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

12. 160
180

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

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

52. Surgical Therapy

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

54. 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

55. 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