Gadolinium as an alternative contrast agent for diagnostic and interventional angiographic procedures in patients with impaired renal function

Johannes Rieger1,, Thomas Sitter2, Marcel Toepfer2, Ulrich Linsenmaier1, Klaus Jürgen Pfeifer1 and Helmut Schiffl2

1 Department of Radiology and 2 Department of Nephrology, Medizinische Klinik – Innenstadt, Ludwig-Maximilians-University, Munich, Germany



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. The study was designed to investigate the safety and feasibility of gadopentetate dimeglumine, a gadolinium-based contrast medium, as an alternative angiographic contrast agent in patients with impaired renal function and high risk for iodinated contrast-induced nephropathy.

Methods. Gadopentetate dimeglumine was used as the radiographic contrast agent in 32 diagnostic or interventional angiographic procedures in 29 patients (59% diabetics) with severe renal insufficiency (average serum creatinine of 3.6±1.4 mg/dl). The average dose of gadopentetate dimeglumine was 0.34±0.06 mmol/kg body weight. Gadopentetate dimeglumine was used either alone (n=20) or in conjunction with carbon dioxide (n=12).

Results. Thirty-two angiographic procedures (24 diagnostic angiographies and 8 interventional procedures) were performed in 29 patients. For diagnostic purposes, eleven selective renal arteriographies, six angiographies of the iliac arteries and lower extremities, and seven venous angiographies of the upper extremity and central veins were performed. Interventional procedures consisted of two percutaneous transluminal renal angioplasties with stenting, four percutaneous peripheral vascular interventions, and two balloon angioplasties of a dialysis fistula. None of the patients, except one, had evidence of post-procedure contrast material-induced renal failure (increase in serum creatinine >0.5 mg/dl within 72 h) or other complications. This patient had a clinically important increase in serum creatinine level after percutaneous transluminal renal angioplasty and stenting, probably due to cholesterol embolism. Gadopentetate dimeglumine had sufficient radiographic density to allow adequate diagnostic visualization with digital subtraction equipment in all cases.

Conclusions. Gadopentetate dimeglumine is an alternative and safe radiographic contrast agent for angiography and interventional procedures in patients with severe pre-existing renal impairment. In this population with high risk for contrast-induced acute renal failure, it is obviously less nephrotoxic than iodinated contrast media.

Keywords: angiography; contrast induced nephropathy; gadolinium; gadopentetate dimeglumine; renal artery stenosis



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
With the increasing number of diagnostic and interventional angiographic procedures, iodinated contrast-induced nephropathy has become an important cause of iatrogenic acute renal failure [14]. In fact, contrast exposure is the third leading cause of new acute renal failure in hospitalized patients [5]. Many different definitions of contrast nephropathy appear in the literature, but it is commonly defined as an acute decline in renal function following the administration of intravenous contrast in the absence of other causes. For research purposes, a definition such as a rise in serum creatinine >0.5 to 1 mg/dl or >25 to 50% above the baseline value within 48 or 72 h is often used [1,4].

It would be very useful to have a non-nephrotoxic angiographic contrast agent available for use in patients with renal insufficiency. Gadolinium chelates that are widely used in magnetic resonance imaging seem to have no adverse effects on renal function in patients with or without pre-existing renal impairment [68]. Gadopentetate dimeglumine has sufficient radiographic density to allow visualization with digital subtraction equipment [9] and has been described as an alternative contrast agent for digital subtraction angiography for several vascular territories [1013].

We report the use of gadopentetate dimeglumine as radiographic contrast agent in 32 consecutive diagnostic and interventional angiographic procedures in 29 patients (59% diabetics) with impaired renal function (average serum creatinine of 3.6±1.4 mg/dl). The purpose of this prospective study was to determine whether gadopentetate dimeglumine, used in a dose from 0.23 to 0.44 mmol/kg, is a safe and useful angiographic contrast agent in patients with high risk of contrast-induced renal failure.



   Subjects and methods
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
From April 1998 through November 1999, we prospectively evaluated 32 consecutive procedures in 29 patients (12 women, 17 men; mean age 61±11 years; age range 28–80 years) with renal insufficiency (serum creatinine level >1.5 mg/dl (133 µmol/l)). Baseline clinical data are given in Table 1Go. The cause of renal insufficiency was diabetic nephropathy in twelve, atherosclerotic renovascular disease in two, multiple myeloma in one, glomerulonephritis in one, polycystic disease in one, and renal disease of unknown reason in four patients. Eight patients had kidney transplants and impaired transplant function. The number of procedures in diabetic patients was 18 (56%), the number of diabetic patients 17 (59%). None of the patients was on regular haemodialysis, but six patients had severe renal failure. None of the patients were on non-steroidal anti-inflammatory drugs 24 h before the procedure. No additional diuretics were given within 24 h before exposure to the contrast medium. Hydration protocols before and after angiography were not standardized and varied from patient to patient; however, all patients were hydrated receiving intravenous physiologic saline at a rate of at least 1 ml/kg/h for 12 h before and 12 h after contrast medium exposure. In all patients, serum creatinine values were higher than 1.5 mg/dl prior to contrast medium exposure (Table 1Go). Serum creatinine levels were obtained within 24 h before and 24, 48, and 72 h after the procedure. According to the work of Solomon et al. [3], increases in serum creatinine of more than 0.5 mg/dl (44 µmol/l) were considered as clinically important.


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Table 1.  Patient data. Intervention, gadopentetate dimeglumine (Gd) dosage, and renal function. Indication for use of gadopentetate dimeglumine was impaired renal function in all patients

 
All angiographic procedures were performed using a high-resolution digital subtraction system (Siemens Medical Systems, Munich, Germany). For abdominal aortograms, gadopentetate dimeglumine was administered with a power-injector (Siemens Medical Systems, Munich, Germany). Gadopentetate dimeglumine-based contrast material (0.5 mmol/ml; Magnevist, Schering, Berlin, Germany) was administered undiluted or diluted 1:1 with 0.9% normal saline. The total dose of gadopentetate dimeglumine ranged from 0.23 to 0.44 mmol/kg (total volume range 30–70 ml). The choice of gadopentetate dimeglumine compared with other types of gadolinium chelates was based on its routine use in magnetic resonance imaging in our hospital. Gaseous carbon dioxide (CO2), which has no nephrotoxicity [14], has been used as an additional contrast agent in twelve procedures. Written informed consent was obtained from all patients.

The Wilcoxon signed rank test was used to calculate the significance of changes in serum creatinine after gadopentetate dimeglumine contrast. A P-value less than 0.05 was accepted as significant. Results are given as mean±standard deviation.



   Results
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Of the 32 procedures, 24 were diagnostic angiographies and eight were interventional procedures. For diagnostic purposes, eleven selective renal arteriographies were performed, four of them in renal transplants. Six angiographies of the iliac arteries and lower extremities were performed. Seven venous angiographies of the upper extremity and central veins were done for pre-operative evaluation in seven patients requiring a fistula for haemodialysis treatment. Interventional procedures consisted of two percutaneous transluminal angioplasties (PTA) of renal artery with stenting, four peripheral PTAs, and two balloon angioplasties of a dialysis fistula in patients with far advanced renal failure and insufficient development of the fistula.

None of the patients described discomfort during the injection of gadopentetate dimeglumine. Diluted gadopentetate dimeglumine was used for all test injections. Total dose of gadopentetate dimeglumine was 0.34±0.06 mmol/kg of body weight (range 0.23–0.44 mmol/kg, 30–70 ml). In twelve patients, carbon dioxide was used as an additional radiographic contrast material to reduce the amount of gadopentetate dimeglumine. No iodinated contrast agents were used.

The serum creatinine level remained stable after 31 procedures (Table 1Go: mean baseline serum creatinine level 3.6±1.4 mg/dl, at 24 h 3.5±1.5 mg/dl, at 48 h 3.6±1.5 mg/dl, at 72 h 3.6±1.4 mg/dl, no significant changes). In a 68-year-old patient (Table 1Go: no. 22) with a severe renal artery stenosis, who underwent PTA and stent insertion, serum creatinine level rose from 4.5 to 6.7 mg/dl within 48 h. However, extensive atherosclerotic plaques of the abdominal aorta were described and the patient was noted to have post-interventional skin changes (livedo reticularis) suggestive of cholesterol embolism. Serum creatinine returned to the pre-angiogram level within 18 days without the necessity of haemodialysis treatment. Apart from this patient, no patient showed a rise in serum creatinine of more than 0.5 mg/dl.

In two patients with renal artery stenosis, PTA and stent placement was completed successfully using gadopentetate dimeglumine as the sole contrast material. PTA of peripheral arteries was performed successfully in four patients and shunt PTA was performed successfully in two patients.



   Discussion
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Administration of iodinated contrast agents may cause worsening of renal function or development of acute renal failure in patients with pre-existing renal insufficiency [1,4]. Although the use of low-osmolar iodinated contrast agents combined with an adequate hydration can reduce the frequency of contrast-induced nephropathy below 5% [15], the incidence of rise in plasma creatinine concentration of more than 50% above baseline is still 40% or more if the baseline creatinine is higher than 4–5 mg/dl, particularly in patients with diabetic nephropathy [2]. As a consequence, contribution of contrast medium-induced renal failure to all hospital-acquired acute renal failure increased from 5% in a 1977 study to 32% in a 1987 study [16].

Several studies have shown that gadopentetate dimeglumine-based contrast agents may have no apparent nephrotoxic effects [6,7,12]. Further, low dose gadopentetate dimeglumine (to 0.1 mmol/kg) has been shown to be safe in patients with impaired renal function [6]. Prince et al. [7] found no change in serum creatinine level in 64 patients with azotaemia, who underwent magnetic resonance angiography with high doses of gadopentetate dimeglumine (to 0.4 mmol/kg); however, 17% of these patients subsequently developed contrast-induced acute renal failure after conventional angiography with iodinated contrast medium.

Gadopentetate dimeglumine-based contrast agents have the potential for use as an angiographic contrast agent in high-risk patients with renal insufficiency. Several reports of angiographic studies of the abdominal aorta, renal arteries, and peripheral vasculature have been published [1013]. We report the use of gadopentetate dimeglumine in amounts of 0.23–0.44 mmol/kg in 32 angiographic procedures in high-risk patients with compromised renal function. A significant increase of serum creatinine level (>0.5 mg/dl) was observed only in one 68-year-old patient (no. 22) with a severe renal artery stenosis, who underwent PTA and stent insertion. After the procedure, serum creatinine level rose from 4.5 to 6.7 mg/dl within 48 h. However, extensive atherosclerotic plaques were described in this patient and cholesterol embolism as a serious complication of renal artery stenting was believed to be the cause. Creatinine serum levels returned to the pre-angiogram level within 18 days without the necessity of haemodialysis treatment. Apart from this patient, no rise in serum creatinine of more than 0.5 mg/dl was observed in any patient. In fact, there was a minimal decrease in serum creatinine after gadopentetate dimeglumine contrast that presumably reflects the improved hydration from the saline given in combination with the contrast. In our study, creatinine levels were observed for at least 72 h. Porter [17] reported that in patients with contrast-material induced renal failure, serum creatinine rises by 48 h in about 90%.

Renal insufficiency, diabetes mellitus, congestive heart failure, volume depletion, and dose of contrast agent are the most significant risk factors for radiocontrast-induced renal failure [1,4]. The combination of diabetes and renal insufficiency increases the risk at least two-fold compared with that expected from the renal insufficiency alone [3,15,18]. In our study, 59% of the patients were diabetic. All patients were well hydrated, receiving intravenous normal saline at a rate of at least 1 ml/kg/h for 12 h before and 12 h after contrast medium exposure. Further, no additional diuretics were given within 24 h before exposure to the contrast medium. The overall incidence of radiocontrast-induced renal failure in a comparable high-risk group (average serum creatinine of 2.1 mg/dl, 50% diabetic) with the use of low-osmolar iodinated contrast medium and adequate hydration was 11% [3].

Doses of gadopentetate dimeglumine up to 0.4 mmol/kg have been used safely in patients without evidence of nephrotoxicity or significant systemic toxicity in several reports [6,7,10,12,14]. However, lack of nephrotoxicity of gadolinium-based contrast agents is still a topic of discussion. A case of acute renal failure in a 72-year-old patient after angiography with a gadolinium-based contrast agent (0.44 mmol/kg) has been reported recently [19]. Brillet et al. [20] observed a decreased creatinine clearance in isolated ischaemic rat nephrons after perfusion with gadolinium. However, other studies have shown no change in glomerular filtration rate with high doses of gadolinium (0.5–0.6 mmol/kg) in isolated rat kidneys and in vivo in dogs [21,22]. In our series of 32 procedures in a high-risk population with renal insufficiency, elevation of serum creatinine level was less than 0.5 mg/dl in all but one patient.

Gadopentetate dimeglumine has been shown to absorb sufficient energy to be visualized with digital subtraction angiography. Despite theoretically favourable X-ray imaging properties [23], the actual vascularenhancement observed during digital subtraction angiography using gadopentetate dimeglumine is weaker than observed with iodinated contrast agents. This is due to the low concentration of gadopentetate dimeglumine in currently available magnetic resonance imaging contrast agents. However, a higher concentration would increase the total volume of contrast material. Nevertheless, our study and several other reports [1013] have shown that radiographic imaging performed with standard peripheral angiographic techniques results in sufficient diagnostic quality.

The other alternative contrast agent to be considered for the use in angiography in patients with renal failure is CO2, which has no nephrotoxicity [14,24]. However, in most cases of angiographies and in particular interventions, CO2 as a sole contrast agent has not been consistently reliable [14]. In our study, CO2 was used as an additional contrast agent in conjugation with gadopentetate dimeglumine in twelve procedures to reduce the amount of gadopentetate dimeglumine used.

In summary, the findings in this study show that gadopentetate dimeglumine is an alternative contrast agent for angiographic studies in patients with severe renal insufficiency. It has sufficient radiographic density to allow adequate diagnostic visualization in routinely performed digital subtraction angiograms and interventions. Despite the high cost of gadopentetate dimeglumine compared with that of nonionic iodinated contrast material (approximately four times more expensive), it can be used without noticeable side effects and with low risk of nephrotoxicity in patients with impaired renal function. Patients who develop acute renal failure after traditional angiographic procedures usually require prolonged hospitalization and incur additional costs.



   Notes
 
Correspondence and offprint requests to: Johannes Rieger, MD, Institut für Klinische Radiologie – Standort Innenstadt, Poliklinik, Pettenkoferstrasse 8a, D-80336 München. Email: jrieger{at}radin.med.uni-muenchen.de Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 18. 7.00
Accepted in revised form: 18.12.01