Cardiovasc Intervent Radiol (2013) 36:13291335
DOI 10.1007/s00270-013-0563-9
CLINICAL INVESTIGATION
Renal Function Outcomes for Multifocal Renal Neoplasms
Managed by Radiofrequency Ablation
Pushpender Gupta Brian C. Allen
Michael Y. Chen David D. Childs
Gopi Kota Ronald J. Zagoria
Received: 27 September 2012 / Accepted: 26 December 2012 / Published online: 30 January 2013
Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2013
Abstract
Purpose To evaluate renal function changes related to
radiofrequency ablation (RFA) for the treatment of multi-
focal renal neoplasms.
Methods This is an institutional review board-approved,
Health Insurance Portability and Accountability Act com-
pliant retrospective study of all patients treated with
computed tomography guided RFA for multifocal renal
neoplasms at one institution. Fifty-seven subjects, mean
age 70 (range 3788) years, underwent RFA of 169 renal
neoplasms (average size 2.0 cm). Subjects had between 2
and 8 (mean 2.96) neoplasms ablated. Estimated glomer-
ular filtration rate (eGFR) was measured before and after
RFA. Complications related to RFA were recorded.
Results eGFR decreased on average of 4.4 % per tumor
treated and 6.7 % per ablation session (average 1.76
tumors treated per session). For subjects with the largest
neoplasm measuring [3 cm, eGFR decreased an average
P. Gupta
B. C. Allen
M. Y. Chen (&)

D. D. Childs
G. Kota
R. J. Zagoria
Department of Radiology, Wake Forest University School
of Medicine, Medical Center Boulevard, Winston-Salem,
NC 27157, USA
e-mail: mchen@wakehealth.edu
P. Gupta
e-mail: pugupta@wakehealth.edu
B. C. Allen
e-mail: bcallen2@wakehealth.edu
D. D. Childs
e-mail: dchilds@wakehealth.edu
G. Kota
e-mail: gkota@wakehealth.edu
R. J. Zagoria
e-mail: rzagoria@wakehealth.edu
INTERVENTIONAL ONCOLOGY
of 14.5 % during the course of their treatment. If the largest
neoplasm measured 23 cm, eGFR decreased an average
of 7.7 %, and if the largest neoplasm measured \2 cm,
eGFR decreased an average of 3.8 %. Subjects with
reduced baseline renal function were more likely to have a
greater decline in eGFR after RFA. There was a minor
complication rate of 6.3 % (6 of 96 sessions), none of
which required treatment, and a major complication rate of
4.2 % (4 of 96 sessions).
Conclusion RFA for the treatment of multifocal renal
neoplasms results in mild decline of renal function.
Keywords Glomerular filtration rate
Multiple renal cell
carcinoma
Radiofrequency ablation
Renal cell
carcinoma
Introduction
Advances in imaging and an increased use of cross-sec-
tional imaging modalities for a variety of clinical indi-
cations has led to an increased detection of small,
asymptomatic, localized renal cell carcinoma (RCC),
which are amenable to nephron-sparing surgeries such as
partial nephrectomy [13]. Currently, partial nephrectomy
is the standard of care for small (\4 cm) localized RCC
[4, 5].
Percutaneous thermal ablation [predominately radiofre-
quency ablation (RFA) and cryoablation] is a minimally
invasive technique that is increasingly being used for the
treatment of small, localized RCC in subjects who are
poor operative candidates. Although randomized controlled
trials to compare the oncological efficacy of partial
nephrectomy and percutaneous ablation of small, localized
RCC are not available, the short and intermediate term
123
1330 P. Gupta et al.: Radiofrequency Ablation for Multifocal Renal Neoplasms

oncological efficacy of thermal ablation is comparable to Table 1 Demographic data and tumor characteristics
surgical series [6, 7]. Previous work has demonstrated that Characteristic Value
a single application of RFA does not significantly affect
estimated glomerular filtration rate (eGFR) [8]. Because No. of subjects 57
percutaneous ablation can be repeated multiple times, it No. of neoplasms 169
may be a useful alternative in patients with multifocal renal No. of ablation sessions 96
tumors, in patients with multifocal tumors in a solitary Age at treatment, year, mean (range) 70 (3788)
kidney and in patients with syndromic RCC, who are Sex
destined to develop more tumors during their life span. Male 37 (65 %)
There are small series of patients with syndromic RCC, Female 20 (35 %)
treated with RFA, with mixed results, and the effect on Race
renal function in these patients is unclear [9]. White 46 (81 %)
The purpose of this investigation was to evaluate the African American 11 (19 %)
effect on renal function of image-guided RFA in patients Comorbidities
with multifocal RCC. Diabetes 12 (21 %)
Hypertension 29 (51 %)
Chronic renal insufficiency 30 (53 %)
Materials and Methods Unilateral partial nephrectomy 13 (23 %)
Bilateral partial nephrectomy 1 (2 %)
Our institutional review board approved this retrospective Solitary kidney 7 (12 %)
study, which was compliant with the Health Insurance Von HippelLindau syndrome 3 (5 %)
Portability and Accountability Act guidelines. A waiver of Critical renal artery stenosis 2 (4 %)
informed consent was obtained. Congestive heart failure 10 (18 %)
Tumor size, cm (largest)
Patient Population Mean (range) 2 (0.46.0)
\2 cm 110 (65 %)
The radiology information system (RIS) was searched for
23 cm 37 (22 %)
all patients treated with RFA from February 2002 to
[3 cm 22 (13 %)
December 2011, resulting in 558 total subjects. The elec-
Location of neoplasm
tronic medical record and the RIS were then searched for
Right kidney 69 (41 %)
subjects treated for multifocal renal neoplasms. The study
Left kidney 100 (59 %)
population consisted of 57 subjects (37 male, 20 female)
Pathology 57 (100 %)
with a mean age of 70 (range 3788) years. Subjects
Renal cell carcinoma 47 (82 %)
underwent RFA of 169 renal neoplasms in 96 sessions. The
Oncocytic neoplasm 6 (10 %)
baseline characteristics are tabulated in Table 1. Thirty-one
Metastasis 1 (2 %)
(54.4 %) subjects had 2 tumors, 13 (22.8 %) subjects had 3
Angiomyolipoma 1 (2 %)
tumors, seven (12.3 %) subjects had 4 tumors, three
Indeterminate 2 (4 %)
(5.3 %) subjects had 6 tumors, two (3.5 %) subjects had 7
tumors and one (1.8 %) subject had 8 tumors treated. The Baseline renal function
mean number of renal neoplasms treated per patient was eGFR [60 mL/min/1.73 m2 27 (47 %)
2.96 and the mean number of renal neoplasms treated per eGFR 3060 mL/min/1.73 m2 26 (46 %)
session was 1.76. Mean follow-up after an RFA session for eGFR \30 mL/min/1.73 m2 4 (7 %)
the renal function analysis was 2.3 years (range 1 month to eGFR estimated glomerular filtration rate
9 years); five subjects did not have a follow-up eGFR.
Forty subjects had locally performed follow-up imaging
and 30 subjects had more than 1 years imaging follow-up, (CT) or magnetic resonance imaging (MRI) before and
with a mean follow-up of 3.68 (range 19.25) years. after the intravenous (IV) administration of contrast
material, thoracic imaging with a chest radiograph or CT,
Pretreatment Evaluation and laboratory studies including eGFR and coagulation
studies. All masses treated in this series were solid
All subjects were evaluated and referred by a urologist enhancing renal neoplasms.
before RFA. The pretreatment evaluation in all subjects The indications for nonsurgical treatment included previous
included abdominal imaging with computed tomography renal surgery or syndromic RCC and medical comorbidities.

123
P. Gupta et al.: Radiofrequency Ablation for Multifocal Renal Neoplasms
Seven subjects had multifocal tumors in a solitary kidney, 13
had undergone a previous partial nephrectomy, one had
undergone bilateral partial nephrectomy, and 3 subjects had
von HippelLindau (VHL) syndrome. Medical comorbidi-
ties included hypertension (n = 29), moderate to severe
chronic renal insufficiency (n = 30), diabetes mellitus
(n = 12), congestive heart failure (n = 10), and critical
renal artery stenosis (n = 2) (Table 1).
RFA Technique
All neoplasms in a single kidney were treated in a single
session (up to five neoplasms). For subjects with neoplasms
in both kidneys, different sessions were used for each
kidney. Nearly all patients were treated in the prone
position.
In patients with lesions in close proximity to the ureter,
an end-hole ureteric stent was placed immediately before
RFA by the urology service. Eight subjects had stents
placed before ablation. The ureteric stent was perfused with
chilled sterile water and 5 % dextrose solution during the
RFA to cool the ureter and pelvicaliceal system.
All patients were given conscious sedation with con-
tinuous monitoring of vital signs and local anesthesia at the
puncture site. At least one neoplasm in each patient was
sampled via biopsy immediately before the ablation pro-
cedure under CT guidance. A combination of fine needle
aspirates and core biopsies were obtained. All neoplasms
were ablated on the basis of preprocedural imaging, as a
final pathologic diagnosis was not available at the time of
the procedure. If the final pathologic diagnosis was benign,
a single follow-up renal CT or MRI was performed to
assess for complications.
Under CT guidance, RFA was completed with a 200 W
generator system with the impedance control setting and
17-gauge saline-cooled treatment probes (Cool-tip; Covi-
dien, Mansfield, MA). Overlapping ablations were per-
formed on the basis of tumor size and shape, with the intent
to destroy the entire mass and at least a 5 mm margin of
surrounding normal renal parenchyma (Fig. 1). Ablations
were continued for 8 min unless the generator, as a result
of a rapid rise in tissue impedance, automatically switched
to energy pulsing twice. When this occurred, ablation was
continued until the next even minute after a minimum of
4 min. Tissue temperature was recorded after each ablation
and, if below 50 Celsius, another ablation in the same
location was performed. A contrast enhanced (if eGFR
[45 mL/min/1.73 m2) CT after the intravenous adminis-
tration of 125 mL of iohexol [350 mg of iodine per mL
(Omnipaque 350; GE Healthcare, Princeton, NJ)] or an
unenhanced (if eGFR \45 mL/min/1.73 m2) CT scan was
obtained before terminating the ablation session to assess
for the adequacy of tumor ablation and immediate
1331
complications. If continued contrast enhancement within
the neoplasm was identified, this was interpreted as
incomplete tumor ablation, and an additional ablation was
performed with the intent of destroying the remaining
viable tumor. If IV contrast was not administered, unen-
hanced images were reviewed to ensure the ablation zone
completely encompassed the neoplasm. Ten subjects had a
postablation study without contrast.
After the completion of the procedure, patients were
transferred to a short stay area in the hospital where their
vital signs were monitored hourly; antiemetics and anal-
gesics were administered on an as-needed basis. Patients
were discharged the same day if they had no signs of
complication with stable vital signs, no evidence of active
bleeding (stable blood pressure, heart rate, and hemoglobin
level), and no pain requiring IV analgesics. Seven patients
were kept overnight and discharged the day after ablation.
Preprocedure Imaging Analysis
A board-certified, fellowship-trained abdominal imager
with 1 years experience and an abdominal imaging fel-
low measured the preprocedural diameter of each treated
neoplasm on a picture archiving and communication
system with electronic calipers on the axial image dem-
onstrating the greatest diameter. Location of the tumor
was classified by dividing the craniocaudal length of the
kidney into upper, middle and lower thirds. Tumor loca-
tion was categorized as being exophytic (greater than
25 % of tumor circumference contacting the perirenal fat)
or nonexophytic.
Sixty-nine tumors (40.8 %) were located in the right
kidney (upper pole, n = 30; lower pole, n = 21; interpolar,
n = 18) and 100 tumors (59.2 %) were in the left kidney
(upper pole, n = 39; lower pole, n = 33; interpolar,
n = 28). Seventy-six percent (129 of 169) of the tumors
were classified as exophytic and 24 % (40 of 169) of the
tumors were nonexophytic. Tumor size ranged from 0.4 to
6 cm (mean tumor size 2.0 cm). Sixty-five percent (110 of
169) of tumors were 2 cm or smaller in diameter, 22 % (37
of 169) of tumors measured 23 cm in diameter and 13 %
(22 of 169) of tumors were greater than 3 cm in diameter
(Table 1).
Renal Function Analysis
The abbreviated Modified Diet for Renal Disease (MDRD)
equation was used to estimate glomerular filtration rate
(eGFR) [10]. Global renal function was classified by the
Kidney Disease Outcome Quality Initiative (K/DOQI) clas-
sification of chronic renal disease with eGFR [60 mL/min/
1.73 m2 as normal or mild reduction, 3059 mL/min/1.73 m2
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1332 P. Gupta et al.: Radiofrequency Ablation for Multifocal Renal Neoplasms

Fig. 1 Multifocal left RCC in

80-year-old man who had
undergone right nephrectomy
for RCC in the remote past. A,
B Axial T1 weighted, fat-
suppressed and contrast
enhanced MRI [repetition time
(TR) = 4.204, echo time
(TE) = 2.106] after the
intravenous administration of
16 mL of gadobenate
dimeglumine. There is a 3.4 cm
enhancing mass (A, arrow) in
the upper pole of the left kidney
and 1.8 cm enhancing mass (B,
arrow) in the interpolar left
kidney. C, D Unenhanced axial
CT scan demonstrating a RFA
probe positioned within the
mass lesion in the upper pole
(C) and the interpolar left
kidney (D). The patient was
positioned prone for RFA. E,
F Axial T1 weighted, fat
suppressed and contrast
enhanced MRI (TR = 4.196,
TE = 2.012) after intravenous
administration of 16 mL
gadobenate dimeglumine,
approximately 2 years after
RFA, demonstrating ablation
changes in the upper pole (E,
arrow) and interpolar (F, arrow)
left kidney without residual
enhancement to suggest
recurrent neoplasm

as moderate reduction, 1529 mL/min/1.73 m2 as severe Complication Analysis

reduction and \15 mL/min/1.73 m2 as renal failure [11].
Renal function (eGFR) was measured before RFA and at
the last follow-up visit which was more than 6 months
after the last RFA session. Mean follow-up after an RFA
session was 2.3 years (range 1 month to 9 years). Of the
57 subjects, 27 had a baseline eGFR of [60 mL/min/
1.73 m2, 26 had a baseline eGFR of 3060 mL/min/
1.73 m2 and four had an eGFR of \30 mL/min/1.73 m2
(Table 1).
Using the electronic medical record and reviewing post-
procedural clinic visits, emergency department visits, and
imaging study reports, all complications attributable to the
RFA procedure were recorded. Complications were graded
with the Society of Interventional Radiology (SIR) Clas-
sification System for Complications by Outcome [12].
Class A and B complications were considered minor, and
class C or higher complications were considered major.

123
P. Gupta et al.: Radiofrequency Ablation for Multifocal Renal Neoplasms 1333

Statistical Analysis (n = 21), there was no difference in those with [30 %

Results were initially analyzed by descriptive statistics.
The paired Students t test was used to evaluate the sig-
nificance of the effect on renal function of RFA compared
to baseline. All statistical analyses were performed by Stat
View software, version 4.5 (Abacus Concepts, Berkeley,
CA).
Results
Renal Function Results
Renal function results are summarized in Tables 2 and 3.
The mean decrease in eGFR per tumor treated (average
tumor size 2.0 cm) was 4.4 % and the mean decrease in
eGFR per ablation session (mean number of tumors treated
per ablation session 1.76) was 6.7 % (Table 2). Subjects
with reduced baseline renal function were more likely to
experience a [10 % decline in eGFR as a result of the
smaller eGFR denominator (Table 3).
For subjects with the largest neoplasm measuring
greater than 3 cm, eGFR decreased an average of 14.5 %
during the course of their treatment. If the largest neoplasm
measured 23 cm, eGFR decreased an average of 7.7 %. If
the largest neoplasm measured \2 cm, eGFR decreased an
average of 3.8 % (Table 2).
Ten of 52 (19.2 %) subjects experienced a [30 %
decrease in eGFR during the course of ablation treatment.
Of the 10 subjects with more severe renal function loss,
five (50 %) subjects had renal neoplasms measuring greater
than 3 cm. Two subjects (20 %) had four neoplasms
ablated and two subjects (20 %) had three neoplasms
ablated. The one subject that had only small (\2 cm)
neoplasms ablated and severe renal dysfunction had three
neoplasms ablated.
For subjects with a summed tumor diameter of 2.0 to
4.9 cm (n = 39) and a summed tumor diameter of [5 cm
renal function loss (15 %, 6 of 39 and 14 %, 3 of 21) of
subjects, respectively. Only 4 % of subjects with a com-
bined tumor diameter of \1.9 cm had [30 % renal func-
tion loss.
Complications
In 96 ablation sessions, there were six minor complications
(6.3 %) and four major complications (4.2 %). The minor
complications consisted of one asymptomatic pneumotho-
rax that resolved without treatment on the follow-up chest
radiograph (SIR class A). Three minor complications were
small, asymptomatic urinomas that were noted on follow-
up imaging (SIR class A). All urinomas resolved without
treatment. Two minor complications were procedure rela-
ted hematomas that did not require transfusion (SIR class
A). Two major complications consisted of ureteral stric-
tures that occurred despite preprocedural stent placement
and required percutaneous nephrostomy (SIR class C). One
stricture was diagnosed on routine follow-up imaging. The
second stricture was diagnosed when the patient returned to
the emergency department with abdominal pain a week
after the procedure. The third major complication was a
postprocedural retroperitoneal hematoma that required a
blood transfusion (SIR class C). The fourth major com-
plication was a perirenal abscess that required percutane-
ous drainage (SIR class C).
Discussion
Nephron-sparing surgery for the treatment of renal neo-
plasms is increasingly being used to preserve renal function
with a growing body of evidence that general health and
overall survival is dependent upon renal function [1317].
Renal volume reduction has been demonstrated to be the
most significant independent prognosticator for GFR reduc-
tion after partial nephrectomy [18]. This is particularly

Table 2 Average change in estimated glomerular filtration rate (eGFR)

Characteristic Per Per First Second 6-mo Two Three or Largest Largest Largest
tumor session session session follow- tumors more tumors tumor tumor tumor
(%) (%) (%) (%) up (%) (%) (%) [3 cm (%) 23 cm (%) \2 cm (%)

Average -4.4 -6.7 -7.7 -7.6 -9 -9.9 -5.1 -14.5 -7.7 -3.8
Baseline eGFR -4.3 -5.9 -0.4 -9.8 -8.0 -4.2 -8.3 -6.2 -4.6
[60 mL/min/
1.73 m2
Baseline eGFR -8.6 -9.2 -11.1 -8.3 -10.9 -6.1 -18.6 -8.5 -2.5
\60 mL/min/
1.73 m2
eGFR estimated glomerular filtration rate

123
1334
Table 3 Baseline renal function in subjects with [10 % decrease in eGFR
Characteristic First session
Baseline eGFR [60 mL/min/1.73 m2 14.8 % (4/27)
Baseline eGFR \60 mL/min/1.73 m2 53.3 % (16/30)
eGFR estimated glomerular filtration rate
important in the management of multifocal RCC. Percuta-
neous thermal ablation offers a minimally invasive treatment
of renal neoplasms and aims to destroy as few functioning
nephrons as possible. The purpose of this study is to evaluate
the effect on renal function of image-guided RFA in patients
with multifocal RCC.
The mean decrease in eGFR of 4.4 % per tumor treated
(average tumor size 2.0 cm) and decrease in eGFR of
6.7 % per ablation session (mean number of tumors treated
per ablation session 1.76) found in our study compares
favorably to the 1013 % decrease in eGFR after partial
nephrectomy for solitary renal tumors (average tumor size
2.53.6 cm) and 1437 % decrease in eGFR for synchro-
nous renal tumors (average tumor size 2.72.85 cm) [18
21]. The average tumor size in the current series was
smaller than most surgical series; however, nearly three
neoplasms were treated in the average patient in this series,
compared to two tumors treated in the surgical series.
In this series, the largest tumor size treated had the most
pronounced effect on renal function change. Patients with
impaired baseline renal function also faired worse than
patients with normal baseline renal function. A higher
proportion of patients with impaired baseline renal function
experienced [10 % reduction in eGFR per ablation ses-
sion, regardless of tumor size, compared to patients with
normal baseline renal function.
The major complication rate of 4.2 % for RFA of
multifocal renal neoplasm compares favorably to both RFA
of single renal neoplasms and partial nephrectomy of single
renal neoplasms. A meta-analysis comparing both surgical
and percutaneous ablation of renal neoplasms found a
major complication rate of 3 % for the percutaneous
ablation of 665 neoplasms in 578 patients [22]. A recent
study of robotic assisted partial nephrectomy performed at
centers of excellence found a major complication rate of
3.8 % [23]. A small study of partial nephrectomy for the
treatment of multiple ipsilateral renal tumors (16 tumors in
seven patients) found a major complication rate of 14.3 %
(1 of 7); hemorrhage requiring a blood transfusion [24]. A
larger study of 26 patients undergoing partial nephrectomy
for bilateral renal tumors in 50 procedures found a major
complication rate of 10 % (5 of 50) [21]. Complications
included hemorrhage requiring blood transfusions, one
requiring angioembolization, and a prolonged urine leak
requiring a nephroureteral stent.
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P. Gupta et al.: Radiofrequency Ablation for Multifocal Renal Neoplasms
Second session Largest tumor [3 cm Largest tumor \2 cm
0 % (0/11) 25 % (2/8) 6.7 % (1/15)
52.6 % (10/19) 64.3 % (9/14) 30 % (3/10)
There are limitations to this study. The small sample
size and heterogeneous tumor population limit a more
robust multivariate statistical analysis; however, the man-
agement of multifocal renal masses is a relatively
uncommon event. The MDRD equation used in the study
tends to underestimate eGFR, particularly at levels closer
to normal. However, eGFR provides a more sensitive
measure of the changes in renal function as compared to
serum creatinine levels and is widely used in the literature.
The MDRD equation was utilized as opposed to the
Chronic Kidney Disease Epidemiology collaboration
(CKD-EPI) equation, in order to be consistent with com-
parable investigations [1821]. Although the reduction in
renal function after nephron-sparing therapies is presum-
ably related to the destruction of normal surrounding renal
parenchyma and therefore might be greater when treating
nonexophytic tumors, we were unable to control for the
location of tumors (endophytic vs. exophytic), given that
both were often treated during the same ablation session.
Also, given the retrospective nature of this series, and low
number of complications, other factors that could influence
renal function, including chronic diseases and medications
could not be accounted for.
In conclusion, there is a small decline in renal function
after percutaneous RFA in patients with multifocal RCC
and the effect on renal function from RFA compares
favorably with the surgical treatment of multifocal RCC.
Conflict of interest The authors declare that they have no conflict
of interest.
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