Kidney International, Vol. 53 (1998), pp. 503–507
TECHNICAL NOTE
Use of gadopentetate dimeglumine as a contrast agent for
percutaneous transluminal renal angioplasty and stent placement
DAVID J. SPINOSA, ALAN H. MATSUMOTO, J. FRITZ ANGLE, and KLAUS D. HAGSPIEL
Department of Radiology, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA
Use of gadopentetate dimeglumine as a contrast agent for percutaneous
transluminal renal angioplasty and stent placement. Percutaneous transluminal renal angioplasty and stent placement was performed successfully
in a patient with renal artery stenosis and renal insufficiency using
gadopentetate dimeglumine and carbon dioxide as radiographic contrast
agents. No iodinated contrast material was used for the procedure.
Renal revascularization for patients with renal insufficiency
remains a controversial treatment [1]. A meta-analysis of 379
patients treated with percutaneous transluminal renal angioplasty
(PTRA) for renal insufficiency showed that in 55% of these
patients, renal insufficiency was either stabilized or improved [2].
These results suggest that percutaneous revascularization may be
helpful in this group of patients. Pre-existing renal insufficiency is
the most important predisposing factor to the development of
acute renal failure following contrast administration. Therefore, a
non-toxic contrast agent for the angiographic detection and
treatment of renal artery stenosis would be extremely helpful.
Gadolinium-based contrast agents have been used extensively
in magnetic resonance imaging. These agents have also been
shown to be safe in patients with renal insufficiency [3, 4]. These
gadolinium-based contrast agents have also been shown to have
the potential for use as an angiographic contrast agent in selected
patients [5–7]. Therefore, gadolinium-based contrast agents could
have potential for use as an angiographic contrast agent. We
report a case in which diagnostic renal angiography, followed by
percutaneous transluminal angioplasty (PTA) and stent placement were performed using CO2 and gadolinium as the angiographic contrast agents.
METHODS
A 74-year-old white male with non-insulin dependent diabetes
mellitus, coronary artery disease, peripheral vascular disease,
cerebrovascular disease, severe hypertension requiring four antihypertensive medications and cholesterol emboli from previous
angiography five weeks earlier presented with worsening renal
Key words: gadopentetate dimeglumine, contrast agent, angioplasty, stent
placement, renal artery stenosis.
Received for publication July 21, 1997
and in revised form September 16, 1997
Accepted for publication September 16, 1997
© 1998 by the International Society of Nephrology
insufficiency. The patient’s creatinine on this hospital admission
was 3.9 mg/dl, up from a baseline creatinine of 2.2 mg/dl five
weeks earlier. It was unclear whether the increasing creatinine was
due to cholesterol emboli, contrast-induced nephrotoxicity, or
progression of the patient’s underlying renal disease. A renal
ultrasound performed at the time of admission showed the left
kidney to measure 5.5 cm and the right kidney to measure 12.0
cm. Duplex ultrasound examination was suspicious for right renal
artery stenosis and occlusion of the left renal artery.
An attempt to gently hydrate the patient resulted in congestive
heart failure. Following resolution of the patient’s pulmonary
edema, the patient’s serum creatinine was 4.0 mg/dl. He subsequently underwent angiography using a 5 French pigtail catheter
from a right femoral artery approach. The location of the origin of
the right renal artery was determined with digital subtraction
angiography (DSA) using hand injections of CO2 with the patient
in the left posterior decubitus position. The pigtail catheter was
positioned just above the right renal artery and an abdominal
aortogram was performed using intraarterial gadopentetate dimeglumine (0.5 mmol/ml; Magnevist, Schering, Berlin, Germany) at
an injection rate of 15 cc/second for a total of 30 cc (0.1 mmol/kg).
Digital subtraction filming was performed using four exposures
per second for two seconds followed by two exposures per second
for four seconds. Filming parameters included exposure factors of
96 kv and 200 mÅ using a Siemens multiscope unit (Siemens
Medical Systems, Iselin, NJ, USA). Digital subtraction angiography with CO2 suggested the presence of a moderate stenosis of
the right renal artery, although there was some degree of uncertainty (Fig. 1). The DSA using Gadopentetate dimeglumine
revealed a 70% stenosis of the right renal artery (Fig. 2). The left
renal artery was not visualized, consistent with 100% left renal
artery occlusion.
The right renal artery was balloon dilated with a 6 mm 3 2 cm
Courier balloon catheter (Boston Scientific Corp, Natick, MA,
USA). Balloon positioning and post-angioplasty results were
monitored using CO2 as the angiographic contrast agent. The
post-angioplasty result suggested a 40 to 50% residual stenosis.
Therefore, we elected to place an intravascular stent. A Palmaz
154 stent (Johnson & Johnson, Interventional Systems, Warren,
NJ, USA), mounted on a 7 mm 3 2 cm Opta-5 balloon angioplasty catheter (Johnson & Johnson Interventional Systems), was
positioned across the residual renal artery stenosis and deployed.
Stent positioning was monitored with DSA using CO2 as the
contrast agent. Final DSAs were performed using 60 cc of CO2
and 7 cc of Gadopentetate dimeglumine (0.5 mmol/ml). Both
503
504
Spinosa et al: Gadopentetate dimeglumine as a contrast agent
Fig. 1. Digital subtraction abdominal
aortogram performed with CO2 prior to renal
angioplasty suggests significant right renal
artery stenosis (arrow).
agents were hand injected during separate digital acquisitions.
Both the CO2 and gadopentetate dimeglumine studies demonstrated a widely patent right renal artery with correct positioning
of the fully deployed renal stent (Fig. 3). A total of 37 cc of
gadopentetate dimeglumine (0.19 mmol/kg) was administered for
the procedure. No iodinated contrast agents were used.
RESULTS
No immediate complications related to the angiographic procedure were encountered. The patient developed congestive heart
failure five days after the procedure that responded to vigorous
diuresis. The serum creatinine was stable post-angioplasty; the
stent placement measured 4.1 mg/dl at 48 hours following the
procedure and measured 4.0 mg/dl 10 days following the procedure. The patient had no evidence for further cholesterol embolization.
DISCUSSION
Treatment of renal insufficiency with revascularization techniques remains controversial. Surgical revascularization in patients with renal insufficiency results in a higher perioperative
mortality than in patients with serum creatinine levels less than 2.0
mg/dl [2]. Percutaneous intervention is appealing because of the
less invasive nature of PTA and stenting. However, percutaneous
intervention routinely requires the use of iodinated contrast
agents, which, in itself, can lead to acute renal failure in patients
with compromised renal function [8 –10]. Therefore, it would be
very useful to have a non-nephrotoxic angiographic contrast agent
available for use in patients with renal insufficiency.
Gadopentetate dimeglumine demonstrates similar pharmocokinetics to that of iodinated x-ray contrast agents. Gadolinium is
nearly completely excreted by glomerular filtration via the kidneys
with a half life of 1.53 6 0.13 hours [4]. Several studies have shown
that gadolinium has no apparent nephrotoxic effects in patients
with normal renal function, renal insufficiency or renal failure.
Doses up to 0.4 mmol/kg have been used safely in patients without
evidence of nephrotoxicity or significant systemic toxicity [3, 4,
11–14]. In the presence of severe renal sufficiency there is some
concern that there may be a delay in the clearance of gadoliniumDTPA complex. The accumulation of gadolinium-DTPA complex
could in theory result in the release of free gadolinium cation
(Gd31) into the liver and spleen, which would reduce the availability of other metabolically important cations such as zinc,
copper, and calcium [14, 15]. Studies in rats receiving over 1,000
times the usual dose of gadolinium demonstrated histopathologic
findings of zinc deficiency [15]. However, given the large doses
Spinosa et al: Gadopentetate dimeglumine as a contrast agent
505
Fig. 2. Digital subtraction abdominal
arteriogram performed with 30 cc of
gadolinium dimeglumine prior to renal
angioplasty demonstrates a 70% right renal
artery stenosis (arrow).
necessary to produce these findings in rats, relevance of this data
to humans concerning doses of gadolinium for diagnostic studies
is questionable. There has been no evidence in humans to date of
depletion of nutritionally important minerals when gadolinium
has been administered in doses used for diagnostic studies.
Angiographic studies of the abdominal aorta, mesenteric vessels, pelvis and peripheral vasculature using gadolinium as a
contrast agent have been previously reported [6, 7]. The use of
gadolinium as the contrast agent during a percutaneous embolization for the treatment of hemorrhage associated with ruptured
hepatocelluar carcinoma has also been reported [5].
Gadolinium has an atomic number of 64 and a k-edge of 50.
Therefore, Fobbe, Wacker and Wagner have recommended that
110 kv be used when acquiring angiographic images with gadolinium, since the atomic number in k-edge for gadolinium is higher
than that of iodine [6]. Although gadolinium has been shown to
absorb sufficient energy to be visualized with DSA, these authors
have also found that the image quality with gadolinium was
consistently poor when compared to iodine-containing contrast
agents [6]. Kaufman, Geller and Waltman found similar results
using Gadolinium versus iodinated contrast when comparing
image quality [7]. We administered undiluted gadolinium (0.5
mmol/ml) with a power-injector (Medrad Corp., Pittsburgh, PA,
USA), and acquired our data at (96 kv and at 200 mÅ in order to
maximize image quality. We limited our total dose of gadopentetate dimeglumine to less than 0.3 mmol/kg, as doses of this
amount have not been associated with nephrotoxicity in patients
with renal insufficiency.
The use of CO2 as a non-nephrotoxic contrast agent (DSA) has
been previously reported [16]. Our protocol minimizes iodinated
contrast in patients with renal insufficiency (serum creatinine
greater than 1.5). In these patients, we limit iodinated contrast by
performing CO2 angiography. Routinely, the renal artery and
kidney in question are elevated at least 45° by placing a wedge
cushion under the patient to utilize the buoyant properties of CO2
gas to better fill the renal artery in question. Although CO2
angiography suggested the presence of renal artery stenosis, in our
experience, CO2 has not been consistently reliable in the diagnosis
of renal artery stenosis. This is particularly a problem when bowel
motion causes subtraction artifacts over the renal artery being
506
Spinosa et al: Gadopentetate dimeglumine as a contrast agent
Fig. 3. Digital subtraction arteriogram of the right renal artery following percutaneous transluminal angioplasty (PTA) and stent placement using 7cc
of gadolinium dimeglumine reveals full stent deployment (arrow) and no residual renal artery.
studied, as well as in the evaluation of possible branch stenoses. In
the particular patient in this article, we were not confident enough
to proceed to an intervention based upon the CO2 study alone.
Despite the high cost of gadolinium, the use of gadolinium as a
non-nephrotoxic contrast agent could facilitate the angiographic
diagnosis and interventional treatment of renal artery stenosis
without exposing the patient with renal insufficiency to the risk of
contrast-induced nephropathy when CO2 angiography is technically not diagnostic. Patients who develop contrast nephropathy
and acute renal failure after traditional contrast angiographic
studies usually require prolonged hospitalization and incur additional medical costs. In addition, some of these patients may
prematurely develop permanent renal failure, resulting in the
need for long-term dialysis. The use of gadolinium as a contrast
agent could result in the diagnosis and treatment of renal artery
stenosis that may lead to stabilization or improvement of renal
insufficiency in these patients without the use of iodinated contrast material and the risk of contrast nephropathy.
In conclusion, this case suggests that gadolinium can be used as
an alternative to iodinated contrast agents for the angiographic
diagnosis and treatment of patients with renal insufficiency related to renal artery stenosis or in patients with renal artery
stenosis and a history of a life-threatening iodinated contrast
reaction. Further evaluation is necessary to determine if gadolin-
ium is a safe and cost effective alternative to iodinated contrast in
this population of patients.
Reprint requests to David J. Spinosa, M.D., Department of Radiology,
University of Virginia Health Sciences Center, Box 170, Charlottesville,
Virginia 22908, USA.
REFERENCES
1. HALLETT JW JR, FOWL R, O’BRIEN PC, BERNATZ PE, PAIROLERO PC,
CHERRY KJ JR, HOLLIER LH: Renovascular operations in patients
with chronic renal insufficiency: Do the benefits justify the risks? J
Vascular Surg 5:622–227, 1987
2. TEGTMEYER CJ, MATSUMOTO AH, JOHNSON AM: Renal angioplasty,
in Abrams Angiography Interventional Radiology, edited by BAUM S,
PENTECOST MJ, Boston, Little, Brown and Company, 1997, pp 294 –
325
3. PRINCE MR, ARNOLDUS C, FRISOLI JK: Nephrotoxicity of high-dose
gadolinium compared with iodinated contrast. JMRI 6:162–166, 1996
4. HAUSTEIN J, NIENDORF HP, KRESTIN G, LOUTON T, SCHUHMANNGIAMPIERI G, CLAUSS W, JUNGE W: Renal tolerance of gadoliniumDTPA/dimeglumine in patients with chronic renal failure. Invest
Radiol 27:153–156, 1992
5. KINNO Y, ODAGIRI K, ANDOH K, ITOH Y, TARAO K: Gadopentetate
dimeglumine as an alternative contrast material for use in angiography. Am J Roentgenol 160:1293–1294, 1993
6. FOBBE F, WACKER F, WAGNER S: Arterial angiography in high
kilovoltage technique with gadolinium as the contrast agent. First
clinical experience. Eur Radiol 6:224 –229, 1996
Spinosa et al: Gadopentetate dimeglumine as a contrast agent
7. KAUFMAN JA, GELLER SC, WALTMAN AC: Renal insufficiency: Gadopentetate dimeglumine as a radiographic contrast agent during peripheral vascular interventional procedures. Radiology 198:579 –581, 1996
8. KATZBERG RW: New and old contrast agents: Physiology and nephrotoxicity. Urol Rad 10:6 –11, 1988
9. BYRD L, SHERMAN RL: Radiocontrast induced acute renal failure: A
clinical and pathophysiologic review. Medicine (Baltimore) 58:270 –
279, 1979
10. BERNS AS: Nephrotoxicity of contrast material. Kidney Int 36:730 –
740, 1989
11. HOGSTROM B, KRISTOFFERSEN DT, LUNDBY B, SVALAND MG: Safety
of gadodiamide injection in two different age groups. J Magn Reson
Imaging 1:255–257, 1996
12. NIENDORF HP, HAUSTEIN J, LOUTON T, BECK W, LANIADO M: Safety
and tolerance after intravenous administration of 0.3 mmol/kg Gd-
13.
14.
15.
16.
507
DTPA. Results of a randomized, controlled clinical trial. Invest Radiol
26(Suppl 1):S221–S223, 1991
GOLDSTEIN HA, KASHANIAN FK, BLUMETTI RF, HOLYOAK WL, HUGO
FP, BLUMENFIELD DM: Safety assessment of gadopentetate dimeglumine in US clinical trials. Radiology 174:17–23, 1990
ROFSKY NM, WEINREB JC, BOSNIAK MA, LIBES RB, BIRNBAUM BA:
Renal lesion characterization with gadolinium-enhanced MR imaging:
Efficacy and safety in patients with renal insufficiency. Radiology
180:85– 89, 1991
CACHERIS WP, QUAY SC, ROCKLAGE SM: The relationship between
thermodynamics and the toxicity of gadolinium complexes. Magnet Res
Imag 8:467– 481, 1990
HAWKINS IF, CURAN SR: Carbon dioxide digital subtraction angiography, in Current Techniques in Interventional Radiology, edited by
COPE C, Philadelphia, Current Medicine, 1994, pp 11.1–11.17