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Determination of Renal Arterial Stenosis Severity: Comparison of Pressure Gradient and Vessel Diameter¹

¹ From the Franz Volhard Clinic, Max Delbrück Center for Molecular Medicine, Charité, Humboldt University of Berlin, Wiltbergstrasse 50, 13125 Berlin, Germany. Received August 25, 2000; revision requested October 4; final revision received February 12, 2001; accepted March 2. Address correspondence to C.M.G. (e-mail: gross@fvk-berlin.de).

	ABSTRACT

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PURPOSE: To determine the hemodynamic significance of arteriographically detected renal arterial stenosis by obtaining pressure gradients with a miniaturized pressure guide wire.

MATERIALS AND METHODS: Forty-six renal arterial stenoses in 38 patients were assessed in terms of severity and then subjected to gradient determination before and after angioplasty. The patients (mean age, 63 years) had a mean serum creatinine value of 1.3 mg/dL ± 0.4 (114.9 µmol/L ± 35.4 [SD]) and required on average three medications for blood pressure control. The mean degree of stenosis diameter was 51% ± 17 (range, 12%–85%).

RESULTS: The systolic and mean arterial pressure gradients with and those without vasodilatation were highly correlated with stenosis severity, systolic blood pressure, and serum creatinine as a curvilinear fit (r = 0.9, P < .01). At 50% stenosis severity, the mean pressure gradient was 22 mm Hg.

CONCLUSION: Patients with a pressure gradient greater than 20 mm Hg should be good candidates for renal arterial dilatation, and use of the pressure guide wire will facilitate interventional decisions.

Index terms: Renal angiography, 961.122 • Renal arteries, stenosis or obstruction, 961.72 • Renal arteries, US, 961.12984, 961.12989

	INTRODUCTION

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Renal arterial stenosis remains a diagnostic and therapeutic dilemma. A comparison of renal angiograms by three experienced radiologists who evaluated the number of renal arteries and the presence, location, aspect, and severity of renal arterial stenoses showed that the general agreement among the experts was poor (1). The three radiologists were in general agreement about the severity of stenosis; however, they could not distinguish between 50% and 60% stenosis or between 60% and 70% stenosis.

Doppler ultrasonography (US) shows promise in the diagnosis of significant renal arterial stenosis. However, recently van der Hulst et al (2) found that, as a screening test, the technique had considerable shortcomings. Nahman et al (3) measured pressure gradients in patients with renal arterial stenosis to facilitate the interpretation of stenosis severity. They found no correlation between the pressure gradient and systemic blood pressure, renal function, or medication requirements. They did not report a correlation between the pressure gradient and estimates of stenosis severity. They measured the gradient with a pressure transducer connected to the angioplasty catheter before intervention.

The development of miniaturized pressure guide wires permits determination of gradients without introducing confounding disturbances in the gradient or the blood flow (4). The purpose of our study was to determine the hemodynamic significance of arteriographically detected renal arterial stenosis by obtaining pressure gradients with a miniaturized pressure guide wire.

	MATERIALS AND METHODS

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We examined 38 of 50 consecutive patients (31 men, seven women; mean age, 63 years ± 10 [SD]; age range, 38–76 years) referred for angiographic evaluation of possible renal arterial stenosis. They were receiving three medications ± 0.8, their creatinine concentration was 1.3 mg/dl ± 0.4 (114.9 µmol/L ± 35.4), and blood pressure values were well controlled at 141 mm Hg ± 23 for systolic and 74 mm Hg ± 12 for diastolic blood pressure. Thirteen patients had diabetes, 11 remained active smokers, and 20 had hyperlipidemia. Patients were included in the study provided that we concurred with the referring physician’s assessment that the chances for renal arterial stenosis were high on the basis of renal US evaluations, duplex Doppler US studies, and, occasionally, angiograms obtained from another institution. Patients were excluded if the suspicion for renal arterial stenosis was low or if they would not clearly benefit from intervention. All patients included in the study gave written informed consent after approval by the institutional review board was granted.

The renal arteries were examined bilaterally with the femoral approach, and bilateral selective renal arteriograms were obtained. These arteriograms were subsequently graded independently by two board-certified interventional radiologists who were unaware of the pressure measurements. In case of disagreement, a consensus between the radiologists was obtained. The radiologists relied on a software program (CAAS II; Pie Medical Imaging, Maastricht, the Netherlands) to determine the dimensions on the images. The reference segment consisted of an area about 1 mm proximal and extending to 1 mm distal of the stenosis. The program was used to determine the contour of the lumen and measure the minimal and reference lumen diameters. The percentage of stenosis was calculated as minimal lumen diameter divided by reference lumen diameter multiplied by 100.

When a renal arterial stenosis was identified, the intraarterial systemic pressure was measured continuously with a transducer and the miniaturized pressure-gradient wire system (PressureWire; Radi Medical Systems, Uppsala, Sweden). Pressures were recorded by means of a fiber-optic pressure sensor located laterally and 3 cm from the distal end. The basic principle is that the element modulates an optical reflection with pressure-induced elastic movements. The light source is an emitting diode in the control unit. The wire replaces a standard 0.018-inch guide wire.

We first advanced a 7-F guiding catheter from the femoral artery to the ostium of the renal artery (5). We introduced the 0.014-inch wire into the guiding catheter and then moved it to the ostium of the stenosis. After identical pressure of the guiding catheter and the wire was confirmed at this position, the stenosis was traversed by means of the floppy-ended wire, followed by the transducer. We were then able to compare the two pressure curves from the transducer distal to the stenosis and from the guiding catheter within the aorta. We then advanced the dilation equipment through the guiding catheter and across the stenosis, and we left the wire in place. We were thus able to assess the result immediately after the intervention.

The wire was introduced through a Y-shaped adapter in a recirculating perfusion model consisting of tubing with internal diameters of 1.00–4.00 mm. In an earlier study (4) in which the pressure measurements proximal and distal to artificial stenoses caused gradients of 0–100 mm Hg, the wire aided in the correct identification of the pressure difference with an equally high accuracy, 1, 2, and 3 cm after stenoses. After the systolic and mean arterial pressure gradients were determined, we administered nitroglycerin intraarterially to induce renal vasodilation. Increasing doses of nitroglycerin (as much as 0.3 mg) were infused into the stenotic renal artery (6). The pressure gradient was measured with the wire before and during the infusion. Furthermore, the fractional flow reserve, an index of stenosis severity, was determined as previously described (5). When steady-state hyperemia was achieved after vasodilatation, fractional flow reserve was calculated as the ratio of the mean distal intrarenal pressure measured with the wire to the mean arterial pressure measured with the guiding catheter. These measurements were conducted by the radiologist (either J.W. or F.U.) performing the interventions. The system is designed so that the operator can conduct all the necessary procedures.

Statistical comparisons were performed by means of linear and curvilinear (exponential) regression analysis (Statview; SAS Institute, Cary, NC). Specifically, we tested regressions between stenosis severity and the systolic (and mean) pressure gradient and fractional flow reserve. We applied linear, quadratic, and third-order equations. The coefficients obtained were tested against the null hypothesis—namely, the assumption that no association was present.

Renal arterial stenoses not uncommonly occur bilaterally. However, they vary in their severity, even within the same patient. We therefore treated each stenosis as a separate event. To exclude the possibility that two stenoses in the same patient were not independent concerning pressure gradient measurements, we also performed two confirmatory analyses, placing the patients with bilateral stenoses into subgroups (see Results). A P value of less than .05 was considered to indicate a statistically significant difference. We also compared the regressions in terms of setting the y axis to zero (ie, no pressure gradient whatsoever). Data are expressed as the mean plus or minus SD.

	RESULTS

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All procedures were well tolerated, and no complications were observed in any of the 38 patients. More than half of the stenoses were ostial. The stenoses ranged in severity from 12% to 85%; the mean severity was 51% ± 17. Most stenoses were arteriosclerotic in origin. Figure 1 shows the sole exception, an arteriogram obtained in a 31-year-old woman who had fibromuscular dysplasia. The characteristic beaded appearance is seen. Her systolic gradient was 35 mm Hg. In this patient, we initially performed a percutaneous angioplasty, which reduced the gradient only by several millimeters of mercury. We subsequently placed a stent to treat this recalcitrant lesion; the gradient decreased to zero. This patient demonstrated the utility of the wire in immediately assessing the hemodynamic outcome of the procedure. Complex atherosclerotic stenoses were not uncommon.

View larger version (154K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Anteroposterior arteriograms obtained in a 31-year-old woman with fibromuscular dysplasia. The characteristic beaded appearance (top left) is seen. Arrow delineates the lesion. Her systolic gradient was 35 mm Hg, as demonstrated on the pressure curve printout (top right). Percutaneous angioplasty (middle left) was initially performed, which reduced the gradient only by several millimeters of mercury, as seen on the printout (middle right). Arrowhead indicates the position of the wire. We subsequently placed a stent (bottom left), which removed the gradient, as seen on the printout (bottom right). Arrows delineate the margins of the stent.

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. Renal anteroposterior arteriograms obtained in a 68-year-old man with (a) right and (b) left renal arterial stenoses (arrow). The right-sided systolic gradient was 28 mm Hg, which increased to 38 mm Hg following administration of nitroglycerin (NTG), as demonstrated on the pressure curve printouts (bottom panels in a). The left-sided systolic gradient was greater at 60 mm Hg, which increased to 69 mm Hg with nitroglycerin (bottom panels in b). Printouts generated by the software program show the angiographic stenosis severities (DS) judged to be 54% and 63%, respectively. This patient received stents bilaterally (not shown), which removed both gradients. AO [200] and ART [200] depict the equilibration of pressure in the aorta and the arterial system.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. Renal anteroposterior arteriograms obtained in a 68-year-old man with (a) right and (b) left renal arterial stenoses (arrow). The right-sided systolic gradient was 28 mm Hg, which increased to 38 mm Hg following administration of nitroglycerin (NTG), as demonstrated on the pressure curve printouts (bottom panels in a). The left-sided systolic gradient was greater at 60 mm Hg, which increased to 69 mm Hg with nitroglycerin (bottom panels in b). Printouts generated by the software program show the angiographic stenosis severities (DS) judged to be 54% and 63%, respectively. This patient received stents bilaterally (not shown), which removed both gradients. AO [200] and ART [200] depict the equilibration of pressure in the aorta and the arterial system.

View larger version (86K): [in this window] [in a new window] [Download PPT slide]   Figure 3. Anteroposterior arteriograms obtained in a 46-year-old man with a borderline stenosis estimated at 50%. The systolic gradient of this stenosis (arrow) was 8 mm Hg. The gradient increased to 12 mm Hg with nitroglycerin (NTG), as demonstrated on the pressure curve printouts (bottom right). The automated contour detection system delineates the reference diameters, both proximal and distal (yellow lines), as well as the minimal lumen diameter (red lines), as indicated by the vertical bars on the automatically generated printout (top right).

View larger version (80K): [in this window] [in a new window] [Download PPT slide]   Figure 4. Anteroposterior renal arteriograms obtained in a 52-year-old man with a borderline left stenosis judged at 50%. The automatically applied tracings show the vessel contour detection (yellow lines) and the angiographically displayed vessel lumen (red lines). The automatic calculation system shows the percentage of stenosis (top middle). This systolic gradient was 17 mm Hg, which increased to 31 mm Hg with nitroglycerin, as demonstrated on the pressure curve printouts (bottom). On the basis of this finding, the patient received a stent (arrows), which reduced the gradient with nitroglycerin to zero (not shown). The arrowhead indicates the wire.

Figure 5 shows a linear fit with the correlation between the resting gradient and the estimated stenosis severity (r = 0.6; P < .05). A curvilinear third-order exponential fit showed better correlation (r = 0.9; P < .01). We determined the resting gradient when the estimated stenosis was 50%, as can be seen in Figure 5, and found this value to be 22 mm Hg. The curvilinear relationship between the systolic resting gradient and systolic systemic blood pressure also exhibited the same degree of significance. The regression equation for this fit was y = 0 - 0.16x + 0.003x² (r = 0.7; P = .02).

View larger version (30K): [in this window] [in a new window] [Download PPT slide]   Figure 5. Graph of a linear fit (left) shows the correlation between the resting gradient and the estimated stenosis severity (y = -13.3 + 0.8x; r = 0.6; P < .05). Graph of a curvilinear third-order exponential fit (right) showed better correlation (y = 0 + 1.5x - 0.05x2 + 0.001x3; r = 0.9; P < .01). Crosshairs show that 50% stenosis indicates a gradient of 22 mm Hg at the break in the curve. SPG = systolic pressure gradient. = each measurement.

View larger version (32K): [in this window] [in a new window] [Download PPT slide]   Figure 6. Graph shows the relationship between the resting gradient and the measurement after administration of nitroglycerin (NTG). A high degree of correlation was observed, and the steepness of the curve indicates that nitroglycerin reduced intrarenal resistance (y = 0 + 1.3x - 0.001x2; r = 0.9; P < .01). SPG = systolic pressure gradient. = single measurements.

	DISCUSSION

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Our data may extend the observations of the Dutch Renal Artery Stenosis Intervention Cooperative (DRASTIC) investigators (1). They found that their radiologists were good at estimating the stenosis and were generally in agreement, but no better, about the severity of the stenosis. Our findings suggest that radiologists may be helped in making an assessment regarding intervention by conveniently and accurately measuring the gradient directly.

Other options are being developed to assist radiologists in invasive procedures. van der Hulst et al (2) reported their results from a study in which an endovascular flow wire was used to obtain Doppler US waveforms. With this technique, they were able to compare proximal and peripheral Doppler US parameters. They found that Doppler US measurements in the main renal artery correlated well with the stenosis estimates from digital subtraction angiography. However, they also reported that the intrarenal Doppler US spectrum was of no value. Similar results were reported by Privat et al (7). We have conducted no comparisons; however, such determinations are of interest.

Pemsel and Thermann (8) showed in a canine model that at the critical level of one-third of normal diameter (67% stenosis) a further reduction of only 0.5 mm will decrease the flow rate by 50%. They were unable to detect such minimal degrees of stenosis angiographically. Furthermore, turbulence can increase the importance of stenosis in terms of flow reduction. Pemsel and Thermann also observed that the effect of stenosis is dependent on the peripheral resistance in the kidney behind the lesion. Their experimental observations, coupled with the experiences of the DRASTIC investigators, underscore the value of a direct functional measurement obtained during the diagnostic procedure (1,8).

We believe that the wire provides a reliable and useful functional measurement. A recent report (9) from the DRASTIC investigators suggests that an invariable improvement is not necessarily forthcoming in patients treated with angioplasty or stent placement. Their findings underscore the potential value of hemodynamic information. We are currently collecting follow-up data so that better strategies may be used in these patients.

	ACKNOWLEDGMENTS

 
We thank Christine Eichhorn, PhD, for helping with the statistical analysis.

	FOOTNOTES

 
Abbreviation: DRASTIC = Dutch Renal Artery Stenosis Intervention Cooperative

Author contributions: Guarantor of integrity of entire study, C.M.G.; study concepts and design, C.M.G.; literature research, O.W.; clinical studies, J.W., C.M.G., F.U.; data acquisition, O.W.; data analysis/interpretation, C.M.G., J.K.; statistical analysis, J.K.; manuscript preparation, C.M.G., J.K.; manuscript definition of intellectual content, C.M.G., J.K., R.D.; manuscript editing, J.K.; manuscript revision/review, F.C.L., R.D., C.M.G., J.K.; manuscript final version approval, F.C.L., C.M.G., J.K.

	REFERENCES

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1. van Jaarsveld BC, Pieterman H, van Dijk LC, et al. Inter-observer variability in the angiographic assessment of renal artery stenosis: DRASTIC study group—Dutch Renal Artery Stenosis Intervention Cooperative. J Hypertens 1999; 12:1731-1736.
2. van der Hulst VP, van Baalen J, Kool LS, et al. Renal artery stenosis: endovascular flow wire study for validation of Doppler ultrasound. Radiology 1996; 200:165-168.[Abstract/Free Full Text]
3. Nahman NS, Maniam P, Hernandez RA, et al. Renal artery pressure gradients in patients with angiographic evidence of atherosclerotic renal artery stenosis. Am J Kidney Dis 1994; 24:695-699.[Medline]
4. Gorge G, Erbel R, Niessing S, Schon F, Kearney P, Meyer J. Miniaturized pressure-guide-wire: evaluation in vitro and in isolated hearts. Cathet Cardiavasc Diagn 1993; 30:341-347.
5. Pijls NHJ, Kern MJ, Yock PG, De Bruyne B. Practice and potential pitfalls of coronary pressure measurement. Cathet Cardiovasc Diagn 2000; 49:1-16.
6. Wierema TKA, Postma CT, Houben AJHM, et al. Adenosine-induced renal vasodilatation is prolonged in renal artery stenosis. J Hypertens 1998; 16:2109-2112.[Medline]
7. Privat C, Ravel A, Chirossel P, et al. Endovascular Doppler guide wire in renal arteries: correlation with angiography in 20 patients. Invest Radiol 1999; 34:530-535.[CrossRef][Medline]
8. Pemsel HK, Thermann M. Zur hämodynamischen wirksamkeit der nierenarterienstenosen. ROFO Fortschr Geb Rontgenstr Nuklearmed 1978; 129:189-192.
9. van Jaarsveld BC, Krijnen P, Pieterman H, et al. The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis: Dutch Renal Artery Stenosis Intervention Cooperative study group. N Engl J Med 2000; 342:1007-1014.[Abstract/Free Full Text]

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