Hypertension and Atherosclerotic Renal Artery Stenosis: Diagnostic Approach
Pietro C. Zucchelli
Malpighi Department of Nephrology, Policlinico S.Orsola-Malpighi, Bologna, Italy.
Correspondence to Dr. Pietro C. Zucchelli, Professor of Medicine, Malpighi Department of Nephrology, Policlinico S.Orsola-Malpighi, Via P. Palagi 9-40138 Bologna, Italy. Phone: 39-051-30-28-52; Fax: 39-051-63-62-511;
ABSTRACT. Atherosclerotic renovascular disease needs noninvasivediagnostic tools to apply to patients having clinical characteristicsthat can suggest its presence. Color Doppler ultrasonographyis a noninvasive, inexpensive diagnostic procedure that is capable,in an experienced hand, of accurately screening for renovasculardisease. Magnetic resonance angiography and spiral computedtomography angiography play an ancillary role in detecting atheromatousrenovascular disease. Captopril-enhanced renography and scintigraphyand the resistive index at Doppler sonography may be very usefulin patients with renal artery stenosis for predicting the responseto revascularization. E-mail: segret_nefromm@orsola-malpighi.med.unibo.it
Atherosclerotic renal artery stenosis (ARAS) is associated withtwo common clinical syndromes: renovascular hypertension andischemic nephropathy (or Azotemic renovascular disease), whichoften coexist. Ischemic nephropathy has gained recognition overthe past decade as a distinct entity, frequently present eventhough often overlooked, and a potentially curable cause ofend-stage renal disease in aged people (1–4).
The benchmark diagnostic procedure is renal arteriography performedwith intraarterial injection of iodinated contrast media, butthe risk of this procedure is not negligible, requiring noninvasiveassessments of renal artery stenosis. The diagnosis of ARAScan be suspected on clinical grounds and can only be establishedwith specific diagnostic procedures (1–4).
The clinical features suggesting the presence of a significantARAS are listed in Table 1.
Table 1. Clinical features suggestive of atherosclerotic renal-artery stenosis
Proteinuria <1 g/24 h is a discriminatory clinical sign,unless malignant hypertension or association with renal cholesterolcrystal embolization are present (4). Flash pulmonary edema,usually at night, without signs of severely impaired left ventricularfunction, is present in 41% of patients with bilateral ARASand in 12% of patients with unilateral ARAS (5). Notably, ARASseems to be an important cause of renal insufficiency in type2 diabetic patients (4).
The diagnostic procedures can be subdivided into two main groups:those able to show the presence, and the degree, of a ARAS,and those capable of identifying the subgroup of patients whocan benefit from revascularization. Much evidence supports theconcept that hypertension and renal disease are not purely relatedto renal artery narrowing and renal ischemia. Renal insufficiencyis a multifactorial process in which a partial reduction inperfusion pressure with abolition of renal autoregulation leadingto renal ischemia, hypertensive nephrosclerosis, tubulointerstitialdamage secondary to tubular cell polarity alteration, and cholesterolcrystal microembolization play a role (2,3,4).
Procedures for Identifying the Presence of Renal Artery Stenosis
Table 2. Diagnostic strategy for atheromatous renal artery stenosis
The Color and Power Doppler
The color and power Doppler (ultrasonic duplex scanning witha pulsed doppler unit) is the most-saving tool for ARAS screening.It allows a direct visualization of the renal vascular treewhile assessing blood flow velocity and pressure waveforms (4,6–8).The current better machines have practically overcome problemsdue to obesity and bowel gas. Two types of criteria for detectionof renal artery stenosis can be used.
Proximal Criteria: The peak systolic velocity of the Dopplerwaveforms (the fastest velocity recorded in the spectrum afterangle correction) from the renal artery 180 cm/s for stenosisover 60% of the arterial diameter (the mean velocity of thenormal artery is around 100 cm/s) and the renal-aortic ratio>3.5.
Distal (or Intraparenchymal) Criteria: Related toa slow riseof the peak velocity distal to the stenosis, so-calledpulsustardus-parvus, with a prolonged acceleration time (timeto peak)and a reduction of the ipsilateral resistive indexto <0.45.
The sensitivity and specificity of color Doppler sonographyin an experience hand is around 80 to 95%. Recently, the useof enhancers (bolus of contrast agents consisting of microbubblesstabilized in a galactose matrix) have been introduced withsome useful results. Color Doppler flow can detect stenosisthrough a narrowing of the color lumen and changes in colorof the high ejection jet.
Spiral (or Helical) CT Angiography
Spiral (or helical) CT angiography consists of a continuouslyoverlapping transaxial images obtained by means of a rotatingx-ray tube, with the scanning time within a single-breath holdof the patient to eliminate respiratory misregistration (9).
The three-dimensional reconstruction of the vascular tree resultsin a reliable method of visualizing the whole vascular treewith sensitivity and specificity varying form 90 to 99%.
Unfortunately, spiral CT angiography requires up to 150 ml ofiodinated contrast media, which is potentially nephrotoxic andcan only be recommended in patients with serum creatinine <3.0mg/dl.
Magnetic Resonance Angiography
The basis of this technique is magnetic resonance of protonscontained in the water molecules. It is noninvasive and capableof providing a direct visualization of proximal renal arterylesions associated with accurate serial renal size without iodinatecontrast material; it is also capable of measuring the absoluteblood flow rate and GFR (10,11). Two different imaging methodscan be used: the first time of flight, wherein the high velocityof the blood jet at the level of stenosis appears as a lossof signal (black); phase contrast technique, wherein gadoliniumis used as a contrast agent and phase shift difference in movingprotons is used to display the blood flow within the renal arteries.Three-dimensional reconstruction technique offers a sensibilityand specificity of 90 to 100%, but it is very expensive.
Renal Arteriography
Renal arteriography with low-osmolar contrast material is thegold standard diagnostic test for excellent visualization ofall the renal vasculature (1,2). In the 1980s, intraarterialdigital substraction angiography was suggested because of itsminimal invasiveness and very low complication rate. However,in spite of the early optimism, many investigators were unableto reproduce impressive results because its images are oftenblurred by motion artifacts.
Procedures for Identifying the Response to Revascularization
The functional significance of ARAS should be established beforerevascularization. In fact, the causation of renal dysfunctionin ARAS is not clearly understood. The physiologic studies toassess the renin-angiotensin system show great heterogeneityin the great majority of elderly patients in whom sustainedhypertension is not renin-dependent. Therefore, some studies,such as differential renal vein renin determination, besideshigh incidence of technical errors, have highly variable meaningsand do not reliably predict the course of hypertension and/orrenal function after revascularization (1,2,3).
Color Doppler Ultrasonography
A resistive index (1 - [end-diastolic velocity:maximal systolicvelocity] x 100) 80 before revascularization identifies patientswith ARAS in whom revascularization will not improve renal function,BP, or kidney survival (12).
Captopril-Enhanced Renography and Scintigraphy
Captopril-enhanced renography and scintigraphy is preceded by25 or 50 mg of captopril given 1 h before the procedure. Differentradiopharmaceutical agents can be used, such as the 99mTcDTPA,which is excreted by glomerular filtration, and the 131-I orthoiodohippurateand 99mTc mercaptoacetyltriglycine (MAG3), which are excretedby glomerular filtration plus renal tubular secretion.
Time-activity curves give information and measure about thetotal and single-kidney GFR or renal blood flow and mean transittime in the renal parenchyma, yielding vital information. Inaddition, sequential scintigrams can supply important data onrenal perfusion, kidney size, and excretory capacity (3,11).Captopril-enhanced renography and scintigraphy are based onthe assumption that the GFR is angiotensin II-dependent, witha brisk fall in GFR amplifying differences in renal function.The above reported physiologic data explain why the sensitivityand specificity varies enormously in different series between43 to 85%. Multiple limitations are present in bilateral ARASand in patients with advanced atherosclerosis and/or renal failure(serum creatinine 2.5 mg/dl).
In a few cases, renal biopsy can be useful to detect the presenceof important cholesterol crystal renal embolization or severehistopathologic renal damage (high degree of glomerulosclerosisand/or tubulointerstitial sclerosis), which is an importantdeterminant and predictor of renal function outcome.
In summary, tests for screening and diagnosing ARAS should beperformed in patients with moderate-to-high probability of havingthe disease. Color Doppler sonography is the best screeningtest with a predictive value of more than 80%. When the testis positive, other renal imaging procedures must be performed.Spiral CT angiography offers the best procedure to detect thewhole renal vascular tree in subjects with normal or near-normalrenal function. In patients with mild-to-moderate renal insufficiency,magnetic resonance angiography is the recommended procedure.ACE-inhibitor renography and scintigraphy and the renal resistiveindex at Doppler ultrasonography can be very useful in predictingfavorable response to revascularization.
Shal SMA, Scoble JE: "Flash pulmonary oedema" — A diagnosis for both cardiologist and the nephrologist. Nephrol Dial Transplant 16: 1311–1313, 2001[Free Full Text]
Olin JW, Piedmonte MR, Young JR, De Anna S, Grubb M, Childs MB: The utility of doppler ultrasound scanning of the renal arteries for diagnosing significant renal artery stenosis. Ann Intern Med 122: 833–839, 1995[Abstract/Free Full Text]
Kliewer MA, Tupler RH, Carroll BA: Renal artery stenosis: Analysis of Doppler waveform parameters and tardus-parvus pattern. Radiology 189: 779–787, 1993[Abstract/Free Full Text]
Krumme B, Rump LC: Colour Doppler sonography to screen for renal artery stenosis. Technical point to consider. Nephrol Dial Transplant 11: 2385–2389, 1996[Free Full Text]
Rubin GD, Dake MD, Napel S: Spiral-CT of renal artery stenosis: Comparison of three dimensional rendering techniques. Radiology 190: 181–189, 1994[Abstract/Free Full Text]
Gedroyc WM, Neerhut P, Negus R: Magnetic resonance angiography of renal artery stenosis. Clin Radiol 50: 436–439, 1995[CrossRef][Medline]
Pedersen EB: New tools in diagnosis renal artery stenosis. Kidney Int 57: 2657–2677, 2000[CrossRef][Medline]
Radermacher J, Chavau A, Bleck J, Vitzhum A, Stoess B, Gebel MJ, Galanski M, Koch KM, Haller H: Use of Doppler ultrasonography to predict the outcome of therapy for renal-artery stenosis. N Engl J Med 344: 410–417, 2001[Abstract/Free Full Text]
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Abstract
Introduction
180 cm/s for stenosis over 60% of the arterial diameter (the mean velocity of the normal artery is around 100 cm/s) and the renal-aortic ratio >3.5. 
