Diagnosis 2015; 2(1): 61–65
Open Access
Ferat Kepenek, Zehra Pınar Koç*, İrfan Orhan, Tansel Ansal Balcı, Funda Aydın,
Ahmet Fırat Güngör, Tunc Ozan and Cihat Tektas
Classical vs. unit area method in the evaluation
of differential renal function in unilateral
hydronephrosis
Abstract
Background: There are some problematic results in determination of differential renal function (DRF) by means
of Tc-99m DMSA renal scintigraphy in hydronephrotic
kidneys. In this study the classical method (CM) and unit
area methods (UAM) in the estimation of DRF in unilateral hydronephrosis before and after intervention were
compared.
Methods: Twenty patients (12 M, 8 F; mean: 42.6 ± 18.5 years
old) who were candidates for surgery or intervention
because of unilateral hydronephrosis were the subjects
of this study. All the patients were evaluated by Tc-99m
DMSA scintigraphy before and 3–6 months after the
intervention. In order to estimate DRF both CM and UAM
(obtained by division of the counts including the kidney
ROI to pixel of the same ROI) were performed. BlandAltman analyses were performed in order to compare the
DRF values obtained from both methods.
Results: The agreement between CM and UAM was poor in
the preoperative estimation, however, the agreement was
good after the operation or intervention.
Conclusions: In this study it seems that DRF estimation
with CM in unilateral hydronephrosis might be problemat­ic
in the determination of surgery thus UAM might be introduced as the method of choice in the determination of
DRF in unilateral hyronephrosis.
*Corresponding author: Zehra Pınar Koç, MD, Assist Prof.,
Department of Nuclear Medicine, Fırat University Hospital, 23119
Elazig, Turkey, Phone: +904242333555-2094, Fax: +904242388096,
E-mail: [email protected]
Ferat Kepenek and Tansel Ansal Balcı: Fırat University Medical
Faculty, Department of Nuclear Medicine, Elazig, Turkey
İrfan Orhan, Tunc Ozan and Cihat Tektas: Fırat University Medical
Faculty, Department of Urolog, Elazig, Turkey
Funda Aydın and Ahmet Fırat Güngör: Akdeniz University Medical
Faculty, Department of Nuclear Medicine, Antalya, Turkey
Keywords: differential renal function; DMSA; hydro­
nephrosis; unit area.
DOI 10.1515/dx-2014-0044
Received July 17, 2014; accepted September 30, 2014
Introduction
Differential renal function estimation by means of various
radionuclides has been the determining factor in decision
to do renal interventions. Thus reliability of the method
is essential since salvage of the functioning kidney tissue
depends on the differential renal function (DRF) estimation. Static renal scintigraphy with Tc-99m DMSA has
been accepted as the gold standard method in the estimation of renal cortical tissue regarding renal scarring and
the best method to calculate the DRF. DRF evaluation by
means of the renal nuclides like Tc-99m DTPA, Tc-99m
MAG3 and Tc-99m EC with similar results is possible.
Additionally these radionuclides provide information
about the excretion and concentration functions and diuretic response of the obstruction of the kidney. However,
DRF calculation by both dynamic and static scintigraphy
has some drawbacks especially in hydronephrosis [1]. In
fact DRF estimation by means of radionuclide methods
is problematic and the problem is the enlargement of the
kidney which influences the reliability of the results. The
hydronephrotic kidney seems to have increased function
in comparison to the other healthy kidney which is called
‘supranormal function’. The supranormal function were
firstly determined to be a problem related to Tc-99m DTPA
studies and are not present in Tc-99m DMSA studies [2].
However, experimental studies in rats have not confirmed
the discrepancy of the DRF estimation reported in miniature pigs; the discrepant results in these two studies may
be related to differences in the kidneys of the rat and the
©2014, Zehra Pınar Koç et al., published by De Gruyter.
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
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62 Kepenek et al.: Unit area method in hydronephrosis
miniature pig [3]. In humans the deficiency of DRF calculation cannot be attributed to only one radionuclide and
should not be underestimated. Gungor et al. clearly documented the influence of kidney size to the DRF estimation
[4]. Recently, for the first time, as far as we know, Nam
et al. introduced unit area estimation with DRF calculation [5]. However, Nam et al. choose the unit area estimation with nonradionuclide methods (volume calculation
with BT or MRI) and performed their study in Tc-99m
DTPA renal studies. The aim of this study is to compare
the CM and UAM in a prospective study in hydronephrotic
kidneys before and after intervention.
Materials and methods
Patients
Twenty patients (12 male, 8 female; mean: 42.6 ± 18.5 years old) with
diagnosis of unilateral hydronephrosis who are candidates for either
surgery or intervention were included to the study. The patients
under the age of 18 years old, pregnant or lactating women were
excluded from the study population. After obtaining anamnesis and
a physical examination the patients were subjected to further tests.
The diagnosis of hydronephosis was based on ultrasonography or
intravenous pyelography results. The patients with unilateral grade
1–4 hydronephrosis with any etiology were included to the study. All
the patients were subjected to renal ultrasonography and additional
intravenous pyelography, computed tomography and magnetic resonance imaging were performed if necessary. Additional urinary system pathologies were noted.
Static renal scintigraphy
The DMSA scintigraphies were performed before and 3 – 6 months
after the surgery or intervention. The surgery or intervention was performed within 1 month after the first scintigraphy. The scintigraphy
images were obtained by Infinia 2 model SPECT gamma camera (GE
Medical Systems, Israel) equipped with a low energy high resolution parallel hole collimator. The imaging was performed in supine
position with previous intravenous administration of approximately
5 mCi (187.5 MBq) (according to the body weight) of Tc-99m DMSA
2–3 h prior to the imaging. Diuretic administration was not performed
on the patients. The parallel hole images were obtained for 5 min
in anteroposterior projection and additional pin hole images were
obtained in posterior and oblique projections for the right and left
kidneys for 5 min each.
Quantification
Quantification was performed in parallel hole posterior images with
the Xeleris workstations Renal DMSA Uptake Analysis program. The
Figure 1 The image analysis and kidney and background region of
interests.
age, weight and height of the patients were recorded to the system.
Renal regions of interest were drawn manually from the borders
of the kidney and perirenal regions of interest were used for background substraction (Figure 1). The Taylor method was performed
for depth correction. The relative renal functions of the kidneys were
obtained as % percentage.
Two methods were employed for relative renal function estimation:
1. Classical method: % ratio was obtained by subtracting the average cts/pixel in the background ROI from the average cts/pixel
in each renal ROI and then multiplying by the total pixels in the
renal ROI.
2. Unit area method: % ratio was obtained by subtracting the average cts/pixel in the background ROI from the average cts/pixel
in each renal ROI and then multiplying by the total pixels in the
renal ROI. The area of the each kidney was calculated according
to the pixel information in each kidney ROI. After background
subtraction the obtained counts of the kidneys were divided
into the area.
Statistical analysis
In order to compare the classical and unit area methods Pearson
correlation analysis and Bland-Altman analysis were performed
and Bland-Altman plots were obtained. Classification of DRF: The
supranormal function is considered to be > 55% DRF of the kidney
with hydronephrosis, where normal function is 45%–55% and abnormal is < 45%.
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Kepenek et al.: Unit area method in hydronephrosis 63
Interventions: Endoscopic ureteral litotomy operation in ten
patients, nephrostomy operation in four patients and pyeloplasty
operation in one patient were performed.
Results
All the patients had unilateral hydronephrosis and in 19
of the patients the etiology was kidney stone disease and
in one patient the etiology was ureteropelvic junction
obstruction. The unilateral hydronephrosis included the
right kidney in nine (%45) and left in 11 (%55) patients.
The degree of hydronephrosis was between grade 1 and 3.
Twelve patients had grade 1, six had grade 2 and two had
grade 3 hydronephrosis (Table 1). The preoperative and
postoperative mean values of DRF estimations for both
CM and UAM are summarized in Table 2.
In the preoperative period according to CM there were
ten patients with abnormal DRF, one with supranormal
(55% for CM, 51% for UAM); according to UAM there were
ten patients with abnormal DRF (all were also abnormal
for UAM) and none with supranormal other patients’ DRF
results were in normal range.
According to the Pearson correlation analysis relative renal functions calculated with both methods were
in strong correlation in both the preoperative and postoperative period (r = 0.8411–0.9775, p < 0.0001 and r = 0.9959–
0.9997, p < 0.0001, respectively).
Bland-Altman analysis showed that there was no
good agreement between classical and unit area methods
in the preoperative period (Figure 2A) but the agreement
between methods were good in the postoperative period
after correction of the hydronephrosis (Figure 2B).
Table 2 Mean ± SD values of DRF estimation by CM and UAM before
and after intervention for the kidney with hydronephrosis.
Preoperative CM
Postoperative CM
Preoperative UAM
Postoperative UAM
Mean
SD
n
43.01
42.90
41.41
42.32
10.15
8.68
9.14
11.43
20
20
20
20
have described the larger size in supranormal functioning kidneys rather than other hydroneprotic kidneys [6].
DMSA renal scintigraphy has been considered as a less
invasive tool and a better way of determining the DRF
changes after an operation [7]. DMSA is a more reliable
method in DRF estimation and to show subtle changes
in DRF of kidneys after an operation or in the disease
course [7]. Animal studies have confirmed DMSA scintigraphies may provide DRF estimation with low variation
10
8
+1.96 SD
7.5
6
4
Mean
-2.3
2
0
-2
-1.96 SD
-2.9
-4
-6
30
25
35
40
45
50
55
60
1.5
Discussion
1.0
+1.96 SD
0.73
0.5
Supranormal function has been considered as an artifact or technical problem related to the increased size of
kidney. Whether the origin of this problem is technical
or something else it has to be considered as an important problem. In a previous study, Capolicchio et al.
0.0
Mean
-0.53
-0.5
-1.0
-1.5
-1.96 SD
-1.79
-2.0
Table 1 Patient characteristics.
-2.5
Age
Mean:42.6 ± 18.5 years
Range:18–76 years
Grade
wSide
Etiology
Grade 1: n = 12
Left:n = 11
Nephrolithiasis:n = 19
Grade 2:n = 6
Grade 3:n = 2
Right:n = 9
UPJ obstruction:n = 1
0
10
20
30
40
50
60
70
Figure 2 X axis: DRF values, Y axis: 95% CI (confidency interval).
(A) Bland-Altman plots of the classical and unit area methods in
preoperative period. (B) Bland-Altman plots of the classical and unit
area methods in postoperative period.
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64 Kepenek et al.: Unit area method in hydronephrosis
[8]. Thus we preferred to perform this study with this
radiopharmaceutical.
Previously the best method to estimate the DRF has
been determined as infrarenal background ROI and the
Rutland-Patlak correction in dynamic renal studies [9].
In a previous study various factors that may influence
the DRF estimation have been considered like the shape
of background correction ROI, renal ROI and different
operators. Their results showed that the difficulty appears
in single or poorly functioning kidneys [10]. This was an
expected result since in most of the analysis with radiopharmaceutics this is what happens with better results
in normal and variations in abnormal subjects. These
researchers also have suggested the use of the RutlandPatlak plot and perirenal background ROI.
The incidence of supranormal function is between 9%
and 22% [11]. A previous comparative study with DMSA
and MAG 3 in patients with unilateral hydronephrosis has
pointed out that two modalities have significant correlation and good reproducibility [12]. However, performance
of MAG 3 instead of DMSA in DRF analysis is not recommended by the authors especially for high grade hydronephrosis in infants [12]. There are a limited number of
studies in the literature about supranormal function estimation of DMSA [2, 4, 6] however, all these studies point
out the problem especially in high grade hydronephrosis.
Another solution suggestion has been diuretic administration during DMSA studies, however, recently this application has been proven to be unnecessary [13, 14].
In a previous study researchers defined the effect of
the size of kidney ROI on the estimation of DRF and they
have suggested surface area background subtraction to
prevent the effect of the increased size of kidney ROI in the
calculation of DRF [4]. Nam et al. proposed a novel method
in the estimation of DRF associated with the modification
of the classical method according to the renal cross sectional area and have demonstrated significant differences
between the methods [5].
The limitations of our study were the relatively
small number of patients, nonuniformity of the correction method (surgery and other methods) and the lower
degree of hydronephrosis of the patients. It has previously been suggested to perform 24 h imaging or SPECT
imaging in order to improve estimation of renal parenchyma in hydronephrosis, however, we did not perform
any of those images, the aim was to analyze UAM in
routine application. Additionally, not all subjects necessarily underwent USG estimation in post operative
follow-up thus we cannot perform a comparison of preand postoperative degree of hydronephrosis. We unfortunately did not compare the size of the ROIs, however,
standardization of the ROIs was provided by analysis of
the images by the same interpreter. We had intended to
perform the analysis in the patients with supranormal
results, however, the patient groups consisted of patients
with normal and abnormal DRF. This study might be more
informative if it is repeated in only supranormal patients.
There was only one patient with supranormal result
(DRF = 55) in our study population and it was corrected
with UAM (DRF = 50). However, the significant difference
in this kind of patient in our study with mild hidronephrosis is promising for future studies with UAM.
UAM seems to be a more reliable method in the estimation of DRF in the hydronephrotic kidney. Although the
grade of hydronephrosis in our patients was not advanced
we could identify that CM might be problematic in hydronephrosis and UAM corrects this misinterpretation. If the
degree was higher in our study population this discrepancy might be higher. Further future studies are warranted in this area with a higher degree of hydronephrosis
and higher number of patients and maybe the addition of
analysis of the 24 h images.
Author contributions: All the authors have accepted
responsibility for the entire content of this submitted
manuscript and approved submission.
Financial Support: The study was approved by Fırat
­University ethics committee.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played
no role in the study design; in the collection, analysis, and
interpretation of data; in the writing of the report; or in the
decision to submit the report for publication.
References
1. Kraft O, Kuba J, Ullmann V. Determination of d
­ ifferential
renal function using dynamic scintigraphy]. Vnitr Lek
1995;41:699–703.
2. Fung LC, McLorie GA, Khoury AE, Ash JM, Gilday DL,
Churchill BM. Contradictory supranormal nuclear renographic
differential renal function: fact or artifact? J Urol 1995;154:
667–70.
3. van de Wiele C, Everaert K, van der Eecken H, van Haelst JP,
Simons M, Dierckx RA. Differential renal function measured by
99Tcm-DTPA and 99Tcm-DMSA in a complete unilateral renal
obstruction rat model. Nucl Med Commun 1997;18:1036–39.
4. Gungor F, Anderson P, Gordon I. Effect of the size of regions
of interest on the estimation of differential renal function in
children with congenital hydronephrosis. Nucl Med Commun
2002;23:147–51.
Unauthenticated
Download Date | 6/17/17 8:38 PM
Kepenek et al.: Unit area method in hydronephrosis 65
5. Nam JK, Lee SD, Chung MK. Modified differential renal function
measurement revised by renal cross sectional area in children with
ureteropelvic junction obstruction. Korean J Urol 2010;51:271–5.
6. Capolicchio G, Jednak R, Dinh L, Salle JL, Brzezinski A, Houle AM.
Supranormal renographic differential renal function in congenital hydronephrosis: fact, not artifact. J Urol 1999;161:1290–4.
7. Konda R, Sakai K, Ota S, Abe Y, Hatakeyama T, Orikasa S. Ultrasound grade of hydronephrosis and severity of renal cortical
damage on 99m technetium dimercaptosuccinic acid renal scan
in infants with unilateral hydronephrosis during followup and
after pyeloplasty. J Urol 2002;167: 2159–63.
8.Dissing TH, Eskild-Jensen A, Pedersen M, Anderson PJ, Rittig N,
Frøkiaer J, et al. Reproducibility and repeatability of differential renal function in 4-week-old piglets. Nucl Med Commun
2008;29:76–82.
9. Monsieurs MA, Thierens HM, van de Wiele CV, Vral AM, Meirlaen
IA, de Winter HA, et al. Estimation of risk based on biological
dosimetry for patients treated with radioiodine. Nucl Med Commun 1999;20:911–7.
10. Lythgoe MF, Gordon I, Khader Z, Smith T, Anderson PJ.
Assessment of various parameters in the estimation
of differential renal function using technetium-99m
mercaptoacetyltriglycine. Eur J Nucl Med 1999;26:155–62.
11. Oh SJ, Moon DH, Kang W, Park YS, Park T, Kim KS.
Supranormal differential renal function is real but may be
pathological: assessment by Tc-99m mercaptoacetylglycine
renal scan of congenital unilateral hydronephrosis. J Urol
2001;165:2300.
12. Aktaş GE, Inanir S. Relative renal function with MAG-3 and
DMSA in children with unilateral hydronephrosis. Ann Nucl Med
2010;24:691–5.
13. Buyukdereli G, Guney IB, Seydaoglu G. Effectiveness of diuretic
injection on the measurement of differential renal function
using Tc-99m DMSA in patients with a dilated renal pelvis. Clin
Nucl Med 2005;30:721–4.
14. Kabasakal L, Turkmen C, Ozmen O, Alan N, Onsel C, Uslu I. Is
furosemide administration effective in improving the accuracy
of determination of differential renal function by means of
technetium-99m DMSA in patients with hydronephrosis. Eur J
Nucl Med Mol Imaging 2002;29:1433–7.
Article note: Abstract of this study was presented as a poster
presentation at the 23th National Congress of Nuclear Medicinein
Antalya, Turkey, in 6–10 April 2013.
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