AJR Not a Member? Click to Join ARRS!
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Esteves, F. P.
Right arrow Articles by Taylor, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Esteves, F. P.
Right arrow Articles by Taylor, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
DOI:10.2214/AJR.05.1025
AJR 2006; 187:W316-W319
© American Roentgen Ray Society

Original Research

Comparison of Camera-Based 99mTc-MAG3 and 24-Hour Creatinine Clearances for Evaluation of Kidney Function

Fabio P. Esteves1, Raghuveer K. Halkar1, Muta M. Issa2, Sandra Grant3 and Andrew Taylor1,3

1 Department of Radiology, Division of Nuclear Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Atlanta, GA 30322.
2 Department of Urology, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA.
3 Nuclear Medicine Service, Veterans Affairs Medical Center, Atlanta, GA.

Received June 15, 2005; accepted after revision August 8, 2005.

 
R. K. Halkar and A. Taylor receive royalties from the sale of QuantEM software, which is licensed to ELGEMS through Emory University. A. Taylor is a consultant for Mallinckrodt, Inc.

Supported by grant ROI LMN07595 from the National Library of Medicine.

Address correspondence to A. Taylor.

WEB

This is a Web exclusive article.


Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
OBJECTIVE. The 24-hour creatinine clearance is the standard clinical technique for measuring kidney function; however, this measurement is cumbersome and inconvenient for patients. We hypothesized that a camera-based technetium-99m mercaptoacetyltriglycine (MAG3) clearance obtained simultaneously with a standard MAG3 scan would correlate well with the 24-hour creatinine clearance and could serve as a simple marker of kidney function.

MATERIALS AND METHODS. Data were obtained from a retrospective analysis of 28 patients with varying degrees of kidney dysfunction and 85 subjects evaluated for kidney donation. The MAG3 clearance was calculated using a camera-based technique without blood or urine sampling. The creatinine clearance was measured using the plasma creatinine and a 24-hour urine collection. The MAG3 and creatinine clearances were corrected for body surface area, and clearance values in healthy subjects and patients were compared using the paired Student's t test. The linear association between the MAG3 and creatinine clearances was expressed by Pearson's correlation coefficient.

RESULTS. The mean MAG3 clearance in the potential kidney donors was 321 ± 95 mL/min/1.73 m2 (95% CI, 171-546 mL/min/1.73 m2), significantly higher than the mean creatinine clearance of 152 ± 51 mL/min/1.73 m2 (79-278 mL/min/1.73 m2, p < 0.001). The mean MAG3 clearance in patients was 153 ± 70 mL/min/1.73 m2 (32-316 mL/min/1.73 m2) and was also significantly higher than the mean creatinine clearance of 74 ± 36 mL/min/1.73 m2 (21-138 mL/min/1.73 m2, p < 0.001). The ratio of the mean creatinine clearance to the mean MAG3 clearance was essentially the same for volunteers and patients, 0.47 and 0.48, respectively. The Pearson's correlation between the MAG3 and creatinine clearances was 0.80 (0.72-0.86).

CONCLUSION. The camera-based 99mTc-MAG3 clearance correlates well with the 24-hour creatinine clearance and can provide a simple and convenient index of kidney function.

Keywords: camera-based MAG3 clearance • creatinine clearance • genitourinary imaging • kidney disease • kidney function • MAG3 clearance • renal scanning • technetium-99m MAG3 clearance


Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Measurement of kidney function can provide crucial data to assist in scan interpretation and clinical management decisions. The serum creatinine level is often used in clinical practice as an index of kidney function, but abnormal values may not be present until the glomerular filtration rate (GFR) has decreased by 50-80% [1]. Because of the limitations associated with the serum creatinine, the 24-hour creatinine clearance is still the standard clinical technique for measuring GFR, but even this measurement is far from ideal. A 24-hour urine collection is an inconvenient outpatient measurement that restricts mobility; mandates two trips to the hospital or clinic; and requires urine collection, storage, and transport. Most important for both outpatients and inpatients, the creatinine clearance measurement will not be accurate if the urine collection is incomplete. Even if the urine collection is complete, the clearance measurement can be affected by muscle mass and diet. Creatine from ingested meat is converted to creatinine and can account for as much as 30% of total creatinine excretion [2]. Creatinine is excreted not only by glomerular filtration but also by the renal tubule. The secretion of creatinine varies substantially both in the same individuals over time and among different individuals [3, 4]. In addition, the proportion of total renal creatinine excretion due to tubular secretion increases with decreasing kidney function [5]. This is particularly problematic in the follow-up of patients with a significant degree of renal dysfunction because the GFR can fall more rapidly than indicated by either serum creatinine or creatinine clearance.

Technetium-99m mercaptoacetyltriglycine (MAG3) was introduced in 1986 as a replacement for iodine-131 orthoiodohippurate (OIH) [6, 7] and is currently used for 60-70% of the kidney scanning performed annually in the United States [8]. The clearance of 99mTc MAG3 is highly correlated with the clearance of OIH and is used as an index of effective renal plasma flow [9]. Plasma sampling techniques for the measurement of the MAG3 clearance have been recently reviewed [10]; however, the need for a high degree of technical competence to perform plasma-based clearances has led to the development of camera-based techniques that do not require plasma or urine samples [11-14]. The camera-based MAG3 clearance can be generated at the time of routine MAG3 renal scanning on many commercial camera or computer systems. Although MAG3 is primarily eliminated by renal tubular secretion, we hypothesized that tubular secretion and GFR would provide comparable estimates of overall kidney function and that there would be a good correlation between the 99mTc-MAG3 and 24-hour creatinine clearances.


Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patients
Review of patient records was approved by the institutional review board. The study population initially consisted of 89 patients being evaluated for kidney donation at Emory University Hospital between August 1998 and March 2001. Preoperative evaluation included clinical laboratory studies of blood and urine samples, creatinine clearance level, MR renal arteriography, and MAG3 renal scanning. These studies were performed within a week of each other. Twenty-four patients from the Veterans Affairs Medical Center in Atlanta with varying degrees of kidney dysfunction were studied between May 1998 and February 2000, had a creatinine clearance measured within 24 hours of MAG3 renal scanning, and were included in the database. Finally, a reviewer requested additional patients with impaired kidney function. Consequently, a retrospective chart review was performed of all the MAG3 studies performed at Emory Hospital from July 2003 to January 2005. Five patients with an abnormal 24-hour creatinine clearance level measured within 1 week of MAG3 renal scanning were identified and included in this study.

Infiltration was calculated by drawing a region of interest (ROI) over the injection site at the conclusion of the study. Counts in the injection site ROI were corrected for decay and divided by dose of MAG3 injected to obtain a conservative estimate of the infiltrated dose. Five subjects were excluded because of dose infiltration exceeding 1%. The remaining 113 subjects constituted the study group (85 healthy subjects and 28 patients). The ranges of the creatinine clearance for the healthy subjects and patients were 71-309 and 19-139 mL/min/1.73 m2, respectively. For the MAG3 clearance, the ranges for the healthy subjects and patients were 155-635 and 29-334 mL/min/1.73 m2, respectively. Expressing the clearances as mL/min/1.73 m2 adjusts for body surface area (see following text).

Procedure
Each study was performed with 1-11 mCi (37-407 MBq) of 99mTc MAG3 (Mallinckrodt Medical). The patients at Veterans Affairs Medical Center received 1-2 mCi (37-74 MBq), whereas the potential kidney donors and patients at Emory University Hospital received 7-11 mCi (259-407 MBq) of 99mTc MAG3. Radiochemical purity was 95.0% ± 2.7% (Sep-Pak Cartridge, Millipore). The data were processed and the camera-based MAG3 clearance was calculated using the QuantEM software, which was developed specifically by Emory University for 99mTc-MAG3 scanning. The technique is similar to the camera-based technique described to calculate GFR [15].

Briefly, the percentage of the injected dose of MAG3 accumulated by the kidneys in 1-2.5 minutes (VA subjects) or 2-3 minutes (Emory subjects) after injection was converted to a MAG3 clearance using a regression equation [11, 12]. To determine the percentage of injected dose in the kidney at a specific time, the dose injected was counted on the camera. If 7-11 mCi (259-407 MBq) was to be administered, a 1-2 mCi (37-74 MBq) dose was counted on the camera to avoid dead-time losses and the 1-2 mCi (37-74 MBq) dose and the dose to be injected were counted in a dose calibrator; the ratio of counts in the dose calibrator was used to convert the 1-2 mCi dose (37-74 MBq) counted on the camera to the counts injected. An ROI was placed over the whole kidney and time zero was defined as the time the bolus reached the kidney. Counts in the kidney were determined at 1- to 2.5- or 2- to 3-minute intervals and corrected for background and attenuation using an attenuation coefficient of 0.123 [11, 12]. The kidney counts were divided by the counts injected to obtain a percentage of dose in the kidney at 1-2.5 or 2-3 minutes after injection. This percentage dose in the kidney was then converted to a MAG3 clearance using regression equations derived from a multicenter study that related the percentage of injected dose in the kidney at 1-2.5 or 2-3 minutes to a multiple plasma sample MAG3 clearance [12].

The creatinine clearance was determined from a 24-hour-urine creatinine level with the serum creatinine measured at the end of the 24-hour urine collection. Each clearance measurement was corrected for body surface area (BSA) using the following equation:

Formula
The clearances were corrected for BSA because the magnitude of the GFR, effective renal plasma flow, and MAG3 clearances correlates with BSA; larger individuals have higher clearances and smaller individuals have lower clearances [17]. The BSA correction adjusts for the effect of size on the absolute clearance measurement and reduces variability; BSA-corrected clearances standardized to 1.73 m2 provide a better comparison with standard normal values.

For statistical analysis, Pearson's correlation coefficient was used to express the linear association between the BSA-corrected MAG3 and creatinine clearances. The linear relationship between the MAG3 and creatinine clearances was determined by regression analysis, with the MAG3 clearance as the independent variable and the creatinine clearance as the dependent variable. The Student's t test was used to compare clearance results between the MAG3 and creatinine clearances. A p value of 0.05 or less was considered to be significant.


Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The 85 potential kidney donors were 59% women and 41% men, had a mean age of 41 ± 11 years, a mean BSA of 1.90 ± 0.24 m2, and a mean creatinine clearance level of 152 ± 51 mL/min/1.73 m2 (95% CI, 79-278 mL/min/1.73 m2), which was significantly less than the mean camera-based MAG3 clearance of 321 ± 95 mL/min/1.73 m2 (171-546 mL/min/1.73 m2, p < 0.001). The patients were 27 men and one woman having a mean age of 66 ± 8.6 years, a mean BSA of 2.03 ± 0.25 m2, and a mean creatinine clearance level of 74 ± 36 mL/min/1.73 m2 (21-138 mL/min/1.73 m2), which was also significantly less than the mean MAG3 clearance of 153 ± 70 mL/min/1.73 m2 (32-316 mL/min/1.73 m2, p < 0.001).

The MAG3 and creatinine clearances (Fig. 1) correlated significantly (r = 0.80, p < 0.001). Linear regression was used to derive the following equation:

Formula
The SE of measurement for the intercept (20 mL/min/1.73 m2) was 8.75 mL/min/1.73 m2. The 95% CI for the intercept ranged from 2.2 to 36.8 mL/min/1.73 m2, and the intercept was greater than 0 (p = 0.03).


Figure 1
View larger version (14K):
[in this window]
[in a new window]
[as a PowerPoint slide]
  		Fig. 1 —Scatterplot shows correlation between camera-based technetium-99m mercaptoacetyltriglycine (MAG3) and creatinine clearances (in mL/min/1.73 m2). Pearson's correlation is 0.80.

 


Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Technetium-99m MAG3 is a radiotracer with a rate of urinary excretion essentially equivalent to 131I OIH [6-9]. Compared with 131I OIH, MAG3 has the advantages of less radiation exposure to the patient and better imaging characteristics because of the 140 keV photon of 99mTc. The renal clearance of MAG3 is substantially greater than the renal clearance of 99mTc-DTPA, and MAG3 has become the radiopharmaceutical of choice for renal scanning in many clinical contexts, especially in patients with suspected obstruction and patients with impaired kidney function [8, 10, 18]. Measurement of the MAG3 clearance at the time of scanning adds important functional information to help direct patient management and to detect an early loss in kidney function when the images and the renogram curves may still appear normal [8]. A camera-based MAG3 clearance can be obtained at the time of scanning without blood or urine sampling, and the camera-based measurement correlates well with the more complex methods that involve plasma sampling [11-14].

The line of regression (Fig. 1) comparing the camera-based MAG3 and creatinine clearances has an intercept of 20 mL/min/1.73 m2 (95% CI, 2.2-36.8 mL/min/1.73 m2). If the MAG3 and creatinine clearances provided a perfectly equivalent measurement of kidney function, then a MAG3 clearance of 0 would correspond to a creatinine clearance of 0. In fact, the intercept (Fig. 1) was slightly greater than 0 (p = 0.03). There are several possible explanations for the observation that the intercept was slightly greater than 0: First, the MAG3 and creatinine clearances may not be perfectly correlated. Second, the camera-based MAG3 clearance is not a perfect measure of the MAG3 clearance; principal sources of error of the camera-based technique include corrections for attenuation and background subtraction. Third, there were not enough patients with very poor kidney function to accurately determine the intercept. Finally, and perhaps most important, the creatinine clearance level is not a perfect measure of GFR. Although GFR can be estimated from the Cockcroft-Gault [19] and MDRD (Modification of Diet in Renal Disease) [20] formulas, these estimates may deviate substantially from the true GFR in patients with fluid overload, hepatic insufficiency, and azotemia.

GFR can be measured using iodine-125 iothalamate, but this is a tedious and time-consuming technique and is far too labor-intensive to be used in a general radiology practice [10]. At our institution, the standard measure of GFR in potential kidney donors is the creatinine clearance level. Using the creatinine clearance to measure GFR is not as much of a problem in patients with normal kidney function, but the creatinine clearance overestimates GFR in patients with poor kidney function because of the secretion of creatinine by the tubules [3, 4]; tubular secretion may explain the fact that the intercept was greater than 0. Conceivably, the MAG3 clearance may correlate better with an inulin or 125I iothalamate clearance than with a creatinine clearance.

Technetium-99m MAG3 is excreted primarily via proximal tubular secretion; consequently, its clearance is a measurement of tubular cell function and is not a measure of GFR [9]. For this reason, the regression equation should not be used to calculate the creatinine clearance from the MAG3 clearance; nevertheless, the regression equation does show that, on average, the creatinine clearance is about 40% of the MAG3 clearance. If a loss in kidney function results in a proportional loss in GFR and tubular function, then either measurement will serve as an acceptable index of kidney function.

Our study suggests that despite being handled differently by the kidneys, the BSA-corrected MAG3 and creatinine clearances are highly correlated (r = 0.80). Consequently, in healthy patients and those with chronic kidney impairment, either measurement can serve as an index of kidney function. This argument is further supported by the fact that the SD of the MAG3 and creatinine clearances (expressed as a percentage of the mean) in healthy subjects was 30% for the MAG3 and 34% for the creatinine clearance, suggesting that the two measurements are similar for defining normality. Finally, preliminary data suggest that the camera-based MAG3 clearance is more reproducible than creatinine clearance in patients with stable kidney disease [21].

In summary, the camera-based MAG3 clearance avoids the cumbersome nature, inconvenience, and incomplete urine collections associated with a 24-hour creatinine clearance and can easily be obtained at the time of MAG3 renal scanning. The camera-based MAG3 clearance correlates highly with the creatinine clearance and provides a simple, safe, and convenient test of kidney function.


References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Hood B, Attman PO, Ahlmen J, Jagenburg R. Renal hemodynamics and limitations of creatinine clearance in determining filtration rate in glomerular disease. Scand J Urol Nephrol1971; 5:154 -161[Medline]
  2. Lew S, Bosch JP. Effect of creatinine clearance and excretion in young and elderly healthy subjects and in patients with renal disease. J Am Soc Nephrol 1991;2 : 856-865[Abstract]
  3. Sjostrom PA, Odlind BG, Wolgast M. Extensive tubular secretion and reabsorption of creatinine in humans. Scand J Urol Nephrol 1988; 22:129 -131[Medline]
  4. Levey AS, Berg RL, Gassman JJ, Hall PM, Walker WG. Creatinine filtration, secretion and excretion during progressive renal disease. Modification of Diet in Renal Disease (MDRD) Study Group. Kidney Int Suppl 1989; 27:S73 -S80[Medline]
  5. Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28:830 -838[Medline]
  6. Fritzberg AR, Kasina S, Eshima D, Johnson DL. Synthesis and biological evaluation of technetium-99m MAG3 as a hippuran replacement. J Nucl Med 1986;27 : 111-116[Abstract/Free Full Text]
  7. Taylor A Jr, Eshima D, Fritzberg AR, Christian PE, Kasina S. Comparison of iodine-131 OIH and technetium-99m MAG3 renal imaging in volunteers. J Nucl Med 1986;27 : 795-803[Abstract/Free Full Text]
  8. Taylor A. Radionuclide renography: a personal approach. Semin Nucl Med 1999;29 : 102-127[CrossRef][Medline]
  9. Eshima D, Taylor A Jr. Technetium-99m mercaptoacetyltriglycine: update on the new 99mTc renal tubular function agent. Semin Nucl Med 1992;22 : 61-73[CrossRef][Medline]
  10. Blaufox MD, Aurell M, Bubeck B, et al. Report of the Radionuclides in Nephrourology Committee on renal clearance. J Nucl Med 1996; 37:1883 -1890[Abstract/Free Full Text]
  11. Taylor A Jr, Corrigan PL, Galt J, et al. Measuring technetium-99m-MAG3 clearance with an improved camera-based method. J Nucl Med 1995;36 : 1689-1695[Abstract/Free Full Text]
  12. Taylor A, Manatunga A, Morton K, et al. Multicenter trial validation of a camera-based method to measure Tc-99m mercaptoacetyltriglycine, or Tc-99m MAG3, clearance. Radiology 1997;204 : 47-54[Abstract/Free Full Text]
  13. Inoue Y, Ohtake T, Ikuo Y, Yoshikawa K, Asai S, Ohtomo K. Evaluation of renal function from 99mTc-MAG3 renography without blood sampling. J Nucl Med 1999;40 : 793-798[Abstract/Free Full Text]
  14. Bocher M, Shrem Y, Tappiser A, et al. Tc-99m mercaptoacetyltriglycine clearance: comparison of camera-assisted methods. Clin Nucl Med 2001;26 : 745-750[CrossRef][Medline]
  15. Gates GF. Glomerular filtration rate: estimation from fractional renal accumulation of 99mTc DTPA (stannous). AJR 1982; 138:565 -570[Abstract/Free Full Text]
  16. Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition 1989; 5:303 -311[Medline]
  17. Kasiske BL, Keane WF. Laboratory assessment of renal disease: clearance, urinalysis, and renal biopsy. In: Brenner B, ed. The kidney. Philadelphia, PA: Saunders, 2000:1129 -1170
  18. O'Reilly P, Aurell M, Britton K, Kletter K, Rosenthal L, Testa T. Consensus on diuresis renography for investigating the dilated upper urinary tract. J Nucl Med 1996;37 : 1872-1876[Free Full Text]
  19. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16 : 31-41[Medline]
  20. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130 : 461-470[Abstract/Free Full Text]
  21. Taylor A, Myrick S, Grant S, Issa M, Halkar R, Alazraki NP. A prospective study to compare the reproducibility of camera-based MAG3 and creatinine clearance measurements. (abstr) J Nucl Med1999; 40:52P

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Esteves, F. P.
Right arrow Articles by Taylor, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Esteves, F. P.
Right arrow Articles by Taylor, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS