International Journal of Urology (2011) 18, 570574

Original Article: Clinical Investigation

doi: 10.1111/j.1442-2042.2011.02791.x

iju_2791

570..575

Mercaptoacetyltriglycine-3 renogram is not superior to

estimated glomerular ltration rate measurement for the
prediction of long-term renal function after nephrectomy
Hiroshi Kanamaru, Masakazu Yamamoto, Kanji Nagahama, Yusuke Yagihashi, Keiji Kato,
Tomoyuki Oida, Toru Kannno, Noriyasu Takao, Yusuke Shimizu and Yasumasa Shichiri
Department of Urology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan

Objective: To evaluate the clinical usefulness of effective renal plasma ow (ERPF) measured using preoperative
mercaptoacetyltriglycine-3 (MAG3) renogram for the prediction of chronic renal insufciency after nephrectomy.
Methods: A total of 47 patients underwent preoperative MAG3 renal scintigraphy and subsequent unilateral nephrectomy. Correlations between the 5-year postoperative estimated glomerular ltration rate (eGFR) and the preoperative ERPF
of the contralateral kidney (cERPF), ERPF of the diseased kidney (dERPF), total ERPF (tERPF), cERPF to dERPF ratio, serum
creatinine (sCr) level, eGFR, as well as the inuence of preoperative comorbidities (diabetes, hypertension) on the postoperative eGFR, were evaluated with both univariate and multivariate analyses.
Results: Multiple linear regression analysis showed that preoperative cERPF signicantly correlated with postoperative
eGFR. However, a much stronger correlation was observed between the preoperative and postoperative eGFR. Multiple
logistic regression analysis showed that only preoperative eGFR was a signicant predicator of the development of
advanced-stage chronic kidney disease (CKD).
Conclusions: Preoperative MAG3 renogram is not superior to eGFR measurement as a prognostic indicator of long-term
renal function after unilateral nephrectomy.
Key words: chronic kidney disease, mercaptoacetyltriglycine-3 renogram, nephrectomy.

Introduction

Methods

Surgical treatments for kidney disease are associated with

the risk of postoperative chronic kidney disease (CKD).
Among renal surgeries, nephrectomy has the greatest risk
for CKD, because one of the two renal units is permanently
removed.16 Therefore, it is important to accurately predict
long-term postoperative renal function before nephrectomy.
It is possible to preoperatively assess differential renal
function using renal scintigraphy and other modalities
(computed tomography, magnetic resonance imaging).7,8
However, the predictability of such modalities for CKD after
a long observation period has not been reported. The present
study was carried out to evaluate the clinical usefulness of
effective renal plasma flow (ERPF) measured using
mercaptoacetyltriglycine-3 (MAG3) renogram for the prediction of renal function 5 years after nephrectomy, as compared with other clinical parameters.

Patients

Correspondence: Hiroshi Kanamaru M.D., Ph.D., Department of

Urology, Kitano Hospital, Tazuke Kofukai Medical Research
Institute, 2-4-20, Ohgimachi, Kita-ku, Osaka 530-8480, Japan.
Email: h-kanamaru@kitano-hp.or.jp
Received 15 November 2010; accepted 14 May 2011.
Online publication 12 June 2011
570

Between 2002 and 2005, 88 patients underwent unilateral

nephrectomy in Kitano Hospital, Osaka, Japan. MAG3 renal
scintigraphy was carried out in 74 of the 88 patients before
surgery. The present study included 47 out of the 74 patients
who were followed for more than 5 years. The reason for
surgery was as follows: 25 cases of renal cell carcinoma, 16
cases of urothelial cancer, two cases of pyonephrosis, two
cases of angiomyolipoma, one case of urolithiasis and one
case of oncocytoma. Out of the 37 male and 10 female
patients, the mean age was 65 years, with a range of 3882.
A preoperative medical history of diabetes mellitus and
hypertension were noted in eight and 20 patients, respectively. The present study was approved by the institutional
ethics committee.

MAG3 renogram
After an intravenous injection of 333 MBq of technetium99m-mercaptoacetyltriglycine (99mTc-MAG3), a renal scan
was carried out using a gamma-camera (Forte; ADAC, Milpitas, CA, USA). The MAG3 plasma clearance was calculated based on the renal uptake of 99m-Tc-MAG3 from 1 to
2011 The Japanese Urological Association

MAG3 renogram before nephrectomy

Table 1 Data of preoperative and 5-year postoperative renal parameters

Preoperative

sCr (mg/dL)
eGFR (mL/min/1.73 m2)
cERPF (mL/min/1.73 m2)
dERPF (mL/min/1.73 m2)
tERPF (mL/min/1.73 m2)
cERPF to dERPF ratio

5-Year postoperative

Range

Mean

Range

Mean

0.483.04
12.5112.4
65.3408.1
33.0323.8
125.5732.0
0.777.91

0.96*
64.8**
213.7
156.1
369.7
1.87

0.788.94
3.873.6

1.41*
45.6**

*P = 0.001; **P = 0.0001. cERPF, effective renal plasma ow of the contralateral kidney; dERPF, effective renal plasma ow of the
diseased kidney; tERPF, total effective renal plasma ow; eGFR, estimated glomerular ltration rate; sCr, serum creatinine.

2 min postinjection, according to the method described by

Oriuchi,9 and effective renal plasma flow (ERPF), which
was normalized to a body surface area of 1.73 m2, was
determined. The ERPF from the kidney that would remain
after nephrectomy was designated the contralateral ERPF
(cERPF). The ERPF from the kidney that would be removed
on operation was designated the diseased ERPF (dERPF).
The sum of ERPF from bilateral kidneys was designated
total ERPF (tERPF).

eGFR
Serum creatinine (sCr) was measured before the surgery and
5 years later. The eGFR levels were calculated using the
following formula, which was developed by the Japanese
Society of Nephrology:10 eGFR = 194 sCr-1.094 age-0.287
(0.739 if female).

Statistics
We used the paired t-test to compare the differences between
preoperative and postoperative renal parameters (sCr and
eGFR). Students t-test was used to compare postoperative
eGFR between patients with and without preoperative
comorbidities. The correlations between preoperative renal
parameters and postoperative eGFR were analyzed using
Pearsons correlation test. Multiple linear regression analysis was carried out to evaluate the contribution of preoperative renal parameters to predicting postoperative eGFR.
Logistic regression analysis was carried out to evaluate the
preoperative parameters used to predict advanced-stage
CKD (eGFR <30 mL/min/1.73 m2). A P-value of 0.05 was
considered to be statistically significant. The data were analyzed using the Statistical Package for Social Systems software, version 17.0 for Windows (SPSS, Chicago, IL, USA).

Results
The mean value and range of preoperative renal parameters
(sCr, cERPF, dERPF, tERPF, cERPF to dERPF ratio and
2011 The Japanese Urological Association

Table 2 Inuence of comorbidities on the postoperative

estimated glomerular ltration rate
Preoperative
comorbidities
Hypertension
+

Diabetes mellitus
+

No.

Mean postoperative
eGFR (mL/min/1.73 m2)

20
27

39.6
50.0

0.014

8
39

38.0
47.1

0.213

P-value

eGFR, estimated glomerular ltration rate.

eGFR), as well as 5-year postoperative parameters (sCr,

eGFR), are shown in Table 1. sCr significantly increased
and eGFR significantly decreased 5 years after nephrectomy. Correlations between each of the six preoperative
renal parameters and the postoperative eGFR are shown in
Figure 1. cERPF, dERPF, tERPF, sCr and eGFR significantly
correlated with postoperative eGFR. Among these five
parameters, the correlation coefficient was highest between
preoperative and postoperative eGFR.
We also analyzed the influence of the presence of comorbidities (diabetes mellitus and hypertension) on the postoperative eGFR. The presence of hypertension before surgery
was significantly associated with lower postoperative eGFR.
The presence of diabetes was associated with lower postoperative eGFR, but the difference was not statistically significant (Table 2).
A multiple linear regression analysis including the five
preoperative renal parameters (cERPF, dERPF, tERPF, sCr
and eGFR), which were significant variables on univariate
analysis, showed that two variables (cERPF and eGFR) had
a significant association with postoperative eGFR (Table 3).
The preoperative eGFR showed an odds ratio that was
higher than that of cERPF.
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H KANAMARU ET AL.

(b)

(a)

Postop eGFR (mL/min/1.73m2)

Postop eGFR (mL/min/1.73m2)

80

80

60

60

40

40
r = 0.421
P = 0.003

20

r = 0.515
P = 0.0001

20

0
100

200
300
Preop cERPF (mL/min/1.73m2)

400

(c)

100
200
300
Preop dERPF (mL/min/1.73m2)

400

(d)
Postop eGFR (mL/min/1.73m2)

Postop eGFR (mL/min/1.73m2)

80

80
r = 0.260
P = 0.077

60

60

40

40
r = 0.566
P = 0.0001

20

0
100

200

300
400
500
600
Preop tERPF (mL/min/1.73m2)

700

(e)

20

800

4
6
Preop cERPF to dERPF ratio

(f)
Postop eGFR (mL/min/1.73m2)

Postop eGFR (mL/min/1.73m2)

80

80
r = 0.672
P = 0.0001

60

60

40

40

20

20

r = 0.798
P = 0.0001

0
0

2
Preop sCr (mg/dL)

20

40
60
80
Preop eGFR (mL/min/1.73m2)

100

120

Fig. 1 (a) Correlation between preoperative effective renal plasma ow (ERPF) of the contralateral kidney (cERPF) and 5-year
postoperative estimated glomerular ltration rate (eGFR). (b) Correlation between preoperative ERPF of the diseased kidney (dERPF)
and 5-year postoperative eGFR. (c) Correlation between preoperative total ERPF (tERPF) and 5-year postoperative eGFR. (d) Correlation between preoperative cERPF to dERPF ratio and 5-year postoperative eGFR. (e) Correlation between preoperative serum
creatinine (sCr) and 5-year postoperative eGFR. (f) Correlation between preoperative eGFR and 5-year postoperative eGFR.

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MAG3 renogram before nephrectomy

Table 3 Multivariate analysis of the predictive factors for 5-year postoperative estimated glomerular ltration rate
Statistical method

Dependent variable

Independent variable

Odds ratio

P-value

95% CI

Multiple linear regression analysis

(Stepwise method)
Multiple logistic regression analysis
(Stepwise method)

Postoperative eGFR
(continuous variable)
Postoperative eGFR
(<30 mL/min/1.73 m2 vs
30 mL/min/1.73 m2)

Preoperative eGFR
Preoperative cERPF
Preoperative eGFR

0.510
0.048
1.086

0.0001
0.0080
0.017

0.3890.630
0.0130.084
1.0151.162

cERPF, effective renal plasma ow of the contralateral kidney; eGFR, estimated glomerular ltration rate.

There were six patients who developed advanced-stage

CKD (eGFR less than 30 mL/min/1.73 m2) 5 years after the
operation. A multiple logistic regression analysis including
preoperative eGFR, cERPF and hypertension showed that
only preoperative eGFR was a significant predictor for
advanced-stage CKD (Table 3).
We divided the patients into two subgroups according to
the preoperative eGFR using the cut-off value of 60 mL/
min/1.73 m2. The 5-year postoperative eGFR remained
>30 mL/min/1.73 m2 in all the patients whose preoperative
eGFR were >60 mL/min/1.73 m2. By contrast, 5-year postoperative eGFR were less than 30 mL/min/1.73 m2 in 27%
(6/22) of the patients whose preoperative eGFR were
<60 mL/min/1.73 m2.

Discussion
Recent comparative studies have reported that nephrectomy
is associated with a greater decrease in renal function than
nephron sparing surgery.36 The treatment strategy for small
renal cell carcinoma, therefore, has shifted toward nephron
sparing surgery instead of total nephrectomy.11 However,
nephrectomy will continue to be a treatment option, not only
for renal cell cancer, but also for other renal diseases. When
nephrectomy is planned for a patient, urologists have to
make a careful decision of whether surgery is associated
with a high risk of chronic renal insufficiency in that patient.
At the current time, the method of preoperative renal function assessment is not standardized. Although renal scintigraphy is an effective modality to evaluate differential renal
function, a recent survey of the American Urological Association showed that it is carried out less commonly as compared with other renal function tests.12
In the present study, we evaluated the usefulness of a
preoperative MAG3 renogram for the prediction of renal
function 5 years after nephrectomy. As shown here, the
cERPF to dERPF ratio ranged widely from 0.77 to 7.91,
which showed that the impact of the loss of one renal unit on
the postoperative renal function of the other would vary in
individual cases. We therefore expected that the preoperative
evaluation of contralateral (not to be removed) kidney func 2011 The Japanese Urological Association

tion would provide accurate information in terms of future

kidney function after unilateral nephrectomy.
Multivariate analyses of our data showed that cERPF
significantly correlated with the eGFR 5 years after the
operation, as we expected. However, a much stronger correlation was observed between the preoperative and postoperative eGFR. Furthermore, only preoperative eGFR was a
significant predictor of advanced-stage CKD on multiple
logistic regression analysis.
There have been few reports studying the relationship
between preoperative renal scintigraphy and postnephrectomy renal function. Mulleard13 used a dimercaptosuccinic
acid (DMSA) scan to evaluate the risk for chronic renal
insufficiency, and reported a positive correlation between
preoperative DMSA uptake of the contralateral kidney and
the postoperative creatinine clearance. Using MAG3 scintigraphy, Shirasaki14,15 reported that the preoperative ERPF
from the contralateral kidney correlated with postoperative
creatinine clearance. However, the observation period of
these two studies was relatively short (1 year after nephrectomy) compared with the present study (5 years), and eGFR
was not used as the study readout.
GFR is the most important index reflecting overall kidney
function, and can be measured accurately using inulin,
which is cleared solely by glomerular filtration. However,
the inulin renal clearance test is not used for the routine
clinical assessment of GFR, as it is time-consuming and
necessitates specific laboratory expertise. The most widely
used test has been creatinine clearance, although it overestimates true GFR, because some creatinine is cleared
through proximal tubules.
In recent years, a number of sCr-based equations,16,17
including age, sex and other variables, have been developed
to improve the accuracy of GFR estimation. After a multiinstitutional prospective study, the Japanese Society of
Nephrology now recommends the use of a new GFRestimating equation for the Japanese population.10 We used
this formula in the present study.
The reason why preoperative eGFR rather than cERPF
more effectively predicted postoperative eGFR remains
unclear. One possible explanation is the influence of the
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H KANAMARU ET AL.

preoperative function of the resected (diseased) kidney on

the postoperative compensatory response of the contralateral kidney. Funahashi18 studied the change in renal parenchymal volume (RPV) after unilateral nephrectomy and
reported that the increase in RPV of the contralateral kidney
was positively associated with preoperative DMSA uptake
of the diseased kidney. We therefore analyzed the impact of
two diseased kidney-related parameters (cERPF to dERPF
ratio and dERPF) on postoperative eGFR. However, cERPF
to dERPF ratio did not show a significant correlation with
postoperative eGFR. Although dERPF was significantly correlated with postoperative eGFR on univariate analysis, it
failed to be an independent predictor of postoperative eGFR
on multivariate analysis.
The other possible explanation is that RPF is closely
related , but physiologically not equivalent, to GFR. The
limitations of the present study are the relatively small
sample size and the fact that we did not assess postoperative
ERPF. If we could include both eGFR and ERPF as postoperative renal parameters, a more detailed analysis would be
possible.
In conclusion, the present study showed that a preoperative MAG3 renogram is not superior to simple and inexpensive eGFR measurements as a prognostic indicator of future
renal function after unilateral nephrectomy.

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