Case PresentationBy:Kristine ChoyAdolf Malala

CASEYou are consulting to advise on another antihypertensive agent for a patient with difficult to control hypertension. Despite high dose of a beta blocker, the patient remains hypertensive. The estimated glomerular filtration rate is 75ml/min per 1.73 sq meters. On physical examination, there is no exophthalmos and no thyroid bruit. The great vessels are without bruit as well. Abdominal examination reveals bruit loudest in the bilateral flanks, as well as a left femoral bruit. Peripheral pulses are intact. An ultrasound confirms the presence of bilateral artery stenosis. Which medication class would not be a good choice to add to this patient’s regimen?

Renal Artery Stenosis• Renal artery stenosis is a blockage of an artery

to the kidneys. It may cause kidney failure and hypertension (high blood pressure).

• Renal artery stenosis (narrowing) is a decrease in the diameter of the renal arteries. The resulting restriction of blood flow to the kidneys may lead to impaired kidney function (renal failure) and high blood pressure(hypertension), referred to as renovascular hypertension, or RVHT ("reno" for kidney and "vascular" for blood vessel).

Renovascular hypertension occurs when the artery to one of the kidneys is narrowed (unilateral, or one-sided, stenosis), while renal failure occurs when the arteries to both kidneys are narrowed (bilateral, or two-sided, stenosis). The decreased blood flow to both kidneys increasingly impairs renal function.

Renal Artery Stenosis

PATHOPHYSIOLOGY

Renin-Angiotensin-Aldosterone System • The renin-angiotensin system (RAS) or the renin-

angiotensin-aldosterone system (RAAS) is a hormone system that regulates blood pressure and water (fluid) balance.

• When blood volume is low, juxtaglomerular cells in the kidneys secrete renin. Renin stimulates the production of angiotensin I, which is then converted to angiotensin II. Angiotensin II causes blood vessels to constrict, resulting in increased blood pressure. Angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal cortex.

Renin-Angiotensin-Aldosterone System • Aldosterone causes the tubules of the kidneys to

increase the reabsorption of sodium and water into the blood. This increases the volume of fluid in the body, which also increases blood pressure.

• If the renin-angiotensin-aldosterone system is too active, blood pressure will be too high. There are many drugs that interrupt different steps in this system to lower blood pressure. These drugs are one of the main ways to control high blood pressure (hypertension), heart failure, kidney failure, and harmful effects of diabetes.

Renovascular diseaseRenovascular disease is a progressive condition that causes narrowing or blockage of the renal arteries or veins.These are the blood vessels that take blood to and from the kidneys. It's the general term used for three disorders: renal artery occlusion, renal vein thrombosis, and renal atheroembolism.

Renovascular DiseaseRenal Artery Stenosis may be associated with all stages of hypertension, but it is more commonly found with stage 3 or resistant hypertension and, when bilateral, can lead to reduced kidney function.

Clinical clues to renovascular disease include:

• Onset of hypertension, without a family history.

• abdominal bruit

• Resistant hypertension

• Pulmonary edema

• Renal failure of uncertain cause, especially with a normal unrinary sediment

Bilateral Artery Stenosis

CASEYou are consulting to advise on another antihypertensive agent for a patient with difficult to control hypertension. Despite high dose of a beta blocker, the patient remains hypertensive. The estimated glomerular filtration rate is 75ml/min per 1.73 sq meters. On physical examination, there is no exophthalmos and no thyroid bruit. The great vessels are without bruit as well. Abdominal examination reveals bruit loudest in the bilateral flanks, as well as a left femoral bruit. Peripheral pulses are intact. An ultrasound confirms the presence of bilateral artery stenosis. Which medication class would not be a good choice to add to this patient’s regimen?

Choices

a. Thiazide Diuretics

b. Calcium Channel Blocker

c. Angiotensin II blocker

d. Centrally acting alpha blocker

Findings• GFR – 75 ml/min – normal range is 90 - 120ml/min. (stage

2 )

• No exophthalmos and no thyroid bruit.

• Abdominal examination reveals bruit loudest in the bilateral flanks, as well as a left femoral bruit.

• Ultrasound confirms the presence of bilateral artery stenosis.

Drugs given:Thiazide diureticMOA: increases urinary excretion of sodium and water by inhibiting sodium reabsorption in the cortical diluting tubule of the nephron, thus relieving edemaInhibit NaCl reabsorption by binding to the synporter responsible for the electroneutral co-transport of Na/Cl.Common side effects:• Hypokalemia• Hypocalcemia• Hyperuricemia• Hyponatremia

Thaizide drugs decrease the circulating blood volume, leading to a reduced cardiac output. If therapy continues, cardiac output stabilizes, but fluid volume decreases.

Diuretic-induced extracellular fluid volume contraction would potentiate this untoward effect of reduced perfusion pressure on renal function

Flash pulmonary edema has been discussed as a clinical clue to bilateral artery stenosis. (These episodes occur frequently in bilateral patients)

Thiazide can be given to renovascular hypertension of the GFR if more than 30ml/1.73m2/min.

Drugs given:Calcium Channel blockerMOA: blocking voltage-gated calcium channels (VGCCs) in cardiac muscle and blood vessels. This decreases intracellular calcium leading to a reduction in muscle contraction. In the heart, a decrease in calcium available for each beat results in a decrease in cardiac contractility.Common Side effects:-Excessive vasodialtion-Dizziness-Hypotension-Ankle edema

Calcium antagonist have been found to be quite effective in patients with pressumed renovascular hypertension.,

Effect is primarily due to direct arteriolar vasodilation,

Calcium antagonists appear to induce less impairment of renal function in patients with renovascular hypertension. Nifedipine, produced a smaller decrement in the GFR than did ACEI in patients with Bilateral artery stenosis. Other calcium channel blocker may better maintain renal blood flow and GFR because of their preferential afferent arteriolar vasodilatory effect.

Drugs given:Central acting alpha blockers

MOA: lower blood pressure by blocking alpha-receptors in the smooth muscle of peripheral arteries throughout the tissues of the body. alpha-blockers cause the peripheral arteries to widen (dilate) and lower the blood pressure.

Common Side Effects:

•Orthostatic and exercise hypotension

•Sexual dysfunction

•Diarrhea

These regarded as agents of last choice, being added to therapy that has not achieved target BP. Alpha blocker lead to vasodilation and a drop in BP. They may, however be useful for diabetic patient.

ANSWER: Angiotensin II receptor BLOCKERSMOA: block the activation of angiotensin II AT1 receptors. Blockade of AT1 receptors directly causes vasodilation, reduces secretion of vasopressin, reduces production and secretion of aldosterone, amongst other actions – the combined effect of which is reduction of blood pressure.Common side effects:-dizziness, -headache, -Hyperkalemia-Mild reduction in GFR

ANSWER: Angiotensin II receptor BLOCKERS

Angiotensin II receptor blocker shouldn’t be used in patients with renal artery stenosis. In these patients, drugs use may cause renal function to detoriarate, progressing from oliguria to azotemia, and renal failure.

ARB should not be given because the drugs can markedly reduced renal perfusion in patients with bilateral artery stenosis.

ANSWER: Angiotensin II receptor BLOCKERS

ACE inhibitors, angiotensin II receptor blockers, or renin inhibitors can be used in unilateral but not in bilateral renal artery stenosis. These drugs can reduce GFR and increase serum BUN and creatinine levels.

Both ACEI and Angiotensin II Blocker cause loss of efferent arteriolar vasoconstriction with a resultant decrease on the glomerular capillary pressure and GFR.

SUMMARY:

Thiazide diuretics, calcium channel blocker, or centrally acting alpha blocker are better choices for an antihypertensive agent in a patient with bilateral renal artery stenosis.

The end