Renal Artery Stenosis: Prevalence and Associated Risk Factors in Patients Undergoing Routine Cardiac
1
Michael B. Harding, L. Richard Smith, Stevan I. Himmelstein, Kevin Harrison, Harry R. Phillips, Steve J. Schwab,2 James B. Hermiller, Charles J. Davidson, and Thomas M. Bashore
sociated variable. These data reveal the previously MB. Harding, L.R. Smith, SI. Himmelstein, K. Harrison, undetected high prevalence of renal artery disease H.P. Phillips. S.J. Schwab, J.B. Hermiller. C.J. Davidson, in patients undergoing cardiac catheterization and J.M. Bashore, Duke University Medical Center, Dur- provide clinical and angiographic features that as- ham, NC sist in predicting its presence. (J. Am. Soc. Nephrol. 1992; 2:1608-1616) Key Words: Renal artery stenosis, cardiac catheterization, renovascular disease
ABSTRACT The purposes of this study were to determine the R enal artery stenosis may be a cause of hyperten- prevalence of angiographically significant renal or- sion and may result in renal ischemia and loss tery stenosis in a patient population referred for di- of renal mass. Stenosis of the renal arteries usually agnostic cardiac catheterization and to develop a results from atheromatous lesions that can bead to model that predicts the highest-risk subset of patients progressive arterial occlusion in many patients ( 1 - 3). Atherosclerotic renovascubar disease is a fre- who have significant renal artery narrowing. A pros- quently overbooked clinical entity and may be a com- pective validation cohort study was undertaken in a mon cause of progressive renal insufficiency (4.5). referral-based university hospital. After left ventricu- Renal artery stenosis is a potentially correctable lography, abdominal aortography was performed problem because revascularization techniques in- to screen for the presence of renal artery disease. A cluding surgery and percutaneous renal artery angio- convenience sample of 1,302 of 1,651 consecutive plasty have been shown to be effective in treating patients undergoing diagnostic cardiac catheteri- renal artery stenosis and preserving renal function zatlon were enrolled In the study. Of the 1,302 ab- (6-11). dominal aortograms performed, I .235 (95%) were The prevalence of renal arterial disease in the gen- deemed of adequate quality for the evaluation of eral population is poorly defined. Necropsy studies suggest a frequency of “severe” stenosis to be 25% in renal artery anatomy. Renal artery disease was iden- subjects 40 yr of age or older (12). Renovascular tlfled In 30% of the patients. Insignificant renal artery hypertension is present in 5 to 1 0% of the total stenosis was found in 187 (15%) and significant hypertensive population, but renal artery stenosis ( 50% diameter narrowing) stenosis was found in I 88 can be demonstrated in 35 to 43% of patients evalu- (15%). Significant unilateral disease was present in ated for renovascular hypertension ( 1 3. 1 4). The oc- I 1%, and bilateral disease was present in 4%. By currence of renal artery stenosis in patients with unlvariable and multivariable logistic regression atherosclerosis elsewhere, especially in patients with analysis, the association of both clinically and cath- abdominal aortic and aortoiliac disease, is as high as eterlzatlon-derived variables with renal artery dis- 39% (1 5). Small series have also noted significant ease was assessed. Multivariable predictors in- renal artery stenosis in 29% of patients with coro- nary artery disease (16). cluded age, severity of coronary artery disease, The population of patients referred for cardiac congestive heart failure, female gender, and periph- catheterization often exhibits many clinical features eral vascular disease. Hypertension was not an as- that one might anticipate would be associated with atherosclerotic renal artery disease, such as ad- vanced age. evidence of diffuse atherosclerosis, hy- I Rceived September 20. 1991. Accepted January 4. 1992. 2 Correspondenceto Dr. 5.J. Schwab, Duke University MedicalCenter, Box 3014. pertension, renal insufficiency, and the presence of Durham, NC 27710. coronary artery disease (1 2. 1 5- 1 8). Thus, abdominal f046-6673/021 1-1608303.00/0 aortography at the time of cardiac catheterization Journal of the American 5ociety of Nephrology Copyri9ht C 1992 by the American Society of Nephrology provides a low-risk, readily performed means of
1608 Volume 2 - Number II . 1992 Harding et al
screening for the presence of renal artery stenosis in phy was performed in the anterior-posterior projec- a population likely to have renal artery disease. tion with lohexol (Omnipaque 350; Winthrop, Bronx, The purpose of this study is twofold. The first is to NY) power injected at a rate of 20 mL/s to a total determine the prevalence of angiographically signif- volume of 30 mL. The injection was recorded on 35- icant renal artery stenosis in a large, diverse popu- mm cine film at 30 frames per second. lation referred for cardiac catheterization. The sec- ond is to develop a model based on clinically and cardiac catheterization-derived parameters that pre- Aortography Analysis dicts the highest-risk subset of patients who have Aortograms were reviewed by a single observer significant renal artery narrowing. thus facilitating blinded to the clinical information. The adequacy of the screening procedure. the study and the presence or absence of renal artery disease were noted. Renal artery percent stenosis METHODS was classified as a minor irregularity (<25% narrow- ing) or 25, 50, 75. 95, or 100% luminal diameter Patient Population narrowing. By convention. an angiographically sig- During a 5-month period, 1 ,302 of 1 .65 1 consecu- nificant lesion was defined as a 50% luminal tive patients undergoing elective diagnostic cardiac diameter narrowing of a major renal artery catheterization at Duke University Medical Center (12,15,16.22-25). Accessory renal arteries with dis- were screened for the presence of renal artery disease ease were felt to be significant if more than one third through the use of abdominal aortography. Patients of the renal mass was estimated to be supplied by not screened were excluded at the discretion of the the vessel. Lesion location was classified as ostial, angiographers. main artery. or branch vessel. Ostial lesions were Before patients had cardiac catheterization. demo- defined as stenotic if the segment of the renal artery graphic data. medical history. physical findings. and lumen immediately contiguous with the aorta was blood chemistries were recorded and entered into a compromised. Lesions of the main segment of the computerized medical information system (19). Pe- renal artery began at least 2 to 3 mm beyond the ripheral vascular disease was defined as a history of ostial segment. Branch lesions were defined as sten- claudication, previous vascular procedure, a history otic lesions originating beyond the first bifurcation of stroke or transient ischemic attack, or physical of the renal artery. The stenotic lesions were desig- evidence of carotid, femoral, or abdominal bruits. nated as atherosclerotic if they did not demonstrate Symptoms of congestive heart failure were recorded a distinctive string-of-beads appearance character- and classified in accordance with the New York Heart istic of fibromuscular dysplasia (26). No complica- Association criteria (20). Hypercholesterolemia was tions related specifically to the aortogram were ob- defined as evidence of a cholesterol level elevated served. Retroperitoneal bleeding (0.002%). laceration above 200 mg/dL. Hypertension was defined as dia- of the femoral artery (0.002%), contrast nephrotox- icity (increase in serum creatinine >0.5 mg/%, 6%; stolic blood pressure >90 mm Hg when subjects were measured as outpatients during the time before >1 mg/%. 1 .4%). and cholesterol embolization in the study group catheterization. Hypertension was also considered (0.00 1 5%) were not increased present if the patient was taking antihypertensive compared with retrospective controls who received cardiac catheterization only. Patients were followed- medications and if it could be confirmed that the Indication for use was hypertension and not angina. up at 24 h and as outpatients. It is reasonable to Blood pressure was measured several times before assume that the risk of renal arteriography is at least as low as combined coronary and renal arteriograpy. and after catheterization but, because of the anxiety and discomfort surrounding the procedure, was not considered as basal blood pressure. Statistical Analysis
Stepwise univariate and mubtivariate logistic Angiography regression was performed in order to identify clinical Coronary angiography was performed via femoral and angiographic variables predictive of significant artery approach by the Judkins technique (2 1 ). The renal artery stenosis. A binary logistic model (27) was presence and severity of coronary atherosclerotic le- used to identify univariate predictors of significant sions were determined in the routine fashion. Coro- renal artery stenosis. The variables that were signif- nary artery lesions graded as >70% narrowing of the icant in the univarlate model were then entered into luminal diameter were classified as significant. After a stepwise logistic regression model to identify the left ventriculography. the pigtail catheter was with- best set of independent predictors of significant renal drawn into the abdominal aorta and positioned a few artery stenosis. From these data, a model was devel- centimeters superior to the renal arteries. Aortogra- oped to predict the probability of significant renal
Journal of the American Society of Nephrology 1609 Renal Artery Stenosis Prevalence at Cardiac Catheterization
artery stenosis in patients undergoing cardiac cath- TABLE 1. Demographic data of the 1.235 patients eterization. with adequate abdominal aortograms
Mean age (yr) 60±11 RESULTS White:Nonwhite 1054: 181 Men: Women 736:499 Of the 1 ,302 studies performed, 67 (5%) were Hypertension 581 (49%) deemed technically inadequate because of either poor Congestive Heart Failure I85 (15%) opacification of the renal vessels or the presence of Peripheral Vascular Disease#{176} 210 ( I7%) overlying mesenteric vessels obscuring the renal Smoking 764 (62%) anatomy. The remaining 1 ,235 studies were consid- Diabetes 226 (18%) ered technically adequate for the evaluation of the 599 (49%) renal artery anatomy and form the basis of this Serum Creatinine (Mmol/L) study. A representative cine angiographic visualiza- Mean (range) 93.7 (17.7-937.0) 208 (17%) tion of renal artery obstruction is shown in Figure 1. >106 Significant CADb The demographic data from the study patients are One Vessel 299 (24%) summarized in Table 1 . The mean age of the group Two Vessel 211 (17%) was 60 ± 1 1 yr. Sixty percent were men. and 85% Three Vessel 266 (22%) were white. Many had risk factors for atherosclero- Left Main 41 (3.3%) sis. About half of the patients had a history of hyper- tension. The serum creatinine ranged from 0.2 to 0 See text for definition. 1 0.6 mg/dL with a mean of 1 .06 mg/dL. Abnormal b CAD, coronary artery disease; see text for definition. lipids were noted in 599 (49%) patients. Congestive heart failure was noted in 185 (15%) patients. The prevalence of renal artery disease in this pop- patients or 1 5.2% of the study group had angiograph- ulation is illustrated in Figure 2. Lesions were desig- ically significant renal artery narrowing observed at nated as being atherosclerotic 97% of the time. All the time of cardiac catheterization. lesions classified as fibromuscular dysplasia ap- More severe stenosis ( 75% luminal diameter nar- peared angiographically insignificant. Bilaterally rowing) was seen unilaterally in 76 (6%) patients and normal renal arteries were identified in 70% of the bilaterally in 1 7 (1 .4%) patients. Eight patients had patients screened. Insignificant renal artery stenosis in essence one functional kidney either because of (<50% luminal narrowing) of at least one renal artery congenital absence, surgical removal, or total occlu- was seen in 1 87 (1 5%) patients. Significant unilateral sion of one renal artery. Of these eight patients, one renal artery stenosis ( 50%luminab narrowing) was had significant disease in the renal artery supplying identified in 1 36 (1 1 %) patients. and 52 (4%) had the solitary kidney. significant bilateral renal artery stenosis. Thus. 188 The overwhelming majority of lesions were located in the ostium or the main segment of the renal artery, with even distribution between these two locations (Figure 3). Of the 253 significant lesions observed in the 1 88 patients, 48% were in the ostium, 49% were in the main segment of the renal artery. and only 3% were beyond the first bifurcation of the renal artery in a branch vessel.
Predictors of Renal Artery Stenosis By univariate logistic regression, 14 variables were analyzed to identify associations that were more com- mon in patients with significant renal artery disease. The predictive clinical variables (shown in descend- ing order according to x2 values) are shown in Table 2. Older age was the most important predictor of significant renal artery stenosis. The mean age of the patients with significant renal artery stenosis was 66 ± 1 0 yr compared with 58 ± 1 1 yr for patients with insigificant or no renal artery disease. Next in order of importance were the evidence of peripheral vascular disease and then congestive heart failure. A Figure 1 . Severe bilateral renal artery stenosis. creatinine of > 106 mol/L (1 .2 mg/dL), cigarette
1610 Volume 2 . Number II . 1992 Harding et al
187 ( 15% ) Insignificant RAS 860 ( 70% ) Normal
136 ( 11 % ) Significant Unilateral RAS
52 ( 4% ) Significant Bilateral RAS
Figure 2. The prevalence of renal artery stenosis as determined by cine abdominal aortography at the time of cardiac catheterization (N = I .235). Insignificant renal artery stenosis is defined as <50% luminal narrowing. Significant renal artery stenosis is defined as 5O% luminal narrowing.
NO. OF variable predictors of renal artery stenosis were: LESIONS older age, the severity of coronary artery disease, a history of congestive heart failure, female gender, 250 and the presence of peripheral vascular disease. From these data, a model was developed to predict 200 the probability of significant renal artery stenosis in patients undergoing cardiac catheterization. As an example, the probability of finding significant renal 150 artery stenosis in a 65-yr-old man with three-vessel coronary artery disease, peripheral vascular disease, 100 and congestive heart failure is 0.43, or 1 0 times greater than the probability of 0.040 for a 55-yr-old 50 man without these associated findings.
DISCUSSION Ostial Main Branch The prevalence of renal artery disease in the gen- Figure 3. Location and distribution of renal artery lesions. eral population is unknown ( 1 7). In most cases, the diagnosis of renovascular disease is established dur- ing the course of evaluation for systemic hyperten- smoking, and female gender were also more com- sion. More recently. the effect of ischemic renal dis- monly seen in those with significant renal artery ease and the robe of revascularization in preserving stenosis. Hypertension, however, by itself, proved renal function have been debated (5,7). Obstructive unhelpful in identifying patients with renal artery renal artery lesions are potentially treatable by sur- stenosis. Of the 581 patients with hypertension, 481 gical or angioplastic techniques (6- 1 1). The presence (83%) patients had insignificant or no renal artery of renal arterial disease may also complicate the stenosis whereas only 1 00 (1 7%) patients had signif- medical management of patients with hypertension icant renal artery stenosis. and/or congestive heart failure (28). Because athero- Table 3 shows the results of the univariate analysis sclerosis is the primary cause of renal arterial ob- of the data obtained at cardiac catheterization. As struction and considering the diffuse nature of ath- the severity of coronary artery disease increased erosclerotic disease, patients with coronary artery (from no significant disease to left main or three- disease would logically seem to be at an increased vessel coronary artery disease). the likelihood of sig- risk for renal artery disease (7), which was confirmed nificant renal artery stenosis increased. A decreasing in this study. Abdominal aortography at the time of ejection fraction was also more common in patients cardiac catheterization offers a safe and effective with significant renal artery stenosis. means for evaluating the renal vascubature in this Multivariable logistic regression of all variables potentially high-risk group. These data suggt st that identified five risk factors predictive of significant screening for this process can be improved by the renal artery stenosis (Table 4). The strongest multi- use of certain predictors of disease.
Journal of the American Society of Nephrology loll Renal Artery Stenosis Prevalence at Cardiac Catheterization ..,. . . . . . . #{149}
TABLE 2. Clinical variables analyzed by univariate logistic regression to identify predictors of significant renal artery stenosis (N= 1,235)
Significant No RAS#{176} Variable RAS x2 P Value N- I 047 -, (N= 188)
MeanAge(yr) 58±11 00±10 60.43b 0.0001 Peripheral Vascular Disease 156 54 20.24 0.0001 Congestive Heart Failure 138 47 10.80 0.0001 Creatinine >106 Mmol/Lc 160 48 9.63 0.00 19 Smoking 664 100 7.00 0.0081 Female 408 91 5.84 0.0156 Hypertension 481 100 3.35 0.0022 White 886 168 2.82 0.0930 Diabetes Mellitus 184 42 2.41 0.1207 History of CADd 494 83 0.59 0.4429 Hyperlipidemia 510 89 0.12 0.7293
C) No or insignificant RAS (renal artery stenosis).
b Analyzed by 10-yr increments.
, One hundred thirty-six (1 1%) patients had missing data.
ci CAD. coronary artery disease.
TABLE 3. Cardiac catheterization-derived variables TABLE 4. Multivariate logistic regression analysis of analyzed by univariate logistic regression to identify both clinically and catheterization-derived predictors of significant renal artery stenosis variables
Variable No RAS#{176}Significa nt RAS x2 P Value . 2 Risk Odds Variable 1 x P Value . Ratio
No. of vessels 5345C 0.0001 with signifi- Age#{176} 0.0529 33.4 0.0001 1.70 cant CADb ExtentofCADb 0.4408 33.4 0.0001 1.55 0 418 39 CHFC 0.6062 8.5 0.0036 1.83 I 267 32 Sex -0.4374 6.1 0.0138 0.65 2 172 39 PVDd 0.4237 4.6 0.0327 1.52 3 189 77 LeftMainDisease 25 16 16.32 0.0001 0 Analyzed by 10-yr increments. Ejection Fraction 55 ± 12 51 ± 13 17.Old 0.0001 b Analyzed by one-vessel disease increments. CAD, coronary artery disease.
C CHF, congestive heart failure. () No or insignificant PAS (renal artery stenosis).
b CAD, coronary artery disease. d PVD, peripheral vascular disease; see text for definition.