reno vascular hypertension

Kenar D Jhaveri, MD, FASNAsst Prof of Medicine

Division of Kidney Diseases and Hypertension

North Shore/LIJ Health SystemsHofstra School of Medicine

www.nephronpower.comwww.onlinetransplantcenter.blogspot.com

8/3/2010

“ Reno-vascular - hypertension”

What an Urologist needs to know?

What is my role in knowing all the medical management of reno vascular disease?

What does it matter to me? I don’t treat Hypertension

Lets ask these questions again at the end of the talk!

FACT

Only 34% of people who have Essential HTN have good blood pressure control in the USA.

FACTThe term “Essential” was coined at a time

when high BP was thought to be required (essential) to surmount the established vascular disease in order to achieve target organ perfusion. Hence, in those days, it was discouraged to treat HTN as vascular disease was thought to have preceded HTN. It was not till 1960 when everyone realized that HTN was not really “essential”

Causes of 2nd HTN Obstructive Sleep Apnea Renal Disease Renovascular Disease Pregnancy Primary aldosteronism Pheochromocytoma Cushing’s Syndrome Thyroid Disease Primary Hyperparathyroidism Coarctation of Aorta Acromegaly Drug Induced Drug Related

Hypertension (let’s think)lets connect this concept!CatecholamineFluid overloadHigh reninHypertensionIncreased nor epinephrineVolumeESRDRENAL ARTERY STENOSISPheochromocytoma

Case 1A 32 y old male comes in with

hypertension, acute kidney injury, hematuria and proteinuria. He is diagnosed with IgA Nephropathy. His BP is 156/89. What is the cause of his HTN?

A Renal DiseaseB Reno Vascular DiseaseC Renal Atherosclerotic diseaseD Renal Artery Stenosis

Renal disease can lead to HTNAnytime you have a patient with INTRINSIC

Renal disease that can cause Hypertension

May not need to look for another cause

WHAT DO YOU Kidneys do if they can’t get rid of all that fluid that they are supposed to get rid off? ???? VOLUME VOLUME VOLUME mediated!!!

*** some renal diseases can lead to a renin mediated HTN component.

Case 1A just for you!

A 67 y old male with lymphoma comes to the ER since he has not urinated in 2 days and feels weak. His Crt is 5 and K is 5.7. A renal US shows severe bilateral obstruction. His Blood pressure is 178/78. His HTN is from ?

A Reno vascular diseaseB Intrinsic Renal DiseaseC Obstructive Renal DiseaseD Who cares?

Urinary Tract Obstruction and Reflux and HYPERTENSIONVesico ureteric reflux is seen in 2% of children and

can lead to chronic Hypertension, renal scarring and ESRD ( this is renal parenchymal disease)

Unilateral or Bilateral Obstruction can lead to HTN. In rat models, when you obstruct the ureters or urethra, RENIN is activated and lead to HTN.

Other mechanism could be chronic obstruction leading to parenchymal renal damage leading to fluid mediated HTN.

Relief of obstruction can lead to resolution of hypertension. YOU ACTUALLY CAN TREAT THIS without MEDICATION, just one device--- FOLEY/ STENT or Nephrostomy Tubes!

Berka et al. J Hypertens 1994;12:735-743 Rule et al. Ann Inter Medicine 2004:141:929-37.

Case 2A 67 y old male presents to the ER with his third

episode of pulmonary edema in the last few months. He has known coronary artery disease with multiple stents in his heart. His SBP at presentation is 178/90 and HR is 89.

On examination, he has bilateral crackles and no specific bruits are heard on his abdomen.

His medications : “ I don’t remember, call my pharmacy?”

The ER gets a chest CT to rule out Pulmonary embolism and notes severe stenosis in the Right renal artery?

The Hypertension here is from?A Renal DiseaseB Reno Vascular DiseaseC Renal Atherosclerotic diseaseD Renal Artery Stenosis

Case 3A 34 y old female with no past medical

history presents with sudden onset hypertension 156/78 and Renal US shows renal artery stenosis bilaterally?

A Renal DiseaseB Reno Vascular DiseaseC Renal Atherosclerotic diseaseD Renal Artery Stenosis

Lets take it from the start

L. Gabriel Navar and L. Lee Hamm

A figure explains it all!

Concept map of renal ischemia

Can you tell the difference?

Sometimes you cannot tell the difference between a PLAQUE related renal artery stenosis vs. Just a RENAL ARTERY STENOSIS from another cause!

KIDNEY IS NOT SEEING OXYGEN!!!

Reno vascular HTN = hypertension due to RENAL ANGINA OR ISCHEMIA!

Not all reno vascular disease will lead to renal vascular hypertension. Because the disease is more common then hypertension.

Half of normo-tensive patients older than 60 have atherosclerotic lesions in the renal vessels.

PREVALENCEEPIDEMIOLOGY:

5% OF HTN 2-4 million in USAUTOPSY STUDIES: PATHOLOGYAUTOPSY STUDIES: PATHOLOGY

Holley 1964 – 295 consecutive autopsy RAS 27% with HTN 56% without HTN 17% > 70 years old 62%

Schwartz 1964 <64 years old 5% 65-74 years old 18% >75 years old 42% Bilateral if present 50%

Clinical SyndromesHypertension

Abrupt onset after age 55Worsening BP in patients with mild

HypertensionRenal abnormalities

Unexplained renal insufficiency in setting of HTN

Progressive azotemia in setting of hypertensionAzotemia in setting of CAD or PVD

OtherFlash pulmonary edemaACEI - induced ARF

ACEI Induced ARF108 pts with suspected RASProtocol: ACEI followed by diuretics and

eventual angiogramEnd point 20% increase in CreatinineBilateral Disease (n=72)

Severe: >50% stenosis (n=51)Moderate <50% stenosis (n=21)

Unilateral disease (n=20)No renal disease (n=15)

Van de Ven PJ et al; Kidney Int. 1998 53: 986 Van de Ven PJ et al; Kidney Int. 1998 53: 986

RESULTS (>20% increase in creatinine)64% ACEI induced ARF

4 days 38%14 days 45%Only after diuretics 17%

100% with severe (>50%) bilateral disease15% normals

CONCLUSIONS100% sensitivity for bilateral disease70% specificity

Van de Ven PJ et al; Kidney Int. 1998 53: 986Van de Ven PJ et al; Kidney Int. 1998 53: 986

DiagnosisRenin Studies

Renal vein renin studies abandoned because of high cost and complexity and lack of specificity

ACEI-stimulated PRA

Captopril Renal ScanSensitivity 73%, Specificity 90%Decreased sensitivity/specificity if poor renal

function Decreased sensitivity if bilateral RAS

DiagnosisUltrasound and Duplex Doppler

Size difference greater than 1.5cm implies unilateral renal disease.

Velicometry provides measurements of maximal blood flow velocity in the renal arteries relative to the aorta. An increase of greater than 3-fold in one renal artery detects renal artery stenosis.

A resistive index and be calculated from the rate of rise of flow over the aorta and within the arcuate vessels of the kidney. An abnormal index implies increased vascular resistance which, in the context of renovascular disease, likely reflects irreversible vascular changes in the kidney.

Sensitivity and specificity reported 70-90% depends on institution

MRASensitivity 100% Sensitivity 100% Specificity 65%Specificity 65% False PositivesFalse Positives

AngiogramGreater than 70% stenosis with pressure gradient >30mmHgGreater than 70% stenosis with pressure gradient >30mmHg

Natural History220 subjects referred for HTN and/or CKD

Age 68HTN 95%Creatinine 1.5mg/dl

Patients who were not revascularization candidates

Renal duplex scanning every 6 months.

Caps, et al, Circulation. 1998;98:2866-2872Caps, et al, Circulation. 1998;98:2866-2872

RESULTS

Risk Factor RR PSBP 160 mm Hg 2.1 0.006Diabetes mellitus 2.0 0.009High-grade ipsilateral ARAS 1.9 0.004High-grade contralateral ARAS 1.7 0.04High-grade, 60% stenosis or occlusion.

Progression

•31% overall

Risk Factors for Progression


Survival Probability

00.10.20.30.40.50.60.70.80.9

1

0 1 2 3 4 5 6 7 8

YEARS

Su

rviv

al

Pro

ba

bil

ity <75% RAS<75% RAS

>75% RAS>75% RAS

Conlon PJ et al, Kidney Int 2001 60: 1490-1497Conlon PJ et al, Kidney Int 2001 60: 1490-1497

SUMMARYAtherosclerotic renal artery disease is

prevalent among patients older than 50 with co morbid conditions, including hypertension and extra renal atherosclerotic vascular disease.

Atherosclerotic stenosis of the renal arteries, when high grade, has a high likelihood of progressing over a 2-year period.

Progression is marked by deleterious changes in renal function as well as excessive mortality.

Renal functional abnormalities are related to the extent of renal Renal functional abnormalities are related to the extent of renal parencymal injury more than the degree of RASparencymal injury more than the degree of RAS

Medical therapyAngioplasty

Surgery

Treatment

Medical therapyACEI , captopril most effective and most

studiedUse in solitary kidneys or b/l renal artery

stenosis questioned?CCB next in line ( especially post kidney

transplant patients)

Again, why do I need to know this?You are the UROLOGIST about to operate on a

donor nephrectomy and you just noticed that in your evaluation, the blood pressure of this 23 y old male is 145/99 and you wonder if you should consider taking this kidney out or not?

Basic knowledge of Hypertension and reno-vascular HTN will be very useful and will save you a lot of agony and time. A lot of urologists become donor Surgeons and many recipient surgeons as well. Knowledge of Transplant related RENAL ARTERY STENOSIS is also important.

AngioplastyFirst report in 1978.Widespread use of it in the 90s and early

2000sHigh rate of re stenosis with balloon

angioplasty led to increase use of stents especially with Atherosclerotic disease ostial lesions; even in the post transplant setting

Bruno et al. Transplantation 2003;76:147-153 Zeller et al. Circulation 2003;108:2244-2249.

Surgery

Overall results when compared to technically successful angioplasty is comparable

Post op mortality is usually higher about 5% in the first month

Arteritis surgery is usually better and only option.

Nephrectomy has been used in refractory hypertension and in atrophic non functioning kidney but still causing renin mediated HTN.

Aurell et al, Nephron 1997;75:373-383.Cherr et al, J Vasc Surg 2002;35:236-245Weaver et al, J Vasc Surg 2004;39:749-757.

Factors indicative of response to re vascularization for atherosclerotic disease

Is the Stenosis the Problem

HEART HEART KIDNEYKIDNEY

OVERALL DATA?Overall review of medical literature:- 50%

of patents with Reno vascular disease have NO change in renal function while 25% improve and 25% lose renal function.

Textor et al. Ann Intern Med 1985;102:308 Textor et al. JASN 2004;15:1974.

PTA vs PTA + stentsPTA alone without stenting had been used

primarily for non ostial lesions : success rate 35-50%.

Now most performed with stents: Review of 14 studies of renal artery stent placement in 678 patients and 10 studies of renal PTA alone in 644 patients with both

Stenting was associated with a significant lowering of restenosis rate than PTA alone ( follow up 30 months)

Leertouwer et al. Radiology 2000;216:78.

Medical Therapy vs PTA+ stents? Which one to pick????Drastic Trial to ASTRAL Trial

Journey well travelled!We have answers now!

Treatment and HTN

AngioplastyAngioplasty

Pre treatmentPre treatment

MedicalMedical

Pre treatmentPre treatment

AngioplastyAngioplasty

Post treatmentPost treatment

MedicalMedical

Post treatmentPost treatment

BPBP 179/104179/104 180/103180/103 169/99169/99 176/101176/101

CreatinineCreatinine 1.21.2 1.31.3 1.21.2 1.21.2

No. MedsNo. Meds 22 22 1.91.9 2.52.5

DRASTIC Trial NEJM 2000DRASTIC Trial NEJM 2000

106 patients with known RAS106 patients with known RASHTNHTNcreatinine <2.3creatinine <2.3

Randomized to medical or interventional treatmentRandomized to medical or interventional treatment

Survival: Cleveland Clinic

Uzzo et al; Transplantation Proceedings 34 2002Uzzo et al; Transplantation Proceedings 34 2002

RANDOMIZED27 medical vs 25 surgical

Pre ASTRAL era!PCA with STENTING is reasonable in patients who have progressive

kidney disease associated with bilateral renal artery stenosis or

renal artery stenosis in a solitary functioning

kidney

ACC/AHA

ASTRAL TRIALLargest trial to date806 patients with either unilateral or bilateral

atherosclerotic RAS who were randomly assigned to either medical therapy alone vs medical therapy plus revascularization (most with PTA with stents).

59% had stenosis greater than 70% and 60% had baseline crt greater than 1.7

After 3 years of follow up, there was no significant difference in rate of progression of renal impairment, similar rates of renal events including new onset acute renal failure, initiation of dialysis and nephrectomy and death. Even major CVD events and deaths were similar.

Dworkin LD et al. NEJM 2009;361:1972Modrall et al. J Vasc surgery 2008;48:317Wheatley et al. NEJM 2009:361:1953.Bax e tal. Ann Intern Med 2009;150:840.

Data on Surgery? The stuff you care about?There are no randomized trials comparing

surgery to anything!Observational studies suggest success

rates of 85-90% Procedures: Aorto renal bypass most

commonIleorenal and splenorenal and hepatorenal

as well used

ACC/AHA

Surgery is recommended in patients with atheroscloerotic RAS who have clinical indications for revascularization, particularly if they have multiple small renal

arteries, early primary branching of the main renal artery or require

aortic re construction near the renal arteries for other indications

like aneurysms, arteritis)

SummaryMechanismPrevalenceDiagnosisTreatmentKnow about it, try to manage it, call us for

help when needed! We are always available!

What an Urologist needs to know?What is my role in knowing all the medical

management of reno vascular disease?What does it matter to me? I don’t treat

Hypertension

Lets ask these questions again at the end of the talk!

THANK YOU

reno vascular hypertension

Education