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

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)

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

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

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

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

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”

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

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

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)

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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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

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

Surgical Therapy

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

Surgical Therapy Right sided aortorenal grafts: retrocaval position usually best

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

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

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

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

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

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

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

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

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

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

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

Surgical Therapy Results for surgical tx of renal artery fibrodysplasia for control of arterial HTN good

Surgical Therapy

Surgical Therapy Change in clinical profile over the years: Older age at presentation Longer duration of HTN Higher prevalence of extrarenal atherosclerosis

Conclusions Renovascular HTN should be excluded in young patients presenting with HTN and older patients with resistant HTN, acute renal dysfunction induced by ACE inhibitors, or unexplained episodes of flash pulmonary edema Arterial fibrodysplasia as a cause for renovascular HTN is uncommon relative to atherosclerotic disease as a cause for renovascular HTN Etiology unknown

Conclusions PTRA is most successful in renal artery fibrodysplasia in adults Less successful in children and for atherosclerotic disease PTRA and surgical revascularization for renal artery fibrodysplasia comparable A large randomized trial evaluating best medical therapy with and without revascularization using endpoints of BP control, renal outcome and cardiovascular mortality is needed