Evaluation of Renovascular Hypertension

Indication Overview

Cause of high blood pressure is unknown in about 90% of patients with hypertension (i.e., idiopathic hypertension). In approximately 10% of cases, a cause such as renal hypertension can be identified and, in many cases, a specific treatment may be available. Renal hypertension refers to high blood pressure related to renal artery stenosis (RAS). RAS is the narrowing of one or more renal arteries which supply blood to the kidneys. When the renal arteries are narrowed, the kidneys receive less blood flow and respond as though an individuals' blood pressure is too low.1 Hormones are released which cause blood vessels to constrict and the body to retain sodium and water. The constriction of blood vessels and the retention of water lead to hypertension (high blood pressure). RAS is usually caused by hardening of the renal arteries due to plaque build-up from cholesterol (atherosclerosis).2 Another cause of renal artery stenosis is fibromuscular dysplasia.

There are a number of clinical factors that can lead to suspicion of renal hypertension. These include hypertension that remains uncontrolled following the use of three or more hypertensive medications, sudden onset or sudden worsening of uncontrolled hypertension, malignant hypertension, and unexplained azotemia (higher than normal levels of urea or other nitrogen compounds in the blood). It is important to properly diagnose renal hypertension in order for treatment to be initiated.3 Treatment for renal hypertension includes pharmaceutical therapy, angioplasty of the narrowed renal arteries, with or without stent, and surgical revision of renal artery stenosis.4

Population: Patients with suspected renal hypertension.

Intervention: Renal scintigraphy.

Renal scintigraphy refers to nuclear medicine imaging of the kidneys. For the diagnosis of renal hypertension, renal scintigraphy is augmented by the use of an angiotensin-converting enzyme (ACE) inhibitor, usually captopril. The following illustrates why we use ACE inhibitors in renovascular hypertension renal scintigraphy. When blood flow to the kidneys is reduced due to renal artery stenosis, the kidney releases renin, a hormone responsible for the activation of ACE, which converts angiotensin I to angiotensin II. Angiotensin II promotes increased blood pressure in a number of ways including: increased water retention (i.e., increased pituitary antidiuretic hormone secretion); increased sodium retention (i.e., increased adrenal aldosterone secretion); and, widespread vasoconstriction (i.e., specifically arteriolar).

In captopril renal scintigraphy, patients are administered the ACE inhibitor prior to being injected with a radiopharmaceutical. Radiopharmaceuticals used in renal captopril scintigraphy include technetium-99m-labelled-diethylenetriamine pentaacetic acid (99mTc-DTPA), technetium-99m-labelled mercaptoacetyl trigylcine (99mTc-MAG3) and, historically, 123I-orthoiodohippurate (123I-OIH).5 Captopril inhibits the conversion of angiotensin I to angiotensin II and therefore causes blood vessels to become less constricted, including those vessels in the kidneys which, in the presence of RAS, constrict to maintain adequate renal blood flow and function. In patients with RAS, ACE inhibitors cause a temporary change in renal function2,6 including decreased glomerular filtration and maintained effective renal plasma flow (ERPF). These changes in renal function can be measured over time based on the uptake pattern of the injected radiopharmaceutical in the kidneys.

Uptake of the radiopharmaceutical is measured using multiple images taken with a gamma camera over time. Results from captopril renal scintigraphy are compared to results from a baseline renal scintigraphy taken without captopril. Compared to baseline measurements, captopril renal scintigraphy shows a decrease in glomerular filtration (i.e., 99mTc-DTPA studies) or progressive renal cortical retention (i.e., 99mTc-MAG3) in patients who have significant renal artery stenosis.2

Comparators: For this report, the following diagnostic tests are considered as alternatives to renal scintigraphy:

  • Catheter angiography: During catheter angiography patients are placed on an X-ray table; a catheter is inserted through the skin, with the help of a needle and wire, and is pushed into the aorta. A contrast dye is injected through the catheter into the kidney artery in order to better visualize it. After the injection of contrast dye, X-ray images of the artery are taken,7 which show where an artery may be blocked or narrowed. The degree of the blockage can be measured. A blockage of at least 50% is often considered clinically significant.7 Bones and tissues around the kidney may be "subtracted" out by a computer, which allows for only the blood vessels with contrast dye in them to be visible. An angiogram that includes subtraction is referred to as digital subtraction angiography (DSA).7
  • Computed tomography angiography (CTA): A CTA scan is a computed tomography (CT) scan that visualizes blood vessels in the body. Images are taken with a rotating X-ray device that moves around the patient and takes multiple detailed images of the blood vessels being investigated. Patients are injected with a contrast dye before images are taken in order to better visualize the blood vessels.
  • Magnetic resonance angiography (MRA): An MRA is a magnetic resonance imaging (MRI) test that captures detailed images of the body's blood vessels, which include the renal arteries.6 Patients undergoing MRA are placed onto a table that is moved into the centre of the MRI machine. Patients are often given contrast material before the MRA is undertaken to help visualize the blood vessels.
  • Ultrasound (U/S): During a U/S, a transducer is placed over the organ of interest. The transducer produces sound waves that pass through the body, producing echoes which are analyzed by a computer to develop images of the body part being analyzed.8 Using Doppler U/S, the diagnosis of renal artery stenosis is based upon changes in blood flow velocity across the length of the renal artery.6  

Outcomes: Eleven outcomes (referred to as criteria) are considered in this report:

  • Criterion 1: Size of the affected population
  • Criterion 2 : Timeliness and urgency of test results in planning patient management
  • Criterion 3: Impact of not performing a diagnostic imaging test on mortality related to the underlying condition
  • Criterion 4: Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition
  • Criterion 5: Relative impact on health disparities
  • Criterion 6: Relative acceptability of the test to patients
  • Criterion 7: Relative diagnostic accuracy of the test
  • Criterion 8: Relative risks associated with the test
  • Criterion 9: Relative availability of personnel with expertise and experience required for the test
  • Criterion 10: Accessibility of alternative tests (equipment and wait times)
  • Criterion 11: Relative cost of the test.

Definitions of the criteria are in Appendix 1.

Methods

The literature search was performed by an information specialist using a peer-reviewed search strategy.

Published literature was identified by searching the following bibliographic databases: MEDLINE with In-Process records via Ovid; The Cochrane Library (2011, Issue 1) via Wiley; PubMed; and University of York Centre for Reviews and Dissemination (CRD) databases. The search strategy was comprised of both controlled vocabulary, such as the National Library of Medicine's MeSH (Medical Subject Headings), and keywords. The main search concepts were radionuclide imaging and renal hypertension.

Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses (HTA/SR/MA), randomized controlled trials, non-randomized studies, and diagnostic accuracy studies. No date or human limits were applied to the HTA/SR/MA search. For primary studies, the retrieval was limited to documents published between January 1, 2001 and April 5, 2011, and the human population. Both searches were also limited to English language documents. Regular alerts were established to update the search until October 2011. Detailed search strategies are located in Appendix 2.

Grey literature (literature that is not commercially published) was identified by searching relevant sections of the CADTH Grey Matters checklist. Google was used to search for additional web-based materials. The searches were supplemented by reviewing the bibliographies of key papers. See Appendix 2  for more information on the grey literature search strategy.

Targeted searches were done as required for the criteria, using the aforementioned databases and Internet search engines. When no literature was identified addressing specific criteria, experts were consulted.

Search Results

There were 22 articles identified through the MA/SR/HTA search. Of those, 115,9-18 underwent full-text review. One systematic review12 was identified from the full-text review that compared the diagnostic accuracy of renal scintigraphy with the alternative imaging modalities (U/S, CTA, MRA, catheter angiography).

The systematic review was published in 2001 and included studies published up to August 2000. For the current report, a search for primary studies evaluating renal scintigraphy, and at a least one of its alternatives (U/S, CTA, MRA, catheter angiography), published after 2000, was conducted. Seven primary studies were included: six comparing renal scintigraphy to catheter angiography,19-24 two comparing renal scintigraphy to CTA,21,25 two comparing renal scintigraphy to MRA,21,25 and three comparing renal scintigraphy to U/S.20,21,25

One article from the primary study search was used to help address criterion #1.26 Literature from targeted searches was used to supplement the articles identified in the primary and grey literature searches for the remaining criteria.

Summary table

Table 1: Summary of Criterion Evidence

Domain 1: Criteria Related to the Underlying Health Condition
Criterion Synthesized Information
1 Size of the affected population RAS has been identified as the primary cause of hypertension in 1% to 5% of individuals. Using 1% as an estimate, the prevalence of renal hypertension in Canada can be estimated to be 2.21 per 1,000 people (0.22%).

Therefore, the size of the affected population is more than 1 in 1,000 (0.1%) and less than or equal to 1 in 100 (1%).
2 Timeliness and urgency of test results in planning patient management According to the urgency classifications developed by the province of Saskatchewan, it is recommended that renal scintigraphy for hypertension with suspected renal artery stenosis be conducted within eight to 30 days from the time and date the request for an examination is received by the imaging department, to the date the examination is performed. (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011).

Imaging has minimal impact on the management of the condition or the effective use of heath care resources.
3 Impact of not performing a diagnostic imaging test on mortality related to the underlying condition No studies assessing the impact of diagnostic imaging tests on the mortality of individuals with renovascular hypertension were identified.

If an imaging test for diagnosing renal hypertension is not available, patients may not receive appropriate treatment to deal with the underlying condition causing their hypertension. Hypertension can lead to conditions with large impacts on mortality including myocardial infarction, stroke, congestive heart failure, and renal failure.

Diagnostic imaging test results are assumed to have a minimal impact on mortality.
4 Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition  Correct diagnosis and subsequent appropriate treatment of renal hypertension may reduce the risk of developing conditions linked to hypertension including myocardial infarction, stroke, congestive heart failure, and renal failure, all of which may contribute to morbidity and reduced QoL.

Diagnostic imaging test results are assumed to have a minimal impact on morbidity or QoL.

 

Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses
Criterion Synthesized Information
5 Relative impact on health disparities To be scored locally.
6 Relative acceptability of the test to patients  Renal scintigraphy: Patients may have concerns about radiation exposure and the intravenous injection of a radiopharmaceutical agent.

Catheter angiography: Patients may have concerns about radiation exposure and injection of a contrast agent. The catheter is inserted through the groin, with the help of a needle and wire, and is pushed into the aorta.

CTA: Patients undergoing CT scan may have concerns about radiation exposure and may also feel claustrophobic while in the scanner (MIIMAC expert opinion). They may also have concerns about reactions to the CT contrast agent, and in the case of reduced renal function, of further renal impairment (MIIMAC expert opinion).

MRA: MRA is an MRI-based technique. Patients undergoing MRI are susceptible to anxiety, during and after the test.27,28 Up to 30% of patients experience apprehension and 5% to 10% endure some severe psychological distress, panic, or claustrophobia.27 Approximately 90% of patients would be willing to undergo an MRI exam again.29,30

U/S: Overall, patients are satisfied with U/S.

Renal scintigraphy using 99mTc-radiolabelled isotopes:

  • is significantly more acceptable than catheter angiography
  • is moderately more acceptable than CTA
  • is minimally less acceptable than MRA
  • is minimally less acceptable than U/S.
7 Relative diagnostic accuracy of the test

One meta-analysis from 200112 and one primary study21 compared the diagnostic accuracy of renal scintigraphy to all of its alternatives. Another primary study25 compared the diagnostic accuracy of renal scintigraphy to all of its alternatives except for catheter angiography.

Meta-analysis of Diagnostic Accuracy of Tests for Renovascular Hypertension12
Test Diagnostic Accuracy
Renal scintigraphy 0.92
Catheter angiography Reference
CTA 0.99
MRA 0.99
U/S 0.93

CTA = computed tomography angiography; MRA = magnetic resonance angiography; U/S = ultrasound.

Primary Studies of Diagnostic Accuracy of Tests for Renovascular Hypertension21,25
Test Eklof et al.21 Eriksson et al.25
Sensitivity Specificity Sensitivity Specificity
Renal scintigraphy 0.59 0.50 0.42 1.00
Catheter angiography 0.95 0.91 NR NR
CTA 1.00 0.56 Reference test
MRA 0.98 0.70 0.81 0.79
U/S 0.80 0.54 0.70 0.89

CTA = computed tomography angiography; MRA = magnetic resonance angiography; NR = not reported; U/S = ultrasound.

Based on the available evidence, the diagnostic accuracy of renal scintigraphy using 99mTc- radiolabelled isotopes is:

  • minimally lower than catheter angiography
  • similar to CTA
  • similar to MRA
  • similar to U/S.
8 Relative risks associated with the test

Non-radiation-related Risks

Renal scintigraphy: AEs from renal scintigraphy are rare but may include allergy to the radiopharmaceutical, rash, fever, or chills.31 There is also a relative contraindication in the administration of captopril in patients with a solitary kidney, as it may precipitate transient acute renal failure if kidneys have physiologically significant renal artery stenosis (MIIMAC expert opinion).

Catheter angiography: Risks of catheter angiography include side effects from contrast dye that is used during the procedure, arterial occlusion, and damage to the artery or artery wall, which can lead to blood clots.7

CTA: Patients may experience side effects from contrast dye. A recent large retrospective study found that 0.15% of patients given CT contrast material experienced side effects, most of which were mild.32 The percentage of patients experiencing a serious side effect (defined as cardiovascular collapse, moderate or severe bronchospasm, laryngeal edema, loss of consciousness, or seizure) was 0.005%.32

MRA: MRA (which uses an MRI machine) does not expose patients to any radiation.33 The toxicity of the MRA contrast agent Gd is of particular concern for patients with renal failure. In such patients, Gd has been linked to nephrogenic fibrosis — a serious disease affecting the skin, internal organs, and muscles.32,34

U/S: U/S does not expose patients to any radiation.33 There are no reported risks associated with U/S in the literature that was reviewed.

Radiation-related Risks

Effective Doses of Radiation Associated with Diagnostic Tests
Test Effective Radiation Dose (mSv)35 
Renal scintigraphy with 99mTc-DTPA 1.8
Renal scintigraphy with 99mTc-MAG3 2.6
Catheter angiography 2.6
CTA 8.0
MRA 0
U/S 0
Average background dose of radiation per year 1 to 3.035-37

CTA = computed tomography angiography; MRA = magnetic resonance angiography; mSv = millisievert; 99mTc-DTPA = technetium-99m diethylenetriamine pentaacetic acid;  99mTc- MAG3 = 99mTc- technetium-99m mercaptoacetyl triglycine; U/S = ultrasound.

Overall, renal scintigraphy using 99mTc-radiolabelled isotopes is:

  • significantly safer than catheter angiography
  • moderately safer than CTA
  • minimally safer than MRA
  • minimally less safe than U/S.
9 Relative availability of personnel with expertise and experience required for the test Renal scintigraphy: Requires nuclear medicine physicians or diagnostic radiologists with training in nuclear imaging. Nuclear medicine technologists are also required to conduct renal scans.

Catheter angiography: Catheter angiography is an X-ray based test performed by diagnostic radiologists with a thorough understanding of vascular anatomy, angiographic equipment, and radiation safety considerations.7

CTA: For the performance of CT scan, medical radiation technologists who are certified by CAMRT, or an equivalent licensing body recognized by CAMRT, are required. The training of technologists specifically engaged in CT should meet with the applicable and valid national and provincial specialty qualifications.

MRA: MRA is an MRI-based test. For the performance of MRI, medical technologists must have CAMRT certification in magnetic resonance or be certified by an equivalent licensing body recognized by CAMRT.

U/S: Sonographers should be graduates of an accredited school of sonography or have obtained certification by the CARDUP. They should be members of their national or provincial professional organization. Sonography specialties include general sonography, vascular sonography, and cardiac sonography.38 In Quebec, sonographers and MRTs are grouped together; in the rest of Canada, sonographers are considered a distinct professional group.38

Assuming the necessary equipment is available, if 99mTc imaging using renal scintigraphy is not available, it is estimated that:

  • 25% to 74% of the procedures can be performed in a timely manner using catheter angiography
  • more than 95% of the procedures can be performed in a timely manner using CTCA
  • 25% to 74% of the procedures can be performed in a timely manner using MRA
  • 25% to 74% of the procedures can be performed in a timely manner using U/S.
10 Accessibility of alternative tests (equipment and wait times) Catheter angiography

Based on the experiences of hospitals in a large Canadian city, the average wait time for an elective angiography procedure was 21 days.39 Renal catheter angiography requires the use of an angiography suite. As of 2007, there were 179 angiography suites available in Canada. This is equivalent to 5.5 angiography suites per one million people.38

CTA

No CT scanners are available in Nunavut.40 The average weekly use of CT scanners ranged from 40 hours in Prince Edward Island to 69 hours in Ontario, with a national average of 60 hours.38 In 2010, the average wait time for a CT scan in Canada was 4.2 weeks.41

MRA

There are no MRI scanners available in the Yukon, Northwest Territories, or Nunavut.40 According to CIHI's National Survey of Selected Medical Imaging Equipment database, the average number of hours of operation per week for MRI scanners in 2006–2007 ranged from 40 hours in Prince Edward Island to 99 hours in Ontario, with a national average of 71 hours.38 In 2010, the average wait time for MRI in Canada was 9.8 weeks.41

U/S

The average wait time for a U/S in Canada was estimated to be 4.5 weeks in 2010.41 No information was found on the number of U/S machines available in Canada.

Assuming the necessary expertise is available, if 99mTc imaging using renal scintigraphy is not available it is estimated that:

  • 25% to 74% of the procedures can be performed in a timely manner using catheter angiography
  • more than 95% of the procedures can be performed in a timely manner using CTA
  • 25% to 74% of the procedures can be performed in a timely manner using MRA
  • more than 95% of the procedures can be performed in a timely manner using U/S.
11 Relative cost of the test

According to our estimates, the cost of scintigraphy with 99mTc-based radioisotopes is $327.38.  There is essentially no difference between the cost of renal scintigraphy and the cost of CT. MRA and RCA are moderately more costly tests. U/S is a minimally less costly alternative.

Relative Costs
Test Total Costs ($) Cost of Test Relative to 99mTc-based Test ($)
Renal scintigraphy 327.38 Reference
CT 306.82 -20.56
MRA 670.15 +342.77
RCA 717.96 +390.58
U/S 88.25 -239.13

 

AE = adverse event; CAMRT = Canadian Association of Medical Radiation Technologists; CIHI = Canadian Institute for Health Information; CT = computed tomography; CTA = computed tomographic angiography; Gd = gadolinium; MRA = magnetic resonance angiography; MRI = magnetic resonance imaging; MRT = medical radiation technologist; mSv = millisievert; NR = not reported; QoL = quality of life; RAS = renal artery stenosis; RCA = renal catheter angiography; 99mTc-DTPA = technetium-99m-diethylenetriamine pentaacetic acid; 99mTc-MAG3 = technetium-99m mercaptoacetyl triglycine; U/S = ultrasound.

Criterion 1: Size of affected population (link to definition)

No estimates of point prevalence of renal hypertension in Canada were found in the literature. However, two recent Canadian-based studies that estimated the prevalence and incidence of hypertension were identified.42,43

Tu et al.42 estimated the number of adults with hypertension in Ontario based on physician billing claims from the Ontario Health Insurance Plan (OHIP) database and hospital discharge data from the Canadian Institute of Health Information (CIHI) database. Individuals were considered to have hypertension if they had two physician billing codes or one hospital discharge with a diagnosis of hypertension within a two-year period. The prevalence of hypertension in 2005 was estimated to be 244.8 per 1,000 people. The annual incidence of physician-diagnosed hypertension was estimated to be 32.1 per 1,000 patients.

The prevalence of hypertension across Canada was estimated using the Canadian Chronic Disease Surveillance System (CCDSS)43 — a network of provincial and territorial surveillance systems. For each province, health insurance, physician billing, and hospitalization databases are linked together. Similar to the assumptions made in Tu et al.,42 individuals were considered to have hypertension if they had two physician billing codes or one hospital discharge with a diagnosis of hypertension within a two-year period. As of 2006–2007, the overall prevalence of hypertension in Canada was estimated to be 196 per 1,000 people.

Renal artery stenosis has been identified as the primary cause of hypertension in 1% to 5% of individuals.26 If 1% of all hypertension is due to renal artery disease and the prevalence of all hypertension in Canada is 221 per 1,000 people, the prevalence of renal hypertension can be estimated as 2.21 per 1,000 population (11.1 = 221 × 1%).

Return to Summary Table.

Criterion 2: Timeliness and urgency of test results in planning patient management (link to definition)

Saskatchewan hospital guidelines recommend that renal scintigraphy for hypertension with suspected renal artery stenosis be conducted within eight to 30 days of symptom onset (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011).

Return to Summary Table.

Criterion 3: Impact of not performing a diagnostic imaging test on mortality related to the underlying condition (link to definition)

If a test for diagnosing renal hypertension (i.e., renal scintigraphy or relevant comparators) were not available, patients may not receive appropriate treatment to deal with the underlying condition causing their hypertension. Hypertension can lead to conditions with large impacts on mortality including myocardial infarction, stroke, congestive heart failure, and renal failure.

No studies were identified that assessed the mortality impact of renal hypertension. However, one Canadian-based study was found that measured the mortality impact of hypertension in general.43 Individuals diagnosed with hypertension were identified using the CDSS. The CDSS reported that, in fiscal 2006–2007, the all-cause mortality for adult women (20 years of age or older) with and with without hypertension in Canada was 6.7 per 1,000 and 5.0 per 1,000, respectively. For men, these numbers were reported to be 10.2 per 1,000 and 7.1 per 1,000. Based on this data, the relative risk of mortality for women and men with hypertension can be estimated to be 1.34 and 1.44, respectively.

Return to Summary Table.

Criterion 4: Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition (link to definition)

If a test for diagnosing renal hypertension is not available, appropriate treatment may not be provided. Though hypertension itself is usually non-symptomatic, it is linked with increased risk of events such as myocardial infarction, stroke, congestive heart failure, and renal failure, which significantly impact quality of life (QoL). Correct diagnosis and subsequent appropriate treatment of renal hypertension may reduce the risk of developing these conditions.

The QoL impact of hypertension was assessed in a systematic review (SR) and meta-analysis (MA) by Trevisol et al.44 published in 2011. The authors reviewed studies that assessed health-related QoL associated with hypertension, measured using the generic health status questionnaires Short Form 36 (SF-36) or Short Form 12 (SF-12). The SF-36 instrument contains eight domains: physical function, role-physical, bodily pain, general health, vitality, social function, role-emotional, mental health; and two summary scores: physical component score (PCS) and mental component score (MCS). Scores are all standardized and range from zero to 100, with higher scores indicating better QoL. The SF-12 is a shorter version of SF-36; performance is comparable to that of SF-36, with the advantage of it being easier and quicker to complete.45 Six of the 20 articles included in the SR (published between January 1980 and August 2009) presented scores of QoL in all domains and were therefore included in the MA.

Selected results from the MA are provided in Table 2. Trevisol et al.44 found hypertensive patients to have a lower PCS and MCS compared to individuals without hypertension. The differences in the PCS and MCS scores for hypertensive individuals was estimated to be –2.4 (95% confidence interval [CI], –4.8 to –0.1) and –1.7 (95% CI, –2.1 to –1.2), respectively. For all individual domains, pooled scores were lower for hypertensive patients compared to non-hypertensive individuals.

It is difficult to conclude whether the lower QoL for hypertensive patients is due to the QoL impact of health conditions caused by hypertension or by other factors. The authors discussed that the lower of QoL may be due to patients simply being aware that they have hypertension. Another factor may be side effects from antihypertensive medications.

Table 2: Selected Results Reported in Trevisol et al.44

Component Scores Mean Difference (95% Confidence Interval)
    Physical Component Score –2.4 (–4.8 to –0.1)
    Mental Component Score –1.7 (–2.1 to –1.2)
Domain Scores  
   Physical Functioning –8.3 (–12.9 to –3.7)
   Bodily Pain –5.9 (–9.6 to –2.3)
   Vitality –4.2 (–6.7 to –1.7)
   Role-Emotional –4.4 (–8.3 to –0.4)
   Role-Physical –8.1 (–14.0 to –3.7)
   General Health –8.9 (–13.1 to –4.8)
   Social Functioning –3.7 (–5.9 to –1.5)
   Mental Health –2.7 (–4.3 to –1.1)

Return to Summary Table.

Criterion 5: Relative impact on health disparities (link to definition)

To be scored locally.

No information was found on the potential health disparity for alternative imaging tests.

Return to Summary Table.

Criterion 6: Relative acceptability of the test to patients (link to definition)

Renal scintigraphy
Overall, renal scan is reported to be well-tolerated.46 However, patients may have concerns about radiation exposure and the intravenous injection of a radiopharmaceutical agent. Intravenous fluids might be required if the adequacy of hydration is a concern.47 Because a full bladder may slow drainage of the radiopharmaceutical from the upper part of the urinary tract, the bladder should be emptied frequently.

Catheter angiography
Catheter angiography is a relatively invasive test. Patients are placed on a table and a catheter is inserted through the groin, with the help of a needle and wire, and is pushed into the aorta.7

CTA
Patients undergoing CT scan may have concerns about radiation exposure and may also feel claustrophobic while in the scanner; however, this may be less of a problem with new CT scanners, if available (Medical Isotopes
and Imaging Modalities Advisory Committee [MIIMAC] expert opinion).

MRA
Because of the closed space of an MRI, patients may experience feelings of claustrophobia, as well as being bothered by the noise; however, this may be less of a problem with new MRI machines, if available. It has been reported that up to 30% of patients experience apprehension and 5% to 10% endure some severe psychological distress, panic, or claustrophobia.27,28 Some patients may have difficulty remaining still during the scan. Patients are not exposed to radiation during an MRI scan, which may be more acceptable to some.

U/S: Research from the literature demonstrates that, overall, patients are satisfied with U/S.43,48

Return to Summary Table.

Criterion 7: Relative diagnostic accuracy of the test (link to definition)

One systematic review12 was identified that evaluated the diagnostic accuracy of renal scintigraphy, U/S, CTA, and MRA using renal catheter angiography (RCA) as the gold standard. Receiver operating characteristic (ROC) curves were created for each test. Diagnostic accuracy was measured as the area under the curve for each test. This MA was published in 2001 and included studies published up to August 2000. Because the MA was somewhat dated, a search for primary studies evaluating renal scintigraphy and at a least one of its alternatives (U/S, CTA, MRA, catheter angiography) published after 2000 was conducted. Seven primary studies were included: six comparing renal scintigraphy to catheter angiography,19-24 two comparing renal scintigraphy to CTA,21,25 two comparing renal scintigraphy to MRA,21,25 and three comparing renal scintigraphy to U/S.20,21,25 Table 3 provides an overview of the included studies reporting diagnostic accuracy data and the comparators included in each study (indicated by an X). Details of the diagnostic accuracy studies can be found in Appendix 3.

Table 3: Summary of Included Studies Reporting Diagnostic Accuracy 

Date Author Study Type RS vs. U/S RS vs. CTA RS vs. MRA RS vs. RCA
2001 Vasbinder et al.12 SR/MA X X X X
2010 Abdulsamea et al.24 Obs       X
2010 Eriksson et al.25 Obs X X X  
2006 Eklof et al.21 Obs X X X X
2003 Coen et al.20 Obs X      
2002 Huot et al.22 Obs       X
2002 Karanikas et al.23 Obs       X
2001 Balink et al.19 Obs       X

CTA = computed tomography angiography; MA = meta-analysis; MRA = magnetic resonance angiography; Obs = observational study design; RCA = renal catheter angiography; RS = renal scintigraphy/scan; SR = systematic review; U/S = ultrasound; vs. = versus.

Renal scintigraphy versus catheter angiography
Table 4 presents the accuracy summary statistic reported in one systematic review12 and the sensitivity and specificity reported in five primary studies19,21-24 that compared renal scintigraphy with catheter angiography for the detection of renal hypertension. Sensitivity and specificity values for renal scintigraphy were estimated in the ranges of 48%24 to 83%19 (sensitivity) and 50%21 to 75%19 (specificity). Catheter angiography was the gold standard in the majority of studies comparing renal scintigraphy and catheter angiography.12,19,22-24 Eklof et al. were the only authors to report sensitivity (95%) and specificity (91%) values for catheter angiography, using measurement of transstenotic pressure gradient as the gold standard.21

Table 4: Results from Studies Reporting Sensitivity, Specificity, or Accuracy of Renal Scintigraphy and Catheter Angiography

Author Year Renal Scintigraphy Catheter Angiography
n Acc (%) Sens (%) Spec (%) n Acc (%) Sens (%) Spec (%)
Meta-analysis
Vasbinder et al.12 2001 14 92 NR NR Gold standard
Primary studies
Eklof et al.21 2006 56 NR 59 50 56 NR 95 91
Huot et al.22 2002 169 NR 74 59 Gold standard
Balink et al.19 2001 158 NR 83 75 Gold standard
Karanikas et al.23 2002 33 NR 76 NR Gold standard
Primary studies — pediatric population
Abdulsamea et al.24 2009 49 NR 48 73 Gold standard

Acc = Accuracy; Sens = Sensitivity; Spec = Specificity; n = number of patients (or for meta-analysis = number of studies); NR =not reported.

Table 5 presents the positive and negative predictive values reported in primary studies comparing renal scintigraphy with catheter angiography. Coen et al. (2003),20 Huot et al. (2002),22 and Abdulsamea et al. (2010)24 reported the positive predictive value of renal scintigraphy to be 0.72 , 0.58, and 0.76, respectively. Coen et al.,20 Huot et al.,22 and Abdulsamea et al.24 reported the negative predictive value of renal scintigraphy to be 0.29, 0.75, and 0.51, respectively.

Table 5: Results from Studies Reporting Positive Predictive Value or Negative Predictive Value for Renal Scintigraphy and U/S

Author Year Renal Scintigraphy Catheter Angiography
n PPV NPV n PPV NPV
Primary studies
Coen20 2003 35 0.72 0.29 Reference gold standard
Huot22 2002 169 0.58 0.75 Reference gold standard
Primary studies — pediatric population
Abdulsamea24 2009 49 0.76 0.51 Reference gold standard

n = number of patients or studies; NPV = negative predictive value; PPV = positive predictive value; U/S = ultrasound.

Renal scintigraphy versus CTA
Table 6 presents the accuracy summary statistic reported in one systematic review,12 and the sensitivity and specificity reported in two primary studies21,25 that compared renal scintigraphy with CTA for the detection of renal artery stenosis.

In their meta-analysis, Vasbinder et al. (2001)12 calculated ROC curves for all the tests they evaluated including renal scintigraphy and CTA. The area under each test was used as a measurement of overall diagnostic accuracy. The overall accuracy of renal scintigraphy was estimated to be 92%, while the overall accuracy of CTA was estimated to be 99%. CTA was found to have a statistically significant better diagnostic accuracy than renal scintigraphy.

Eklof et al. (2006)21 estimated the sensitivity and specificity to detect renal artery stenosis of a number diagnostic tests including renal scintigraphy and CTA in their prospective study of patients suspected of having RAS. Using the patient as the unit of analysis, the sensitivities of renal scintigraphy and CTA were estimated to be 59% and 100%, respectively. The specificities of renal scintigraphy and CTA were estimated to be 50% and 56%, respectively. The authors reported that the sensitivity of CTA was statistically significantly higher than that of renal scintigraphy.

Eriksson et al. (2010)25 compared the diagnostic accuracy of renal scintigraphy and CTA in their prospective study of patients with mild renal impairment suspected of renal hypertension. The sensitivity and specificity of renal scintigraphy was reported to be 42% and 100%, respectively, with CTA as the gold standard.

Table 6: Results from Studies Reporting Sensitivity, Specificity, or Accuracy of Renal Scintigraphy and CTA

Author Year Renal Scintigraphy CTA
n Acc (%) Sens (%) Spec (%) n Acc (%) Sens (%) Spec (%)
Meta-analysis
Vasbinder12 2001 14 92 NR NR. 5 99 NR NR
Primary studies
Eklof21 2006 56 NR 59 50 44 NR 100 56
Eriksson25 2010 47 NR 42 100 47 NR Gold standard

Acc = Accuracy; CTA = computed tomography angiography; n = number of patients (or for meta-analysis = number of studies); NR = not reported; Sens = Sensitivity; Spec = Specificity.

Renal scintigraphy versus MRA
Table 7 presents the accuracy summary statistic reported in one systematic review,12 and the sensitivity and specificity reported in two primary studies21,25 that compared renal scintigraphy with MRA for the detection of RAS. In their meta-analysis, Vasbinder et al. (2001)12 calculated ROC curves for all tests they evaluated including renal scintigraphy and MRA. The area under each test was used as a measurement of overall diagnostic accuracy. The authors presented results separately for studies evaluating MRA with contrast and MRA without contrast. The overall accuracy of renal scintigraphy was estimated to be 0.92, while the overall accuracy of MRA with contrast was estimated to be 0.99. The overall accuracy of MRA without contrast was reported to be 0.97.

The authors found overall accuracy to be statistically significantly greater for both enhanced MRA and non-enhanced MRA compared with renal scinitigraphy. Eklof et al. (2006)21 estimated the sensitivity and specificity to detect RAS of a number diagnostic tests including renal scintigraphy and MRA in their prospective study of patients suspected of having RAS. Using the patient as the unit of analysis, the sensitivity of renal scintigraphy and MRA was estimated to be 0.59 and 0.98, respectively. The specificity of renal scintigraphy and MRA was found to be 0.50 and 0.70, respectively. The authors report that sensitivity was statistically significantly greater for MRA compared with renal scintigraphy.

Eriksson et al. (2010)25 compared the diagnostic accuracy of renal scintigraphy and U/S in their prospective study of patients with mild renal impairment suspected of renal hypertension. The sensitivity of renal scintigraphy and MRA was reported to be 0.42 and 0.81, respectively. The specificity of renal scintigraphy and U/S was found to be 1.0 and 0.79, respectively.

Table 7: Results from Studies Reporting Sensitivity, Specificity, or Accuracy of Renal Scintigraphy and MRA

Author Year Renal Scintigraphy MRA
n Acc Sens Spec n Acc Sens Spec
Meta-analysis
Vasbinder et al.12 2001 14 0.92 NR NR 16 0.99 NR NR
Primary studies
Eklof et al.21 2006 56 NR 0.59 0.50 53 NR 0.98 0.70
Eriksson et al.25 2010 47 NR 0.42 1.00 45 NR 0.81 0.79

Acc = accuracy; n = number of patients (or for meta-analysis = number of studies); MRA = magnetic resonance angiography; NR = not reported; Sens = Sensitivity; Spec = Specificity.

Renal scintigraphy versus U/S

Table 8 presents the accuracy summary statistic reported in one systematic review,12 and the sensitivity and specificity reported in two primary studies21,25 that compared renal scintigraphy with U/S for the detection of renal hypertension. In their meta-analysis, Vasbinder et al. (2001)12 calculated ROC curves for all the tests they evaluated including renal scintigraphy and U/S.     The area under each test was used as a measurement of overall diagnostic accuracy. The overall accuracy of renal scintigraphy was estimated to be 0.92, while the overall accuracy of U/S was estimated to be 0.93. No statistical difference was found between the overall accuracy of renal scintigraphy and U/S.

Eklof et al. (2006)21 estimated the sensitivity and specificity to detect RAS of a number of diagnostic tests including renal scintigraphy and U/S in their prospective study of patients suspected of having RAS. Using the patient as the unit of analysis, the sensitivity of renal scintigraphy and U/S was estimated to be 0.59 and 0.80, respectively. The specificity of renal scintigraphy and U/S was found to be 0.50 and 0.54, respectively. The authors report that sensitivity was statistically significantly better for U/S compared to renal scintigraphy.

Eriksson et al. (2010)25 compared the diagnostic accuracy of renal scintigraphy and U/S in their prospective study of patients with mild renal impairment suspected of renal hypertension. The sensitivity of renal scintigraphy and U/S was reported to be 0.42 and 0.70, respectively. The specificity of renal scintigraphy and U/S was found to be 1.0 and 0.89, respectively.

Table 8: Results from Studies Reporting Sensitivity, Specificity, or Accuracy of Renal Scintigraphy and U/S

Author Year Renal Scintigraphy Ultrasonography
n Acc Sens Spec n Acc Sens Spec
Meta-analysis
Vasbinder et al.12 2001 14 0.92 NR NR 24 0.93 NR NR
Primary studies
Eklof et al.21 2006 56 NR 0.59 0.50 57 NR 0.80 0.54
Eriksson et al.25 2010 47 NR 0.42 1.00 36 NR 0.70 0.89

Acc = Accuracy; n = number of patients (or for meta-analysis = number of studies); NR = not reported; Sens = Sensitivity; Spec = Specificity.

Table 9 presents the positive and negative predictive values reported in primary studies comparing renal scintigraphy with U/S. Coen et al. (2003)20 reported the positive predictive value of renal scintigraphy and U/S to be 0.722 (95% CI, 0.465 to 0.903) and 0.943 (95% CI, 0.808 to 0.993) respectively. The negative predictive value of renal scintigraphy and U/S was reported to be 0.294 (95% CI, 0.103 to 0.56) and 0.870 (95% CI, 0.664 to 0.972), respectively.

Table 9: Results from Studies Reporting Positive and Negative Predictive Values or Renal Scintigraphy and U/S

Author Year Renal Scintigraphy Ultrasonography
n PPV NPV n PPV NPV
Coen et al.20 2003 35 0.722 0.294 35 0.943 0.870

n = number of patients; NPV = negative predictive value; PPV = positive predictive value; U/S = ultrasound.

Other
It should be noted that not all people with RAS have renovascular hypertension, and not all patients with renovascular hypertension and RAS will necessarily benefit from surgical intervention (MIIMAC expert opinion). The objective of the study by Krijnen and colleagues was to identify subgroups of patients with hypertension and RAS who benefit from immediate intervention with costly angioplasty and drug therapy.49 Of 106 patients with RAS (≥ 50% of lumen diameter by digital subtraction angiography), the authors found that only those patients with bilateral RAS benefited from immediate intervention with angioplasty. Patients had a normal or mildly impaired renal function (serum creatinine concentration ≤ 2.3 mg/dL) at study entry but, after one year of follow-up, their renal function had improved if angioplasty had taken place immediately after diagnosis. However, renal function deteriorated if angioplasty had been delayed for three months. None of the other subgroups had a clear benefit of immediate intervention regarding renal function or blood pressure control.

Return to Summary Table.

Criterion 8: Relative risks associated with the test (link to definition)

Non–radiation-related Risks

Renal scintigraphy: Adverse events from renal scintigraphy are rare but may include allergy to the radiopharmaceutical, rash, fever, or chills.31 There is also a relative contraindication in the administration of captopril in patients with a solitary kidney, as it may precipitate transient acute renal failure if the kidney has physiologically significant RAS (MIIMAC expert opinion).

Catheter angiography: Risks of catheter angiography include side effects from contrast dye that is used during the procedure, arterial occlusion, and damage to the artery or artery wall, which can lead to blood clots.7

CTA: Patients may experience side effects from contrast dye that is sometimes injected into the patient before imaging. A recent large retrospective study found that 0.15% of patients given CT contrast material experienced side effects.32 Most of these were mild side effects such as nausea, vomiting and hives. The percentage of patients experiencing a serious side effect (defined as cardiovascular collapse, moderate or severe bronchospasm, laryngeal edema, loss of consciousness, or seizure) was 0.005%.32

MRA: MRA (which uses an MRI machine) does not expose patients to any radiation.33 Patients undergoing MRA may experience headaches, sweating, nausea, and fatigue. Patients may experience side effects from contrast dye that is sometimes injected into the patient before imaging. A recent large retrospective study found that 0.04% of patients given MRA contrast material experienced side effects.32 Most of these were mild side effects such as nausea, vomiting, and hives. Serious side effects (defined as cardiovascular collapse, moderate or severe bronchospasm, laryngeal edema, loss of consciousness, or seizure) occurred in 0.003% of patients. Toxicity of the MRA contrast agent Gd is of particular concern for patients with renal failure. In such patients, Gd has been linked to nephrogenic fibrosis, a serious disease affecting the skin, internal organs, and muscles.34

U/S: U/S does not expose patients to any radiation.33 There are no reported risks associated with U/S in the literature that was reviewed.

Radiation-related Risks

Among the diagnostic tests for renal hypertension, renal scintigraphy, RCA, and CTA expose the patient to ionizing radiation. The average effective radiation dose delivered with these procedures is reported in Table 10. The biological effects of this low-dose radiation remain unclear. In 2003, Brenner et al. reviewed the epidemiological evidence regarding low-dose radiation exposure and concluded that there is good evidence of an increase in risk of cancer at acute doses greater than 50 millisievert (mSv), and reasonable evidence for an increase in some cancer risks at doses above about 5 mSv.50

Table 10: Effective Radiation Doses for Various Imaging Tests

Test Effective Radiation Dose (mSv)
99mTc-DTPA renal scan 1.835
99mTc-MAG3 renal scan 2.635
Catheter angiography 2.3651
CTA 8.035
MRA 0
U/S 0
Average background dose of radiation per year 1 to 3.035-37

CTA = computed tomography angiography; MRA = magnetic resonance angiography; mSv = millisievert; 99mTc-DTPA = technetium-99m-labelled- diethylenetriamine pentaacetic acid; 99mTc-MAG3 = technetium-99m-labelled mercaptoacetyl triglycine; U/S = ultrasound.

Renal scintigraphy: The radioisotopes used in scintigraphy expose patients to radiation. As shown in Table 10, the average effective dose for renal scintigraphy using 99mTc-DTPA is 1.8 mSv. The average effective dose for renal scintigraphy using 99mTc-MAG3 is 2.6 mSv.35 This can be compared with the average annual effective dose from background radiation of about 1 to 3 mSv.35-37

Catheter angiography: Renal catheter angiography exposes patients to radiation. As shown in Table 10, the average effective dose for RCA is 2.36 mSv.51

CTA: As shown in Table 10, the average effective radiation dose for abdominal CT is 8.0 mSv.35

Return to Summary Table.

Criterion 9: Relative availability of personnel with expertise and experience required for the test (link to definition)

The personnel required for the performance of the imaging tests to evaluate renovascular hypertension are presented by modality. A summary of the availability of personnel required for the conduct of renal scanning or any of the alternative imaging modalities is provided in Table 11. No information was found regarding the number of radiologists specialized in interventional radiology.

Renal scintigraphy: In Canada, physicians involved in the performance, supervision, and interpretation of renal scans should be nuclear medicine physicians or diagnostic radiologists with training/expertise in nuclear imaging. Nuclear medicine technologists are required to conduct renal scintigraphy. Technologists must be certified by the Canadian Association of Medical Radiation Technologists (CAMRT) or an equivalent licensing body.

All alternative imaging modalities: Service engineers are needed for system installation, calibration, and preventive maintenance of the imaging equipment at regularly scheduled intervals. The service engineer's qualification will be ensured by the corporation responsible for service and the manufacturer of the equipment used at the site. Qualified medical physicists (on site or contracted part-time) should be available for the installation, testing, and ongoing quality control of CT, MRI, U/S machines, and nuclear medicine equipment.52

Catheter angiography: To perform RCA, diagnostic radiologists must have a thorough understanding of vascular anatomy, angiographic equipment, and radiation safety considerations.7 Medical radiation technologists (MRTs) must be certified by CAMRT or an equivalent licensing body.

CTA: For the performance of CT scan, MRTs who are certified by CAMRT or an equivalent licensing body recognized by CAMRT are required.

MRA: Medical technologists must have CAMRT certification in magnetic resonance or be certified by an equivalent licensing body recognized by CAMRT.

U/S: Sonographers (or ultrasonographers) should be graduates of an accredited school of sonography or have obtained certification by the Canadian Association of Registered Diagnostic Ultrasound Professionals (CARDUP). They should be members of their national or provincial professional organization. Sonography specialties include general sonography, vascular sonography, and cardiac sonography.38 In Quebec, sonographers and MRTs are grouped together; in the rest of Canada, sonographers are considered a distinct professional group.38

Table 11: Medical Imaging and Relevant Health Professionals in Canada38

Jurisdiction Diagnostic Radiology Physicians Nuclear Medicine Physicians MRTs Nuclear Medicine Technologists Sonographers Medical Physicists
NL 46 3 263 15 NR NR
NS 71 5 403 71 NR NR
NB 47 3 387 55 NR NR
PEI 7 0 57 3 NR 0
QC 522 90 3,342 460 NR NR
ON 754 69 4,336 693 NR NR
MB 58 8 501 42 NR NR
SK 61 4 359 36 NR NR
AB 227 18 1,229 193 NR NR
BC 241 21 1,352 212 NR NR
YT 0 0 – – NR 0
NT 0 0 26 1 NR 0
NU 0 0 – – NR 0
Total 2,034 221 12,255 1,781 2,900* 322*

AB = Alberta; BC = British Columbia; MB = Manitoba; NB = New Brunswick; MRT = medical radiation technologist; NL = Newfoundland and Labrador; NR = not reported by jurisdiction; NS = Nova Scotia; NT= Northwest Territories; NU = Nunavut; ON = Ontario; PEI= Prince Edward Island; QC = Quebec; YT = Yukon.
* This represents a total for all of the jurisdictions.

Return to Summary Table.

Criterion 10: Accessibility of alternative tests (equipment and wait times) (link to definition)

There are notable variations in the availability of medical imaging technologies within hospitals across Canada. Nuclear medicine cameras are not available in the Yukon, the Northwest Territories, and Nunavut. Table 12 provides an overview of the availability of equipment required to evaluate renovascular hypertension. Data for nuclear medicine cameras (including SPECT) are current to January 1, 2007. The number of CT, MRI, and SPECT/CT scanners is current to January 1, 2010. Data were not available for U/S.

Renal scintigraphy
For renal scans, nuclear medicine facilities with gamma cameras (including SPECT) are required. Three jurisdictions — the Yukon, the Northwest Territories, and Nunavut — do not have any nuclear medicine equipment.40 In 2007, the latest year for which data are available, the average time for renal scintigraphy in McGill University Health Centre (MUHC) hospitals was 13 days. However, the wait times were reported to be less than one day for emergency cases.39

Catheter Angiography
Renal catheter angiography requires the use of an angiography suite. As of 2007, there were 179 angiography suites available in Canada. This is equivalent to 5.5 angiography suites per one million people.38 Based on the experiences of hospitals in a large Canadian city, the average wait time for an elective angiography procedure was 21 days.39 The average wait time for an emergency angiography was 12 hours.39

CTA
No CT scanners are available in Nunavut.38 The average weekly use of CT scanners ranged from 40 hours in Prince Edward Island to 69 hours in Ontario, with a national average of 60 hours.38 In 2010, the average wait time for a CT scan in Canada is 4.2 weeks.41

MRA
No MRI scanners are available in the Yukon, Northwest Territories, or Nunavut.38 According to CIHI's National Survey of Selected Medical Imaging Equipment database, the average number of hours of operation per week for MRI scanners in 2006–2007 ranged from 40 hours in Prince Edward Island to 99 hours in Ontario, with a national average of 71 hours.38 In 2010, the average wait time for MR imaging in Canada was 9.8 weeks.41

U/S
U/S machines are widely available across the country. According to the Fraser Institute, the average wait time for U/S in 2010 was 4.5 weeks.41

Table 12: Diagnostic Imaging Equipment in Canada38,40

  Nuclear Medicine Cameras Angiography Suites CT Scanners MRI Scanners SPECT/CT Scanners
Number of devices 60338 17938 46040 21840 9640
Average number of hours of operation per week (2006-2007)38 40 39 60 71 n/a
Provinces and Territories with no devices available YT, NT, NU YT, NT, NU NU YT, NT, NU PEI, YT, NT, NU

CT = computed tomography; MRI = magnetic resonance imaging; NT = Northwest Territories; NU = Nunavut; PEI = Prince Edward Island; SPECT = single-photon emission computed tomography; YT= Yukon.

Return to Summary Table.

Criterion 11: Relative cost of the test (link to definition)

Fee codes from the Ontario Schedule of Benefits were used to estimate the relative costs of Captopril-enhanced renal scintigraphy and its alternatives. Technical fees are intended to cover costs incurred by the hospital (i.e., radiopharmaceutical costs, medical/surgical supplies, and non-physician salaries). Maintenance fees are not billed to OHIP — estimates here were provided by St. Michael's Hospital in Toronto. Certain procedures (i.e., PET scan, CT scan, MRI scan) are paid for, in part, out of the hospital's global budget; these estimates were provided by The Ottawa Hospital. It is understood that the relative costs of imaging will vary from one institution to the next. 

According to our estimates (Table 13), the cost of scintigraphy with 99mTc-based radioisotopes is $327.38. There is essentially no difference between the cost of renal scintigraphy and the cost of CT. Magnetic resonance angiography and RCA are moderately more costly tests. U/S is a minimally less costly alternative.

Table 13: Cost Estimates Based on the Ontario Schedule of Benefits for Physician Services Under the Health Insurance Act (September 2011)53

Fee Code Description Tech. Fees ($) Prof. Fees ($) Total Costs ($)
Renal scintigraphy
J835 Computer-assessed renal function — includes first transit 135.10 73.00 208.10
J880 Computer-assessed renal function — repeat after pharmacological intervention 46.00 22.50 68.50
Maintenance fees — from global budget 50.78   50.78
TOTAL 231.88 95.50 327.38
CT
X126 CT — abdomen — with and without IV contrast   114.00 114.00
Technical cost — from global budget 150.00   150.00
Maintenance fees — from global budget 42.82   42.82
TOTAL 192.82 114.00 306.82
MRA
X451C MRA — abdomen — multislice sequence   77.20 77.20
X455C (×3) Repeat (another plane, different pulse sequence; to a maximum of 3  repeats)   38.65 (×3) = 115.95 115.95
X487C When gadolinium is used   38.60 38.60
X499C 3-D MRI acquisition sequence, including post-processing (minimum of 60 slices; maximum 1 per patient per day)   65.40 65.40
Technical cost — from global budget 300.00   300.00
Maintenance fees — from global budget 73.00   73.00
TOTAL 373.00 297.15 670.15
Renal catheter angiography
X181B and  X181C Abdominal, thoracic, cervical, or cranial angiogram by catheterization — using film changer, cine, or multiformat camera — non-selective 61.20 32.50 93.70
X182B and  X182C (×2) Abdominal, thoracic, cervical, or cranial angiogram by catheterization — using film changer, cine, or multiformat camera — selective (per vessel, 2) 81.35 (×2) = 162.70 39.40 (×2) = 78.80 241.50
J021 Angiography — by catheterization — abdominal, thoracic, cervical, or cranial — insertion of catheter (including cut-down, if necessary), and injection, if given   121.40 (spec) 90.06 (anes) 211.46
J022 (x2) selective catheterization — add to catheter insertion fee (per vessel, 2)   60.15 (x2) = 120.30 120.30
Maintenance fees — from global budget 51.00   51.00
TOTAL 274.9 443.06 717.96
U/S
J135 Abdominal scan — complete 50.00 34.95 84.95
Maintenance fees — from global budget 3.30   3.30
TOTAL 53.30 34.95 88.25

3-D = three-dimensional; CT = computed tomography; IV = intravenous; MRA = magnetic resonance angiography; MRI = magnetic resonance imaging; Prof. = professional; Tech. = technical.; U/S = ultrasound.

Return to Summary Table.

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  39. Atwood CV, McGregor M. Wait times at the MUHC. No.4: diagnostic imaging revisited adult hospitals of the MUHC. Has there been progress? Where are the bottlenecks? How can they be removed? [Internet]. Montreal: Technology Assessment Unit of the McGill University Health Centre (MUHC); 2008 Feb 29. Report No.: 32. [cited 2011 Apr 15]. Available from: http://www.mcgill.ca/tau/publications/2008/
  40. Canadian Institute for Health Information (CIHI). Selected medical imaging equipment in Canada [Internet]. Ottawa: The Institute; 2010 Jan 1. Report No.: MI5. [cited 2011 Jun 29]. Available from: http://apps.cihi.ca/MicroStrategy/asp/Main.aspx?server=torapprd30.cihi.ca&project=Quick+Stats&uid=pce_pub_en&pwd=&evt=2048001&visualizationMode=0&documentID=50A7B0D5472B6AE40A9AE7AA062D42EC Source: National Survey of Selected Medical Imaging Equipment, CIHI, 2010.
  41. Barua B, Rovere M, Skinner BJ. Waiting your turn: wait times for health care in Canada [Internet]. 20th ed. Vancouver (BC): Fraser Institute; 2010 Dec. 90 p. [cited 2011 Apr 15]. (Studies in health care policy). Available from: http://www.fraserinstitute.org/uploadedFiles/fraser-ca/Content/research-news/research/publications/waiting-your-turn-2010.pdf
  42. Tu K, Chen Z, Lipscombe LL. Prevalence and incidence of hypertension from 1995 to 2005: a population-based study. CMAJ [Internet]. 2008 [cited 2011 May 11];178(11):1429-35. Available from: http://www.cmaj.ca/cgi/reprint/178/11/1429
  43. Public Health Agency of Canada. Report from the Canadian Chronic Disease Surveillance System: hypertension in Canada, 2010 [Internet]. Ottawa: The Agency; 2010. [cited 2011 May 11]. Available from: http://www.phac-aspc.gc.ca/cd-mc/cvd-mcv/ccdss-snsmc-2010/pdf/CCDSS_HTN_Report_FINAL_EN_20100513.pdf
  44. Trevisol DJ, Moreira LB, Kerkhoff A, Fuchs SC, Fuchs FD. Health-related quality of life and hypertension: a systematic review and meta-analysis of observational studies. J Hypertens. 2011;29(2):179-88.
  45. Gandek B, Ware JE, Aaronson NK, Apolone G, Bjorner JB, Brazier JE, et al. Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol. 1998 Nov;51(11):1171-8.
  46. Goldfarb CR, Srivastava NC, Grotas AB, Ongseng F, Nagler HM. Radionuclide imaging in urology. Urol Clin North Am. 2006;33(3):319-28.
  47. Taylor A, Nally JV. Clinical applications of renal scintigraphy. AJR Am J Roentgenol [Internet]. 1995 [cited 2011 Apr 14];164(1):31-41. Available from: http://www.ajronline.org/cgi/reprint/164/1/31
  48. Middleton GW, Williams JH. Diagnostic accuracy of 99Tcm-HIDA with cholecystokinin and gallbladder ejection fraction in acalculous gallbladder disease. Nucl Med Commun. 2001 Jun;22(6):657-61.
  49. Krijnen P, van Jaarsveld BC, Deinum J, Steyerberg EW, Habbema JD. Which patients with hypertension and atherosclerotic renal artery stenosis benefit from immediate intervention? J Hum Hypertens [Internet]. 2004 [cited 2011 Sep 14];18(2):91-6. Available from: http://www.nature.com/jhh/journal/v18/n2/pdf/1001641a.pdf
  50. Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Natl Acad Sci U S A [Internet]. 2003 Nov 25 [cited 2011 Jul 28];100(24):13761-6. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC283495
  51. Seymour HR, Matson MB, Belli AM, Morgan R, Kyriou J, Patel U. Rotational digital subtraction angiography of the renal arteries: technique and evaluation in the study of native and transplant renal arteries. Br J Radiol [Internet]. 2001 [cited 2011 Jun 1];74(878):134-41. Available from: http://bjr.birjournals.org/cgi/reprint/74/878/134
  52. Royal College of Physicians and Surgeons of Canada. Objectives of training in nuclear medicine [Internet]. Ottawa: The College; 2009. [cited 2011 Jun 13]. Available from: http://rcpsc.medical.org/residency/certification/objectives/nucmed_e.pdf
  53. Ontario Ministry of Health and Long-Term Care. Schedule of benefits for physician services under the Health Insurance Act: effective September 1, 2011 [Internet]. Toronto: OMHLTC; 2011. [cited 2011 Oct 5]. Available from: http://www.health.gov.on.ca/english/providers/program/ohip/sob/physserv/physserv_mn.html

 

Appendix 1: Multi-Criteria Decision Analysis Definitions

Domain 1: Criteria Related to the Underlying Health Condition
Criterion Definition
1. Size of the affected population The estimated size of the patient population that is affected by the underlying health condition and which may potentially undergo the test. The ideal measure is point prevalence, or information on how rare or common the health condition is.
2. Timeliness and urgency of test results in planning patient management The timeliness and urgency of obtaining the test results in terms of their impact on the management of the condition and the effective use of health care resources.
3. Impact of not performing a diagnostic imaging test on mortality related to the underlying condition Impact of not performing the test, in whatever way, on the expected mortality of the underlying condition. Measures could include survival curves showing survival over time, and/or survival at specific time intervals with and without the test.
4. Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition Impact of not performing the test, in whatever way, on the expected morbidity or on the quality of life reduction of the underlying condition. Measures of impact may include natural morbidity outcome measures such as events or disease severity, or might be expressed using generic or disease-specific quality of life rating scales with and without the test.
Domain 2: Criteria Comparing 99mTc with an Alternative, or Comparing between Clinical Uses
Criterion Definition
5. Relative impact on health disparities Health disparities are defined as situations where there is a disproportionate burden (e.g., incidence, prevalence, morbidity, or mortality) amongst particular population groups (e.g., gender, age, ethnicity, geography, disability, sexual orientation, socioeconomic status, and special health care needs).

Impact on health disparities is assessed by estimating the proportion of current clients of the 99mTc-based test that are in population groups with disproportionate burdens.

(Explanatory note: The implication of this definition is that, everything else being the same, it is preferable to prioritize those clinical uses that have the greatest proportion of clients in groups with disproportionate burdens.)
6. Relative acceptability of the test to patients Acceptability of the 99mTc-based test from the patient's perspective compared with alternatives. Patient acceptability considerations include discomfort associated with the administration of the test, out-of-pocket expenses or travel costs, factors that may cause great inconvenience to patients, as well as other burdens. This criterion does not include risks of adverse events but is about everything related to the experience of undergoing the test.
7. Relative diagnostic accuracy of the test Ability of the test to correctly diagnose the patients who have the condition (sensitivity) and patients who do not have the condition (specificity) compared with alternatives.
8. Relative risks associated with the test Risks associated with the test (e.g., radiation exposure, side effects, adverse events) compared with alternatives. Risks could include immediate safety concerns from a specific test or long-term cumulative safety concerns from repeat testing or exposure.
9. Relative availability of personnel with expertise and experience required for the test Availability of personnel with the appropriate expertise and experience required to proficiently conduct the test and/or interpret the test findings compared with alternatives.
10. Accessibility of alternatives (equipment and wait times) Availability (supply) of equipment and wait times for alternative tests within the geographic area. Includes consideration of the capacity of the system to accommodate increased demand for the alternatives. Excludes any limitation on accessibility related to human resources considerations.
11. Relative cost of the test Operating cost of test (e.g., consumables, heath care professional reimbursement) compared with alternatives.

 

Appendix 2: Literature Search Strategy

OVERVIEW
Interface: Ovid
Databases: Ovid MEDLINE In-Process & Other Non-Indexed Citations and Ovid MEDLINE <1948 to April 5, 2011>
Date of Search: April 6, 2011
Alerts: Weekly search updates began April 6, 2011 and ran until October 2011.
Study Types: Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies, and diagnostic accuracy studies.
Limits: No date limit for systematic reviews; publication years 2001 – April 2011 for primary studies

English language

Human limit for primary studies
SYNTAX GUIDE
/ At the end of a phrase, searches the phrase as a subject heading
MeSH Medical subject heading
.fs Floating subheading
exp Explode a subject heading
* Before a word, indicates that the marked subject heading is a primary topic; or, after a word, a truncation symbol (wildcard) to retrieve plurals or varying endings
? Truncation symbol for one or no characters only
ADJ Requires words are adjacent to each other (in any order)
ADJ# Adjacency within # number of words (in any order)
.ti Title
.ab Abstract
.hw Heading word: usually includes subject headings and controlled vocabulary
.tw Text word: searches title, abstract, captions, and full text
.mp Keyword search: includes title, abstract, name of substance word, subject heading word and other text fields
.pt Publication type
.nm Name of substance word: used to search portions of chemical names and includes words from the CAS Registry/EC Number/Name (RN) fields
.jw Journal words: searches words from journal names
/du Diagnostic use
/ri Radionuclide imaging

 

Ovid MEDLINE Strategy
Line # Search Strategy
1 Technetium/
2 exp Technetium Compounds/
3 exp Organotechnetium Compounds/
4 exp Radiopharmaceuticals/
5 radioisotope*.mp.
6 (technetium* or Tc-99* or Tc99* or Tc-99m* or Tc99m* or 99mTc* or 99m-Tc* or 99mtechnetium* or 99m-technetium*).tw,nm.
7 Radionuclide Imaging/ or Perfusion Imaging/ or Radioisotope Renography/
8 ri.fs.
9 ((radionucl* or nuclear or radiotracer* or perfusion or gamma camera*) adj2 (imag* or scan* or test* or diagnos*)).tw.
10 (SPECT or scintigraph* or scintigram* or scintiphotograph* or scintiscan*).tw.
11 Tomography, Emission-Computed, Single-Photon/
12 (single-photon adj2 emission*).tw.
13 ((renal* or kidney*) adj7 (imaging or perfusion* or scan*)).tw.
14 (renograp* or reno-graph* or renogram*).tw.
15 (MAG3 or MAG-3 or Mercaptoacetyltriglycine or Mertiatide or TechneScan or Mercaptoacetylglycylglycylglycine or Mercaptoacetyl triglycine).tw.
16 (DTPA or diethylenetriaminepentaacetic acid* or diethylenetriamine penta-acetic acid*).tw.
17 125224-05-7.rn.
18 or/1-17
19 exp Hypertension, Renal/
20 ((renal or reno-vascular* or renovascular*) adj3 hypertensi*).tw.
21 (goldblatt adj (syndrome or hypertensi*)).tw.
22 Renal Artery Obstruction/
23 (renal adj3 (obstruction* or stenos* or stenotic lesion*)).tw.
24 or/19-23
25 Meta-Analysis.pt.
26 Meta-Analysis/ or Systematic Review/ or Meta-Analysis as Topic/ or exp Technology Assessment, Biomedical/
27 ((systematic* adj3 (review* or overview*)) or (methodologic* adj3 (review* or overview*))).tw.
28 ((quantitative adj3 (review* or overview* or synthes*)) or (research adj3 (integrati* or overview*))).tw.
29 ((integrative adj3 (review* or overview*)) or (collaborative adj3 (review* or overview*)) or (pool* adj3 analy*)).tw.
30 (data synthes* or data extraction* or data abstraction*).tw.
31 (handsearch* or hand search*).tw.
32 (mantel haenszel or peto or der simonian or dersimonian or fixed effect* or latin square*).tw.
33 (met analy* or metanaly* or health technology assessment* or HTA or HTAs).tw.
34 (meta regression* or metaregression* or mega regression*).tw.
35 (meta-analy* or metaanaly* or systematic review* or biomedical technology assessment* or bio-medical technology assessment*).mp,hw.
36 (medline or Cochrane or pubmed or medlars).tw,hw.
37 (cochrane or health technology assessment or evidence report).jw.
38 or/25-37
39 exp "Sensitivity and Specificity"/
40 False Positive Reactions/
41 False Negative Reactions/
42 du.fs.
43 sensitivit*.tw.
44 (predictive adj4 value*).tw.
45 distinguish*.tw.
46 differentiat*.tw.
47 enhancement.tw.
48 identif*.tw.
49 detect*.tw.
50 diagnos*.tw.
51 accura*.tw.
52 comparison*.tw.
53 Comparative Study.pt.
54 (Validation Studies or Evaluation Studies).pt.
55 Randomized Controlled Trial.pt.
56 Controlled Clinical Trial.pt.
57 (Clinical Trial or Clinical Trial, Phase II or Clinical Trial, Phase III or Clinical Trial, Phase IV).pt.
58 Multicenter Study.pt.
59 (random* or sham or placebo*).ti.
60 ((singl* or doubl*) adj (blind* or dumm* or mask*)).ti.
61 ((tripl* or trebl*) adj (blind* or dumm* or mask*)).ti.
62 (control* adj3 (study or studies or trial*)).ti.
63 (non-random* or nonrandom* or quasi-random* or quasirandom*).ti.
64 (allocated adj "to").ti.
65 Cohort Studies/
66 Longitudinal Studies/
67 Prospective Studies/
68 Follow-Up Studies/
69 Retrospective Studies/
70 Case-Control Studies/
71 Cross-Sectional Study/
72 (observational adj3 (study or studies or design or analysis or analyses)).ti.
73 cohort.ti.
74 (prospective adj7 (study or studies or design or analysis or analyses or cohort)).ti.
75 ((follow up or followup) adj7 (study or studies or design or analysis or analyses)).ti.
76 ((longitudinal or longterm or (long adj term)) adj7 (study or studies or design or analysis or analyses or data or cohort)).ti.
77 (retrospective adj7 (study or studies or design or analysis or analyses or cohort or data or review)).ti.
78 ((case adj control) or (case adj comparison) or (case adj controlled)).ti.
79 (case-referent adj3 (study or studies or design or analysis or analyses)).ti.
80 (population adj3 (study or studies or analysis or analyses)).ti.
81 (cross adj sectional adj7 (study or studies or design or research or analysis or analyses or survey or findings)).ti.
82 or/39-81
83 Case Reports.pt.
84 82 not 83
85 18 and 24 and 38
86 limit 85 to english language
87 18 and 24 and 84
88 limit 87 to (english language and humans and yr="2001 -Current")

 

OTHER DATABASES
PubMed Same MeSH, keywords, limits, and study types used as per MEDLINE search, with appropriate syntax used.
Cochrane Library
Issue 1, 2011		 Same MeSH, keywords, and date limits used as per MEDLINE search, excluding study types and Human restrictions. Syntax adjusted for Cochrane Library databases.

 

GREY LITERATURE SEARCHING
Dates for Search: April 2011
Keywords: Included terms for radionuclide imaging and renal hypertension.
Limits: No limits

The following sections of the CADTH grey literature checklist, "Grey matters: a practical search tool for evidence-based medicine" (http://www.cadth.ca/en/resources/grey-matters) were searched:

  • Health Technology Assessment Agencies (selected)
  • Clinical Practice Guidelines
  • Databases (free)
  • Internet Search

 

Appendix 3: Study Descriptions

Vasbinder et al.12

Vasbinder et al.12 conducted a systematic review and meta-analysis of studies evaluating the diagnostic accuracy of non-invasive or minimally invasive tests for the diagnosis of renal hypertension. The tests that were considered included captopril renal scintigraphy, computed tomography angiography (CTA), magnetic resonance angiography (MRA), and ultrasound (U/S). The authors searched MEDLINE, Embase and Cochrane databases for relevant articles. In order to be included in the meta-analysis, studies had to have the following characteristics:

  • use renal catheter angiography (RCA) as the gold standard test
  • have a patient population suspected of renal hypertension
  • the criteria for a positive test result was explicitly stated
  • the number of patients by diagnosis status (i.e., true-positives, false-negatives, true-negatives, false-positives) reported or able to be derived from data presented.

Diagnostic data from included studies were pooled by creating receiver-operator characteristic (ROC) curves for each test. The diagnostic performance of each test was measured by the area under the ROC for each test. A higher area under the curve indicated better diagnostic performance.

The number of studies identified in the literature search that evaluated captopril scintigraphy, U/S, CTA, and MRA was 172, 314, 343, and 306, respectively. The number of studies that were included in the meta-analysis for captopril scintigraphy, U/S, CTA, and MRA was 14, 24, five, and 16, respectively. The area under the ROC curve for captopril renal scintigraphy was calculated to be 0.92. Compared with renal scintigraphy, the area under the ROC curve was estimated to be higher for ultrasonography (0.93), CTA (0.99), and MRA (0.99 gadolinium- enhanced, 0.97, non–gadolinium-enhanced). Based on between-test comparisons, captopril renal scintigraphy had a statistically significantly worse diagnostic performance compared with CTA, gadolinium-enhanced MRA and non–gadolinium-enhanced MRA. No statistically significant difference was found between captopril renal scintigraphy and U/S.

The authors concluded that their main finding was that MRA and CTA has better diagnostic accuracy than the other test evaluated, including renal scintigraphy. However, they do offer some potential methodological issues. Specifically, they state that the use of catheter renal angiography as the gold standard may lead to underestimation of the diagnostic accuracy of functional tests such as renal scintigraphy. They also note that the unit of analysis for MRA and CTA was most often at the artery level, while for renal scintigraphy people were most often used as the unit of analysis. They speculate that this may overestimate the diagnostic accuracy of MRA and CTA compared with renal scintigraphy.

Abdulsamea et al.24

Abdulsamea et al. evaluated the diagnostic accuracy of captopril renal scintigraphy in children suspected of having renal artery stenosis. Subjects included all children (age ≤18 years) that were investigated with both renal scintigraphy and digital subtraction angiography between 1986 and 2008 in a hospital in Egypt. All subjects had hypertension and were suspected of having renal artery stenosis. 

Pre- and post-captopril tests were performed separately with both technetium-99m dimercaptosuccinic acid (99mTc-DMSA) and technetium-99m mercaptoacetyl triglycine        (99mTc-MAG3). Based on 81 patients, the sensitivity and specificity of a combination of        99mTc-DMSA and 99mTc-MAG3 renal scintigraphy studies were 0.48 and 0.73, respectively. The positive predictive value and negative predictive value of renal scintigraphy were reported to be 0.76 and 0.51, respectively. The authors also reported diagnostic accuracy separately for renal scintigraphy using 99mTc-DMSA and 99mTc-MAG3. The sensitivity and specificity of scintigraphy using the 99mTc-DMSA was reported to be 0.46 and 0.90, respectively. The sensitivity and specificity of scintigraphy using the 99mTc-MAG3 was reported to be 0.45 and 0.85, respectively.

Ericksson et al.25 

Ericksson et al.25 investigated the accuracy of various diagnostic tests in patients with moderate renal impairment suspected of having renal artery stenosis. The study was comprised of 47 consecutive adult patients from a Swedish hospital, with moderate renal impairment (serum creatine 150-300 µmol/L) and with suspicion of renal hypertension. Patients were investigated with captopril renal scintigraphy plus renin analysis, magnetic resonance angiography (MRA), and computed tomography angiography (CTA) within a two-day period. Though not part of the original protocol, 36 of the 47 patients also underwent Doppler U/S. The authors reported the sensitivity and specificity of various diagnsotic tests using CTA as the reference standard. A positive test result was defined as CTA with ≥ 50% diameter reduction. 

The sensitivity of MRA (n = 45), U/S (n = 36), and renal scintigraphy (n = 47) was reported to be 0.806 (95% Confidence Interval [CI], 0.625 to 0.925), 0.704 (95% CI, 0.498 to 0.862), and 0.424 (95% CI, 0.255 to 0.608), respectively. The specificity of MRA (n = 45), U/S (n = 36), and renal scintigraphy (n = 47) was reported to be 0.786 (95% CI, 0.492 to 0.953), 0.889 (95% CI, 0.518 to 0.997), and 1.0 (95% CI, 0.807 to 1.0), respectively.

The authors also presented the sensitivity and specificity of alternatives evaluated on the kidney level instead of the patient level. The sensitivity of MRA, U/S, and renal scintigraphy evaluated at the kidney level was reported to be 0.756, 0.528, and 0.295, respectively. The specificity of MRA, U/S, and renal scintigraphy evaluated at the kidney level was reported to be 0.816, 0.806, and 0.860, respectively.

The authors also reported diagnostic accuracy using "functional and morphologic stenosis" as an alternate gold standard. Based on this gold standard, RAS was defined as positive if either CTA and MRA showed ≥ 50% diameter reduction and either renal scintigraphy plus rennin or U/S indicated the presence of significant stenosis.

Based on this alternate gold standard, the sensitivity of CTA (n = 34), MRA (n = 434), U/S         (n = 34), and renal scintigraphy (n = 34) was reported to be 1.00 (95% CI, 0.867 to 1.000),      0.90 (95% CI, 0.683 to 0.988), 0.905 (95% CI, 0.696 to 0.988), and 0.667 (95% CI, 0.430 to 0.854), respectively. If it is assumed that the threshold for a positive test is 70% diameter reduction, the sensitivity for CTA and MRA decreases to 0.810 and 0.600, respectively. 

The specificity of CTA (n = 34), MRA (n = 34), U/S (n = 34), and renal scintigraphy (n = 34) was reported to be 0.615 (95% CI, 0.316 to 0.681), 0.692 (95% CI, 0.386 to 0.909), 1.0 (95% CI, 0.794 to1.000), and 1.0 (95% CI, 0.794 to 1.000), respectively. If the threshold for a positive test was assumed to be 70% diameter reduction, the specificity for CTA and MRA becomes 1.0 and 0.846, respectively.

The authors also presented the sensitivity and specificity of alternatives evaluated on the kidney level instead of the patient level. Using the alternate reference standard, the sensitivity of CTA, MRA, U/S, and renal scintigraphy evaluated at the kidney level was reported to be 0.964, 0.852, 0.714, and 0.5005, respectively. The specificity of MRA, U/S, and renal scintigraphy evaluated at the kidney level was reported to be 0.758, 0.788, 0.970, and 0.970, respectively.

Eklof et al.21 

In a prospective study, Eklof et al.21 evaluated the diagnostic accuracy of four non-invasive tests to detect renal artery stenosis. The tests evaluated included captopril renal scintigraphy, U/S, CTA, and MRA. Renal catheter angiography with pressure gradient measurement was used as the gold standard test. Specifically, the gold standard was digital subtraction angiography (DSA) with transstenotic pressure gradient measurement (PGM).

Patients with suspicion of RAS were recruited from various departments of a Swedish hospital. A total of 58 patients participated in the study. The number of patients who underwent captopril renal scintigraphy, U/S, CTA, and MRA were 56, 57, 44, and 53, respectively. The median time from first exam to RCA was two days. 99mTc-MAG3 was used as the radiopharmaceutical for captopril renal scintigraphy. The authors state that renal scintigraphy findings were classified as low, intermediate, or high probability of renal artery stenosis. The authors state that the scoring classification is based on guidelines, which are referenced. Details of the guidelines were not provided in the article. Tests that were scored high or intermediate probability of RAS were considered to be positive.  

The authors state that the criteria for a positive U/S test was based on aortic and renal artery peak systolic velocity (PSV). For MRA, CTA, and RCA, the degree of stenosis was assessed by comparing the diameter of the narrowest stenotic segment with the diameter of a normal renal artery segment.

Sensitivity and specificity were estimated on both a per person basis and on a per kidney basis. On a per patient basis, the sensitivity of renal scintigraphy, U/S, CTA, MRA, and digital subtraction angiography was estimated to be 0.59, 0.80, 1.0, 0.98, and 0.95, respectively. Specificity was estimated to be 0.50, 0.54, 0.56, 0.70, and 0.91, respectively.

Based on a per kidney basis, the sensitivity of renal scintigraphy, U/S, CTA, MRA, and digital subtraction angiography was estimated to be 0.52, 0.73, 0.94, 0.93, and 0.91, respectively. Specificity was estimated to be 0.63, 0.71, 0.62, 0.91, and 0.93, respectively. The authors found that sensitivity was statistically significantly higher in U/S, CTA, and MRA compared with renal scintigraphy.

Coen et al.20 

Coen et al.20 investigated the diagnostic performance of duplex U/S and renal scintigraphy to in-patients with either arterial hypertension or chronic renal disease suspected of renal artery stenosis. The study investigated 269 consecutive patients referred to an Italian nephrology clinic with arterial hypertension, chronic renal failure, or both. Renal angiography by means of MRA or RCA was considered the gold standard.

For U/S, the criteria for significant stenosis were:

  • systolic peak velocity above 180 cm/sec
  • and renal aortic ratio defined as the ratio between systolic peak velocity in the renal artery and peak velocity in the abdominal aorta in the supra-renal tract with a normal value of < 3.5.

Renal scintigraphy was performed with a gamma camera, with either 99mTc-DTPA or           99mTc-MAG3. Criteria for a positive test were:

  • parenchymal transit time > 4 minutes
  • a difference in split renal function > 30%
  • Tmax > 5 minutes, with a difference between kidneys >1 minute.

A captopril test was performed in 161 out of the 224 patients undergoing renal scintigraphy. Criteria for a positive test following captopril administration with 99mTc-DTPA is a fall in glomerular filtration rate of the affected side > 5%. With 99mTc-MAG3, the criteria were an increase of at least 0.15 of the 20 minutes/peak count ratio; or a lengthening of > 2minutes of Tmax, or a delay of tracer elimination in the pelvis of > 2 minutes.

Of the 49 patients that had a Doppler U/S positive for renal artery stenosis, 35 received either MRA or RCA. Based on these 35 patients, the positive predictive value for U/S was reported to be 94.3% (80.8%, 99.3%). The negative predictive value was found to be 87.0% (66.4%, 97.2%).

Of the 24 patients that had a Doppler U/S positive for renal artery stenosis, 18 received either MRA or RCA. Of the 200 negative cases, 17 patients underwent angiography. Based on the 35 patients that received both renal scintigraphy and angiography, the positive predictive value for scintigraphy was reported to be 0.722 (0.465, 0.903). The negative predictive value was found to be 0.294 (0.103, 0.56).

Huot et al.22 

Huot et al.22 conducted a retrospective study to investigate the diagnostic accuracy of captopril renal scintigraphy. Subjects included all patients at an American hospital who underwent both renal scintigraphy and RCA within a six-month period. Kidneys were the unit of analysis. A total of 169 kidneys from 86 patients were included in the analysis. Results from the RCA were considered the gold standard.

The criteria for a positive renal scintigraphy included:

  • time to peak activity of more than 11 minutes on either pre-captopril or post-captopril scan
  • or glomerular filtration greater than 1.5 between the two kidneys on the post-captopril scan.

Criteria of positive test results for RCA were stenosis of more than 75% or stenosis of more than 50%, with post-stenotic dilatation.

The sensitivity and specificity of renal scintigraphy was found to be 0.74 (0.62, 0.86) and 0.59 (0.49, 0.69), respectively. The positive predictive value of renal scintigraphy was reported to be 0.58 (0.47, 0.68), while the negative predictive value was estimated to be 0.75 (0.64, 0.84).

Karanikas et al.23 

Karanikas et al.23 compared the sensitivity of captopril renal scintigraphy with valsartan renal scintigraphy. Valsartan is an angiotensin receptor blocker. The study included 25 hypertensive patients confirmed to have renal artery stenosis by means of RCA. The 25 patients in the study had a total of 33 stenosed vessels. Vessels were the unit of analysis.

 All subjects received captopril scintigraphy, valsartan scintigraphy, and baseline renal scintigraphy within 48 hours. 99mTc-MAG3 was used as the radiopharmaceutical for all renal scintigraphy tests.

Criteria for a positive captopril renal scintigraphy and valsartan renal scintigraphy were either: 

  • an increase in Tmax of at least two minutes or 40% after captopril or valsartan compared with baseline scintigraphy
  • or an increase of at least 0.15 in the ratio of the amplitude at 20 minutes to the amplitude at Tmax of the curves after captopril or valsartan scintigraphy.

A criterion for a positive test with RCA was 50% or greater stenosis.

The authors reported the sensitivity for captopril renal scintigraphy to be 0.76. This compares to a sensitivity of 0.30 found for valsartan renal scintigraphy.

Balink et al.19 

Balink et al.19 studied the diagnostic accuracy of captopril renal scintigraphy using bilateral identical curves. The study population included 158 patients suspected of renal hypertension undergoing both renal scintigraphy and RCA.

Criteria for a positive renal scintigraphy was relative uptake in one of the kidneys of < 40% or if the Tmax in one or both kidneys was ≥ to six minutes. A criterion for a positive RCA was renal artery stenosis of 50% or more.

The authors reported the sensitivity of renal scintigraphy to be 0.83, while the specificity of renal scintigraphy was estimated to be 0.75. In the 42 patients that had bilateral renal artery stenosis detected by RCA, renal scintigraphy diagnosed 0.46 of patients as having bilateral renal artery stenosis.

Krijnen et al.49 

In a secondary analysis of the DRASTIC (Dutch Renal Artery Stenosis Intervention Cooperative) study, Krijnen and colleagues retrospectively evaluated different subgroups of patients: patients with positive captopril-renin scintigraphy, abnormal captopril renogram, recently developed hypertension, bilateral stenosis, and severe stenosis.49 The authors found that only those patients with bilateral RAS benefited from immediate intervention with balloon angioplasty. Patients had a normal or mildly impaired renal function (serum creatinine concentration ≤ 2.3 mg/dL) at study entry; but after one year of follow-up, their renal function had improved if angioplasty had taken place immediately after diagnosis, although renal function deteriorated if angioplasty had been delayed for three months. None of the other subgroups had a clear benefit of immediate intervention regarding renal function or blood pressure control.

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