Controversies in renal Controversies in renal

arterial interventions.arterial interventions.Controversies in renal Controversies in renal

arterial interventions.arterial interventions.

ACHILLES CHATZIIOANNOU, MDACHILLES CHATZIIOANNOU, MDAssoc. Professor of RadiologyAssoc. Professor of RadiologyAmerican Board of RadiologyAmerican Board of Radiology

• 60-year old male.

• Hypertension (180/100)

• 3 anti-HTN medications

• Cr: 2,1 mg/dl

• 60-year old male.

• Hypertension (180/100)

• 3 anti-HTN medications

• Cr: 2,1 mg/dl

Herculink 6X18-mmHerculink 6X18-mm

•Normotensive with one medicationNormotensive with one medication..•Cr=1.1mg/dlCr=1.1mg/dl

Renovascular Renovascular

Hypertension (RVH)Hypertension (RVH)

Renovascular Renovascular

Hypertension (RVH)Hypertension (RVH)• Classic studies by Goldblatt (1930): RAS is the Classic studies by Goldblatt (1930): RAS is the

cause of RVH.cause of RVH.

• RAS causing RVH: prevalence 3-5% of the RAS causing RVH: prevalence 3-5% of the hypertensive patients.hypertensive patients.

• Atherosclerosis: 70-90% of RHV. FMD: 10-30% Atherosclerosis: 70-90% of RHV. FMD: 10-30% of RVH.of RVH.

• Classic studies by Goldblatt (1930): RAS is the Classic studies by Goldblatt (1930): RAS is the cause of RVH.cause of RVH.

• RAS causing RVH: prevalence 3-5% of the RAS causing RVH: prevalence 3-5% of the hypertensive patients.hypertensive patients.

• Atherosclerosis: 70-90% of RHV. FMD: 10-30% Atherosclerosis: 70-90% of RHV. FMD: 10-30% of RVH.of RVH.

Atherosclerotic diseaseAtherosclerotic diseaseAtherosclerotic diseaseAtherosclerotic disease

• The prevalence of RAS is increasing The prevalence of RAS is increasing because of population aging, and because of population aging, and increased survival.increased survival.

• >60% RAS in 6.8% of individuals > 65y.>60% RAS in 6.8% of individuals > 65y.

• RAS in pts undergoing coronary DSA: RAS in pts undergoing coronary DSA: 18%-20%.18%-20%.

• RAS in pts undergoing peripheral DSA: RAS in pts undergoing peripheral DSA: 35%-50%.35%-50%.

• The prevalence of RAS is increasing The prevalence of RAS is increasing because of population aging, and because of population aging, and increased survival.increased survival.

• >60% RAS in 6.8% of individuals > 65y.>60% RAS in 6.8% of individuals > 65y.

• RAS in pts undergoing coronary DSA: RAS in pts undergoing coronary DSA: 18%-20%.18%-20%.

• RAS in pts undergoing peripheral DSA: RAS in pts undergoing peripheral DSA: 35%-50%.35%-50%.

Fibromuscular Dysplasia

(FMD)

Fibromuscular Dysplasia

(FMD)• Young patients –more commonly females.

• Medial fibroplasia (80%).

• Location: distal main renal artery, 25% into 1st order branches.

• >50% of patients have bilateral disease.

• Commonly asymptomatic (3%-6% in Transplant donors).

• Young patients –more commonly females.

• Medial fibroplasia (80%).

• Location: distal main renal artery, 25% into 1st order branches.

• >50% of patients have bilateral disease.

• Commonly asymptomatic (3%-6% in Transplant donors).

Atherosclerotic diseaseAtherosclerotic disease

• Patient 6th decade or older.

• More often male.

• The majority of the lesions are incidental findings.

• Ostial lesions: within 1-cm from aorta.

• Truncal lesions (less than 10%): more than 1-cm.

• 50% have bilateral disease.

• 12%-20% of stenoses>75% will progress to total occlusion within one year (?)

• Patient 6th decade or older.

• More often male.

• The majority of the lesions are incidental findings.

• Ostial lesions: within 1-cm from aorta.

• Truncal lesions (less than 10%): more than 1-cm.

• 50% have bilateral disease.

• 12%-20% of stenoses>75% will progress to total occlusion within one year (?)

Manifestations of Renovascular

Disease (Textor SC, 2004)

Manifestations of Renovascular

Disease (Textor SC, 2004)

Renal Artery Stenosis

Incidental RAS

Renovascular Hypertension

Ischemic Nephropathy

AcceleratedCV Disease

CHFStroke

Endovascular treatment (PTA-Endovascular treatment (PTA-

stents) is always indicated in stents) is always indicated in

RAS? RAS?

Endovascular treatment (PTA-Endovascular treatment (PTA-

stents) is always indicated in stents) is always indicated in

RAS? RAS? • 7660 interventions in 19967660 interventions in 1996• 18520 interventions in 200018520 interventions in 2000• 2.8-fold increase by 2.8-fold increase by

interventional cardiologists interventional cardiologists (“drive-by”).(“drive-by”).

• 7660 interventions in 19967660 interventions in 1996• 18520 interventions in 200018520 interventions in 2000• 2.8-fold increase by 2.8-fold increase by

interventional cardiologists interventional cardiologists (“drive-by”).(“drive-by”).

Medicare data

Δεκαετία του 1990... μη ελεγχόμενες μελέτες

Αγγειοπλαστική ή χρήση ενδοαυλικού νάρθηκα

Σημαντική μείωση της Α.Π.8,9

Σταθεροποίηση την χρόνιας νεφρικής ανεπάρκειας10,11

8. Blum U et al. N Engl J Med 1997 9. Burket MW et al. Am Heart J 2000

10. Harden PN et al. Lancet 199711. Watson PS et al. Circulation 2000

12. Murphy TP et al. AJR Am J Roentgenol 2004

364%12

Treat RAS whenever found (easier Treat RAS whenever found (easier when early, avoid progression to when early, avoid progression to

occlusion). occlusion).

Treat RAS whenever found (easier Treat RAS whenever found (easier when early, avoid progression to when early, avoid progression to

occlusion). occlusion).

1.1. Progressive nature of ARVD, Progressive nature of ARVD, progressing at the rate of 10% progressing at the rate of 10% per year (45%-60% progression per year (45%-60% progression rate in 4-7 year f-u)rate in 4-7 year f-u)

2.2. Pre-occlusive lesions (70-90%): Pre-occlusive lesions (70-90%): risk of occlusion 40%. .risk of occlusion 40%. .

1.1. Progressive nature of ARVD, Progressive nature of ARVD, progressing at the rate of 10% progressing at the rate of 10% per year (45%-60% progression per year (45%-60% progression rate in 4-7 year f-u)rate in 4-7 year f-u)

2.2. Pre-occlusive lesions (70-90%): Pre-occlusive lesions (70-90%): risk of occlusion 40%. .risk of occlusion 40%. .

JVIR 2002

Ischemic nephropathyIschemic nephropathyIschemic nephropathyIschemic nephropathy• Progressive disease

– Lesion progression 20% per year.– Renal atrophy 10% per year.– Artery occlusion 5% per year.

• RAS is a marker of increased cardiovascular mortality, predictors:– Older age– Impaired renal function– Bilateral RAS

• Progressive disease– Lesion progression 20% per year.– Renal atrophy 10% per year.– Artery occlusion 5% per year.

• RAS is a marker of increased cardiovascular mortality, predictors:– Older age– Impaired renal function– Bilateral RAS

Acute renal failure in patients with RASAcute renal failure in patients with RASAcute renal failure in patients with RASAcute renal failure in patients with RAS

• 1-14 days after the initiation of 1-14 days after the initiation of treatment with ACE inhibitors.treatment with ACE inhibitors.

• After the use of diuterics or other After the use of diuterics or other antihypertensive drugs.antihypertensive drugs.

• After major surgery.After major surgery.

• After the spontaneous progression After the spontaneous progression of RAS to total occlusion.of RAS to total occlusion.

• 1-14 days after the initiation of 1-14 days after the initiation of treatment with ACE inhibitors.treatment with ACE inhibitors.

• After the use of diuterics or other After the use of diuterics or other antihypertensive drugs.antihypertensive drugs.

• After major surgery.After major surgery.

• After the spontaneous progression After the spontaneous progression of RAS to total occlusion.of RAS to total occlusion.

Results of revascularization for ischemic Results of revascularization for ischemic

nephropathynephropathy

Results of revascularization for ischemic Results of revascularization for ischemic

nephropathynephropathy

• 32 patients with unexplained renal impairment and RAS were treated with renal artery stent.

• In 70% of the patients the renal function improved or stabilized (p<0.007).

• 32 patients with unexplained renal impairment and RAS were treated with renal artery stent.

• In 70% of the patients the renal function improved or stabilized (p<0.007).

Harden et al, Lancet

1997

Harden et al, Lancet

1997

Results of revascularization for ischemic Results of revascularization for ischemic

nephropathynephropathy

Results of revascularization for ischemic Results of revascularization for ischemic

nephropathynephropathy

• 33 patients with bilateral RAS or RAS in 33 patients with bilateral RAS or RAS in solitary kidney.solitary kidney.

• Follow up: 20±11 months.Follow up: 20±11 months.

• Significant improvement in 72%; mild Significant improvement in 72%; mild improvement in 28%.improvement in 28%.

• Preservation of renal size in all patients.Preservation of renal size in all patients.

• 33 patients with bilateral RAS or RAS in 33 patients with bilateral RAS or RAS in solitary kidney.solitary kidney.

• Follow up: 20±11 months.Follow up: 20±11 months.

• Significant improvement in 72%; mild Significant improvement in 72%; mild improvement in 28%.improvement in 28%.

• Preservation of renal size in all patients.Preservation of renal size in all patients.

Watson et al. Circulation 2000Watson et al. Circulation 2000

Signs that a patient with ischemic nephropathy Signs that a patient with ischemic nephropathy

will benefit from revascularizationwill benefit from revascularization

Signs that a patient with ischemic nephropathy Signs that a patient with ischemic nephropathy

will benefit from revascularizationwill benefit from revascularization

1. Normal distal arterioles.

2. Bilateral disease.

3. Recent onset of renal insufficiency.

4. Resistive Index (Doppler sonography) <80

5. Extremely limited renal function (cr>2,5 mg/dl or 220 μmol/l)*

1. Normal distal arterioles.

2. Bilateral disease.

3. Recent onset of renal insufficiency.

4. Resistive Index (Doppler sonography) <80

5. Extremely limited renal function (cr>2,5 mg/dl or 220 μmol/l)*

• *Uder M, Huke U CVIR 2005*Uder M, Huke U CVIR 2005• *Uder M, Huke U CVIR 2005*Uder M, Huke U CVIR 2005

Percutaneous Percutaneous

revascularizationrevascularization

Percutaneous Percutaneous

revascularizationrevascularization• Technical success:98-100%Technical success:98-100%

• Long term patency rate 85%-98%Long term patency rate 85%-98%

• Complications:Complications:

– Mortality 1-3%Mortality 1-3%

– Major complications: 3-5%Major complications: 3-5%

– Minor complications 10-20%Minor complications 10-20%

• Technical success:98-100%Technical success:98-100%

• Long term patency rate 85%-98%Long term patency rate 85%-98%

• Complications:Complications:

– Mortality 1-3%Mortality 1-3%

– Major complications: 3-5%Major complications: 3-5%

– Minor complications 10-20%Minor complications 10-20%

An analysis of the pooled results of

studies of

conventional balloon angioplasty in

1118

patients

An analysis of the pooled results of

studies of

conventional balloon angioplasty in

1118

patients

• Hospital death 0.5%

• Nephrectomy 0.3%

• Renal surgery 2%

• Occlusion of a side branch of the renal artery 2.2%

• Cholesterol embolization 1.1%

• Injury at the site of vascular access 2.3%

• Hospital death 0.5%

• Nephrectomy 0.3%

• Renal surgery 2%

• Occlusion of a side branch of the renal artery 2.2%

• Cholesterol embolization 1.1%

• Injury at the site of vascular access 2.3%

The indications and results of PTA and stenting in renal artery stenosis. SeminVasc Surg 1996;9:188-197

13. Van Jaarsveld BC et al. N Eng J Med 200014. Plouin PF et al. Hypertension 1998

15. Webster J et al. J Hum Hypertens 199816. The ASTRAL investigators. N Eng J Med 2009

17. Bax L et al. Ann Intern Med 200918. Cooper CJ. N Eng J Med 2014

6 έχουν πραγματοποιηθεί μέχρι τώρα.... και οι 6

απέτυχαν

να δείξουν όφελος από την ενδαγγειακή θεραπεία της στένωσης της νεφρικής αρτηρίας

Εν συνεχεία... Ελεγχόμενες τυχαιοποιημένες μελέτες13, 14, 15, 16, 17, 18

EvidenceEvidenceEvidenceEvidence

3 randomized controlled trials compared medical treatment to percutaneous renal

revascularization:

• DRASTIC: Dutch Renal Artery Stenosis Intervention Cooperative Study Group

• EMMA: Essai Multicentrique Medicaments vs Angioplastie Study Group

• SNRASCG: Scottish and Newcastle Renal Artery Stenosis Collaborative Group

3 randomized controlled trials compared medical treatment to percutaneous renal

revascularization:

• DRASTIC: Dutch Renal Artery Stenosis Intervention Cooperative Study Group

• EMMA: Essai Multicentrique Medicaments vs Angioplastie Study Group

• SNRASCG: Scottish and Newcastle Renal Artery Stenosis Collaborative Group

ConclusionsConclusions

1. In patients whose blood pressure could be controlled with medical therapy alone, no trial was able to demonstrate a statistically significant difference in blood pressure between balloon angioplasty and medical therapy.

2. In patients with refractory hypertension to medical therapy, the results of the DRASTIC trial demonstrated that balloon angioplasty was better than medical therapy in respect of more efficient blood pressure control.

1. In patients whose blood pressure could be controlled with medical therapy alone, no trial was able to demonstrate a statistically significant difference in blood pressure between balloon angioplasty and medical therapy.

2. In patients with refractory hypertension to medical therapy, the results of the DRASTIC trial demonstrated that balloon angioplasty was better than medical therapy in respect of more efficient blood pressure control.

Renal functionRenal function

No significant difference in serum creatinine or creatinine clearance between the two groups in any of the trials.

No significant difference in serum creatinine or creatinine clearance between the two groups in any of the trials.

•Nordman. Cochrane Library of Systematic Reviews. 2004:;vol 2

“The majority of patients with significant RAS and hypertension or renal function loss can be treated medically without the risk of mortality or progression to end-stage disease”.

“The majority of patients with significant RAS and hypertension or renal function loss can be treated medically without the risk of mortality or progression to end-stage disease”.

Exceptions: Bilateral RAS; RAS in solitary kidney.

2X mortality risk; 1.5X risk of renal failure.

Care if renal mass loss OR loss of renal function when ACE inhibitor is used!

Exceptions: Bilateral RAS; RAS in solitary kidney.

2X mortality risk; 1.5X risk of renal failure.

Care if renal mass loss OR loss of renal function when ACE inhibitor is used!

AAngioplastyngioplasty andand S Stenttent forfor

RRenalenal A Arterialrterial L Lesionsesions

AAngioplastyngioplasty andand S Stenttent forfor

RRenalenal A Arterialrterial L Lesionsesions

• Multicenter Randomized clinical trial.Multicenter Randomized clinical trial.

• Approx 1000 pts will be randomized to Approx 1000 pts will be randomized to optimal medical therapy or to stenting optimal medical therapy or to stenting with optimal medical therapywith optimal medical therapy

• Multicenter Randomized clinical trial.Multicenter Randomized clinical trial.

• Approx 1000 pts will be randomized to Approx 1000 pts will be randomized to optimal medical therapy or to stenting optimal medical therapy or to stenting with optimal medical therapywith optimal medical therapy

Revascularization versus Medical Therapy for Renal-Artery Stenosis

The ASTRAL Investigators

Background Percutaneous revascularization of the renal arteries improves patency in atherosclerotic renovascular disease, yet evidence of a clinical benefit is limited.

Methods In a randomized, unblinded trial, we assigned 806 patients with atherosclerotic renovascular disease either to undergo revascularization in addition to receiving medical therapy or to receive medical therapy alone. The primary outcome was renal function, as measured by the reciprocal of the serum creatinine level (a measure that has a linear relationship with creatinine clearance). Secondary outcomes were blood pressure, the time to renal and major cardiovascular events, and mortality. The median follow-up was 34 months.

Results During a 5-year period, the rate of progression of renal impairment (as shown by the slope of the reciprocal of the serum creatinine level) was –0.07x10–3 liters per micromole per year in the revascularization group, as compared with –0.13x10–3 liters per micromole per year in the medical-therapy group, a difference favoring revascularization of 0.06x10–3 liters per micromole per year (95% confidence interval [CI], –0.002 to 0.13; P=0.06). Over the same time, the mean serum creatinine level was 1.6 µmol per liter (95% CI, –8.4 to 5.2 [0.02 mg per deciliter; 95% CI, –0.10 to 0.06]) lower in the revascularization group than in the medical-therapy group. There was no significant between-group difference in systolic blood pressure; the decrease in diastolic blood pressure was smaller in the revascularization group than in the medical-therapy group. The two study groups had similar rates of renal events (hazard ratio in the revascularization group, 0.97; 95% CI, 0.67 to 1.40; P=0.88), major cardiovascular events (hazard ratio, 0.94; 95% CI, 0.75 to 1.19; P=0.61), and death (hazard ratio, 0.90; 95% CI, 0.69 to 1.18; P=0.46). Serious complications associated with revascularization occurred in 23 patients, including 2 deaths and 3 amputations of toes or limbs.

Conclusions We found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease.

Revascularization versus Medical Therapy for Renal-Artery Stenosis

The ASTRAL Investigators

Background Percutaneous revascularization of the renal arteries improves patency in atherosclerotic renovascular disease, yet evidence of a clinical benefit is limited.

Methods In a randomized, unblinded trial, we assigned 806 patients with atherosclerotic renovascular disease either to undergo revascularization in addition to receiving medical therapy or to receive medical therapy alone. The primary outcome was renal function, as measured by the reciprocal of the serum creatinine level (a measure that has a linear relationship with creatinine clearance). Secondary outcomes were blood pressure, the time to renal and major cardiovascular events, and mortality. The median follow-up was 34 months.

Results During a 5-year period, the rate of progression of renal impairment (as shown by the slope of the reciprocal of the serum creatinine level) was –0.07x10–3 liters per micromole per year in the revascularization group, as compared with –0.13x10–3 liters per micromole per year in the medical-therapy group, a difference favoring revascularization of 0.06x10–3 liters per micromole per year (95% confidence interval [CI], –0.002 to 0.13; P=0.06). Over the same time, the mean serum creatinine level was 1.6 µmol per liter (95% CI, –8.4 to 5.2 [0.02 mg per deciliter; 95% CI, –0.10 to 0.06]) lower in the revascularization group than in the medical-therapy group. There was no significant between-group difference in systolic blood pressure; the decrease in diastolic blood pressure was smaller in the revascularization group than in the medical-therapy group. The two study groups had similar rates of renal events (hazard ratio in the revascularization group, 0.97; 95% CI, 0.67 to 1.40; P=0.88), major cardiovascular events (hazard ratio, 0.94; 95% CI, 0.75 to 1.19; P=0.61), and death (hazard ratio, 0.90; 95% CI, 0.69 to 1.18; P=0.46). Serious complications associated with revascularization occurred in 23 patients, including 2 deaths and 3 amputations of toes or limbs.

Conclusions We found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease.

Volume 361:1953-1962 November 2009Volume 361:1953-1962 November 2009

The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962

Renal Function in Patients with Renal-Artery Stenosis Treated with Revascularization or Medical Therapy Alone

The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962

Kaplan-Meier Curves for the Time to the First Renal and Cardiovascular Events

The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962

Kaplan-Meier Curves for Overall Survival

The ASTRAL Investigators. N Engl J Med 2009;361:1953-1962

Systolic and Diastolic Blood Pressure

ACC/AHA οδηγίες

Ανθεκτική υπέρταση: ≥ 3 αντιϋπερτασικά

• Στένωση ΝΑ ≥ 60%• Α.Π. ≥ 155 mmHg + ≥ 2 αντιϋπερτασικά φάρμακα και/ή• GFR ≤ 60 ml/1.73 m2

19. Arendhorst WJ, Navar LG. Diseases of kidney and urinary tract, 7 th ed. Vol 1, Lippincott W&W 200120. Imanishi M et al. Angiology 1992

Stenting μετρίου βαθμού στένωσης της νεφρικής αρτηρίας δεν οδηγεί σε κλινική βελτίωση του ασθενούς λόγω της μεγάλης νεφρικής εφεδρίας σε αιμάτωση και οξυγόνωση19

Πειραματικά μοντέλα20 δείχνουν αύξηση της Α.Π. σε στενώσεις > 75%και επιδείνωση νεφρικής λειτουργίας > 80%

Ενδείξεις επαναιμάτωσης νεφρικής αρτηρίας

RI (DUS) < 0.8

DTPA

Εκλεκτική αγγειογραφία της νεφρικής αρτηρίας

Στένωση >75-80%

Συμπερασματικά...Συμπερασματικά...• Δυστυχώς, οι ενδείξεις για επαναιμάτωση του

νεφρού δεν είναι ακόμη ξεκάθαρες (evidence- based).

• Στηριζόμενοι στις σημερινές κατευθυντήριες οδηγίες οδηγίες (guidelines), πιθανόν να υποβληθούν ασθενείς σε αγγειοπλαστική, χωρίς να το έχουν πραγματικά ανάγκη.

• Ο συνδυασμός των κλινικών οδηγιών με επεμβατικές και μη μεθόδους ελέγχου της νεφροπάθειας αυξάνει την πιθανότητα να βρούμε την υποκατηγορία των ασθενών με στένωση νεφρικής αρτηρίας που θα ωφεληθούν .

• Δυστυχώς, οι ενδείξεις για επαναιμάτωση του νεφρού δεν είναι ακόμη ξεκάθαρες (evidence- based).

• Στηριζόμενοι στις σημερινές κατευθυντήριες οδηγίες οδηγίες (guidelines), πιθανόν να υποβληθούν ασθενείς σε αγγειοπλαστική, χωρίς να το έχουν πραγματικά ανάγκη.

• Ο συνδυασμός των κλινικών οδηγιών με επεμβατικές και μη μεθόδους ελέγχου της νεφροπάθειας αυξάνει την πιθανότητα να βρούμε την υποκατηγορία των ασθενών με στένωση νεφρικής αρτηρίας που θα ωφεληθούν .