Evaluation of Renal Function Post-Transplant

Indication Overview

Kidney transplantation is a treatment option for end-stage renal disease (ESRD). It can help to restore patients' quality of life and reduces morbidity and mortality rates in patients with renal failure.1 However, several complications can occur after transplantation and may result in impaired renal function. These complications can be classified as surgical or medical. Immediate surgical complications include renal artery thrombosis or stenosis, renal vein thrombosis, or urinary leak. Medical complications include organ/tissue rejection, drug toxicity related to anti-rejection treatments (e.g., cyclosporine), acute tubular necrosis (ATN), infection, and transplantation-related malignancies (e.g., post-transplantation lymphoproliferative disorder or lymphoma).2-4 Obstruction in a renal transplant can also occur and result in paranchymal damage due to increased pressure in the collecting system.5

The most common complication of kidney transplantation is allograft dysfunction (dysfunction of the transplanted kidney). This can take place as early as in the operating room (considered "very early" dysfunction), as an early dysfunction (one to 12 weeks post-transplant), or as a late dysfunction (later than three months).6 Symptoms include an acute rise in serum creatinine, decreased urine production, increased blood pressure, pyuria (white blood cells in urine), and proteinuria (protein in the urine). The focus of this report is on acute rejection.

Acute rejection, ATN, and cyclosporine toxicity are the most common causes of early transplant failure.4,7,8 These complications may result in deterioration of renal function as a late permanent event. Therefore, careful monitoring of patients following a kidney transplant is required to detect complications before severe damage occurs.1,9 The common methods of monitoring include the clinical assessment of the patient, ultrasound (U/S) examinations (grey scale and Doppler), isotope-based studies (e.g., renal scintigraphy), needle core biopsy, and fine-needle aspiration biopsy with cytology.1,8,9

Population: Patients who received kidney transplants being evaluated for acute rejection.

Intervention: Renal scintigraphy (also referred to as renal scan) using technetium-99m(99mTc)–labelled radiopharmaceuticals.

Renal scintigraphy has been used to assess the structure, blood flow, and function of kidney transplants.3,5 With nuclear imaging, the radiolabelled isotopes permit the mapping of blood flow through the kidney. This allows the imaging of blood flow, obstructions, or leaks in the newly transplanted kidney.10

During renal scintigraphy, a radiopharmaceutical is administered, and gamma rays emitted from the patient are externally detected with a gamma camera to produce images that reflect the distribution of the radioactive agent.11 Two 99mTc-labelled radiopharmaceuticals that have been used for dynamic renal scintigraphy include 99mTc-diethylenetriamine pentaacetic acid (DTPA) and 99mTc-mercaptoacetyl triglycine (MAG3).1299mTc-DTPA does not defuse into cells due to its lipid insolubility, and is almost entirely removed from circulation by glomerular filtration. Early images with this agent provide information about renal perfusion, whereas delayed images provide information about glomerular filtration rate (GFR), indicating changes in renal function.1299mTc-MAG3 is rapidly taken by the kidneys and excreted into the urinary tract.11 Because of the higher extraction efficiency, 99mTc-MAG3 may be preferred over 99mTc-DTPA, especially in patients with decreased renal function.12,13 Using renal scintigraphy, graft function can be assessed both qualitatively and quantitatively.14

The quantitative evaluation of the graft (i.e., transplanted kidney) function is based on the time-activity curves, known as renograms, which reflect three sequential phases of renal function:5,15,16

  • Vascular phase, or flow study, shows the transit of radiotracer through the blood vessels (performed within approximately five seconds after administration of the radiopharmaceutical)
  • Parenchymal or function phase is the period in which the nephrons extract the tracer from the blood and excrete it by glomerular filtration or tubular secretion (performed two to three minutes after administration of the radiopharmaceutical)
  • Washout or excretory phase is the period during which the tracer drains through the renal pelvis to the bladder (performed 20 to 30 minutes after administration of the radiopharmaceutical in a normally hydrated patient).

A renogram of a normal kidney shows rapid increase during the vascular and parenchymal phases, followed by rapid decline during the excretory phase.11

Various quantitative indices have been proposed to evaluate the handling of the tracer by the kidney. The two widely used indices in vascular phase, Hilson's perfusion index and Kirchner's kidney/aorta ratio, reflect the relationship between renal blood flow in the graft and the blood flow in the iliac artery or abdominal aorta. These indices allow the differential diagnosis between ATN and acute rejection. Blood flow of the transplanted kidney is less affected in patients with ATN than in patients with acute rejection.5 To evaluate the function of transplanted kidney, two types of quantitative measures are used: indices of renal function (e.g., tracer uptake capacity, GFR, effective renal plasma flow [ERPF], clearance index) and indices of tracer transit (e.g., mean transit time, excretory index).5 Decreased uptake in the parenchymal phase and prolonged washout in the excretory phase are quantitative scintigraphic features of ATN and acute rejection.11 Accumulation of radiotracer activity in the collecting system is often observed in patients with obstruction.5

Comparators: For this report, the following diagnostic test is considered as an alternative to renal scintigraphy:

  • U/S is commonly performed in renal transplant patients, from the immediate post-operative period to long-term follow-up.7,8 This modality can also be used to guide other more invasive diagnostic tests. For example, it is used to guide the needle in renal biopsy so that a desired tissue can be removed with less damage and complications.14 In U/S, both the internal renal morphology (e.g., renal enlargement, heterogeneity of renal cortex, hypoechogenicity of renal pyramids and cortex, thickening of the walls of the renal collecting system) and the perinephric complications of kidney transplant, such as perinephric fluid collection, can be examined.4,14 Doppler U/S is used for detection of vascular complications.4,8 The two most commonly used quantitative Doppler indices include resistive index and pulsatility index.1,4 Other measures such as systolic-to-diastolic and diastolic-to-systolic ratios have also been used to show the Doppler spectrum.1 More advanced U/S techniques, including duplex U/S and colour Doppler, may be used to diagnose vascular complications in a transplanted kidney.4 Sequential ultrasonographic studies may be required in the early post-operative period.1

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 and daily updates via Ovid; The Cochrane Library (2011, Issue 2) via Wiley; and PubMed. 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 kidney transplantation.

Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, and non-randomized studies, including diagnostic accuracy studies. The search was limited to English language documents. No date or human limits were applied for the systematic reviews search. For primary studies, the retrieval was limited to the human population and to documents published between January 1, 1996 and March 14, 2011.  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 five potential clinical articles identified through the meta-analyses/systematic review/health technology assessment (MA/SR/HTA) filtered search, none of which were relevant. A total of 404 potential primary studies were identified with the primary studies search and 47 articles underwent full-text review. No randomized controlled trials (RCTs) reporting on the accuracy of diagnostic tests of interest, patients outcomes, or quality of life were found. Seven observational studies reported on the relative diagnostic accuracy of renal scintigraphy and the alternative tests of interest.17-23

The original search did not capture studies evaluating the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) compared to renal scintigraphy or vice versa. One older study comparing FNAB, renal scintigraphy, and U/S to core needle biopsy was found from the reference lists of the included articles.24 The remaining articles from the database searches, along with other articles found through searching the grey literature, articles from the targeted searches, or articles from the reference lists of the identified potential articles, were used to abstract information relevant to 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 The potential population requiring post-transplant renal scintigraphy or its alternatives includes all patients who have received kidney transplants. The prevalence rate of patients living with kidney transplants was 4.57 per 10,000 population in 2009.25

It is assumed that fewer than 20% of these patients require imaging in a given year. The size of the affected population is less than 1 in 10,000 (0.01%).
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 be performed within the first 24 hours after transplantation in cases of suspected acute rejection (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011). Early diagnosis and careful management of complications prevents premature loss of the kidney transplant and reduces patient mortality and morbidity.1,4,26,27

The target time frame for performing the test is in 24 hours or less, and obtaining the test results in the appropriate timely manner for the underlying condition has moderate to significant 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 evaluating the effect of diagnostic modalities as factors influencing patient survival after kidney transplants were identified. However, two studies28,29 reported that renal transplant complications can significantly reduce graft and patient survival rates. Based on the risks associated with renal transplant complications, early recognition and intervention are important.

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 Two studies28,29 reported that renal transplant complications can significantly reduce graft and patient survival rates. Patients with graft failure may resume dialysis or be listed for repeat transplantation.28 They also may experience a higher number of rejection episodes per year, a higher number of hospitalizations, and longer hospital stays.30 Patients who return to dialysis after transplant failure may show poorer quality of life.31 Graft failure may be followed by grief and denial, and may trigger a depressive state.31 Based on the risks associated with renal transplant complications, early recognition and interventions are important.

Diagnostic imaging results are assumed to have a significant impact on morbidity and quality of life.

 

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 scan is reported to be well-tolerated.12 Patients may have concerns about radiation exposure and the intravenous injection of a radiopharmaceutical agent. Bladder catheterization may be required and catheterization may be associated with some discomfort, particularly in pediatric patients.32

Some discomforts associated with U/S include cold, unspecified pain, and tenderness. This test may be preferred in pediatric patients, as there is no exposure to ionizing radiation and U/S does not require sedation.

Renal scan using 99mTc-radiolabelled isotopes:

  • is minimally less acceptable than U/S.
7 Relative diagnostic accuracy of the test

Four observational studies17,18,24,33 on the relative diagnostic accuracy of renal scintigraphy, U/S, and biopsy were included in this review. Biopsy was used as the gold standard in the majority of the included studies.

Study (year) Renal Scan U/S
  Sensitivity (%) Specificity (%) Sensitivity (%) Specificity (%)
Kim et al. (2005)33 N/A N/A 85 90
Isiklar et al. (1999)18 59 57 81 57
Aktas et al. (1998)17 45 to100 N/A 36 to 88 N/A
Delaney, et al. (1993)24 70 N/A 43 N/A

N/A = not available; U/S = ultrasound.

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

  • similar to that of U/S.
8 Relative risks associated with the test

Adverse events from renal scintigraphy are rare but may include reaction to the radiopharmaceutical, rash, fever, or chills.34 Patients are exposed to ionizing radiation.

There are no reported risks associated with U/S in the literature that was reviewed.

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

  • minimally less safe than U/S.
9 Relative availability of personnel with expertise and experience required for the test

As of 2006 in Canada, there were 2,034 diagnostic radiologists, 221 nuclear medicine physicians, 12,255 radiological technologists, 1,781 nuclear medicine technologists, and 2,900 sonographers available across Canada. YT, NT, and NU do not have the available personnel to perform and interpret tests to evaluate renal function in transplant patients. Other jurisdictions (e.g.,PEI) may offer limited nuclear medicine services.

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

  • more than 95% of the procedures can be performed in a timely manner using U/S.
10 Accessibility of alternative tests (equipment and wait times) For renal scans, nuclear medicine facilities with gamma cameras (including SPECT) are required. No nuclear medicine cameras are available in the YT, NT, or NU.35 In 2007, the latest year for which data are available, the average wait time for renal scintigraphy at MUHC hospitals was 13 days. However, the wait times were reported to be less than one day for emergency cases.36 In 2009, there were 23 active kidney transplant programs in Canada, operating in seven provinces (AB, BC, MB, NS, ON, QC, and SK).25

No information was found on the accessibility of U/S in Canada. According to the Fraser Institute, the average wait time for U/S in 2010 was 4.5 weeks.37 Ontario had the shortest wait time (two weeks), whereas patients in Quebec experienced the longest wait time (eight weeks)   for U/S.37

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

  • 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 renal scintigraphy with 99mTc-based radioisotopes is $241.95. U/S is a minimally less costly alternative.

Relative Costs
Test Total Costs ($) Cost of Test Relative to 99mTc-based Test ($)
Renal scintigraphy 241.95 Reference
U/S 44.60 –197.35

 

AB = Alberta; BC = British Columbia; MB = Manitoba; MUHC = McGill University Health Centre; N/A = not available; NS = Nova Scotia; NT = Northwest Territories; NU = Nunavut;        ON = Ontario; PEI = Prince Edward Island; QC = Quebec; SK = Saskatchewan; SPECT = single-photon emission tomography;99mTc = technetium-99m; U/S = ultrasound; YT = Yukon.

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

The potential population requiring post-transplant renal scintigraphy or its alternatives includes patients who have received kidney transplants. This includes newly transplanted kidneys (incident cases), as well as the total number of patients living with functioning transplanted kidneys (prevalent cases). According to the Canadian Organ Replacement Register (CORR), a registry of the Canadian Institute for Health Information,25 1,171 Canadians adults and 53 children received kidney transplants in 2009. As of December 31, 2009, the prevalence of people living with a functioning kidney transplant in Canada was 15,434 (4.57 per 10,000).25 Of 10,641 kidney transplant procedures registered with CORR between 2000 and 2009, 1,141 (11%) were retransplants.25 It is assumed that only a proportion of these patients require imaging in a given year.

Return to Summary Table.

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

Early diagnosis and careful management of complications prevents premature loss of the kidney transplant and reduces patient mortality and morbidity.1,4,26,27 Timely diagnosis is particularly important in young children: renal graft outcomes can be less favourable than in older recipients, due to more intense immune-reactivity and higher graft rejection rates in children, as well as inconsistent adherence to medication in this group of transplant recipients.27 Baseline imaging studies should be performed immediately after transplantation, as the diagnosis of complications can be made based on changes in the results of imaging studies over time.4

According to the Saskatchewan hospital guidelines, renal scintigraphy should be performed within the first 24 hours after transplantation in cases of suspected acute rejection (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011). The suggested renal scintigraphy wait time targets for patients with suspected renal artery stenosis, urinary leak, or obstructive uropathy after transplantation is two to seven days (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011). The same guidelines indicate that U/S for diagnosis of renal transplant rejection should be conducted within two to seven days after transplantation (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011). However, the use of U/S is suggested within the first 24 hours in cases with suspected thrombosis of renal artery or vein (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011).

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

Kidney transplant patients are at risk of complications, including loss of transplant function. Timely diagnosis of these complications is important in order to reduce patient mortality and morbidity.4 Some cases of acute rejection and ATN may not present clinical symptoms.1 Failure to perform the appropriate imaging tests may result in increased rates of graft dysfunction (due to delayed or inappropriate treatment) and post-transplant mortality.

Two studies evaluating the relationship between kidney graft function and patient survival were identified through targeted searches.28,29

In 2005, Knoll et al. published a retrospective cohort study on the effects of functional renal transplant loss on patient survival, using the data from the CORR (n = 4,743 primary renal transplant recipients transplanted between 1994 and 1999).28 In five years of follow-up, 411 patients (8.7%) died.28 One-hundred and three deaths were attributed to graft failure.28 The unadjusted death rate was 5.14 per 100 patients with kidney transplant failure.28 After controlling for possible confounding variables (e.g., recipient age, gender, race, cause of ESRD, comorbidity, pretransplant dialysis time, donor source, and donor age), transplant failure was shown to significantly increase the risk of death more than three times, as compared with patients who maintained transplant function (adjusted hazard ratio = 3.39; 95% Confidence Interval [CI], 2.75 to 4.16; P < 0.0001).28 The authors concluded that kidney transplant failure following renal transplantation is a significant predictor of mortality.28

A previous study (1999) by Woo et al. investigated the association between graft and patient survival rates (n = 589 patients who received their first kidney transplants from deceased donors between 1984 and 1993).29 The median follow-up time was seven years.29 Patient survival rates were 95%, 82%, and 65% at one, five, and 10 years after transplantation, respectively.29 One-hundred and sixty-eight patients (28.5%) died during follow-up; 79 (47% of all deaths) were due to transplant failure. In this study, good graft function (serum creatinine levels < 200 µmol/L) at three months was associated with significantly improved long-term graft survival (P < 0.001). Long-term survival was higher for patients with functioning grafts (85% and 70% at five and 10 years, respectively) than for those who had graft failure (75% and 56%, at five and 10 years, respectively; P = 0.004 for log-rank test). The authors concluded that patient survival after kidney transplant is related to graft outcomes, and that patients with early graft rejection, or early graft loss, are at increased risk of mortality.

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

One of the main goals of kidney transplantation is to improve patient quality of life.38

Two studies evaluating the relationship between kidney graft function and patient morbidity or quality of life were identified through targeted searches.30,31

In 2006, Ouellette et al.31 performed a qualitative literature review on the psychological impacts of renal graft loss. The following findings of the reviewed studies were discussed in the article:

  • Patients who return to dialysis after graft failure show a poorer health-related quality of life (HQoL) than dialysis patients who have never received a renal transplant.
  • Reaction to graft failure and its impact on quality of life may vary from patient to patient.
  • Patients may react to graft loss in two different ways: grief and denial.
  • The grieving process may include feelings of guilt, depression, irritability, anger, or sadness, as well as concerns about the impact of graft loss on patient's future lifestyle.
  • Patients who go through the denial process after graft loss do not show any emotional response to graft failure.
  • People who experience graft failure may also report feelings of loss of control over their life, guilt about the donated kidney being wasted, and failure in fulfilling others' expectations.

A 1999 study by Aultman et al.30 followed 179 consecutive renal transplant recipients grouped according to their length of graft success: failure within six months of implantation (n = 18), failure between six months and three years (n = 41), and grafts surviving longer than three years (n = 120). As would be expected, those transplant recipients with grafts surviving longer than three years experienced the greatest benefit.30 Patients with primarily successful renal transplants (grafts surviving longer than six months, but less than three years) experienced a significantly greater number of complications and more serious, life-threatening outcomes (i.e., bacterial sepsis, pneumonia, severe wound infection) when compared with either of the two other groups (see Table 2).30

Table 2: Morbidity Associated With Graft Rejection30

  Group 1: Graft Failure Within Six Months of Implantation (n = 18) Group 2: Graft Failure Between Six Months and Three Years (n = 41) Group 3: Grafts Surviving Longer Than Three Years (n = 120) P
Rejections per patient/year 0.6 2.4 0.5 < 0.0001
Hospitalizations per year 1.3 3.0 0.8 < 0.0001
Days in hospital per year 20 31 6 < 0.0001
Complications per patient 1.1 1.3 0.6 < 0.0001
Patient survival (%) 83 76 90  

If a test was not available to monitor the transplanted kidney, patients would risk more severe and permanent complications — such as graft lost, for example. Patients with known graft failure may resume dialysis, or be listed for repeat transplantation.28

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

To be scored locally.

Health disparity might be present if disadvantaged social groups systematically experience worse health or more health risks than do more advantaged social groups.39 Disadvantaged groups can be defined based on gender, age, ethnicity, geography, disability, sexual orientation, socioeconomic status, and special health care needs. Our targeted search found disparity concerns in the following disadvantage groups:

Racial and ethnic groups
Matsuda-Abedini et al.(2009)40 conducted a retrospective, single Canadian centre database review to determine the short- and long-term outcomes of kidney transplantation in Aboriginal children compared to non-Aboriginals in British Colombia. Of the 159 kidney transplant recipients included in this study, 15% were Aboriginal.40 At the end of first year post-transplant, there was no difference between Aboriginal and non-Aboriginal children regarding early transplant outcomes such as delayed graft function, episodes of acute rejection, and estimated glomerular function rate.40 However, Aboriginal kidney recipients had a significantly lower long-term transplant survival than the non-Aboriginal group (delayed rejection rate: 50% versus 26.7%, P = 0.03).40 Assuming uniform access to health care across the province of British Columbia, the authors attributed the difference in outcomes observed in Aboriginal and non-Aboriginal children to a combination of factors:

  • the different etiology of ESRD (glomerulonephritis is the most common cause of ESRD among Aboriginals versus congenital abnormalities of the urinary tract among non-Aboriginals)
  • the different rates of pre-emptive transplants (none of the Aboriginal patients received a preventative transplantation versus 22% of non-Aboriginals transplant recipients who had not been exposed to dialysis).40

Health care centre variations
Kim et al.(2004)41 studied 5,082 Canadian patients who received kidney transplantation between 1988 to 1997, across 20 transplant centres. Patients were followed from the date of transplantation to the time of graft failure, death, or end of study (December 31, 1997).41 Centre-specific, covariate-adjusted hazard ratios were calculated.41 These can be interpreted as the covariate-adjusted rate for a given centre, divided by the covariate-adjusted rate for all remaining centres.41 Graft failure (including patient death) hazard ratios varied from 0.51 (approximately 49% lower graft failure, relative to the remaining centres) to 1.77 (approximately 77% higher graft failure rates, relative to the remaining centres).41 Covariate-adjusted hazard ratios for mortality varied from 0.44 to 1.84.41 Six centres showed significantly elevated rates of graft loss (range: 1.36 to 1.84; i.e., 36% to 84% higher than other centres), whereas five centres showed significantly decreased rates (range: 0.44 to 0.65; i.e., 35% to 66% lower than other centres).41 Patient death and graft loss rates were lower in larger centres (with ≥ 200 transplants over the study period).41 The variation in transplant outcomes persisted after adjustment for known prognostic factors such as recipient age, proportion of deceased- and living-donor transplants performed, and the percentage of patients with diabetes.41 In addition, disparities in centre-specific outcomes increased with increasing time from transplantation (at one, three, and five years).41 The authors concluded that significant centre-specific variation in the success of renal transplantation exists in Canada.41 This disparity could be impacted by a lack of availability to imaging, particularly if smaller centres have more difficulties acquiring 99mTc-based radiopharmaceuticals and accessing alternate imaging modalities.

Gender
Liu et al. (2007)42 evaluated the effect of gender on HQoL in 66 female and 72 male kidney transplant recipients in one American transplant centre. HQoL was measured using the SF-36 Health Survey.42 Women reported significantly lower scores on the SF-36 physical functioning (P = 0.049), role-physical (P = 0.014), and bodily pain (P = 0.028) scales.42 The authors concluded that women may experience worse physical functioning and more body pain and face more problems with work and other daily activities than men.42 They suggested that the study findings could be used in developing interventions to optimize HQoL in renal transplant patients.42

Level of education
Schaeffner et al.(2008)43 investigated the relationship between level of education and transplantation outcomes in 670 American patients who received renal transplants between 1996 and 1997.43 There was no significant association between educational level and graft failure.43 However, the rates of graft loss from causes other than death significantly decreased from lowest to highest level of education, so that patients who had a college degree had 43% lower rates of graft loss than the ones who did not complete high school (relative risk: 0.57, 95% CI, 0.31 to 1.04; P-value for trend = 0.03).43 The authors suggested that the greater risk of graft loss in patients with lower education might be related to comorbidities and poor medication adherence.43

Socioeconomic status
In a single-centre study in the United Kingdom, Stephens et al. (2010) investigated the impact of socioeconomic deprivation on post-transplant outcomes in 621 renal transplant recipients.44 Patients in the most income-deprived group had a significantly higher rate of acute rejection than the ones in the least income-deprived group (36% versus 27%, P = 0.013).44 Income deprivation was significantly associated with five-year graft survival (log-rank test for least deprived versus most deprived, P = 0.018).44 The authors concluded that socioeconomic deprivation might adversely influence outcomes following renal transplantation.44

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

Renal scintigraphy
Overall, renal scan is reported to be well-tolerated.12 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.45 Because a full bladder may slow drainage of the radiopharmaceutical from the upper part of the urinary tract, the bladder should be emptied frequently. Bladder catheterization may be required, especially in pediatric patients. Catheterization may be associated with some discomfort, particularly in children.32

U/S
Some discomforts associated with U/S include cold, unspecified pain, and tenderness. This test may be preferred in pediatric patients, as there is no exposure to ionizing radiation, and the test does not require sedation.

Return to Summary Table.

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

Four observational studies17,18,24,33 on the relative diagnostic accuracy of renal scintigraphy and U/S were included in this report. The studies focus primarily on the diagnostic accuracy of 99mTc-labelled radiotracer scintigraphy compared with renal biopsy. One study directly compared U/S to renal scintigraphy.33 One older study comparing FNAB, renal scintigraphy, and U/S to core needle biopsy was found from the reference lists of the included articles.24 Detailed descriptions of the individual studies can be found in Appendix 4. The methods and results of the included studies are summarized in tabular form in Appendix 5.

Table 3: Relative Diagnostic Accuracy of Renal Scan and U/S

Study (year) Population (n) Outcome Standard of Reference Renal Scan U/S
Sens. (%) Spec. (%) Sens. (%) Spec. (%)
Kim et al. (2005)33 Adults (100) Evaluation of renal perfusion Renal scan N/A N/A 85 90
Isiklar et al. (1999)18 Adults (29) Acute renal transplant rejection Renal biopsy 59 57 81 57
Aktas et al. (1998)17 Patients with biopsy-proven acute rejection (26) Acute renal transplant rejection Renal biopsy 45 to 100 N/A 36 to 88 N/A
Delaney et al. 1993)24 Adults (150); episodes of allograft dysfunction, 128 transplant recipients) Acute renal transplant rejection Core needle biopsy 70 N/A 43 N/A

ATN = acute tubular necrosis; N/A = not available; Sens. = sensitivity; Spec = specificity; U/S = ultrasound.

Renal scintigraphy versus U/S
One study33 compared the diagnostic accuracy of harmonic U/S (with microtubular contrast agent) to renal scintigraphy in the diagnosis of renal perfusion abnormalities.33 In this study, the sensitivity and specificity of harmonic U/S was reported to be 85% and 90%, respectively.33

Two studies17,18 compared the diagnostic accuracies of renal scintigraphy and U/S, using renal biopsy as the gold standard. Isiklar et al. (1999) found power Doppler U/S to be more sensitive than renal scintigraphy (81% versus 59%) in detecting post-transplant renal perfusion impairments.18 A year earlier, Aktas et al. (1998) reported the overall sensitivity of renal scintigraphy to be higher than that of both gray scale and Doppler U/S.17

Renal scintigraphy, Doppler U/S, and FNAB versus biopsy
Delaney et al.(1993)24 compared renal scintigraphy, Doppler U/S, and FNAB, using biopsy as the gold standard. Scintigraphy was found to be the most sensitive method for detection of acute rejection (70%) during the early post-transplant period, FNAB had a sensitivity of 52%, and U/S a sensitivity of 43%.

Return to Summary Table.

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

Non–radiation-related Risks

Renal scan
Adverse events from renal scintigraphy are rare but may include reaction to the radiopharmaceutical, rash, fever, or chills.34 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 renal artery stenosis (MIIMAC expert opinion).

U/S
There are no reported risks associated with U/S in the literature that was reviewed.

Radiation-related Risks

The radiation doses of radiopharmaceuticals used for renal scintigraphy are summarized in Table 4. As the table shows, the effective dose equivalent (weighted organ radiation doses) with 37 megabecquerels (MBq) of 99mTc-MAG3 (0.37 millisieverts [mSv]) or 99mTc-DTPA (0.33 mSv) is less radiation than a plain abdominal X-ray in adults (1.4 mSv).3

Table 4: Radiation Dose Estimates for the Radiopharmaceuticals Used for Post-Transplant Renal Scintigraphy3

Organ Estimated Radiation Dose (mSv)
MAG3 DTPA
Bladder voiding every 4.8 hrs Bladder voiding at 30 min. and every 4 hrs Bladder Voiding Every 4.8 hrs Bladder voiding at 30 min. and every 4 hrs
Kidneys 0.148 0.144 0.141 0.137
Ovaries 0.215 0.085 0.199 0.126
Bone marrow 0.037 0.018 0.055 0.044
Bone surface 0.52 0.025 0.081 0.067
Testes 0.148 0.592 0.141 0.089
Urinary bladder wall 4.440 1.665 3.478 1.924
Uterus 0.481 0.189 0.407 0.244
Total body 0.052 0.024 0.067 0.048
Effective dose equivalent 0.370 0.155 0.329 0.199

DTPA = diethylenetriamine pentaacetic acid; hrs = hours; MAG3 = mercaptoacetyl triglycine; min. = minutes; mSv = millisevert.

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 imaging tests for post-transplant renal scintigraphy are presented by imaging modality. A summary of the availability of personnel required for the conduct of methods for post-transplant renal scintigraphy, by renal scan or any of the alternative imaging modalities, is provided in Table 5.

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. Physicians should have a Fellowship of Certification in Nuclear Medicine or Diagnostic Radiology with the Royal College of Physicians and Surgeons of Canada and/or the Collège des médecins du Québec. Nuclear medicine technologists are required to conduct renal scans. Technologists must be certified by the Canadian Association of Medical Radiation Technologists or an equivalent licensing body.

All alternative imaging modalities
In Canada, physicians involved in the performance, supervision, and interpretation of diagnostic computed tomography (CT) scans, MRI, and U/S should be diagnostic radiologists35 and must have a Fellowship or Certification in Diagnostic Radiology with the Royal College of Physicians and Surgeons of Canada and/or the Collège des médecins du Québec. Foreign-trained radiologists also are qualified if they are certified by a recognized certifying body and hold a valid provincial licence.46

Medical radiation technologists must be certified by the Canadian Association of Medical Radiation Technologists or an equivalent licensing body.

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 nuclear medicine equipment.46

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. They should be members of their national or provincial professional organization. Sonography specialties include general sonography, vascular sonography, and cardiac sonography.35 In Quebec, sonographers and medical radiation technologists are grouped together; in the rest of Canada, sonographers are considered a distinct professional group.35

Table 5: Medical Imaging Professionals in Canada35

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 across Canada. Table 6 provides an overview of the availability of equipment required for post-transplant renal scintigraphy. Data for nuclear medicine cameras (including single-photon emission computed tomography [SPECT]) are current to January 1, 2007. The number of SPECT/CT scanners is current to January 1, 2010. Data were not available for U/S.

Table 6: Diagnostic Imaging Equipment in Canada35,47

  Nuclear Medicine Cameras SPECT/CT Scanners
Number of devices 60335 9647
Average number of hours of operation per week (2006-2007)35 40 n/a
Provinces and Territories with no devices available YT, NT, NU PEI, YT, NT, NU

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

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.35 In 2007, the latest year for which data are available, the average time for renal scintigraphy at McGill University Health Centre hospitals was 13 days. However, the wait times were reported to be less than one day for emergency cases.36

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.37

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 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 7), the cost of renal scintigraphy with 99mTc-based radioisotopes is $241.95. U/S is a minimally less costly alternative.

Table 7: Cost Estimates Based on the Ontario Schedule of Benefits for Physician Services under the Health Insurance Act (September 2011)48

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
Maintenance fees — from global budget 33.85   33.85
TOTAL 168.95 73.00 241.95
U/S
J205 Doppler evaluation of organ transplantation (arterial and/or venous) 22.60 18.70 41.30
Maintenance fees — from global budget 3.30   3.30
TOTAL 25.90 18.70 44.60

Prof. = professional; Tech. = technical; U/S = ultrasound.

Return to Summary Table.

References

  1. Baxter GM. Imaging in renal transplantation. Ultrasound Q. 2003 Sep;19(3):123-38.
  2. Neimatallah MA, Dong Q, Schoenberg SO, Cho KJ, Prince MR. Magnetic resonance imaging in renal transplantation. J Magn Reson Imaging. 1999 Sep;10(3):357-68.
  3. Itoh K. 99mTc-MAG3: review of pharmacokinetics, clinical application to renal diseases and quantification of renal function. Ann Nucl Med. 2001 Jun;15(3):179-90.
  4. el-Maghraby TA, de Fijter JW, Wasser MN, Pauwels EK. Diagnostic imaging modalities for delayed renal graft function: a review. Nucl Med Commun. 1998 Oct;19(10):915-36.
  5. Dubovsky EV, Russell CD, Bischof-Delaloye A, Bubeck B, Chaiwatanarat T, Hilson AJ, et al. Report of the Radionuclides in Nephrourology Committee for evaluation of transplanted kidney (review of techniques). Semin Nucl Med. 1999 Apr;29(2):175-88.
  6. Kadambi PV, Brennan DC. Differential diagnosis of renal allograft dysfunction. 2011 Feb 11 [cited 2011 Jul 7]. In: UpToDate [Internet]. Version 19.1. Waltham (MA): UpToDate, Inc.; c2005 - . Available from: http://www.uptodate.com Subscription required.
  7. Lockhart ME, Robbin ML. Renal vascular imaging: ultrasound and other modalities. Ultrasound Q. 2007 Dec;23(4):279-92.
  8. Rajiah P, Lim YY, Taylor P. Renal transplant imaging and complications. Abdom Imaging. 2006 Nov;31(6):735-46.
  9. Pascoe MD, Hughes DA. Fine needle aspiration biopsy and cytology in renal transplantation. Curr Opin Nephrol Hypertens. 2000 Nov;9(6):689-94.
  10. Chon WJ, Brennan DC. Acute renal allograft rejection: diagnosis. 2010 Jan 19 [cited 2011 Jul 7]. In: UpToDate [Internet]. Version 19.1. Waltham (MA): UpToDate, Inc.; c2005 - . Available from: http://www.uptodate.com Subscription required.
  11. Inoue Y, Minami M, Ohtomo K. Isotopic scan for diagnosis of renal disease. Saudi J Kidney Dis Transpl. 2004 Jul;15(3):257-64.
  12. Goldfarb CR, Srivastava NC, Grotas AB, Ongseng F, Nagler HM. Radionuclide imaging in urology. Urol Clin North Am. 2006;33(3):319-28.
  13. Expert Panel on Musculoskeletal Imaging, Roberts CC, Daffner RH, Weissman BN, Bancroft L, Bennett DL, et al. ACR Appropriateness Criteria©: metastatic bone disease [Internet]. Reston (VA): American College of Radiology (ACR); 2009. 11 p. [cited 2011 Oct 13]. Available from: http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/pdf/ExpertPanelonMusculoskeletalImaging/MetastaticBoneDiseaseDoc14.aspx
  14. Brown ED, Chen MY, Wolfman NT, Ott DJ, Watson NE Jr. Complications of renal transplantation: evaluation with US and radionuclide imaging. Radiographics. 2000 May;20(3):607-22.
  15. Aktas A, Aras M, Colak T, Demirhan B. The significance of Tc-99m DTPA renal scintigraphy for the demonstration of progressive functional changes that accompany chronic allograft nephropathy. Transplant Proc. 2005 Sep;37(7):3124-9.
  16. el Maghraby TA, van Eck-Smit BL, de Fijter JW, Pauwels EK. Quantitative scintigraphic parameters for the assessment of renal transplant patients. Eur J Radiol. 1998 Oct;28(3):256-69.
  17. Aktas A, Isiklar I, Gulaldi NC, Dermirag A, Demirhan B. Sensitivity of radionuclide imaging, Doppler, and gray-scale ultrasound to detect acute rejection episodes, based on the pathologic grade of acute rejection. Transplant Proc. 1998 May;30(3):786-7.
  18. Isiklar I, Aktas A, Uzuner O, Demirag A, Haberal M. Power Doppler ultrasonography compared with scintigraphy in the diagnosis of renal allograft dysfunction. Transplant Proc. 1999 Dec;31(8):3330-1.
  19. Aktas A, Karakayali H, Bilgin N, Akkoc H, Moray G, Emiroglu R. Serial radionuclide imaging in acute renal allograft dysfunction. Transplant Proc. 2002 Sep;34(6):2102-5.
  20. Qureshi JI, Al-Saeedy AR, Barret J, Al-Ghamdi G, Al-Flaiw A, Hejaili F, et al. Can renal scan findings predict biopsy-proven allograft rejection? Exp Clin Transplant. 2005 Jun;3(1):338-40.
  21. Sanches A, Etchebehere EC, Mazzali M, Filho GA, Lima MC, Santos AO, et al. The accuracy of (99m)Tc-DTPA scintigraphy in the evaluation of acute renal graft complications. Int Braz J Urol. 2003 Nov;29(6):507-16.
  22. Sundaraiya S, Mendichovszky I, Biassoni L, Sebire N, Trompeter RS, Gordon I. Tc-99m DTPA renography in children following renal transplantation: its value in the evaluation of rejection. Pediatr Transplant. 2007 Nov;11(7):771-6.
  23. Prommegger R, Wimmer G, Profanter C, Sauper T, Sieb M, Kovacs P, et al. Virtual neck exploration: a new method for localizing abnormal parathyroid glands. Ann Surg. 2009 Nov;250(5):761-5.
  24. Delaney V, Ling BN, Campbell WG, Bourke JE, Fekete PS, O'Brien DP, et al. Comparison of fine-needle aspiration biopsy, Doppler ultrasound, and radionuclide scintigraphy in the diagnosis of acute allograft dysfunction in renal transplant recipients: sensitivity, specificity, and cost analysis. Nephron. 1993;63(3):263-72.
  25. Canadian Institute for Health Information. Canadian Organ Replacement Register annual report: treatment of end-stage organ failure in Canada, 2000 to 2009 [Internet]. Ottawa: The Institute; 2011. [cited 2011 May 9]. Available from: http://secure.cihi.ca/cihiweb/products/2011_CORR_Annual_Report_final_e.pdf
  26. Mucelli RP, Bertolotto M. Imaging techniques in acute renal failure. Kidney Int Suppl. 1998 May;66:S102-5.
  27. Their M, von Willebrand E., Taskinen E, Ronnholm K, Holmberg C, Jalanko H. Fine-needle aspiration biopsy allows early detection of acute rejection in children after renal transplantation. Transplantation. 2001 Mar 27;71(6):736-43.
  28. Knoll G, Muirhead N, Trpeski L, Zhu N, Badovinac K. Patient survival following renal transplant failure in Canada. Am J Transplant. 2005 Jul;5(7):1719-24.
  29. Woo YM, Jardine AG, Clark AF, MacGregor MS, Bowman AW, Macpherson SG, et al. Early graft function and patient survival following cadaveric renal transplantation. Kidney Int. 1999 Feb;55(2):692-9.
  30. Aultman DF, Sawaya DE, Zibari GB, McMillan RW, Lynn ML, Work J, et al. Are all successful renal transplants really successful? Am J Kidney Dis. 1999 Jul;34(1):61-4.
  31. Ouellette A, Achille MA, Vachon M. Psychological impact of kidney graft failure and implications for the psychological evaluation of re-transplant candidates. Dial Transplant. 2006;35(6):354-61.
  32. Renogram with Lasix© [Internet]. St. Paul (MN): Children's Hospitals and Clinics of Minnesota; 2007. [cited 2011 Apr 14]. (Patient/family education). Available from: http://www.childrensmn.org/Manuals/PFS/TestProc/116517.pdf
  33. Kim JH, Eun HW, Lee HJ, Goo DE, Choi DL. Clinical use of renal perfusion imaging by means of harmonic sonography with a microbubble contrast agent in patients after renal transplantation: preliminary study. J Ultrasound Med. 2005 Jun;24(6):755-62.
  34. Modric J. Gallbladder tests: ultrasound, CT, HIDA Scan, ERCP [Internet]. In: Burlingame (CA): Healthhype.com; 2009 [cited 2011 Apr 4]. Available from: http://www.healthhype.com/gallbladder-tests-ultrasound-ct-hida-scan-ercp.html.
  35. Canadian Institute for Health Information. Medical imaging in Canada 2007 [Internet]. Ottawa: The Institute; 2008. 199 p. [cited 2011 Apr 12]. Available from: http://secure.cihi.ca/cihiweb/products/MIT_2007_e.pdf
  36. 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/
  37. 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
  38. Humar A, Denny R, Matas AJ, Najarian JS. Graft and quality of life outcomes in older recipients of a kidney transplant. Exp Clin Transplant. 2003 Dec;1(2):69-72.
  39. Braveman P. Health disparities and health equity: concepts and measurement. Annu Rev Public Health. 2006;27:167-94.
  40. Matsuda-Abedini M, Al-AlSheikh K, Hurley RM, Matsell DG, Chow J, Carter JE, et al. Outcome of kidney transplantation in Canadian Aboriginal children in the province of British Columbia. Pediatr Transplant. 2009 Nov;13(7):856-60.
  41. Kim SJ, Schaubel DE, Jeffery JR, Fenton SS. Centre-specific variation in renal transplant outcomes in Canada. Nephrol Dial Transplant. 2004 Jul;19(7):1856-61.
  42. Liu H, Feurer ID, Dwyer K, Speroff T, Shaffer D, Wright PC. The effects of gender and age on health-related quality of life following kidney transplantation. J Clin Nurs. 2008 Jan;17(1):82-9. Epub 2007 Feb 21.
  43. Schaeffner ES, Mehta J, Winkelmayer WC. Educational level as a determinant of access to and outcomes after kidney transplantation in the United States. Am J Kidney Dis. 2008 May;51(5):811-8.
  44. Stephens MR, Evans M, Ilham MA, Marsden A, Asderakis A. The influence of socioeconomic deprivation on outcomes following renal transplantation in the United kingdom. Am J Transplant. 2010 Jul;10(7):1605-12.
  45. 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
  46. 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
  47. 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.
  48. 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, Ovid MEDLINE Daily and Ovid MEDLINE <1946 to March 14, 2011>
Date of Search: March 14, 2011
Alerts: Monthly search updates began March 14, 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: English language

No date limits for systematic reviews;

Publication years 1996-March 14, 2011 for primary studies;

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 Kidney Transplantation/
2 ((kidney* or renal*) adj5 (transplant* or graft* or allograft*)).ti,ab.
3 1 or 2
4 Technetium/
5 exp Technetium Compounds/
6 exp Organotechnetium Compounds/
7 exp Radiopharmaceuticals/
8 (Technetium* or Tc-99* or Tc99* or Tc-99m* or Tc99m* or 99mTc* or 99m-Tc*).tw,nm.
9 Radionuclide Imaging/ or Perfusion Imaging/
10 radionuclide imaging.fs.
11 radioisotope*.mp.
12 ((radionucl* or nuclear or radiotracer*) adj2 (imag* or scan* or test* or diagnos*)).ti,ab.
13 Tomography, Emission-Computed, Single-Photon/
14 (single-photon adj2 emission*).ti,ab.
15 (SPECT or scintigraph* or scintigram* or scintiphotograph*).ti,ab.
16 ((Renal* or kidney*) adj2 (imag* or scan*)).ti,ab.
17 (MAG3 or Mercaptoacetyltriglycine or Mertiatide or TechneScan or Mercaptoacetylglycylglycylglycine or Mercaptoacetyltriglycine).ti,ab.
18 125224-05-7.rn.
19 or/4-18
20 meta-analysis.pt.
21 meta-analysis/ or systematic review/ or meta-analysis as topic/ or exp technology assessment, biomedical/
22 ((systematic* adj3 (review* or overview*)) or (methodologic* adj3 (review* or overview*))).ti,ab.
23 ((quantitative adj3 (review* or overview* or synthes*)) or (research adj3 (integrati* or overview*))).ti,ab.
24 ((integrative adj3 (review* or overview*)) or (collaborative adj3 (review* or overview*)) or (pool* adj3 analy*)).ti,ab.
25 (data synthes* or data extraction* or data abstraction*).ti,ab.
26 (handsearch* or hand search*).ti,ab.
27 (mantel haenszel or peto or der simonian or dersimonian or fixed effect* or latin square*).ti,ab.
28 (met analy* or metanaly* or health technology assessment* or HTA or HTAs).ti,ab.
29 (meta regression* or metaregression* or mega regression*).ti,ab.
30 (meta-analy* or metaanaly* or systematic review* or biomedical technology assessment* or bio-medical technology assessment*).mp,hw.
31 (medline or Cochrane or pubmed or medlars).ti,ab,hw.
32 (cochrane or health technology assessment or evidence report).jw.
33 or/20-32
34 3 and 19 and 33
35 34
36 limit 35 to english language
37 exp "Sensitivity and Specificity"/
38 False Positive Reactions/
39 False Negative Reactions/
40 du.fs.
41 sensitivit*.tw.
42 (distinguish* or differentiat* or enhancement or identif* or detect* or diagnos* or accura* or comparison*).ti,ab.
43 (predictive adj4 value*).tw.
44 Comparative Study.pt.
45 (Validation Studies or Evaluation Studies).pt.
46 Randomized Controlled Trial.pt.
47 Controlled Clinical Trial.pt.
48 (Clinical Trial or Clinical Trial, Phase II or Clinical Trial, Phase III or Clinical Trial, Phase IV).pt.
49 (Clinical Trial or Clinical Trial, Phase II or Clinical Trial, Phase III or Clinical Trial, Phase IV).pt.
50 Multicenter Study.pt.
51 (random* or sham or placebo*).ti.
52 ((singl* or doubl*) adj (blind* or dumm* or mask*)).ti.
53 ((tripl* or trebl*) adj (blind* or dumm* or mask*)).ti.
54 (control* adj3 (study or studies or trial*)).ti.
55 (non-random* or nonrandom* or quasi-random* or quasirandom*).ti.
56 (allocated adj "to").ti.
57 Cohort Studies/
58 Longitudinal Studies/
59 Prospective Studies/
60 Follow-Up Studies/
61 Retrospective Studies/
62 Case-Control Studies/
63 Cross-Sectional Study/
64 (observational adj3 (study or studies or design or analysis or analyses)).ti.
65 cohort.ti.
66 (prospective adj7 (study or studies or design or analysis or analyses or cohort)).ti.
67 ((follow up or followup) adj7 (study or studies or design or analysis or analyses)).ti.
68 ((longitudinal or longterm or (long adj term)) adj7 (study or studies or design or analysis or analyses or data or cohort)).ti.
69 (retrospective adj7 (study or studies or design or analysis or analyses or cohort or data or review)).ti.
70 ((case adj control) or (case adj comparison) or (case adj controlled)).ti.
71 (case-referent adj3 (study or studies or design or analysis or analyses)).ti.
72 (population adj3 (study or studies or analysis or analyses)).ti.
73 (cross adj sectional adj7 (study or studies or design or research or analysis or analyses or survey or findings)).ti.
74 or/37-73
75 3 and 19 and 74
76 75 not case reports.pt.
77 exp animals/
78 exp animal experimentation/
79 exp models animal/
80 exp animal experiment/
81 exp vertebrate/
82 or/77-81
83 exp humans/
84 82 not 83
85 76 not 84
86 85
87 limit 86 to yr="1996 -Current"
88 87
89 limit 88 to english language

 

OTHER DATABASES
PubMed Same MeSH, keywords, limits, and study types used as per MEDLINE search, with appropriate syntax used.

Cochrane Library
(Issue 2, 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: March 10 to 15, 2011
Keywords: Included terms for kidney transplantation and radionuclide imaging
Limits: English language

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: Definitions

Acute tubular necrosis (ATN): A term to describe the functional cellular injury of the renal tubules due to ischemia.

The Banff working classification of kidney transplant pathology: In this schema, intimal arteritis and tubulitis are the principal lesions indicative of acute rejection. Glomerular, interstitial, tubular, and vascular lesions of acute rejection and "chronic rejection" are defined and scored 0 to 3+ to produce an acute and/or chronic numerical coding for each biopsy. Arteriolar hyalinosis (an indication of cyclosporine toxicity) is also scored. Principal diagnostic categories, which can be used with or without the quantitative coding, are: (1) normal, (2) hyperacute rejection, (3) borderline changes, (4) acute rejection (grade I to III), (5) chronic allograft nephropathy ("chronic rejection") (grade I to III), and (6) other.

Effective dose equivalent: The effective dose equivalent is a way of converting the actual complicated process of radioactive intake into a simplified concept of a uniform whole-body dose;, i.e. an equivalent of what an actual localized dose means to the overall body.

Megabecquerel (MBq): The becquerel (symbol Bq), named after Henri Becquerel, a Noble Prize winner for discovering radioactivity, is a unit of radioactivity. One Bq is defined as the activity of a quantity of radioactive material in which one nucleus decays per second. MBq is equal to 106 Bq.

Millisievert (mSv): The sievert (symbol Sv), named after Rolf Sievert, a Swedish medical physicist, is a unit of dose equivalent. It shows the biological effects of radiation, as opposed to the physical aspects, which are characterized by the absorbed dose. A mSv is one-thousandth of a sievert.

The quantitative parameters used by the included studies for interpretation of scintigraphic results:

  • Hilson's perfusion index is the area under the arterial curve to peak divided by the area under the renal curve × 100
  • Peak-to-plateau ratio is the peak activity divided by the plateau activity on the renal perfusion curve
  • Uptake is the ratio of kidney activity to background activity
  • Retention [R20] is the percentage of peak kidney activity retained at 20 minutes
  • Tpeak is the time at the peak of the renal perfusion curve.

Appendix 4: Description of the Studies Included to Assess the Diagnostic Accuracy of Renal Scintigraphy and Its Alternatives

Kim et al. (2005)33

This prospective study was conducted to compare the feasibility and value of harmonic ultrasound (U/S) with a microtubule contrast agent, with 99mTc-DTPA renal scintigraphy, in evaluation of post-transplant renal perfusion abnormalities. The study included 100 renal transplant recipients who underwent both renal scintigraphy and harmonic U/S. The results of both tests were evaluated quantitatively, using the time at the peak of the renogram curve (Tpeak), with a cut-off point of 35 seconds. Compared to renal scintigraphy, harmonic U/S was found to have a sensitivity of 85% and a specificity of 90%. Based on their findings, the authors suggested harmonic U/S with a microtubule contrast agent as an effective sonographic technique for the evaluation of transplanted kidney perfusion. 

Isiklar et al.(1999)18

This prospective study was conducted to compare the diagnostic accuracy of renal scintigraphy and Doppler U/S with that of core needle biopsy in detecting renal transplant dysfunction. Twenty-nine adult transplant recipients were included in the study. 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA) was used as the radiotracer for renal scintigraphy, and Hilson's perfusion index was used for quantitative evaluation of perfusion of the renal cortex. The results of the study (see Table 8 in Appendix 5) showed the sensitivity and specificity of renal scintigraphy to be 59% and 57%, respectively. Power Doppler U/S was more sensitive than renal scintigraphy in the diagnosis of transplanted kidney perfusion impairment. However, both modalities had similar specificities. The authors concluded that power Doppler U/S can be used as a simple, repeatable, and rapidly analyzed method with acceptable sensitivity to investigate perfusion abnormalities in renal transplant recipients.

Aktas et al. (1998)17

This retrospective study was performed with the aim of evaluating the sensitivity of renal scintigraphy, as well as gray-scale and Doppler U/S, in the diagnosis of acute renal transplant rejection. Renal scintigraphy and both U/S examinations were performed in all 26 study participants within 48 to 72 hours. Scintigraphic images were acquired after injection of bolus 99mTc-DTPA. Time-activity curves were generated, and Hilson's perfusion index (perfusion phase), uptake value, and retained activity were used for quantitative evaluation of the kidney perfusion and function. Resistive index was used as a quantitative parameter in evaluation of the U/S results (Appendix 5, Table 8). Core needle biopsies with U/S guidance were conducted in all patients and the results were used as the standard of reference. The diagnosis of acute transplant rejection by biopsy was based on Banff classification. The authors regarded grade I and grade IIA rejections as low-grade and grade IIB and grade III rejections as high grade acute rejection. The sensitivity of renal scintigraphy was 45% to 85% for low-grade and 88% to 100% for high-grade rejections. The overall sensitivity of renal scintigraphy was higher than that of gray-scale and Doppler U/S examinations for both low- and high-grade acute rejections. The report did not include any conclusion or recommendations regarding the use of these modalities.

Delaney (1993)24

This cohort study evaluated patients both prospectively (111 episodes) and retrospectively (39 episodes) in order to compare efficacy and costs of U/S, renal scan, and fine-needle aspiration biopsy (FNAB). At a single institution, over a 12-month period, 150 episodes of allograft dysfunction in 128 renal transplant recipients were evaluated. At least three of four tests (core biopsy, FNAB, Doppler U/S, and renal scintigraphy) were performed on each patient prior to treatment and within 24 hours of deteriorating renal function. Core biopsy was performed on 106 occasions in 92 patients. Based on a combination of response to antirejection therapy and allograft histology, the study authors determined various causes of renal dysfunction. The sensitivities reported were based on the diagnosis of acute rejection, which was confirmed by beneficial response to acute antirejection therapy. Renal scanning was the most sensitive (70%) when compared with FNAB (52%) and U/S (43%). The authors recommended an initial U/S or renal scan, followed by core biopsy, as the most productive approach to diagnosis.

 

Appendix 5: Diagnostic Accuracy

Table 8: Diagnostic Accuracy of Renal Scintigraphy and Its Alternatives

Study (year) Study Design Population/ Condition (sample size) Standard of Reference Test Parameters Evaluated* (cut-off-point for diagnosis) Diagnostic Accuracy
Sensitivity Specificity Other
Aktas (1998)17 Retrospective observational study Adults/ acute renal transplant rejection (26) Renal biopsy RS (99mTc-DTPA) Perfusion phase:      
Hilson's PI ( > 100) 45% to 57% (LGR)
88% (HGR)		 – –
Parenchymal phase:      
Uptake (< 3) 55% to 71% (LGR)
100% (HGR)		 – –
Retention [R20] (> 60%) 64% to 85% (LGR)
100% (HGR)		    
U/S (gray scale) Resistive index (>0.71) 36% to 57% (LGR)
75% (HGR)		 – –
U/S (Doppler) 45% to 71% (LGR)
88% (HGR)		 – –
Isiklar (1999)18 Prospective cohort Adults/ renal transplant dysfunction (29) Renal biopsy RS (99mTc-DTPA) Hilson's PI (> 100) 59% 57% Ac = 58%

PPV = 81%

NPV = 30%

Prevalence† = 75%
U/S (power Doppler) – 81% 57% Ac = 75%

PPV = 85%

NPV = 50%

Prevalence = 75%
Kim (2005)33 Prospective cohort Adults/ impaired renal transplant perfusion RS (DTPA) Harmonic‡ U/S T(peak) 85% 90% r = 0.74
(P = 0.0001)
Delaney (1993)24 Prospective cohort (28% of patents were evaluated retrospectively) Patients with renal transplant dysfunction (140)

Acute rejection
(60)

 Renal biopsy FNAB Corrected increment ≥ 3.5 52% – –
RS (99mTc-DTPA and OIH) Delayed and/or decreased 99mTc-DTPA perfusion or OIH excretion 70% – –
U/S (Doppler) Resistive index (≥ 0.72) 43% – –

Ac= accuracy; FNAB= fine-needle aspiration biopsy; HGR= high-grade rejection (grades IIB and III of Banff classification); LGR= low-grade rejection (grades I and IIA of Banff classification); 99mTc DTPA= 99mTc-diethylenetriamine pentaacetic acid; MAG3= 99mTc-mercaptoacetyl triglycine; NPV= negative predictive value; OIH= 131I o-iodohippurate; PI= perfusion index; PPV= positive predictive value; r = correlation coefficient; RS= renal scintigraphy; U/S = ultrasound.

† Calculated based on data provided in the article
‡ Harmonic US: U/S with microtubule contrast agent
* Quantitative parameters:

Hilson's perfusion index ? the area under the arterial curve to peak divided by the area under the renal curve × 100

Peak-to-plateau ratio ? peak activity divided by the plateau activity on the renal perfusion curve

Uptake ­? the ratio of kidney activity to background activity
Retention [R20] ? the percentage of peak kidney activity retained at 20 minutes
Tpeak ? the time at the peak of the renal perfusion curve.