Renovascular Hypertension [PDF]

Zitiervorschau

RENOVASCULAR HYPERTENSION Dr. Villaflor February 5, 2016

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MODULE 04 LECTURE 05



m When confronted with a patient with renal hypertension, we have to rule out if there is really artery stenosis. − Is the stenosis causing the hypertension? − If we get the stenosis or dilate it, will the hypertension actually be relieved? − There are instances where because of the prolonged RAS, even if we relieve the artery stenosis there is now a complicating renal ischemic parenchymal damage that will cause the hypertension (because you know that artery stenosis and parenchymal destruction will cause hypertension) m RAS as a secondary hypertension can actually be reversed. It is important that when you identify patients that are still in the reversibility period, make sure that you do so because you want to make the patient pill – free for the rest of his life – that the patient won’t drink antihypertensive medications. Etiology • Atherosclerosis (ARAS) – 70%-90% of cases Usually involves the ostium and/or proximal third of the main renal artery, with non-ostial lesions comprising only 15-20% of cases • Fibromuscular dysplasia (FMD) – 10-20% • Renal thromboembolic disease • Renal atheroembolic disease • Autorenal dissection • Vasculitis involving the renal artery (i.e. PAN) • AVMs involving the renal artery • Nephroangiosclerosis (hypertensive injury) • Trauma • Irradiation of the renal artery • Scleroderma m Remember ARAS and FMD because they are the most important. *Based on another source the etiologies of RVH are: 1. Renal artery stenonsis* 2. Fibromuscular dysplasia (FMD)* 3. Nutcracker syndrome* 4. Renal vein thrombosis* 5. Aneurysm and pseudo-aneurysm 6. Arterio-venous communications 7. Renal Mass 8. Miscellaneous indications *95% of cases

SUMMARY/OUTLINE I.

Etiology IV. Diagnosis a. Renal Artery Stenosis a. Captopril Renography b. Fibromuscular Dysplasia b. Functional Studies c. Nutcracker Syndrome c. Anatomic Studies II. Pathophysiology V. Treatment a. Unilateral RAS VI. Conclusions b. Bilateral RAS c. Ischemic Renal Disease III. Clinical Features th LEGEND: Lecture Audio &/Box Harrisons 19 Ed Prev yr notes (SGD)





RENOVASCULAR HYPERTENSION Defined as: • The presence of systemic hypertension due to a stenotic or obstructive lesion within the renal artery • The mechanism of hypertension is generally related to activation of the renin-angiotensin system. • Two patients are at risk for this disorder: o Older arteriosclerotic patients o Patients with fibromuscular dysplasia • Form of secondary hypertension, accounting for an estimated 0.5% to 4% of cases in unselected hypertensive patients • The simultaneous presence of renal artery stenosis (RAS) and systemic hypertension should not lead to the conclusion that the patient has RVH; • Strictly speaking, the definitive diagnosis of RVH can only be made retrospectively when hypertension improves upon correction of the stenosis • In practice, obtaining complete “reversal” of hypertension is rarely possible • Important to recognize that renovascular disease o Often accelerates preexisting hypertension, o Can ultimately threaten the viability of the poststenotic kidney and o Impair sodium excretion in subjects with congestive heart failure • When to suspect RVH: o Severe or refractory HPN o Recent loss of hypertension control o Recent onset of moderately severe HPN o Unexplained deterioration of renal function o Deterioration of renal function associated with ACE inhibitor If BP is adequately controlled with a simple antihypertensive regimen and renal function remains stable, there may be little impetus to pursue an evaluation for renal artery stenosis m When we speak of renovascular hypertension, it should be remembered that if you have RAS (renoarterial stenosis) you will eventually have renal hypertension.

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Renal Artery Stenosis Stenosis of the renal artery is due to atrerosclerotic disease in the vast majority of patients, or to fibromuscular dysplasia of the arterial wall in the younger, generally female patient. RAS may cause hypertension and may eventually cause renal failure. It is frequently bilateral, and is responsible for up to 15% of patients who require long-term dialysis. It is associated with aortic aneurysm, neurofibromatosis or can be traumatic in origin It is estimated that ~5% of cases of hypertension are caused by renal artery stenosis (RAS). Autopsy studies in patients dying of stroke revealed that at least 1 renal artery is >75% stenosed in 10% of the patients studied. The common cause in the middle-aged and elderly is an atheromatous plaque at the origin of the renal artery. Bilateral involvement is present in half of the affected cases. Renal hypotrophy is detectable in 20% of affected kidneys. In younger women (15–50 years), stenosis is due to intrinsic structural abnormalities of the arterial wall caused by fibromuscular dysplasia. In addition to stimulation of renin release, renovascular disease is associated with increased sympathetic neural activity, resulting in frequently described flushing, loss of nocturnal blood pressure (BP) decrease, autonomic instability, and rapid BP swings. Glomerular filtration rate (GFR) is 30% increase in serum creatinine.

Post stenotic dilatation

main RA Branching points

artery Others (carotids)

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Frequent

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Fibromuscular dysplasia (FMD) A condition in which at least one of your arteries has abnormal cluster of cells growing in the artery wall. This cluster causes artery to narrow, which can cause damage to the organs that receive blood through that narrowed artery. It can cause number of complications such as high blood pressure and a bulging area of the artery. It appears most commonly in the arteries leading to the kidneys. 10% of cases of RVH are due to FMD Mainly in younger women Strong predilection for young Caucasian women (M:F = 8:1) Medial fibroplasia – most common variant (2/3 of patients) Bilateral renal artery involvement with extension into the distal portion of the artery and its branches is common Smoking is a prominent risk factor Fibromuscular dysplasia may occur at any age, it has a strong predilection for young women. The prevalence in females is eightfold that in males There are several histologic variants of fibromuscular dysplasia, including medial fibroplasia, perimedial fibroplasia, medial hyperplasia, and intimal fibroplasia. Medial fibroplasia is the most common variant and accounts for approximately two-thirds of patients. The lesions of fibromuscular dysplasia are frequently bilateral, and in contrast to atherosclerotic renovascular disease, tend to affect more distal portions of the renal artery.



** Important: Please take note of this chart. Atherosclerosis FMD >90% 50 y/o - Abrupt onset of HTN - Severe or Resistant HTN - Deteriorating BP control in long standing, compliant hypertensive patients - Deterioration in renal function with ACEI - Evidence of secondary hyperaldosteronism (low plasma potassium, high renin) - Recurrent “flash” pulmonary edema and hypertensive urgency (more common with bilateral RAS) m Sometimes your patient is so stable and suddenly he will have pulmonary edema and there are episodes of hypertensive urgency. - Elderly patients with PVD (peripheral vascular dse) - Abdominal bruit (OR 11.5) m It is important to auscultate the major vessels in the abdomen. - Unexplained renal azotemia - >1.5 cm difference in kidney size on US (70% of atrophic kidneys in the elderly are associated with ARAS) m When you do diagnostic procedures, you will be able to appreciate the difference in size of the kidneys. You may wonder, why does one kidney have a different size from the other? Maybe it might be stenotic.

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It is important to search for evidence of underlying irreversible parenchymal renal disease, as this subgroup will not likely benefit from therapy: - Moderate to severe proteinuria - Severe renal atrophy distal to obstruction - Unilateral RAS with renal insufficiency m Hambalon mo, ano pa ni ang humuon ko? Kay lain na ni gali. Abi mo RVH. Iya sang RVH macorrect but the parenchymal disease is still there. m You should suspect that because if it is pure RVH, our urine is bland. But if you have some degree of proteinuria, your kidneys have shrunk, and then unilateral RAS, and you have renal insufficiency. Most likely there is now a concomitant ischemic renal damage. &

Clinical findings associated with RVH:











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**highlighted = mentioned / emphasized by doc in the audio. Nice to know: Iloilo has CT angiography. J Functional Studies Diagnostic Study Pros Cons Renal Vein Renin Useful in Poor sensitivity Measurements confirming the functional Non lateralization significance of a not predictive of lesion the failure of HTN demonstrated by to improve with anatomical studies therapy – particularly if bilateral disease if present Nuclear imaging Allows calculation Difficult to 99 with Tc -MAG or of single kidney differentiate 99 Tc -DTPA to GFR and/or RBF reversible from estimate fractional intrinsic disease flow to each kidney Conventional Useful as both a Lower sens/spec Renography screening test and compared to ACEI functional study renography ACEI Renography Test of choice for Reduce sens/spec the diagnosis of in patients with RVH in many renal insufficiency centers (PCr>2.0) Operator dependent Anatomic Studies “If you’re searching for a lesion, look at the vessel.” Diagnostic Study Pros Cons Renal Gold standard Direct contrast Arteriography load to kidneys Can visualize accessory vessels Sometimes and intrarenal difficult to branches well distinguish between critical and non-critical lesions Doppler Non invasive Extremely Ultrasonography Inexpensive, operator widely available dependent Does not evaluate accessory vessels well Bowel gas patterns/Obesity interfere

Diagnosis There are two groups of diagnostic studies used to evaluate RAS. Anatomic studies: ü Renal angiography – gold standard m This is the gold standard because you want to look and are looking at the vessels. We delineate the vessels – the renal artery- as it supplies the kidneys. ü Doppler ultrasonography ü Spiral CT angiography ü MR angiography Functional studies: ü Renal-vein-renin measurement m Because your arteries are constricted, you expect that your renin is high. There is actually measurement of your renal vein renin but it is invasive. 125 ü Nuclear imaging with I iothalamate or DTPA to determine GFR ü Conventional renography ü ACEI renography Captopril Renography • Captopril renography is a nuclear study which takes advantage of the fact ACEI can abruptly reduce function in an ischemic kidney. Patients are given radio-labeled agents that are 99 exclusively filtered (Tc -DTPA) thus estimating GFR 99 or agents that are filtered and secreted (Tc -MAG) 131 or I -hippurate) thus estimating RBF A baseline study is done on day 1 and 50 mg of captopril is given 1 hr prior to the second study on day 2 The difference between the left and right kidney with regard to uptake, excretion, kidney size and asymmetry can be determined by this study. 99 Either a slowing of the excretion of Tc -DTPA or a 99 reduction of the uptake of the Tc -MAG can be used to identity the effect of the ACEI in removing the protective action of high levels of ATII on the autoregulation of GFR and on maintenance of renal blood flow. Diagnostic Study Sens. Spec. PPV NPV Renal Vein Renins 62% 70-80% Doppler 80-98% 98% 99% 88-97% Ultrasonography Conventional 75% 85% 33% Renography ACEI Renography 75-90% 94% 92% 88% CT angiography 92% 98% 87% 99% MRA 100% 93% 90% 100%

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CT angiography

MRA

Antihypertensive Drug Therapy • Blockade of the Renin Angiotensin System o ACE Inhibitors o Angiotensin Receptor Blockers o Direct Renin Inhibitors (Aliskiren) [efficacy questionable] • Calcium Channel Blocking Agents • Diuretics • Mineralocorticoid Receptor Blockade • Additional classes: Beta-blockade, alpha-receptor blockade, sympatholytic agents, vasodilators Cardiovascular Risk Reduction • Removal of tobacco use • Treatment of Dyslipidemia: Statins, Fibrates, Others • Treatment of Obesity: Obstructive Sleep Apnea • Management of Glucose Intolerance/ Diabetes Renal Revascularization • Endovascular revascularization: o PTRA: Primary Fibromuscular Dysplasia o PTRA with Stenting: Atherosclerotic Disease – most commonly used treatment for renovascular HPN • Surgical: o Renal Artery Bypass/Endarterectomy (reserved for complex aorto-renal disease, aneurismal disease, failed endovascular stent procedures, etc.) Nephrectomy • Open or Laparoscopic removal of pressor kidney; usually non-functional Management for RVH caused by ARAS • No general consensus among physicians on the ideal therapy for this condition o Numerous randomized prospective studies have found no evidence of improvement in BP control in patients undergoing angioplasty over medical therapy alone • One of the largest trials, o The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) study, ü 806 renal failure patients (mean serum creatinine approximately 2 mg/dL) with atherosclerotic renal vascular disease included ü Randomized to receive either revascularization and medical therapy or medical therapy alone ü On average, patients had 75% RAS ü At 1-year follow-up there were no differences in the change in serum creatinine level (it rose by 0.2 mg/dL in both groups) or in rates of renal events, including acute renal failure • Currently, at least three major studies are under way to

Excellent High-contrast visualization of the requirement vessels in 3D Less reliable for visualizing distal segments and small accessory arteries Noninvasive Expensive Provides excellent Prior stents images produce artifacts Non-nephrotoxic, Blood flow thus useful in turbulence can patients with renal exaggerate insufficiency measured stenosis

m If you localize the anatomic lesion, the renal arteriography is the gold standard because you actually visualize the artery plus the accessory vessels. − You may see that your main renal artery stenosed and because your main renal artery is stenosed, you will develop collaterals because your collaterals will supply the rest. You have accessory vessels and some have intrarenal branches. This procedure entails the use of contrast. Treatment • To date, there has been no large randomized clinical controlled trial comparing medical therapy to newer stenting procedures or surgery m When you say stent, you place a tube so that you will be able to dilate the stenosed area. If it is surgical and you repair it, you cut and you anastomose. m For medical therapy, you just control the BP. • In addition, most of the reported date as to therapy have been non-experimental reports • As result, no improvements in survival, freedom from dialysis or protection from adverse cardiovascular disease events have been demonstrated relative to an equivalent non-interventional comparison group RENOVASCULAR HYPERTENSION (RVH): MANAGEMENT

Treatment options include 1. Pharmacological therapy with various antihypertensive medications, 2. Percutaneous angioplasty with or without stent placement, and 3. Surgical revision of RAS Availability of potent antihypertensive drugs and the advances in endovascular techniques, as well as stents, has made surgical treatment rarely necessary

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help decipher optimum treatment for patients with ARAS o STAR o RAS-CAD o CORAL STAR study o The STent placement and blood pressure and lipidlowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery (STAR) study aims to compare ü The effects of renal artery stent placement together with medication versus medication alone on renal function in 140 ARAS patients ü Medication consists of statins, antihypertensive drugs, and antiplatelet therapy RAS-CAD o A trial looking at cardiac endpoints, the stenting of Renal Artery Stenosis in Coronary Artery Disease (RAS-CAD), ü Randomized study aiming to recruit 168 patients ü Designed to study the effect of medical therapy alone versus medical therapy plus renal artery stenting on Ø left ventricular hypertrophy progression (primary endpoint), and Ø cardiovascular morbidity and mortality (secondary endpoints), in patients affected by ischemic heart disease and RAS CORAL o The Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study is a National Institutes of Health–funded multicenter trial testing the hypothesis that ü Stenting atherosclerotic RAS in patients with systolic hypertension reduces the incidence of cardiovascular and renal events ü The CORAL study has completed enrollment with over 900 patients, but results will not be available for some time At this time, there is no clear benefit of revascularization for ARAS, o Especially in patients for whom BP can be controlled easily and who have no evidence of ischemic nephropathy o The risks of the procedure may outweigh any potential benefits Angioplasty with or without stenting may be of benefit in o Patients with HT that is difficult to control in the setting of decreased renal perfusion, because uncontrolled hypertension is a major cardiovascular risk factor Accordingly, aggressive treatment of hypertension with medications is recommended Antihypertensive treatment may also include o ACE inhibitors and ARBs provided that ü Renal function is stable and that close follow-up is available o Medical therapy should also include

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Statins to prevent further progression of atherosclerotic plaques in the renal arteries and Cardiac prophylaxis with lowdose aspirin Smoking should be strongly discouraged

Management for RVH caused by FMD • Percutaneous angioplasty is the treatment of choice, o Often resulting in relief of the stenosis and marked improvement (or cure) of the hypertension • Stents may be used o In patients with suboptimal results with angioplasty alone • Surgery is considered to be the last option, particularly o For patients for whom endovascular procedures have failed

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Conclusions Natural History and Pathophysiology ARAS is clearly a progressive disease The initial degree of stenosis/burden of vascular disease is most predictive of IRD progression m So if it is atherosclerotic, since the formation takes a long time, most likely there is ischemic renal disease. Once patients with IRD are dialysis dependent, their prognosis is extremely poor. The pathogenesis of IRD is multifactorial and predicting the degree of reversible vs irreversible disease in a particular patient is challenging. High RI, slow progression of IRD, significant proteinuria and advanced age seem to be predictors of irreversible disease Normal RI, minimal proteinuria and fast progression of renal insufficiency seem to be predictors of reversible disease m Multifactorial because there is renin, volume, cardiovascular events that will make the patient prone to this complication.

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Diagnosis and Therapy The diagnosis of IRD secondary to ARAS should be based on anatomical studies. Functional studies such as ACEI renography and renal-vein-renin sampling are insensitive in detecting significant stenosis in patients with renal insufficiency. Functional studies do not reliably predict who will respond to therapy Given the paucity of controlled, randomized data, it is difficult to make any level I recommendations for the treatment of RVH or IRD due to ARAS: However, the following statements are reasons based on the above data: 1. PTRA/S is not the initial treatment of choice in patients with RVH secondary to ARAS. Page 8 of 9



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Surgery appears to be more efficacious that PTRA/S for both RVH and IRD but is also associated with a much higher morbidity/mortality rate. 3. Surgery appears to be appropriate for patients with a high burden of disease (bilateral or effective bilateral ARAS) who have minimal preoperative risks factors for preoperative death. 4. Rate of renal decline and underlying parenchymal damage affect the likelihood of renal improvement with therapy. m We have successes in surgery especially if the condition is diagnosed early. Medical therapy is still the mainstay. m This is good actually with minimal perioperative risk factors for perioperative death.



Juntado, R. | Lacson | Lagon | Lucero, S. Pathophysiology of Renovascular Hypertension:

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