Präinterventionelle Diagnostik und Indikation zur Behandlung von Nierenarterienstenosen: Stent PTA

Erich MinarMedizinische Universität Wien

Wiener Gesprächstage, Juni 2013

Renal-Artery StenosisSafian R and Textor S;N Engl J Med 2001; 344:431-442

NAST = Renovaskuläre Hypertonie

Definition der renovaskulären Hypertonie

Hämodynamisch signifikante Stenose einer oder beider Nierenarterien, die zur Blutdruckerhöhung führt (Goldblattmechanismus)

Derzeitig einziger Beweis für das Vorhandensein einer renovaskulären Ursache der Hypertonie liegt in der Beseitigung der signifikanten Stenose mit darauf einsetzender Normalisierung/ Reduktion des Blutdruckes

NAST im Trend (USA 1992-2004)

Atherosclerotic renovascular disease in the United States Kalra et al; Kidney Int 2010;77: 37-43

White CJ et al. Indications for renal arteriography at the time of coronary arteriography: ascience advisory from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Councils on Cardiovascular Radiology and Intervention and on Kidney in Cardiovascular Disease. Circulation 2006; 114:1892– 1895

Circulation 2006; 114:1892– 1895

Der Oculostenotische Reflex(Reflexangioplastie) [Topol EJ, Nissen SE; Circulation 1995]

Unklarer Benefit - Unklare Kosten - Mögliche Komplikationen?

Jatrogenosis fulminansSoran O et al. Circulation 2000

Courtesy M.Haumer

Conlon PJ et al, Kidn Int 2001; 60: 1490-97

Amighi J et al. Eur J Clin Invest 2009;39:784-92

NAST Prognose(Wien 2004 – 2006; n=487 )

NAST <30%NAST 30-59%NAST ≥60%

Schlechte Prognose bei NAST oder durch NAST?

Eur Heart J. 2011 Aug 26. [Epub ahead of print

Screening auf renovaskuläre Hypertonie bei Verdacht

* Therapierefraktäre Hypertonie (≥ 3 Antihypertensiva-Klassen)

* Schwere Atherosklerose in peripheren Gefäßen, Koronarien, Carotis

* Exazerbation einer gut eingestellten Hypertonie

* Nierenfunktionsverschlechterung bei ACE-Hemmer, ARB

* Rezidivierendes Lungenödem

* > 1.5 cm Seitenunterschied der Nierengröße bei der Sonographie

Diagnostic strategies for RADRecommendations Class Level

DUS is recommended as the first-line imaging test to establish the diagnosis of RAS.

I B

CTA (in patients with creatinine clearance >60 mL/min) is recommended to establish the diagnosis of RAS.

I B

MRA (in patients with creatinine clearance >30 mL/min) is recommended to establish the diagnosis of RAS.

I B

When the clinical index of suspicion is high and the results of non-invasive tests are inconclusive, DSA is recommended as a diagnostic test (prepared for intervention) to establish the diagnosis of RAS.

I C

Captopril renal scintigraphy, selective renal vein renin measurements, plasma renin activity, and the captopril test are not recommended as useful screening tests to establish the diagnosis of RAS.

III B

1 CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.

Diagnostic strategies for RADRecommendations Class Level

DUS is recommended as the first-line imaging test to establish the diagnosis of RAS.

I B

CTA (in patients with creatinine clearance >60 mL/min) is recommended to establish the diagnosis of RAS.

I B

MRA (in patients with creatinine clearance >30 mL/min) is recommended to establish the diagnosis of RAS.

I B

When the clinical index of suspicion is high and the results of non-invasive tests are inconclusive, DSA is recommended as a diagnostic test (prepared for intervention) to establish the diagnosis of RAS.

I C

Captopril renal scintigraphy, selective renal vein renin measurements, plasma renin activity, and the captopril test are not recommended as useful screening tests to establish the diagnosis of RAS.

III B

1 CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.

Diagnostic strategies for RADRecommendations Class Level

DUS is recommended as the first-line imaging test to establish the diagnosis of RAS.

I B

CTA (in patients with creatinine clearance >60 mL/min) is recommended to establish the diagnosis of RAS.

I B

MRA (in patients with creatinine clearance >30 mL/min) is recommended to establish the diagnosis of RAS.

I B

When the clinical index of suspicion is high and the results of non-invasive tests are inconclusive, DSA is recommended as a diagnostic test (prepared for intervention) to establish the diagnosis of RAS.

I C

Captopril renal scintigraphy, selective renal vein renin measurements, plasma renin activity, and the captopril test are not recommended as useful screening tests to establish the diagnosis of RAS.

III B

1 CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.

Diagnostic strategies for RADRecommendations Class Level

DUS is recommended as the first-line imaging test to establish the diagnosis of RAS.

I B

CTA (in patients with creatinine clearance >60 mL/min) is recommended to establish the diagnosis of RAS.

I B

MRA (in patients with creatinine clearance >30 mL/min) is recommended to establish the diagnosis of RAS.

I B

When the clinical index of suspicion is high and the results of non-invasive tests are inconclusive, DSA is recommended as a diagnostic test (prepared for intervention) to establish the diagnosis of RAS.

I C

Captopril renal scintigraphy, selective renal vein renin measurements, plasma renin activity, and the captopril test are not recommended as useful screening tests to establish the diagnosis of RAS.

III B

1 CTA = computed tomography angiography; DSA = digital subtraction angiography; DUS = duplex ultrasonography; MRA = magnetic resonance angiography; RAS = renal artery stenosis.

•

May AG et al. Hemodynamic effects of arterial stenosis.Surgery 1962;53:513-524

Pressure drop & severity of RAS

Renal Artery Stenosis- Severity

N Engl J Med 2001;344:410-7

RI als Erfolgsprädiktor ?

RI = {1-[Vmin/Vmax]} x 100

Clinical outcomes after percutaneous revascularization versus medical management in patients with significant renal artery stenosis: A meta-analysis of randomized controlled trialsKumbhani DJ ; Am Heart J 2011;161:622-630

Mean FU 29 Mo

Clinical outcomes after percutaneous revascularization versus medical management in patients with significant renal artery stenosis: A meta-analysis of randomized controlled trialsKumbhani DJ ; Am Heart J 2011;161:622-630

ConclusionsIn patients with RAS, percutaneous renal revascularization in addition to medical therapy may result in a lower requirement for antihypertensive medications, but not with improvements in serum creatinine or clinical outcomes, as compared with medical management over an intermediate period of follow-up. Further studies are needed to identify the appropriate patient population most likely to benefit from its use.

N Engl J Med 2009;361:1953-62

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

Angioplasty and Stenting for Renal Artery Lesions

ASTRAL Studiendesign Nierenarterienstenose

Randomisierung 9/2000 – 10/2007 58 Zentren - 806 Patienten

Revaskularisation (N=403)(Angioplastie (7%) oder Stent (93%) und medikamentöse Therapie

Keine Revaskularisation (N=403) Nur medikamentöse Therapie

14 Patienten/ Zentrum 2 Patienten/Zentrum/Jahr

Primary Endpoint at 2 years

Stenting versus konservativ

N Engl J Med 2009;361:1953-62

ASTRAL – Limitationen/Probleme im Design* Selektions-Bias: wenn der Untersucher sich bezüglich der Therapie sicher war, wurde der Patient nicht randomisiert. Frage: weiß einer von uns wirklich was er bei NAST tun soll?

* Primärer Endpunkt war Nierenfunktion: allerdings: bei 25 % war diese normal und bei weiteren 15 % fast normal viele Patienten hatten unilaterale Erkrankung

* Es gabe kein Core-Labor zur Adjudizierung der morphologischen Daten. Dies führt erfahrungsgemäß zur Überschätzung des Stenosegrades.

* Die Patienten hatten generell eine mäßige Erkrankung, oft sogar unilateral: 40% hatten 50-70% Stenose bzw wahrscheinlich sogar weniger.

* Die Studienzentren hatten offensichtlich wenig Erfahrung ( 42% rekrutierten 1-5 Patienten im Verlaufe von 7 Jahren)

* Nebenwirkungen viel häufiger als in anderen Studien.

Nierenfunktionsverschlechterung nach Intervention bei 3 – 30%

* NAST nicht Ursache der Niereninsuffizienz * KM-induzierte Nephropathie * Distale Atheroembolisation

http://www.tctmd.com/expert-presentations/table-2.html?product_id=6210&sort_key=45&large_image_p=0

Das wichtigste Kriterium für eine klinische Verbesserung nach Revaskularisation einer Nierenarterienstenose ist die geeignete Patientenselektion!

Treatment of Renal Artery Fibromuscular Dysplasia with BalloonAngioplasty: a Prospective Follow-up StudyM. Birrer et al Eur J Vasc Endovasc Surg 2002; 23: 146

Gradient 71 mm Hg

RR 196/104 – 3 verschiedene Antihypertensiva

Sollte man ?

JA !!

Kein Update der Sektion “Nierenarterien” bei Fassung 2011

NAST Angioplastie und Überleben

RCT: PTRA + BMT vs. BMTn=1.080Einschlusskriterien

1) aNAST ≥60% und 20 mmHg Gradsyst oder ≥ 80% 2) Systolische Hypertonie 155 mmHg trotz ≥2 Antihypertensiva

1°EP Tod (CV oder renal) / MI / Hosp.

(CHF), Insult / S-Krea x 2 / Dialyse2°EP

Tod (gesamt) / Nierenfunktion / Offenheitsrate / Blutdruck

Bitte warten bis 2014

Kalra PA, Zeller T et al. The benefit of renal artery stenting in patients with atheromatous renovascular disease and advanced chronic kidney disease. Cath Cardiovasc Intervent 2010;75:1-10.

• Parameter included into multivariate analysis: – Age, intermittent dialysis, diabetes mellitus, ACE-inhibitor- or AT1-RB,

statin therapy, CKD stage, pulse pressure.

Relative risk for death (CI) P-value

Revascularization 0,55 (0,34-0,88) 0,013

Age 1,03 (1,0-1,1) 0,04

CKD stage 1/ 2 1

CKD stage 3 3,00 (1,49- 6,03) 0,002

CKD stage 4/ 5 4,30 (2,06- 8,97) <0,0001

Multivariate Cox regression analysis for mortality risk

Medical Therapy vs. Stent-Angioplasty Survival

Zusammenfassung

Es gibt eine Gruppe von Patienten , die von einer Intervention der NAST maximal profitiert.

Es gibt allerdings derzeit keine Methode, die mit absoluter Sicherheit vorhersagen kann, welcher Patient von der Intervention profitiert.

Inte

rven

tioni

stN

ephrologe

Resistente HTNNAST ja PTA/Stent ??

Courtesy M.Haumer

Inte

rven

tioni

stN

ephrologe

Resistente HTN

NAST nein RDN

Courtesy M.Haumer

Inte

rven

tioni

stN

ephrologe

Resistente HTNNAST ja PTA/Stent ??NAST nein RDN Courtesy

M.Haumer

Treatment strategies for RAD (1)Medical therapy

Recommendations Class Level

ACE inhibitors, angiotensin II receptor blockers, and calcium channel blockers are effective medications for treatment of hypertension associated with unilateral RAS.

I B

ACE inhibitors and angiotensin II receptor blockers are contraindicated in bilateral severe RAS and in case of RAS in a single functional kidney.

III B

ACE = angiotensin-converting enzyme; RAS = renal artery stenosis.

as hypokalemia, an abdominal bruit, the absence of a family history of essential hypertension, a duration of hypertension of less than one year, and the onset of hypertension before the age of 50 years, are more suggestive of renovascular hypertension than of other types of hypertension,11 but none have strong predictive value. In fact, the majority of patients with renal-artery stenosis who have hypertension have essential hypertension, as suggested by the fact that the hypertension usually persists despite successful revascularization

Angioplastie der Nierenarterien bringt Nichts zur •Verbesserung der RR-Einstellung•Verbesserung der Nierenfunktion•Verbesserung der Prognose

.

Aktuelle Metaanalysen?

Lesaar MA et al. JACC 2009;53:2363-71.

NAST - Angioplastie und BlutdruckPrädiktor für Erfolg

Hyperämischer systolischer Druckgradient [Papaverin] ≥21mmHg

Globale Testgenauigkeit [AUC ROC

] 0.87

NAST Angioplastie und Blutdruck3 randomisierte Studien

Limitation STAR ASTRAL CORAL

N 140 806 1080

Indikation CRI CRI CRI

Stenosegrad ≤70% 33% 40% NA

Ischämienachweis nein nein ja/nein

eGFR [mL/min/1.73m2] 45 40 (25% >50) ?

S-Krea [mg/dL] 1.7 2.0 <3.0

1°EP eGFR 20% 1/S-Krea S-Krea x2

STAR Ann Intern Med 2009;150:840-8; ASTRAL NEJM 2009;361:1953-62; CORAL Am Heart J 2006;59-66.

Inclu

sion

Bias

!

Kumbhani DJ et al. Am Heart J 2011;161:622-30.

NAST Angioplastie und Nierenfunktion4 randomisierte Studien

Mean FU 29 Mo

Kumbhani DJ et al. Am Heart J 2011;161:622-30.

NAST Angioplastie und Nierenfunktion6 randomisierte Studien

Holden A et al. Kidney Int 2006;70:948-55.

NAST Angioplastie und NierenfunktionBeobachtungs-Studien

Mögliche Indikationen für PTRA

nach Garovic VD, Textor SC Circulation 2005;112:1362-74.

NEJM 2001

Klinische Anhaltspunkte für NAST

• Onset HTN nach 55 Jahren• Exacerbation einer gut eingestellten

HTN• Maligne or refraktäre HTN• Epigastrisches Geräusch

(systolic/diastolic)• Unerklärte Azotämie• Azotämie während ACEI, ARB• Atrophe Nieren, Diskrepanz in Grösse• Rekurrente CHF or ‘flash’ Lungenödem• Atherosklerose irgendwo

RI als Erfolgsprädiktor nach PTA

Radermacher J, et al. Hypertension. 2002;39:699-703.

RI = {1-[Vmin/Vmax]} x 100

Treatment strategies for RAD (2)Endovascular and surgical therapy

Recommendations Class LevelEndovascular therapyAngioplasty, preferably with stenting, may be considered in the case of >60% symptomatic RAS secondary to atherosclerosis.

IIb A

In the case of indication for angioplasty, stenting is recommended in ostial atherosclerotic RAS.

I B

Endovascular treatment of RAS may be considered in patients with impaired renal function.

IIb B

Treatment of RAS, by balloon angioplasty with or without stenting, may be considered for patients with RAS and unexplained recurrent congestive heart failure or sudden pulmonary oedema and preserved systolic left ventricular function.

IIb C

Surgical therapySurgical revascularization may be considered for patients undergoing surgical repair of the aorta, patients with complex anatomy of the renal arteries, or after a failed endovascular procedure.

IIb C

RAS = renal artery stenosis.

NAST – PTA-Indikationen

klinische Situation Empfehlung Evidenzgrad vorher unbekannt

plötzlich auftretendes Lungenödem + hypertensive Entgleisung I B nein

akzeleriert, therapierefraktäre oder maligne Hypertonie mit Endorganschäden IIa B nein

Niereninsuffizienz + bilaterale NAST oder funktionelle Einzelniere IIa B nein

instabile Angina pectoris IIa B jaAsymptomatische bilaterale NAST oder funktionelle Einzelniere IIb C ja

Unilaterale Stenose ± Niereninsuffizienz IIb C ja

Renovaskuläre Hypertoniewer soll getestet werden

• Schwere, therapierefraktäre Hypertonie

• Neuauftreten oder akute

Verschlechterung

• Akuter Kreatininanstieg (ev. unter

ACEI)

• pAVK und unilateral kleine Niere (<9

cm)

• Rezidivierende Lungenödeme

• ACEI-sensible Patienten

Indikationen für Revaskularisation• Bilaterale Stenose >60% oder Einzelniere + eingeschränkte

Nierenfunktion

• Bilaterale Stenose>60% oder Einzelniere + therapierefraktäre Hypertension

• Uni oder bilaterale Stenose > 60% + flush Lungenödem

• Uni oder bilaterale Stenose >60% + Hypertension oder inzipiente Nephropathie + RI <80

• Uni oder bilaterale Stenose >60% + Hypertonie + FMD

• Uni oder bilaterale Stenose >60% + eingeschränkte Nierenfunktion + FMD

Courtesy A.Rosenkranz

ASTRALCourse of Blood Pressure

N Engl J Med 2009;361:1953-62.

Patients were enrolled in the trial only if their own physicianwas uncertain as to whether revascularization would provide a worthwhile clinical benefit.

Controlled Unilateral RAS

After Stenting: Graded Renal Stenoses

What is a “significant” renal artery stenosis?

Inflation of the balloon(1 mm smaller than the stent)

to produce a Controlled Gradient

Pd / Pa of ....

1

0.9

0.8

0.7

0.6

0.5

1

10 min

10 min

10 min

10 min

10 min

10 min

Dosage of reninB. De Bruyne et al JACC 2006

Prediction of Hypertension Improvement After Stenting of Renal Artery StenosisComparative Accuracy of Translesional Pressure Gradients, Intravascular Ultrasound, and AngiographyLesaar MA et al. J Am Coll Cardiol 2009;53: 2363–71

Conclusions An HSG ≥ 21 mm Hg provided the highest accuracy in predicting hypertension improvement after stenting of RAS, suggesting that an HSG ≥ 21 mm Hg is indicative of significant RAS

Nordmann AJ et al. Am J Med 2003;114:44-50.

NAST Angioplastie und Blutdruck3 randomisierte Studien

Nordman et al., Am J Med 2003;114:44-50

Revascularization of RADBlood Pressure Control – RCT‘s prior to ASTRAL

ASTRAL - PLOT OF SCr OVER TIMEPrimary Endpoint at 2 years

30% & 46% lost for follow-up!

N Engl J Med 2009;361:1953-62

P = 0.06

ANGIOGRAPHIC DATA BY RANDOMIZED TREATMENT

Revasc. Medical P-value

% Stenosis 76% (40 – 100%) 75% (20 – 100%) 0.3

Renal length 9.7cm (6 – 14) 9.7cm (6 – 20) 0.5

Location of ostial/distal ARVD lesion

Left kidney 24% 20% 0.2

Right kidney 18% 17%

Both 50% 57%

Missing data 8% 6%

N Engl J Med 2009;361:1953-62

49% of patients < 70% diameter stenosisby visual estimation

RAD and HypertensionSummary of data of uncontrolled studies

Fibromuscular dysplasia

Atherosclerotic RAD

cured cured &improved

50 – 85% 85 - 100%

5 – 15% 50 – 70%

Zeller T. Renal artery stenosis. Current Treatment Options in Cardiovascular Medicine 2007:9:90

1(BL1) 1 (BL 2) 0.9 0.8 0.7 0.6 0.5 1 (End)

0

100

200

300

400

500

Degree of Stenosis (Pd/Pa)

Perc

ent I

ncre

ase

in R

enin

After Stenting: Graded Renal Stenoses

What is a “significant” renal artery stenosis?

B. De Bruyne et al JACC 2006