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Society of Nuclear Medicine

Procedure Guideline for
Diagnosis of Renovascular Hypertension
version 3.0, approved June 20, 2003

Authors: Andrew T. Taylor, Jr., MD (Emory University School of Medicine, Atlanta, GA); M. Donald Blaufox, MD, PhD
(Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY); Eva V. Dubovsky, MD, PhD (Univer-
sity of Alabama Hospital, Birmingham, AL); Eugene J. Fine, MD (Jacobi Medical Center, Bronx, NY); Enza Fommei, MD
(Pisa, Italy); Göran Granerus, MD, PhD (Linköping, Sweden); Daniel Kahn, MD (VA Medical Center and University of
Iowa College of Medicine, Iowa City, IA); Joseph V. Nally, Jr., MD (Cleveland Clinic, Cleveland, OH); Hong-Yoe Oei, MD,
PhD (Rotterdam, The Netherlands); Alain Prigent, MD (Paris, France); and George N. Sfakianakis, MD, PhD (University
of Miami School of Medicine, Miami, FL); and S. Ted Treves, MD (Harvard University, Boston, MA)

I. Purpose to a subspecialty center because of refractory hyper-
tension. Clinical features should indicate which pa-
The purpose of this guideline is to assist nuclear
tients have moderate or high risk of renovascular
medicine practitioners in recommending, performing,
hypertension. Clues include abrupt or severe hyper-
interpreting, and reporting the results of renal proce-
tension, hypertension resistant to 3-drug therapy,
dures for diagnosis of renovascular hypertension.
bruits in the abdomen or flank, unexplained
azotemia or recurrent pulmonary edema in an el-
II. Background Information and Definitions derly hypertensive patient, or worsening renal func-
tion during therapy with angiotensin-converting
Renovascular disease includes renal artery stenosis,
enzyme inhibitors (ACEIs). ACEI renography is de-
renovascular hypertension, and azotemic renovas-
signed to be a test for renovascular hypertension, not
cular disease (ischemic nephropathy). It is important
for renal artery stenosis. The optimal reference test
to distinguish between renovascular hypertension
or “gold standard” in future studies should be the
and renal artery stenosis. Stenosis of the renal artery
outcome—the response to successful revasculariza-
is common in nonhypertensive elderly persons and
tion—not angiographic evidence of renal artery
is an associated but noncausative finding in a num-
stenosis.
ber of hypertensive patients. Renovascular hyper-
tension is defined as an elevated blood pressure
caused by renal hypoperfusion, usually resulting III. Common Indications
from anatomic stenosis of the renal artery and acti-
The test is most cost effective if used primarily in pa-
vation of the renin–angiotensin system. Azotemic
tients who have a moderate-to-high risk of renovas-
renovascular disease refers to renal functional im-
cular hypertension. Clinical features associated with
pairment associated with renal atrophy, intrarenal
a moderate-to-high risk of renovascular hyperten-
vascular lesions, and interstitial nephritis and fibro-
sion have been published and include:
sis in the presence of severe atherosclerotic renal
artery stenosis. Causes of renovascular hypertension •Abrupt onset or severe hypertension;
in neonates and infants include renal artery throm- •Hypertension resistant to 3-drug therapy in a
bosis after umbilical artery catheterization and compliant patient;
coarctation of the aorta. The goal of a screening test •Abdominal or flank bruits;
for renovascular hypertension in adults is to detect •Unexplained azotemia in an elderly hyperten-
those patients who have renal artery stenosis as the sive patient;
cause of hypertension and to predict curability or •Worsening renal function during antihyperten-
amelioration of hypertension after intervention. sive therapy, especially with ACEIs or an-
Renovascular hypertension is estimated to affect giotensin II receptor blockers;
fewer than 1%–3% of the unselected hypertensive •Grade 3 or 4 hypertensive retinopathy;
population and up to 15%–30% of patients referred •Occlusive disease in other vascular beds;
98 • RENOVASCULAR HYPERTENSION

•Onset of hypertension under age 30 y or over d, depending on the ACEI. Although no avail-
age 55 y; able data evaluates the effect of angiotensin II re-
•Recurrent pulmonary edema in an elderly hy- ceptor blockers on the sensitivity of ACEI renog-
pertensive patient; raphy, angiotensin II receptor blockers such as
•Hypertension in infants with an umbilical artery losartan may have an effect comparable to ACE
catheter; and/or inhibitors, and these drugs also should be dis-
•Hypertension in children. continued before ACEI renography.
Some patients will present for the test with-
out discontinuing therapeutic ACEIs or an-
IV. Procedure
giotensin II receptor blocking agents. In these cir-
A. Patient Preparation cumstances, it is acceptable to proceed with the
Patients need to be well hydrated before testing. procedure with the understanding that there
If an oral ACEI is used, patients should drink may be a slight loss in sensitivity. When pro-
only water and should not eat a solid meal ceeding with the study without discontinuing
within 4 h of the study. A moderate hydration chronic ACEIs, most practitioners give the test
protocol will likely lead to greater accuracy in ACEI (captopril or enalaprilat) to make sure the
the interpretation of the images and quantitative patient is adequately inhibited, in case the pa-
data. Dehydration and overhydration should be tient has not taken his or her prescribed medica-
avoided. One suggested protocol is 7 mL wa- tion. The chances of a hypotensive response are
ter/kg body weight ingested at a minimum of 30 low, because the patient has shown that he or she
and preferably 60 min before the study. Hydra- tolerates an ACEI without symptomatic hy-
tion should continue between studies when 2 potension.
studies are performed on the same day. An in- Chronic administration of diuretics may lead
travenous line should be placed in high-risk pa- to volume depletion resulting in a decrease in
tients and in those receiving intravenous specificity. Furthermore, the volume depletion
enalaprilat so that normal saline can be promptly associated with chronic diuretic administration
infused if the patients become hypotensive (see may potentiate the effects of ACE inhibition,
IV.C. Precautions). leading to an increased risk of symptomatic hy-
The sensitivity of ACEI renography may be potension. If possible, chronic diuretic adminis-
reduced in patients receiving ACEIs. For this rea- tration should be stopped several days before the
son, short-acting ACEIs, such as captopril, study. The effect of other antihypertensive med-
should be withheld for 3 d before the study. ications upon ACEI renography is not com-
Longer acting ACEIs should be withheld for 5–7 pletely understood but appears small, although

Radiation Dosimetry for Adults
(Normal Renal Function)

Radiopharmaceutical Administered Organ Receiving the Effective
Activity Largest Radiation Dose* Dose Equivalent
MBq mGy/MBq mSv/MBq
(mCi) (rad/mCi) (rem/mCi)

37–370 Bladder wall 0.0054
99m
Tc-DTPA (1–10) 0.051 (0.020)
(0.19)

37–370 Bladder wall 0.0041
99m
Tc-MAG3 (1–10) 0.046 (0.016)
(0.17)

*
Dosimetry calculations assume the patient voids at 30 min postinjection and every 4 h thereafter (Stabin M,
Taylor A. Jr., Eshima D, Wooten W. Radiation dosimetry for technetium-99m-MAG3, technetium-99m-DTPA,
and iodine-131-OIH based on human biodistribution studies. J Nucl Med. 1992;33:33–40.) DTPA = diethylen-
etriaminepentaacetic acid; MAG3 = mercaptoacetyltriglycine.
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL AUGUST 2003 • 99

Radiation Dosimetry in Children
(5 Years Old; Normal Renal Function)

Radiopharmaceutical Activity Organ Receiving the Effective
MBq Largest Radiation Dose* Dose Equivalent
(mCi/kg) mSv/MBq mSv /MBq
(rem/mCi) (rem /mCi)
3.7 Bladder wall 0.012
99m
Tc-DTPA (0.1) 0.086 (0.044)
(0.32)
3.7 Bladder wall 0.015
99m
Tc-MAG3 (0.1) 0.18 (0.056)
(0.67)
*
Treves ST, ed. Pediatric Nuclear Medicine. 2nd ed. New York, NY: Springer-Verlag; 1995:567–569. DTPA = di-
ethylenetriaminepentaacetic acid; MAG3 = mercaptoacetyltriglycine.

bilateral symmetrical abnormalities have been should be measured before the exam, at the con-
reported in patients taking calcium channel clusion of the test, and before patient discharge.
blockers. For this reason, it is reasonable to dis- For patients receiving enalaprilat, blood pres-
continue calcium channel blockers when there is sure also should be measured every 5 min dur-
no contraindication. If hypertension is severe, it ing the exam.
is not necessary to discontinue all antihyperten- C. Precautions
sive medications before the procedure. If the pa- ACEIs can cause significant hypotension. There-
tient’s blood pressure returns to very high pre- fore, blood pressure and pulse should be moni-
treatment levels, the renin–angiotensin system tored and recorded before ACEI and radiophar-
may not be activated and there may be a loss in maceutical administration, every 5–15 min
test sensitivity. thereafter, and at the end of the study. An intra-
B. Information Pertinent to Performing the Proce- venous line should be established in high-risk
dure patients (history of carotid disease, stroke, tran-
A relevant history should be obtained and sient ischemic attack, angina, recent myocardial
should include any history of cardiovascular or infarction, and severe salt depletion after diuret-
cerebrovascular disease, medications, when di- ics) and in patients who receive intravenous
uretics or ACEIs were stopped, serum creatinine, enalaprilat or who are taking diuretics. A patient
and the efficacy of blood pressure control. A sit- should not be sent home unless the standing
ting and standing blood pressure and heart rate mean blood pressure is at least 70% of baseline

Figure 1. Patterns of renographic curves from
normal to blood background type curve. 0 = nor-
mal; 1 = minor abnormalities, but with Tmax > 5
min and a 20-min/max cortical ratio > 0.3; 2 = a
marked delay in excretion rate with preserved
washout phase; 3 = delayed excretion rate with-
out washout phase (accumulation curve); 4 = re-
nal failure pattern with measurable kidney up-
take; 5 =renal failure pattern without measurable
kidney uptake (blood background type curve).
(Adapted from Fommei E, Ghione S, Hilson AJW,
et al. Captopril radionuclide test in renovascular
hypertension: a European multicentre study. Eur
J Nucl Med. 1993;20:625–644.)
100 • RENOVASCULAR HYPERTENSION

and the patient is asymptomatic when standing. view. If only 2 organs can be imaged, the kid-
D. Radiopharmaceuticals ney and bladder should be visualized, unless
The optimal radiopharmaceutical in individuals a time–activity curve over the heart is re-
with normal renal function remains to be deter- quired for data processing. For 99mTc agents
mined. However, 99mTc-mercaptoacetyltriglycine and 123I-orthoiodohippurate (OIH), a low-en-
(MAG-3) and 99mTc-diethylenetriaminepen- ergy, high-resolution, all-purpose collimator
taacetic acid (DTPA) are most commonly used. should be used. Matrix resolution is prefer-
Because of its higher extraction, 99mTc-MAG3 is ably 128 × 128, although 64 × 64 is acceptable.
preferred over 99mTc-DTPA in patients with ele- When a dynamic flow study is desired, higher
vated creatinine. 123I-hippuran is an acceptable al- activities should be injected. The time per
ternative in countries where it is available. frame should be 1–3 s for the first 60 s and
E. Image Acquisition 10–30 s/frame for the remainder of the study.
1. Study protocol The total acquisition time should be 20–30
Both 1- and 2-d protocols are acceptable. If the min. Images should be displayed at 1-, 2-, or 3-
2-d protocol is to be performed, ACEI renog- min intervals. Patients should void before be-
raphy should be performed on the first day ginning the study, and a postvoid image is
and the requesting physician and the patient recommended.
must be aware that the patient may need to re- F. Interventions
turn on a second day for the baseline study to Although captopril has been the most widely
maximize the specificity of the test. If the used ACEI, captopril and enalaprilat are both ac-
ACEI renogram is normal (grade 0 renogram ceptable for ACEI renography. The recom-
curve; see Fig. 1), the chance that the patient mended dose of captopril is 25–50 mg by mouth.
has renovascular hypertension is low, and Crushing the tablets and dissolving them in
there is no need to have the patient return on 150–250 mL water may enhance absorption. Un-
the second day for a baseline study. For this less the patient has delayed gastric emptying or
reason, some centers begin with the 2-d pro- poor absorption from the gastrointestinal tract,
tocol if there is a relatively low likelihood of 25 mg are sufficient. Patients should not eat a
renovascular disease, because the ACEI solid meal within 4 h of the study, because food
renogram is likely to be normal. in the gastrointestinal tract decreases absorption
The 1-d protocol requires that the patient of captopril. The radiopharmaceutical should be
remain in the department for a longer period administered 60 min after captopril administra-
of time, but the entire study is completed in 1 tion, because peak blood levels occur approxi-
d. With the 1-d protocol, baseline renography mately 60 min after oral ingestion and then begin
should be performed first with approximately to decline. Enalaprilat can also be used. The rec-
40 MBq (~1 mCi) of 99mTc-DTPA or 99mTc- ommended dose is 40 µg/kg administered intra-
MAG3. The administered activity for the venously over 3–5 min with a maximum admin-
ACEI renogram should be 200–400 MBq istered dose of 2.5 mg. Radiopharmaceutical
(~5–10 mCi) to overwhelm any residual administration should be delayed at least 15 min
counts from the baseline study. Sufficient after enalaprilat administration. The procedure
time should elapse between the 2 studies to time is slightly shorter than that with captopril,
avoid problems in interpretation of the ACEI and potential problems with gastrointestinal ab-
study that might result from residual activity sorption are avoided. An intravenous line is rec-
from the baseline study. The time required ommended, because enalaprilat may be associ-
will depend on the radiopharmaceutical, the ated with hypotension (see next paragraph).
administered dose for the baseline and ACEI Option: Administration of furosemide with
studies, and method of data processing. When captopril or enalaprilat is not considered to be an
40 MBq (~1 mCi) are administered for the essential component of ACEI renography. Be-
baseline study, the ACEI study can begin as cause furosemide is a loop diuretic, it can wash
soon as the baseline study is concluded. the radiopharmaceutical out of the distal
2. Instrumentation, positioning, and timing of nephron, calyces, and pelvis and thereby im-
images prove detection of cortical retention of radiotrac-
The study should be acquired with the ers, especially tubular agents, such as 99mTc-
gamma camera facing the lower back of the MAG3 and 123I-OIH, and potentially increase the
supine patient. A large-field-of-view camera sensitivity and specificity of the test. One ap-
is preferred, so that the heart, kidneys, and proach is to administer 20 mg furosemide at the
bladder can all be included in the field of beginning of the baseline study simultaneously
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL AUGUST 2003 • 101

with 99mTc-MAG3 administration and a second sion. Bilateral symmetrical changes after ACE in-
dose of 20 mg furosemide with 99mTc-MAG3 at hibition usually do not represent renovascular
the beginning of the ACE inhibition study. hypertension and may be associated with hy-
Furosemide can cause volume depletion and in- potension, salt depletion, the use of calcium
crease the risk of hypotension. If furosemide is channel blockers, and/or a low urine flow rate.
used, an intravenous line and normal saline ad- Criteria associated with renovascular hyperten-
ministration are recommended. Many experi- sion include worsening of the renogram curve,
enced nuclear medicine physicians believe that reduction in relative uptake, prolongation of the
good hydration and attention to parenchymal re- renal and parenchymal transit time, an increase
tention are sufficient. in the 20- or 30-min/peak ratio, and prolonga-
G. Processing tion of the time to maximum activity. A small,
Background subtraction is recommended using poorly functioning kidney (<30% uptake, abnor-
either a ring, elliptical, or perirenal region of in- mal renogram) that shows no change after ACEI
terest (ROI). The 1998 Radionuclides in renography represents an intermediate probabil-
Nephrourology consensus committee suggested ity for renovascular hypertension.
that the renal uptake of 99mTc-MAG3, 123I-OIH, Specific interpretive criteria for 99mTc-
and 99mTc-DTPA be measured at 1–2- or 1–2.5- MAG3 and 123I-OIH. Unilateral parenchymal re-
min intervals after injection of the radiopharma- tention after ACEI is the most important crite-
ceutical, using whole-kidney ROIs. In an ex- rion for 99mTc-MAG3 and 123I-OIH. In patients
tremely well-hydrated patient, some of the tracer with normal renal function and in the absence of
may leave the renal ROI after 2.5 min in 1 or both a unilateral small kidney, this finding represents
kidneys and could conceivably lead to an incor- a high probability (>90%) for renovascular hy-
rect estimate of relative function if relative func- pertension. This can be measured by a change in
tion is measured at 2–3 min. In addition to the renogram grade (see Fig. 1), prolongation of
whole-kidney renogram curves, it is often help- the transit time, and/or, for parenchymal ROIs,
ful to generate renogram curves from ROIs that an increase in the 20- or 30-min/peak ratio of
are selectively assigned to the renal parenchyma 0.15 or greater from the baseline study. It can
(cortical ROI). Exclusion of the pelvis and calyces also be detected as a delay in the excretion of the
is important if there is retention of activity in tracer into the renal pelvis by 2 min after ACEI or
these structures. The time to maximum counts an increase in the Tmax of at least 2–3 min or 40%.
(Tmax) should be determined. A 20-min/peak An increase in Tmax from 5–8 min is much more
min (20 min/maximum) count ratio should be significant than a change from 17–20 min. A de-
calculated for 99mTc-MAG3 and 123I-OIH. A 30- crease in relative uptake of 99mTc-MAG3 or 123I-
min/peak count ratio is equally acceptable. Sim- OIH ≥ 10% (relative uptake decreasing, for ex-
ilar ratios for 99mTc-DTPA may also be helpful. ample, from 50% to 40%) after ACEI is
Option: Some centers measure the renal uncommon, but, when present, represents a high
parenchymal transit time using a parenchymal probability for renovascular hypertension. Fi-
ROI if the software algorithm is available and nally, it is important to distinguish parenchymal
use an ACEI-induced prolongation of the transit (significant) from pelvic (insignificant) retention.
time to detect renovascular hypertension. This Cortical ROIs often are used to evaluate
approach has not been standardized. parenchymal retention, but cortical renogram
H. Interpretation Criteria curves may be noisy when a low dose of 99mTc-
The most specific diagnostic criterion for reno- MAG3 is administered for a baseline exam and
vascular hypertension is an ACEI-induced renal function is poor. In this setting, the whole-
change in the renogram. In patients with normal kidney renogram will provide a better index of
or minimally reduced renal function (creatinine parenchymal function if there is no tracer reten-
< 1.7 mg/dL), ACEI renography has a sensitivity tion in the renal pelvis or calyces.
and specificity of about 90% for diagnosis of ren- Specific interpretive criteria for 99mTc-
ovascular hypertension. In azotemic patients, the DTPA. Reduction in relative uptake >10% after
sensitivity and specificity are reduced. Most im- ACEI indicates a high probability for renovascu-
portant, ACEI-induced renographic findings of lar hypertension. Five to nine percent is consid-
renovascular hypertension indicate a high prob- ered to be an intermediate response, although a
ability that the hypertension will be cured or im- recent study performed under carefully con-
proved after revascularization. trolled conditions suggests that smaller changes
A normal ACEI renogram indicates a low may be significant. High probability is also asso-
probability (<10%) of renovascular hyperten- ciated with a >10% decrease in calculated
102 • RENOVASCULAR HYPERTENSION

glomerular filtration rate (GFR) of the ipsilateral tention is likely to be related to the patient’s state
kidney after ACEI. Marked unilateral parenchy- of hydration but will result in an abnormal
mal retention after ACEI compared with the whole-kidney renogram curve, which may be in-
baseline study also represents a high probability correctly interpreted as representing renovascu-
for renovascular hypertension. lar hypertension. Dehydration and hypotension
I. Reporting may lead to bilateral parenchymal retention and
The post-test probability for disease cannot be renogram curve abnormalities.
determined solely by the results of the test. The
test results must be combined with the pretest
V. Issues Requiring Further Clarification
probability. For this discussion, a pretest proba-
bility of 10%–30% is assumed for the moderate- A. A recent prospective investigation compared si-
to-high-risk patients in whom ACEI renography multaneous 123I-OIH and 99mTc-DTPA captopril
should be performed. When this test is per- renography with the results of angiography (not
formed in lower risk patients, the post-test prob- revascularization). This study included a group
ability will be smaller than the numbers cited of patients with a high prevalence of renal dys-
here. Test results should be interpreted as con- function. In subjects with GFR <50 mL/min,
sistent with high, low, or intermediate probabil- only 15%–20% of test results could be classified
ity of disease. as high probability for renovascular hyperten-
Low probability. Normal findings on ACEI sion, whereas 80%–85% fell into the intermediate
renography indicate a low probability (<10%) for probability category. Among 30 individuals with
renovascular hypertension. Abnormal baseline high probability captopril renograms (all “cor-
findings that improve after ACEI also indicate rect” compared with angiography), the mean
low probability for renovascular hypertension. serum creatinine concentration was 1.2 ± 0.4
Intermediate probability. Patients with an in- mg/dL. Among 30 subjects with either incorrect
termediate probability of disease have abnormal results (7 false-negatives and 2 false-positives) or
baseline findings, but the renogram is un- intermediate probability results (n = 21), the
changed after ACEI. This group often includes mean serum creatinine concentration was 2.0 ±
patients with ischemic nephropathy involving 1 1.2 mg/dL. The false-negative studies may have
or both kidneys. The sensitivity of abnormal occurred because hypertensive patients with
baseline findings that are unchanged after ACEI azotemic renovascular disease may no longer
is quite high (>90%), but the specificity is poor, have a renin-dependent hypertension or because
probably in the range of 50%–75%, depending on renal artery stenosis may not have been the cause
the pretest probability of disease and the coexis- of the hypertension.
tence and severity of renal dysfunction Future studies need to define patient sub-
High probability. The probability is consid- groups and the results of ACEI in these sub-
ered high (>90%) when marked change of the groups (e.g., azotemic versus nonazotemic pa-
renogram curve occurs after ACEI, compared tients; results in patients taking diuretics, beta
with baseline findings. blockers, calcium channel blockers, angiotensin
J. Quality Control II receptor blockers, and ACEIs versus patients
Gamma camera and image display are described not taking these medications; results in patients
in the Society of Nuclear Medicine Procedure with normal baseline studies versus patients
Guideline for General Imaging. Images should with abnormal baseline studies as often ob-
be reviewed in a dynamic format to evaluate for served in azotemic renovascular disease; better
presence of patient motion. An image should be characterization of the effects of salt loading and
obtained over the injection site to exclude infil- the state of hydration; and additional evaluation
tration, because infiltration of the injected dose of the role of aspirin-enhanced renography and
can alter the shape of the renogram curve and in- exercise renography to detect renovascular hy-
terfere with quantitative measures of renal func- pertension).
tion (GFR, effective renal plasma flow, 99mTc- B. Patients with azotemia tend to have a large per-
MAG3 clearance). centage of intermediate probability (abnormal
K. Sources of Error but nondiagnostic) results. In this subset, a posi-
Sources of error include ingestion of food tive captopril test (stimulated plasma renin as-
within 4 h of administering captopril, infiltra- say) may improve the true-positive rate without
tion, pelvic retention, dehydration, hypotension, introducing false-positive results.
and a full bladder impairing drainage. Pelvic re-
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL AUGUST 2003 • 103

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VII. Disclaimer
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stenosis. Eur J Nucl Med. 2002: 29:312–318. The Society of Nuclear Medicine has written and ap-
Ludwig V, Martin WH, Delbeke D. Calcium channel proved guidelines to promote the cost-effective use of
blockers: a potential cause of false-positive captopril high-quality nuclear medicine procedures. These
renography. Clin Nucl Med. 2003: 28:108–112. generic recommendations cannot be applied to all pa-
104 • RENOVASCULAR HYPERTENSION

tients in all practice settings. The guidelines should not population. In addition, the resources available to care
be deemed inclusive of all proper procedures or exclu- for patients may vary greatly from one medical facility
sive of other procedures reasonably directed to obtain- to another. For these reasons, guidelines cannot be
ing the same results. The spectrum of patients seen in a rigidly applied.
specialized practice setting may be quite different from Advances in medicine occur at a rapid rate. The date
the spectrum of patients seen in a more general practice of a guideline should always be considered in deter-
setting. The appropriateness of a procedure will de- mining its current applicability.
pend in part on the prevalence of disease in the patient