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Utility of Captopril Renal Scans for Detecting Renal Artery Stenosis
Stephen J. Huot, MD, PhD;
Joni H. Hansson, MD;
Holly Dey, MD;
John Concato, MD, MPH
Arch Intern Med. 2002;162:1981-1984.
ABSTRACT
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Background Captopril renal scanning (CRS) is commonly recommended as a noninvasive
method for detecting renal artery stenosis (RAS), based on performance characteristics
determined in research settings. Scant data are available, however, regarding
the utility of CRS in clinical practice.
Methods We evaluated the performance characteristics (sensitivity, specificity,
and predictive values) of CRS in a consecutive series of 90 patients who underwent
both CRS and renal arteriography within a 6-month period (January 1, 1991,
through December 31, 1995) at a university hospital.
Results Among 86 eligible patients (and 169 kidneys), the prevalence of RAS
was 43%. The sensitivity of CRS was 74% (95% confidence interval [CI], 62%-83%);
the specificity was 59% (95% CI, 49%-69%); the positive predictive value was
58% (95% CI, 47%-68%); and the negative predictive value was 75% (95% CI,
64%-84%). Also, there was evidence of spectrum bias, because the sensitivity
and specificity (as well as the positive and negative predictive values) were
different for groups with and without vascular disease.
Conclusions The results of CRS were substantially worse in a clinical practice setting
than previously reported in research settings, despite a similar prevalence
of RAS. Captopril renal scanning should not be used as an initial screening
test for diagnosing RAS, even among patients with high clinical likelihood
of disease.
INTRODUCTION
RENOVASCULAR hypertension due to atherosclerotic renal artery stenosis
(RAS) is one of the most common types of secondary hypertension in adults.1-3 The natural history
of RAS is progressive, and treatment options include surgical revascularization
or angioplasty with stenting.4-8
Current guidelines9 recommend using captopril
renal scanning (CRS), duplex Doppler flow studies, or magnetic resonance angiography
as initial noninvasive screening tests9 in
patients who are suspected of having renovascular disease. Although no consensus
exists regarding the single "best" test,1, 10-13
many clinicians rely on CRS as the preferred initial approach because of its
purported role in identifying patients who would benefit (in terms of blood
pressure control) from revascularization.14-17
The proposed rationale for CRS as a diagnostic test for RAS relates
to the physiologic effects of angiotensin II on renal autoregulation of glomerular
filtration rate (GFR), involving differential effects on afferent and efferent
arteriolar tone5, 10 as well as
constriction of mesangial cells. Patients with afferent RAS are dependent
on regulation of efferent arteriolar tone to maintain GFR. Angiotensin-converting
enzyme inhibitors interfere with this angiotensin II–mediated vasoconstriction,
resulting in a decrease in GFR. Accordingly, patients who demonstrate a change
in GFR on their renal scan after administration of the angiotensin-converting
enzyme inhibitor captopril are thought to represent cases in which the RAS
is more likely to be hemodynamically significant.14-17
Captopril renal scanning has been reported14-17
to be highly sensitive (91%-94%) and highly specific (84%-95%) in detecting
RAS, although some investigations have demonstrated less impressive results.18-19 Informal observations from the Yale
Hypertension and Referral Service suggested that the test might not perform
as accurately in clinical practice as had been reported in an earlier study14 at the same institution. We therefore conducted the
current study to determine how well CRS performed in actual clinical practice.
SUBJECTS AND METHODS
All patients at Yale–New Haven Hospital, New Haven, Conn, who
underwent CRS and renal arteriography within a 6-month period (January 1,
1991, through December 31, 1995), were included. Patients were ineligible
if they had undergone a revascularization procedure prior to the study period.
If patients underwent subsequent CRS or renal arteriography more than once
during the study period, only results from the first tests were used in data
analysis.
Medical records, CRS reports and films, and arteriography reports were
reviewed for all eligible patients. The CRS films were independently reviewed
by a nuclear radiologist (H.D.) who was blinded to patient information, prior
readings, and results of artiography. Arteriograms were reviewed if the original
report did not characterize the percentage of stenosis for each renal artery;
interpretation was performed by a vascular radiologist who was blinded to
the prior reading and CRS results.
Using the same institutional protocol as that of an earlier study14 for performing and reporting of CRS, positive scintigraphic
evidence of RAS required a time-to-peak activity of more than 11 minutes on
either the precaptopril or the postcaptopril scan or a calculated glomerular
filtration ratio of greater than 1.5 between the 2 kidneys on the postcaptopril
scan.
Criterion of positive results of renal arteriography in patients with
atherosclerotic disease included stenosis of more than 75% or stenosis of
more than 50% with poststenotic dilitation. Fibromuscular lesions were graded
as mild, moderate, or severe, and moderate or severe lesions were considered
positive for hemodynamically significant RAS, according to criteria previously
applied at our institution.14
Data abstracted from the medical records included age at time of study,
sex, ethnicity, history of diabetes mellitus, history of elevated total cholesterol
levels or of cholesterol-lowering medication use, physical examination findings
of vascular disease, history of vascular disease, history of tobacco use,
and most recent serum creatinine values (in relation to the date of the CRS).
Physical examination findings of vascular disease required the absence of
a femoral pulse or the presence of a femoral, carotid, flank, or abdominal
bruit. History of vascular disease was defined as documented myocardial infarction,
cerebrovascular disease, or peripheral vascular disease.
Data were analyzed for each kidney and each patient as the unit of observation.
Sensitivity, specificity, and positive and negative predictive values (and
corresponding 95% confidence intervals [CIs]) were calculated for all patients
combined, as well as separately for patients with and without evidence of
vascular disease. The results of arteriography were considered the "gold standard"
measurements.
RESULTS
Ninety patients were identified from hospital databases as having undergone
both CRS and renal arteriography during the study period. Among these patients,
1 medical record was not located; the original captopril scan was missing
for another patient; and 2 patients underwent subsequent studies. Accordingly,
a total of 86 patients (96%), representing 169 kidneys, were included in the
analysis (3 of the 86 had previously undergone a nephrectomy).
Sixty patients (70%) had evidence of vascular disease at the time of
study, and 26 did not. Patients with vascular disease were older, and more
likely to be white, than patients without vascular disease (data not shown).
Table 1 shows the prevalence,
sensitivity, specificity, and positive and negative predictive values of CRS
and renal arteriography for all patients.No significant difference was found
in the mean interval of time between CRS and renal arteriography among patients
whose scanning results were false-negative and true-positive: 35.5 ±
54.8 (mean ± SD) days vs 47.6 ± 53.5 days, respectively.
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Table 1. Sensitivity, Specificity, and Predictive Values of Captopril
Renal Scans for All Patients Combined (n = 169 Kidneys)
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Table 2 shows the prevalence,
sensitivity, specificity, and positive and negative predictive values of CRS
and renal arteriography for patients who had evidence of vascular disease
at the time of the study. Table 3
shows the prevalence, sensitivity, specificity, and positive and negative
predictive values of CRS and renal arteriography for patients who did not
have evidence of vascular disease at the time of the study.
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Table 2. Performance Characteristics of Captopril Renal Scans Among
Patients With Vascular Disease (n = 116 Kidneys)
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Table 3. Performance Characteristics of Captopril Renal Scans Among
Patients Without Vascular Disease (n = 53 Kidneys)
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Although complete follow-up data on all patients were not available
(and were not a major focus of the study), the medical records for a subset
of patients did document whether angioplasty or surgical revascularization
was performed in patients with arteriogram-documented RAS. Of the patients
with false-negative CRS results (15 of 19 kidneys), 14 received revascularization.
Of the patients with true-positive CRS results, 34 received revascularization
(40 of 54 kidneys). Follow-up data on blood pressure were not available.
COMMENT
Data from the current investigation demonstrate that the diagnostic
test characteristics of CRS in a practice setting at a large referral center
are not as good as reported14-15
for patients who were enrolled in research studies at the same institution.
For example, a previous publication14 reported
91% sensitivity and 94% specificity among 94 patients. In that study, 44 patients
(47%) had RAS, and the positive predictive value (93%) and the negative predictive
value (92%) were quite impressive. The current study found a similar prevalence
of disease—43% among 86 patients—but the lower sensitivity (79%)
and specificity (59%) were associated with more modest positive (58%) and
negative (75%) predictive values.
One factor contributing to the observed differences in results between
the studies could be that patients in practice are less likely to be monitored
as closely as patients in research studies; therefore, patient preparation
for CRS might not be as rigorous. Differences in conducting the test could
also have a significant effect, particularly with regard to use of "contraindicated"
medications (eg, angiotensin-converting enzyme inhibitors and angiotensin
II receptor antagonists), as well as attention to volume status at the time
of study.
Progression of underlying atherosclerosis during the interval between
CRS and renal arteriography could contribute to the poor CRS performance characteristics
observed in our study, but only if there was greater progression of atherosclerosis
during this interval among the group of patients with false-negative results
on CRS than among the group of patients with true-positive results. Although
we do not have serial arteriograms to compare, the mean number of days between
CRS and renal arteriography was, on average, shorter in the group with false-negative
results on CRS compared with the group with true-positive results: 38 days
vs 48 days, respectively, making this explanation unlikely.
The group of patients with vascular disease (Table 2) most closely resembles the subjects in the earlier study,14 yet sensitivity, specificity, and predictive values
for CRS were substantially lower in the current population. Also, these diagnostic
test characteristics differed for patients with and without vascular disease.
This observation is consistent with spectrum bias: a problem that occurs when
a diagnostic test has different sensitivity or specificity in patients with
different clinical manifestations of disease.20
The most striking finding for clinical practice involves the contrast of positive
predictive values: 70% (95% CI, 57%-81%) for subjects with vascular disease,
and 31% (95% CI, 16%-51%) for subjects without vascular disease. These discordant
values, and nonoverlapping CIs, suggest that CRS performs differently in the
2 populations.
The low specificity and poor positive predictive value among the group
of patients with no evidence of vascular disease and a prevalence of RAS of
17% confirmed an a priori clinical impression regarding unnecessary angiograms
associated with CRS. Although the sensitivity and negative predictive value
of CRS in this group were both 100%, more patients had a false-positive test
result (n = 20) than had a true-positive test result (n = 9); consequently,
20 patients who did not have RAS were exposed to the risks of arteriography.
The finding that most patients with positive results on arteriography
received revascularization, regardless of the CRS result, suggests that CRS
was not being used to determine whether to intervene surgically. Other factors,
including clinical judgment, patient preference, and renal function, are certainly
involved. Unfortunately, we did not have data to determine the predictive
value of CRS on blood pressure outcomes for the patients who had undergone
revascularization.
The original role of CRS9, 14-16
was as a noninvasive test for detecting RAS among patients with a high clinical
likelihood of the disease. These patients were judged most likely to benefit
from blood pressure control after a revascularization procedure, such as bypass
surgery or renal angioplasty. Our data from a practice setting suggest that
CRS is a poor test to "rule in" patients with a low clinical likelihood of
disease and does not perform as well as reported among patients with a high
clinical likelihood of RAS.
We suggest that CRS not be recommended as an initial screening test
for diagnosing RAS and renovascular hypertension, even among patients with
a high clinical likelihood of disease. Rather, the appropriate use of CRS
may involve patients who have known RAS (ie, positive results on magnetic
resonance angiography or renal arteriography), and for whom the physician
is seeking additional information to support a decision about revascularization
to improve blood pressure control. Even when CRS is used for this purpose,
however, strict adherence to the test protocol (including the discontinuation
of selected medications and maintaining proper volume status) is essential.
AUTHOR INFORMATION
Accepted for publication February 6, 2002.
Dr Concato is supported by a Career Development Award from the Department
of Veterans Affairs Health Services Research and Development Service, Washington,
DC.
Corresponding author and reprints: Stephen J. Huot, MD, PhD, Department
of Internal Medicine, Yale University, PO Box 208033, New Haven, CT 05620-8033
(e-mail: stephen.huot{at}yale.edu).
From the Departments of Internal Medicine (Drs Huot, Hansson, and Concato)
and Diagnostic Imaging (Dr Dey), the Section of Nephrology (Dr Huot), and
the Clinical Epidemiology Unit (Dr Concato), West Haven Veterans Affairs Medical
Center, West Haven, Conn.
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