Arterial Fibrodysplasia

1. Arterial Fibrodysplasia Encompasses a heterogenous group of arterial dysplastic lesions affecting small and medium-sized arteries Unknown etiology Described in every artery Most common: Renal

2. Arterial Fibrodysplasia • Dysplastic process usually results in stenosis, but can also cause aneurysms • Occlusive renal artery lesions: most common cause of surgically correctable HTN • Renovascular HTN: • Goldblatt H 1934: Established link between renal ischemia and hypertension using constricting clamp • Atherosclerotic disease most common (>90%) • Fibrodysplastic disease second (0.5% of general population)

3. Arterial Fibrodysplasia • Renal artery fibrodysplasia: • Pathology • Clinical manifestations • Indications for therapeutic intervention • Drug Therapy • PTRA • Role of surgery

4. Pathology • Arterial dysplasia: categorized according to layer of wall involved • 1) intimal fibroplasia • 2) medial hyperplasia • 3) medial fibroplasia • 4) perimedial dysplasia • 5) developmental stenoses Distinct pathologic processes Continuum of same disease

5. Pathology • Intimal fibroplasia: • 5% of all fibrodysplastic renal artery lesions • Affects children and adults equally • Occurs as long tubular stenosis in children, smooth focal stenoses in adults • Progression slower than medial fibroplasia

6. Pathology • Medial hyperplasia: • 1% of fibrodysplastic renal artery lesions • Angiographically similar to intimal hyperplasia • Most often in women (30 to 50 y.o.) • Usually as isolated lesion in midportion of main renal artery

7. Pathology • Medial fibroplasia: • 85% of all dysplastic renal artery lesions • White women (30-40 y.o.) • Bilateral in 55%, when unilateral 80% are on the right • Angiographic appearance: classic “string of beads”

8. Pathology • Perimedial dysplasia: • Accumulation of elastic tissue at media-adventitia junction • 10% of arterial dysplastic lesions • Younger women • Either focal stenoses or multiple stenoses of main renal artery

9. Etiology • Unknown • 3 factors: • Hormonal influences • Arterial wall ischemia • Mechanical stresses

10. Pathology • Higher incidence of arterial dysplasia in women of reproductive years: role of estrogen • ?Ischemia of artery wall secondary to injury of vasa vasorum of vessels • Repeated stretching of vessels may trigger a fibroproliferative response (right renal artery is longer and may be subject to greater axial stretch)

11. Clinical Manifestations Prevalence of renovascular HTN in patients with HTN is low (2-5%) HTN caused by arterial fibrodysplasia is even less common First lesson in dx renovascular HTN: recognizing clinical cues

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13. Pathology • Stanley JC et al. • U Mich series • 88% with renal arterial fibrodysplasia causing renovascular HTN showed atypical media-perimedial dysplasia • 33 boys (mean age 9.5), 24 girls (12) • Average duration of HTN(14.2 months) • Mean BP before drug therapy: 181/117 • Mean BP after drug therapy: 158/104

14. Pathology • Stanley JC et al. • U Mich series • 133 women, 11 men • Mean age: M 31; F 39 • Average duration of HTN: 43 months • BP before therapy: 206/122 • BP after durg treatment: 184/111

15. Indications for Tx • Depend largely on age at presentation • Pediatrics: incidence of essential HTN is negligible • Most instances of HTN in this patient population represent a renovascular etiology • Mod to severe BP elevations in this patient population: detailed diagnostic studies warranted in search of correctable cause of HTN

16. Indications for Tx • Indications for intervention in adults: • Presence of moderate to severe HTN • HD significant renal artery stenosis • Evidence of the functional importance of the stenosis

17. Indications for Tx • Dramatic improvement in drug therapy for HTN has raised the threshold for intervention in renovascular HTN • Has led to older age at presentation and duration of HTN • Functional significance of fibrodysplasia is more challenging since these older patients have higher incidence of essential HTN, atherosclerotic disease

18. Screening Tests • Most commonly used screening studies: • Renal duplex u/s • MRA • Radionuclide scan (Renal scintigraphic captopril test) • Captopril: efferent arteriolar vasodilation reduces driving pressure across glomerulus, reducing GFR • Glomerular radionuclide tracer uptake by kidney is markedly decreased • CTA

19. Indications for Tx • Vasbinder GB et al. Diagnostic tests for renal artery stenosis in patients suspected of having renovascular HTN: a meta-analysis. Ann Intern Med 2001; 135:401-11 • Established the superiority of CTA and MRA over other non-invasive screening tests for renovascular HTN • 98% sensitive, 94% specific

20. Indications for Tx • Once patient has been identified on the basis of clinical clues and/or use of screening studies • Angiography is most useful test for assessing hemodynamic and functional significance of renal artery dysplastic occlusive disease • Gold standard

21. Indications for Tx • Angiographic features to determine hemodynamic significance of dsyplastic renal artery stenosis • Demonstration of collateral vessels (usually develops when pressure gradient across stenosis approaches 10 mmHg) • 10 mm Hg is generally accepted association with increase release of renin from JXA

22. Indications for Tx • Renin assays: • Have been important in determining functional significance of equivocal renal artery stenoses • Most useful in patients with medically controlled HTN and older patients with arterial fibrodysplasia and extrarenal atherosclerosis • Younger patients with poorly controlled HTN or threatened ischemic nephropathy, dx may be made via renin profiling with the renal systemic renin index (RSRI)

23. Indications for Tx • Renal systemic renin index (RSRI): alternative calculation of each kidney’s renin secretory activity • Subtract systemic renin activity from renal vein renin activity and dividing remainder by the systemic renin activity • Renin hypersecretion: RSRI > 0.38 • Suppression of renin secretion by a kidney defined as RSRI < 0.24

24. Indications for Tx • Renal vein renin ratio (RVRR): compares renin activity in venous effluent from ischemic and contralateral kidneys has not been a highly predictive test • Not reliable largely due to bilateral disease • Considered abnormal when > 1.48

25. Drug Therapy • Renin-angiotensin-mediated vasoconstriction is primary mechanism of hypertension in patients with unilateral renal artery stenosis and normal contralateral kidney. • In bilateral renal artery stenosis, renin-angiotensin-aldosterone mediated sodium retention and hypervolemia are the dominant pathophysiologic mechanisms for HTN

26. Drug Therapy • B-blocker often first drug given (Inhibition of renin secretion by B-blockade) • In bilateral renal artery stenoses, the addition of diuretic may be used to treat hypervolemic state in these patients • Thiazide, Lasix • ACE inhibitor, angiotensin II antagonist (good for LVH, heart failure, diabetic nephropathy) • Ca channel blockers • Clonidine • Hydralazine

27. Drug Therapy • Undisputed: optimizing medical therapy reduces cardiovascular morbidity • Unclear: its role in delaying the progression of nephropathy

28. Drug Therapy • At least three randomized controlled trials comparing medical therapy with and without angioplasty • Van Jaarsveld BC et al. N Engl J Med 2000 • Plouin PF et al. Hypertension 1998 • Webster J et al. Scottish and Newcastle Renal Artery Stenosis Collaborative Group J Hum Hypertension 1988 • No difference in BP control or preservation of renal function • However, in largest of these studies (Plouin et al), half crossed over to receive angioplasty for poorly controlled BP within 3 months

29. PTRA • Percutaneous transluminal renal angioplasty (PTRA) has become the dominant mode of tx of renal arterial dysplasia at most institutions • Angioplasty deemed technically successful when preexisting pressure gradients across stenosis are abolished • Anatomic documentation of an adequate dilatation

30. PTRA • The majority of fibrodysplastic lesions may be treated with PTRA alone • Stent placement is reserved for rescue in failed PTRA or renal artery dissection • Mechanism of balloon angioplasty: • Artery wall stretched, separating intima from underlying structures, splitting media, and stretching adeventitia beyond elastic recoil • Dilated artery undergoes fibroproliferative reparative process forming neointima

31. PTRA • Approximately 85% of adult patients with renal artery fibrodysplasia and renovascular HTN benefit from PTRA • Best results with patients with unilateral medial fibroplasia

33. PTRA • Mean overall complication rate after renal angioplasty: 11% • Complications: dissection, perforation • Contraindicated in associated macroaneurysms, extensive branch vessel disease, or complex dissections • Failures correlate with longer duration of HTN and older age of patients at time of presentation for tx • Trends in outcome after PTRA parallel those in surgical management

34. PTRA • Results of PTRA for renal artery fibrodysplasia in pediatric population less encouraging • Renal artery stenosis associated with neurofibromatosis or aortic anomalies are likely to fail PTRA • Watson et al. J Pediatr • 60% of unsuccessful angioplasties resulted in nephrectomies

35. Surgical Therapy • Key: Adequate exposure • Transverse incision (midclavicular to midaxillary on side of renal artery reconstruction) • Midline incision • Right-sided reconstruction: • Expose renal artery,vein, IVC, aorta by mobilizing right colon and hepatic flexure. Kocher maneuver

36. Surgical Therapy

37. Surgical Therapy • For left-sided reconstructions: • Reflection of viscera (mobilization of left colon) • Exposure of left renal artery usually requires mobilization of the renal vein with ligation and transection of gonadal branch inferiorly and adrenal venous branches superiorly

38. Surgical Therapy • Right sided aortorenal grafts: retrocaval position usually best

39. Surgical Therapy • Left sided: grafts usually positioned beneath left renal vein • Other sites for anastomosis: hepatic, splenic, common iliacs • For graft-renal artery anastomosis, end-to-end anastomosis is preferred to end-to-side (spatulation of graft posteriorly and renal artery anteriorly) • In pediatric population, interrupt sutures to allow for anastomotic growth

40. Surgical Therapy • Autologous vein grafts preferred • Autologous hypogastric artery grafts are favored bypass procedures in children • Dacron, PTFE grafts

41. Surgical Therapy • For proximal segmental disease pattern, there are three methods of repair: • Separate implantations of renal arteries into single conduit • In situ anastomosis of involved renal arteries in side-to-side manner to form common orifice

42. Surgical Therapy • Remimplantation of an affected artery beyond its diseased segment into adjacent normal artery (end-to-side) • Ex vivo repairs: • Require mobilization of entire kidney including accompanying vasculature and ureter to the pelvis • Renal artery vein transected • Tourniquet around intact ureter to prevent collateral blood flow

43. Surgical Therapy • Cold LR to flush kidney of venous effluent • Kidney connected to perfusion mannifold • Hypothermic perfusion begun • Dissection of renal artery to level of visible/palpable disease • Iliac artery arterial autograft flushed • Sequential branch anastomoses in end-to-end fashion over metal dilator to prevent narrowing

44. Surgical Therapy • Perfusion cannulas removed, kidney repositioned in retroperitoneum • Proximal aortic anastomosis, renal vein anastomosis completed • In situ repairs: • Appropriate when patient has 2 kidneys requiring primary repair limited to first bifurcation

45. Surgical Therapy • Ex vivo repairs: • Reoperation for failed prior renal arterial repairs • Multiple branch artery lesions in single kidney • Extension of branch vessel disease into renal hilum • Certain branch artery stenoses in children • Traumatic injuries involving the renal hilum • Stenoses involving multiple renal arteries

46. Surgical Therapy • Alternative reconstructions: • Splenorenal bypass (left-sided); must document normal celiac artery • Should not be done in pediatric patients • Complex reconstructions: • Operative tx of fibrodysplastic renovascular HTN in face of aortic hypoplasia or corarctation • Thorocoabdominal bypasses and local aortoplasties with concomitant renal artery construction • Operative mortality 8%, 90% of survivors benefit

48. Surgical Therapy • Incidence of early postoperative aortorenal vein graft thrombosis: 2-7% • Occurs less often with arterial autografts • More common in small-diameter arteries and branch vessel reconstructions • Study of choice to r/o early postoperative graft occlusion: arteriography

49. Surgical Therapy • Late vein graft stenoses: 8% • Intimal hyperplasia • Clamp injury • Traumatic dilator advancement • Marked aneurysmal change in aortorenal grafts: • 2% in adults • 20% of vein grafts in pediatric population

50. Surgical Therapy • “Beneficial outcomes after operative intervention for renovascular HTN are directly proportional to the accurate identification of appropriate surgical candidates and performance of adequate reconstructive procedure” • Cooperative Study of Renovascular HTN: • Less than optimal results: ?errors in patient selection and early technical failures • 577 surgeries in 520 patients with all forms of renovascular HTN • 51% cure, 15% improvement, 34% failure • Renal artery fibrodysplasia more responsive than for atherosclerotic disease