Carbon dioxide as a valuable contrast agent for identifying iatrogenic arteriovenous fistulas in transplanted kidneys

Antonio Nicolini1, Mariano Ferraresso2, Andrea Lovaria1, Pietro Biondetti1, Mauro Raiteri2 and Luisa Berardinelli2

1Vascular Interventional Radiology Unit and 2Division of Vascular Surgery and Kidney Transplantation, Ospedale Maggiore–Policlinico IRCCS, Milan, Italy

Correspondence and offprint requests to: Mariano Ferraresso, MD, PhD, Division of Vascular Surgery and Organ Transplantation, Zonda Bld., Policlinico-University Hospital, IRCCS, Via F. Sforza 35, I-20122 Milan, Italy. Email: mariano.ferraresso{at}unimi.it

Keywords: arteriovenous fistula; carbon dioxide; digital subtraction angiography; interventional radiology; kidney transplantation; therapeutic embolization



   Introduction
 Top
 Introduction
 Case
 Results
 Discussion
 References
 
Biopsying kidney allografts is routinely performed during follow-up to diagnose acute and chronic rejections. However, such a procedure carries risks of complications, including pseudoaneurysm and formation of fistulas between arteries and veins or between arteries and renal calyces. Although these complications have become rare after the use of ultrasound-guided biopsy, they may still occur and result in significant problems and sometimes in irreversible damage: haemorrhages, massive haematuria, anuria due to ureteropelvic obstruction by clotted blood, hypertension and transient acute tubular necrosis [1]. Early diagnosis and timely treatment of symptomatic post-biopsy arteriovenous fistulas may prevent these potential sequelae. Presently, the colour Doppler ultrasound method is used for non-invasive assessments of graft vessels and angiography-guided embolotherapy for the treatment of lesions. A careful choice of agents is necessary to avoid contrast-induced nephropathy and worsening of graft function. Carbon dioxide (CO2) contrast is considered a good alternative to iodine, because CO2 does not cause nephrotoxicity and produces a superior visualization of arteriovenous shunting due to its peculiar physicochemical properties [2,3]. We report the successful use of CO2 contrast for both locating the shunt and for CO2-guided embolotherapy of post-biopsy arteriovenous fistulas in transplant patients with hypertension and progressive deterioration of graft function.



   Case
 Top
 Introduction
 Case
 Results
 Discussion
 References
 
This report describes the clinical course of three female recipients of primary cadaveric kidney grafts, who developed symptoms of post-biopsy fistulas (Table 1.). Two patients had had end-to-side renal artery anastomoses performed to external iliac arteries and one patient had had an end-to-end anastomosis to the internal iliac artery. Two of the patients (B.V. and R.M.) had benign post-operative courses and were discharged from the hospital within 2 weeks after surgery. The first patient (B.V.) underwent a graft biopsy almost 10 years after transplantation to investigate a persistent proteinuria that was associated with slight elevations in the blood creatinine levels. Her histological diagnosis was pyelonephritis. Two weeks after the biopsy, her creatinine level increased from 1.7 to 3.2 mg/dl. The second patient (R.M.) had a kidney biopsy almost 5 years after transplantation due to a sudden deterioration of kidney function. The biopsy revealed a transplant glomerulopathy. Six months after the biopsy, her creatinine levels increased from 2.5 to 4.5 mg/dl.


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Table 1. Patient demography and clinical data

 
The third patient (M.G.) had had complications immediately after transplantation, resulting in a delayed graft function that required intermittent dialysis. Twice during the post-operative period, this patient underwent an ultrasound-guided biopsy to follow changes that were diagnosed as acute tubular necrosis. Within 1 month after grafting, the third patient developed hypertension unresponsive to quadruple therapy. Subsequently, her creatinine levels doubled over a 6 month period.

In all three cases, duplex sonography (Aloka SSD5500PHD) was performed at first to rule out vascular and parenchymal complications. The colour Doppler examination suggested the presence of an arteriovenous shunt at the site of the biopsies. Therefore, after excluding all other complications, such as acute rejections, drugs toxicity or arterial stenosis, we concluded that these patients’ symptoms and laboratory data indicated iatrogenic arteriovenous shunts.

To avoid further damage to the grafts, we opted for CO2 angiography using a digital angiography unit (CGR-DG200). Following percutaneous catheterization of the external iliac artery, ipsilaterally to the graft (two patients) or contralaterally (one patient), 20 c.c. CO2 (99.99% purity) were injected at a pressure of 1.3 bar by a dedicated delivery system (CO2-Angioset; Optimed, Ettingen, Germany). Prior to the procedure, an intravenous bolus of an anticholinergic (20 mg scopolamine) had been given to halt small bowel peristalsis.

In all three patients, the images were acquired at the rate of six frames per second to compensate for the fast diffusion of CO2 and the possibility of bubble generation in the area of imaging. The rapid opacification of the renal and iliac veins seen in the arterial phase of the CO2 angiography indicated the presence of high-flow arteriovenous shunts on the lower poles of transplanted kidneys (Figure 13). After selective catheterization of an abnormal shunt with a 5-French catheter (Terumo, Tokyo, Japan), a mechanical embolization was performed by placing two small coils (Cook, Bloomington, IN, USA) proximal to the shunt (Figure 24). At the end, standard angiography was performed using 3–5 ml gadolinium-based contrast (Magnavist; Berlex Laboratory, Wayne, NJ, USA) diluted 3:1 with normal saline and injected through the small catheter, which had been pulled backwards to the proximal segmental artery. These examinations documented the complete occlusion of the fistulas and the presence of a small peripheral parenchymal infarction.



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Fig. 1. A CO2 digital subtraction angiography. The tip of a 5-French catheter positioned in the iliac artery proximal to the renal artery (1); arteriovenous fistula on the lower pole of the transplanted kidney (2); renal vein (3); external iliac vein (4).

 


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Fig. 3. A CO2 digital subtraction angiography. Common iliac artery (1); hypogastric artery (2); renal artery and vein, side by side (3) the post-biopsy shunt is indicated by the presence of a pseudoaneurysm on the lower pole of the kidney (4); external iliac vein (5). The arrow shows the end-to-end anastomosis of the internal iliac artery with the renal artery.

 


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Fig. 2. Angiographic control with gadolinium-based contrast after super-selective catheterization of the inferior polar branch (1). The embolization site is indicated by the arrow.

 


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Fig. 4. Standard angiography performed with gadolinium-based contrast agent to evaluate a possible parenchymal infarction after mechanical embolization. The arrows show a slight parenchymal infarction distal to the coils.

 
Serum creatinine levels were obtained on the day of and the day after the procedure, as well as on additional days during follow-up. A colour Doppler ultrasound was performed 1 day after the interventional procedure and after the following 6 months.



   Results
 Top
 Introduction
 Case
 Results
 Discussion
 References
 
Overall, angiographic images of good diagnostic quality were obtained in all three patients. In our hands, the CO2 digital subtraction angiography al-lowed very selective trans-catheter embolization of the post-biopsy fistulas with a high degree of confidence. The procedures were well tolerated by the patients, who had a median hospitalization time of only 4 days.

Serum creatinine levels decreased in two patients soon after the procedure: from 3.2 to 2.2 mg/dl in one (B.V.) and from 3.2 to 1.7 mg/dl in the other (M.G.). The kidney function of these two patients remained stable when evaluated 6 and 12 months later. The patient with the sudden onset of hypertension (M.G.) regained her baseline blood pressure 90 days after the biopsy and her antihypertensive therapy has been withdrawn. The renal function of the third patient (R.M.) worsened due to the transplant glomerulopathy, as demonstrated by an increase in her serum creatinine within 24 h after the biopsy from 6.2 to 6.7 mg/dl. The latter value dropped slightly to 5.6 mg/dl one month later and remained stable when measured at the 6 and 12 month follow-ups. Unfortunately, this patient needed to resume dialysis 14 months after the procedure.

Doppler ultrasounds performed 1 day after the procedures showed complete closure of the lesions in all three cases. No relapse of the arteriovenous shunts was present when examined 6 months later. No adverse event was observed with the administration of CO2.



   Discussion
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 Introduction
 Case
 Results
 Discussion
 References
 
Arteriovenous fistulas may occur in >17% of patients following renal allograft biopsy [4]. Although 90% of the patients with fistulas have a benign course, the major complications occurring in 2–9% of the cases include systemic hypertension, graft function impairment, haematuria and hydronephrosis. The best approach to prevent complications is to perform a rapid and safe correction using a radiologically guided procedure. Since renal arteriography is considered the gold standard for examining renal microvasculature, one must take into account the risk of contrast media-induced renal damage. This risk may be particularly great in kidney transplant patients because of pre-existing microvascular damage caused by acute rejection episodes, ongoing chronic rejection, hypertension or immunosuppressive drug toxicities. It has been reported that 20–40% of patients with creatinine levels >=2 mg/dl who have under-gone angiography have developed contrast agent-induced nephropathies that required prolonged hospitalization or even short-term dialysis [5].

Recently described is the use of CO2 angiography in patients with impaired renal function and in patients who have developed severe reactions to iodinated contrast material.

We propose that the benefit of CO2 angiography is such that it should be performed in all kidney transplant patients at risk of complications. The advantages of using CO2 include: lack of toxicity, rapid clearance by the lungs, virtual absence of volume restriction, optimal visualization of arterial anastomosis and main renal and intraparenchymal arteries, with limitless acquisition of images. Moreover, the low viscosity of CO2 (~0.25% of iodinated contrast media) allows much more rapid passage of CO2 through small collaterals and arteriovenous shunts, providing a direct visualization of damaged kidney vessels [6,7]. The use of CO2, unlike traditional imaging agents, presents some drawbacks, which are mostly related to its peculiar physical properties: difficulty of handling, poorer imaging quality, bubble generation, risk of catheter clogging between injections and room air contamination. However, recent technical advances in digital subtraction angiography (post-processing computer software and significantly improved CO2 delivery systems) make CO2 angiography a very appealing alternative to iodinated contrast angiography.

Since the amount of CO2 employed to examine the transplanted kidney is much smaller than the amount necessary for a standard angiogram (performed on lower limbs or native kidneys), the possibility of major complications, such as embolisms, is virtually eliminated. In any event, our preferred system for CO2 delivery is a closed system, which completely prevents both CO2 contamination and inadvertent delivery of a large amount of CO2 to the patient. However, previous experimental studies have documented that renal ischaemia may result from a ‘vapour lock’ caused by consecutive boluses of CO2 without adequate time allowed for its absorption. According to the same published work, a 2–5 min interval between CO2 injections should be sufficient to avoid CO2 trapping in the vessels.

A small amount of gadopentate dimeglutamine is injected after the CO2 examination to provide a nephrogram to rule out procedure-related injuries to the graft, such as infarction. Previous clinical study shows that small quantities of gadolinium-based contrast have not been associated with nephrotoxicity, even in patients with renal dysfunction [8]. The usefulness of gadolinium-based contrast to supplement CO2 angiography to localize the area of abnormality in renal transplant patients has also been reported in one case of post-biopsy arteriovenous shunt management [9]. However, the amount of gadodiamide administered to produce the mechanical embolization was very high, thus, increasing the total cost of the procedure. More recently, a diluted iodine-based contrast agent, which is less expensive than gadolinium, has been proposed as a safer alternative, because it provides better X-ray contrast and lower risk of inducing nephrotoxicity than gadolinium chelates [10]. Since in our experience the CO2 digital subtraction angiography has been sufficient to perform mechanical embolization, we reduced dramatically the amount of gadolinium contrast given to patients. We believe that the virtual absence of contrast-induced side effects (including nephrotoxicity) should counterbalance the higher cost of the combined procedure.

In conclusion, CO2 is a good alternative to iodine for imaging patients with high risk for nephrotoxicity or previous severe idiosyncratic reactions or both. Since CO2 angiography provides reliable information about arterial pathology, it can be employed safely, not only for diagnostic purposes, but also to guide percutaneous interventional procedures.

Conflict of interest statement. None declared.



   References
 Top
 Introduction
 Case
 Results
 Discussion
 References
 

  1. Baquero A, Morris MC, Cope C, Raja R, Bannett AD. Selective embolization of vascular complication following renal biopsy of the transplant kidney. Transplant Proc 1985; 17: 1751–1754[ISI][Medline]
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  8. Kaufman JA, Geller SC, Waltman AC. Renal insufficiency: gadopentate dimeglumine as a radiographic contrast agent during peripheral vascular interventional procedures. Radiology 1996; 198: 579–581[Abstract]
  9. Spinosa DJ, Pao DG, Matsumoto AH, Hagspiel KD, Angle JF, Hooper TN. Carbon dioxide and gadodiamide as contrast agents for diagnosis and embolization of a post-biopsy arteriovenous fistula in a renal allograft. Clin Radiol 2000; 55: 801–803[CrossRef][ISI][Medline]
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Received for publication: 3. 8.01
Accepted in revised form: 18. 4.03





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