**2.2.1 Differential diagnosis**

Some clinical situations have to been addressed in the diffential diagnosis of ARVD (table 3).

Atherosclerotic Renovascular Disease 153

Most of these clinical situations could be differentiataed correctly by the image study such as computed tomography and renal angiography. They are not neccessry mutually exclusive and may be coexisted. For instance, benign hypertensive nephrosclerosis, a renal parenchymal disease can be present together with ARVD. Atheroembolic renal disease is associated with aortic manupulation or occurs spontaneously. The clinical features include abrupt decline of renal functions and evidence of atrial fibrillation with extrarenal embolism (Hazanov, 2004). Fibromuscular dysplasia (FMD) characterized by fibrous thickening in arterial wall usually involves 60%-75% of renal and 25%-30% of carotid artery stenosis (Luscher et al, 1981; Gray et al 1996) and is respoisble for 25 % cases of renovascular hypertension (Pickering, 1989). In angiographic findings, FMD demostrates classic images of " string-of-beads" appearance, aneurysm, and focal or tubular stenosis. In conrast to ARVD, FMD occurs predominantly in young women of childbearing age and involves the middle

With the progression of the technology, a variety of modalities emerge for screening and diagnosis of ARVD (table 4). In addition to renogram and nuclear scintigraphic captopril renogram, doplex ultrasonography has been used successfully to detect the presence of renal artery stenosis due to the non-invasive and contrast-free characteristics. However, it is usually limited by a wide operator-dependent variation, obesity of patient and time consuming. Magnetic resonance (MR) angiography increases the comparability between examinations (Fig. 1A). Both of the sensitivity and specificity are estimated within 90-95%. Till now, multi-detector computed tomography (MDCT) angiography (Fig. 1B) almost replaces the role of catheter angiography as the first diagnostic tool for ARVD because of its

high utility and detection rate in evaluation of other abdominal problems.

angiography 100% 100%

Categories Sensitivity/specificity PPV/NPV Limitations

Captopril renogram 83-90% / 80-93% 70-92% /60-100% Hypotension

Renogram 75% /75% 50-75% /60% Almost for screening only

ultrasonography 75-90% /62-90% 60% /95% Wide operator-dependent

MR angiography 88-95% /90-95% 60-75% /90-98% Gadolinium-induced

MDCT angiography 94-100% / 93-100% 71-100% /95-100% Contrast-induced renopathy

Table 4. Diagnostic modalities for ARVD. PPV: positive predictive value; NPV: negative PV.

As we know, ARVD is highly associated with systemic atherosclerosis and occurs after the occurrence of coronary artery disease and peripheral artery disease. Accordingly, an early medical intervention and risk factors reductions to prevent the development of ARVD in the

variation, time consuming

renopathy

Contrast-induced renopathy, bleeding, arterial dissection, distal embolism

and distal portion of main renal artery (Das et al, 2007).

**2.3 The screening and diagnostic modality** 

Doplex

Catheter

**2.4 Therapeutic indications** 


Table 2. Patients at risk for further ARVD screening. BP: blood pressure; DBP: diastolic BP; FPG: Fasting plasma glucose; OGTT: oral glucose tolerance test; CrCl: creatinine clearance; ACEI: ACE inhibitors; ARB: angiotensin II receptor blockers.


Table 3. Differential diagnosis of ARVD.


**And and any two of the following**:








recommanded but is not necessary to define presense of the syndrome




Splenic arteriovenous fistula, hepatic cirrhosis,

hepatoma, abdominal aortic aneurysm and coarctation, celiac artery compression syndrome, intestinal ischemia,


Categories Criteria

*International Diabetes Federation*:

circumference does not need to be measured.

specific treatment for this lipid abnormality

of previously diagnosed hypertension.



Clinical situations Differential diagnosis

ACEI: ACE inhibitors; ARB: angiotensin II receptor blockers.

Renal artery stenosis -Renal artery dissection

Table 2. Patients at risk for further ARVD screening. BP: blood pressure; DBP: diastolic BP; FPG: Fasting plasma glucose; OGTT: oral glucose tolerance test; CrCl: creatinine clearance;

and pancreatic carcinoma




Physical findings -Abdominal or flank bruit

abnormality.

Metabolic syndorme

Hypertension

Renal insufficiency

Atheroscelrosis

Abdominal bruit

Rrogressive renal insufficiency or renovascular hypertension

Table 3. Differential diagnosis of ARVD.

Most of these clinical situations could be differentiataed correctly by the image study such as computed tomography and renal angiography. They are not neccessry mutually exclusive and may be coexisted. For instance, benign hypertensive nephrosclerosis, a renal parenchymal disease can be present together with ARVD. Atheroembolic renal disease is associated with aortic manupulation or occurs spontaneously. The clinical features include abrupt decline of renal functions and evidence of atrial fibrillation with extrarenal embolism (Hazanov, 2004). Fibromuscular dysplasia (FMD) characterized by fibrous thickening in arterial wall usually involves 60%-75% of renal and 25%-30% of carotid artery stenosis (Luscher et al, 1981; Gray et al 1996) and is respoisble for 25 % cases of renovascular hypertension (Pickering, 1989). In angiographic findings, FMD demostrates classic images of " string-of-beads" appearance, aneurysm, and focal or tubular stenosis. In conrast to ARVD, FMD occurs predominantly in young women of childbearing age and involves the middle and distal portion of main renal artery (Das et al, 2007).

### **2.3 The screening and diagnostic modality**

With the progression of the technology, a variety of modalities emerge for screening and diagnosis of ARVD (table 4). In addition to renogram and nuclear scintigraphic captopril renogram, doplex ultrasonography has been used successfully to detect the presence of renal artery stenosis due to the non-invasive and contrast-free characteristics. However, it is usually limited by a wide operator-dependent variation, obesity of patient and time consuming. Magnetic resonance (MR) angiography increases the comparability between examinations (Fig. 1A). Both of the sensitivity and specificity are estimated within 90-95%. Till now, multi-detector computed tomography (MDCT) angiography (Fig. 1B) almost replaces the role of catheter angiography as the first diagnostic tool for ARVD because of its high utility and detection rate in evaluation of other abdominal problems.


Table 4. Diagnostic modalities for ARVD. PPV: positive predictive value; NPV: negative PV.

#### **2.4 Therapeutic indications**

As we know, ARVD is highly associated with systemic atherosclerosis and occurs after the occurrence of coronary artery disease and peripheral artery disease. Accordingly, an early medical intervention and risk factors reductions to prevent the development of ARVD in the

Atherosclerotic Renovascular Disease 155

Non-CVD/ HbA1c< 6.5 % CVD/ LDL-C < 7.0 %

Non-CVD/ BP< 120/85 mg/L CVD/ BP< 140/90mg/dl

Non-CVD/ LDL-C< 100 mg/L CVD/ LDL-C < 70mg/dl

Non-CVD/ hs-CRP< 2mg/L CVD/ not established

Adverse cadiovascualr effects and metabolic abnormalities of antidiabetic agents


Multi-drug interaction and

According to the JUPITER trial only (Ridker et al, 2008)

dose effect related rhabdomyolysis

Risk factors Medications (non) CVD / Goal Precautious

Table 5. Modifiable risk factors for ARVD. CVD: cardiovascular disease including myocardial infarction and ischemic stroke; ACEI: ACE inhibitors; ARB: angiotensin II receptor blockers; BP: blood pressure; BB: beta-blocker; CB: calcium receptor blocker; JUPITER: Justification for the Use of Statins in Primary Prevention: An Intervention Trial

Fig. 2. An atherosclerotic ostial lesion at right renal artery. Panel A: catheter renal angiography (An arrowhead indicates a lesion from ostial to proximal right renal artery; Panel B: post-percutaneous transluminal angioplasty with stenting (An arrowhead indicates

should be aimed for patients with a reversible status of chronic renal insufficiency and resistant hypertension instead of reduing their mortality. A review literature has demonstrated that half of patients with ARVD have no change in renal function, while one fourth improve and one fifth deterioate their renal function after renal stenting (Fig.1A & B)

Insulin, secretagogues, sensitizers, α-glucosidase inhibitors, peptide analogs

> ACEI/ ARB, BB, CB, diuretics

Statin, fibrates, resins, niacin, ezetimibe,


Evaluating Rosuvastatin trial; CRP: C-reactive protein.

Diabetes mellitus

Hypertension

LDL-C

Inflammation

(Leertouwer et al, 2000).

stenting site of right renal artery).

Fig. 1. A: MR angiography demonstrates a right ostial renal artery stenosis (an arrowhead); B: MDCT angiography demonstrates diffuse atherosclerosis of left renal artery (an arrowhead indicate the proximal lesion of left renal artery).

presence of systemic atherosclerosis and many risk factors is important. On the other hand, a critically unilateral or bilateral stenosis of renal artery disease may need further mechanical manipulations such as renal angioplasty, stenting and bypass surgery. We will describe the two parts of therapy in detail in the following paragraphs.

### **2.4.1 Medical treatment**

Life style modification and a control of established risk factors is the golden rule for most atherosclerotic vascular disease including diabetes, obesity, hypertension, low density lipoprotein cholesterol (LDL-C), inflammation and smoking. However, no reports prove the effect of medical control to reduce the occurrence of ARVD or prevent disease progression. It is reasonable that medical treatment should be started in middle-aged persons at risk to prevent ARVD. The choice of pharmacological agents and the goal aimed to achieve with or without vascular events will be listed in table 5.

Among the antihypertensive agents, ACE inhibitors or angiotensin II receptor blockers (ARBs) are observed with the most effectiveness in control of the blood pressure for patients with ARVD (Dworkin & Jamerson, 2007). Surgical intervention should be considered if refractory hypertension persisits. However, adequate control of blood pressure by chronic administration of antihypertensive drugs can not be guarantteed the prevention of stenotic lesions progression and post-stenotic renal.atrophy.
