: 1032

Clinical Features Presenting Feature No. n=33 Incidental finding 9 Cardiac (CCF, palpitations, murmur) 7 Headache +/- vomiting & lethargy 6 Acute hypertensive encephalopathy 3 Cerebrovascular accident 2 Facial palsy 2 Failure to thrive 2 Screening for NF 1 2 Schroff et al. Angioplasty for renovascular hypertension in children: 20 year experience. Pediatrics 2006; 118: 268 -275

Renovascular disease and more widespread arterial involvement Schroff et al 2006 (%) 48 Stadermann et al 2010 (%) 51 Intrarenal disease 45 - Cerebral 21 26 Aortic 24 40 - 23 Bilateral RAS Visceral

Implications of widespread arterial disease • Improved BP control – 11/13 (85%) isolated RAS – 6/20 (30%) associated intra or extra renal disease • Recommend routine cerebrovascular imaging – MR / PET scanning Schroff et al. Angioplasty for renovascular hypertension in children: 20 year experience. Pediatrics 2006; 118: 268 -275

Investigation • Doppler ultrasound • Measurement of plasma renin activity – Captopril plasma renin test – Renal vein sampling • Scintigraphy: DMSA or MAG 3 • CT & MR angiography • Angiography: Gold Standard

DMSA scintigraphy before & after Captopril Tullus et al. Renovascular hypertension in children. Lancet. 2008; 371: 1453 -1463

CT Angiogram Tullus et al. Renovascular hypertension in children. Lancet. 2008; 371: 14531463

MR Angiogram

Angiography • With carefully selected patients, 40% RAS • Important therapeutic opportunity • Visualisation of abdominal vessels

Angiography: Indications • Tulles et al. (2008) – BP >95 th centile not well-controlled on 2 drugs – Other cause not identified • Vo et al. (2006) – Unexplained persistent HT > 95 th centile • Shahdadpuri et al. (2000) – BP > 99 th centile not controlled with 1 drug – Angiography abnormal in 43% patients

A 4 -year-old hypertensive boy Vo et al. Anatomic distribution of RAS in children. Pediatric Radiology 2006; 36: 1032

14 yr old hypertensive girl Vo et al. Anatomic distribution of RAS in children. Pediatric Radiology 2006; 36: 1032

Medical Management • Anti-hypertensives – Multiple often required – Adequate BP control often not possible – Adverse effects common – Avoid ACE inhibitors & angiotensin receptor blockers • Concern re renal function if BP well-controlled due to under-perfusion of kidneys

Angioplasty • 1980 : 1 st successful angioplasty in a child • Balloon diameter equal to proximal artery • Stent if residual diameter stenosis <50% • Complications – Arterial spasm – Dissection – Arterial rupture • Post-procedure: Aspirin 3 -6 months Tullus et al. Renovascular hypertension in children. Lancet. 2008; 371: 1453 -1463

Angioplasty for renovascular hypertension in children: 20 year experience • Retrospective review from GOS • All children undergoing PTA 1984 -2003 – Only stenoses in main or large segmental arteries – Excluded transplants & inflammatory disorders • 33 children, 1. 9 -17. 9 yrs (median 10. 3) – 10 with underlying syndromes – 16 bilateral RAS – 15 intrarenal disease • 48 procedures, including 15 stents Schroff et al. Pediatrics 2006; 118: 268 -275

Angioplasty for renovascular hypertension in children: 20 year experience • Final outcomes of PTA: – 18 (55%) improved BP control • 11/13 (85%) if isolated main RAS – 10 (30%) ongoing HT despite adequate dilation – 5 (15%) PTA unsuccessful – Restenosis in 2/27 native renal arteries after balloon dilatation, 7/19 of stented arteries – 6 (18%) suffered complications, incl 1 death Schroff et al. Pediatrics 2006; 118: 268 -275

Left RAS before & after Angioplasty Schroff et al. Angioplasty for renovascular hypertension in children: 20 year experience. Pediatrics 2006; 118: 268 -275

Surgery • For refractory HT when medical Rx & angioplasty have failed • Nephrectomy • Revascularisation procedures • Aortic reconstruction

Results of surgical treatment for RVH in children: 30 yr single centre experience • • 37 children (65% male) 1979 - 2008 Mean SBP 140 (105 -300) mm. Hg 53 surgical procedures – Nephrectomy – Renovascular surgery – Aortic reconstruction 18 28 7 Stadermann et al. Nephrology Dialysis Transplantation. 2010; 25(3): 807 -813

Results of surgical treatment for RVH in children: 30 yr single centre experience • 12 months post-op: – 16 (43%) normal BP without treatment – 15 (41%) normal/improved BP on 1 -4 drugs – 4 (11%) unchanged • 90% overall improvement • Complications: – Haemorrhage (5) – Septicaemia (5) – Chylous ascites (1) Stadermann et al. Nephrology Dialysis Transplantation. 2010; 25(3): 807 -813

Children not amenable to Angioplasty or Surgery • Diffuse abnormalities of very small intrarenal arteries • Antihypertensive medication – Uncontrolled on 6 -7 drugs not uncommon • Therapeutic trial with ACE inhibitor or angiotensin blocker warranted Tullus et al. Renovascular hypertension in children. Lancet. 2008; 371: 1453 -1463

Suggested Investigations(Tullus 2008) BP >90 th centile, confirm with ABPM Confirmed HT >95 th centile BP 90 -95 th centile Primary Ix incl doppler US Monitor No cause identified BP well-controlled on 1 -2 drugs No further Ix BP poorly controlled on 2 drugs Scintigraphy &/or CT/MR Angiography Findings suggestive/clinical suspicion of RVH Angiography & renal vein sampling

Drug treatment without ACE-I or angiotensin receptor blocker BP not well-controlled or needing >2 drugs Angioplasty Surgery BP >95 th centile - Reconstructive surgery BP still >95 th centile – further drug treatment incl cautious use of ACE -I Tullus et al. Renovascular hypertension in children. Lancet. 2008; 371: 1453 -1463

Our Patient • 3 months post-angioplasty • BP well-controlled on 2 drugs • Close follow-up – BP – Renal function – DMSA • ? Consider cerebrovascular imaging

Any Questions?