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NDT Advance Access published online on November 25, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn638
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Assessment of renal vasoconstriction in vivo after intra-arterial administration of the isosmotic contrast medium iodixanol compared to the low-osmotic contrast medium iopamidol

Marcus Treitl1, Harald Rupprecht2, Stefan Wirth1, Markus Korner1, Maximilian Reiser1 and Johannes Rieger1

1 Department for Clinical Radiology, Clinical Center of the Ludwig-Maximilians- University of Munich 2 Department 5 of Internal Medicine, Nephrology, Clinical Center of Bayreuth, Germany

Correspondence and offprint requests to: Marcus Treitl, Department for Clinical Radiology, University of Munich, Pettenkoferstr. 8a, 80336 Munich, Germany. Tel: +49-89-5160-9280; Fax: +49-89-5160-9282; E-mail: marcus.treitl{at}med.uni-muenchen.de



   Abstract
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 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 References
 
Background. Low-osmotic contrast media (LOCM) such as iopamidol are known to increase the renal resistance index (RRI). The aim of our study was to evaluate in vivo the different effects of intra-arterial administration of LOCM in comparison to isosmotic contrast medium (IOCM) such as iodixanol on the human RRI.

Methods. Twenty patients (16 males, 4 females; 66 years on average) with normal renal function (mean creatinine 1.0 mg/dl) had digital subtraction angiography (DSA) of the abdominal and lower-limb arteries. Ten patients received LOCM, and 10 patients IOCM (150 ml on average, 20 ml/s). The RRI was assessed by an experienced nephrologist with duplex ultrasound from 15 min before until 30 min after the first injection with delays of 1–5 min. The basic value of the RRI and differential RRI were calculated.

Results. The basic value of the RRI was 0.69 in the LOCM group and 0.71 in the IOCM group. After LOCM a significant increase of the RRI to 0.73 on average (P ≤ 0.001) 2 min after the first injection was found, whereas IOCM did not result in a significant change of the RRI (RRI remained 0.71 on average, P ≥ 0.1). In the LOCM group, the RRI returned to the basic value after 30 min (±2.3 min).

Conclusions. Intra-arterial administration of IOCM had no influence on renal vascular resistance as expressed by the RRI, unlike LOCM, which induced a highly significant increase of the RRI for up to 30 min.

Keywords: colour-coded duplex sonography; contrast media; contrast media-induced nephropathy; digital subtraction angiography; renal resistance index



   Introduction
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 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 References
 
Contrast media-induced nephropathy (CIN) remains the third leading cause of hospital-acquired acute renal failure and, therefore, still is the most important complication of iodinated contrast media [1]. CIN is associated with a considerably increased risk for short- and long-term haemodialysis or even renal transplantation, and increases the mortality rate to values of up to 36% [2,3] with survival rates of 19% after 2 years. By definition, CIN manifests as an abrupt decline in renal function within 3 days after contrast media administration in the absence of an alternative aetiology [4]. It is characterized by an increase in the serum creatinine (SCR) level of at least 0.5 mg/dl or 25% as compared to baseline values [4]. Fortunately, CIN can be self-limiting and in the majority of cases it resolves within 10 days [4].

Renal toxicity of iodinated contrast media is regarded to depend on both renal tubulotoxicity [5,6] and changes in intrarenal haemodynamics and blood flow [7]. As demonstrated in animal experiments up to 40 years ago [8–10], the intravascular injection of contrast media results in an increase in renal vascular resistance and a consecutive decrease in renal blood flow (RBF) and glomerular filtration rate (GFR) after an initial and short phase of intrarenal vasodilatation [11–14]. However, most of the knowledge concerning this issue is based on animal and in vitro studies [7].

In 2001, Hetzel et al. published their observation that intra-venous administration of the low-osmotic contrast medium (LOCM) iopamidol in vivo leads to a significant but short and reversible increase of the renal resistance index (RRI) in humans, as assessed by colour-coded duplex sonography (CCDS) [7]. As of yet, no studies exist exploring the effect of isosmotic contrast medium (IOCM) such as iodixanol on the human RBF.

The aim of our study was to examine the different effects of intra-arterial administration of the IOCM iodixanol and the LOCM iopamidol on human RBF. We therefore assessed the RRI and the heart rate (HR) during intra-arterial administration of the IOCM iodixanol or the LOCM iopamidol in humans undergoing digital subtraction angiography (DSA) of the abdominal and lower-limb arteries and compared changes of the RRI and HR to baseline values assessed immediately before DSA.



   Materials and methods
Top
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 References
 
Patient selection
In a prospective study, 20 patients (16 males, 4 females) were examined. Patients were selected between September 2003 and February 2006 from a larger group of consecutive individuals (n = 960) referred to our department for diagnostic angiography of the lower limbs when the following inclusion criteria were met: suffering from peripheral arterial disease in stage IIa or IIb after Fontaine, and with the clinical need for invasive intra-arterial DSA of the lower limbs, no renal disease or renal failure in the medical history, exclusion of renal artery stenosis (RAS) by CCDS, mean SCR level <1.2 mg/dl, no injection of iodinated contrast agents within the last 6 months and no incidence of CIN in the medical history. Patients were excluded from study participation if one of the following medications was in their drug regime: nifedipine or other calcium channel antagonists, angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, or theophylline, since they all could possibly influence contrast media-induced vasomotor changes. Medication with beta- or alpha-blockers was not a criterion for study exclusion. However, none of the patients eligible for study participation received one of these drugs during the study period. Patients were excluded from study participation if there were contraindications for the administration of iodinated contrast media such as a known allergy, and when one of the inclusion criteria was missing. History concerning pre-existing renal disease was surveyed by an experienced nephrologist. Indication for DSA of the lower limb was established by an experienced specialist in vascular medicine. The patients' characteristics are summarized in Table 1. Patients were informed about the study protocol and their potential inclusion in the study 24 h prior to the DSA. Only patients who gave their written informed consent were included. Enrolled patients were allotted to one of the two study groups by a study nurse. The first 10 eligible patients received iopamidol (control group, LOCM; Solutrast 300TM, Bracco ALTANA Pharma GmbH, Konstanz, Germany; iodine concentration 300 mg/ml), and the second 10 consecutive patients received iodixanol (study group, IOCM; Visipaque 320TM, GE Healthcare Limited, Buckinghamshire, United Kingdom; iodine concentration 320 mg/ml). Only the study nurse knew which contrast medium was applied. None of the examinators, neither the nephrologist performing the measurements of the RRI nor the radiologist performing the DSA, did know which contrast medium was in use in order to minimize examinator related bias as much as possible. The distribution of sexes was identical in both groups (eight men and two women each). There was a mean age difference of 4 years between both groups (Table 1). The baseline renal function characteristics of both groups were comparable. Individuals within the LOCM group were younger and had a mean SCR level that was slightly lower than that within the IOCM group (0.94 mg/dl versus 1.01 mg/dl), and their mean GFR was higher (87.3 ml/min versus 84.2 ml/min). However, for both groups all values were within the age-related normal range and differences between both groups were statistically not significant (P = 0.623). SCR levels were obtained 24 h before and for 4 days after contrast medium administration to detect the possible development of CIN.


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  		Table 1 Patient characteristics of both groups

 
The study protocol was approved by the institutional review board (IRB) of the University of Munich. The principles of the Declaration of Helsinki were followed.

Patient preparation
Patients fasted for 12 h prior to DSA. During this period, neither nicotine nor coffee was allowed due to their possible impact on the vascular tone and blood pressure. All patients received an intra-venous infusion of 500 ml saline 2 h prior to DSA in order to establish a comparable hydration and glomerular flow rate.

Angiography
Uniplanar intra-arterial angiography of the abdomen, pelvis and the lower limbs was performed using DSA equipment with a 40-cm screen (Polystar T.O.P.®, Siemens Medical AG, Erlangen, Germany). After retrograde puncture of the right common femoral artery, the tip of a 4F pigtail catheter was placed under fluoroscopic control into the suprarenal part of the abdominal aorta immediately above the first lumbar spine. With this catheter position, a first DSA series was obtained to depict the abdominal aorta with both renal arteries (injected contrast medium volume = 20 ml, flow rate = 17 ml/s). After this first series, the catheter tip was retracted shortly above the aortic bifurcation in order to decrease the loss of contrast medium into the splanchnic arteries and to increase opacification of the lower-limb arteries. With this catheter position, angiographic images of the iliac, femoral, popliteal, crural and pedal arteries were obtained in single projections. The injected volume of contrast medium was adapted to the patient's HR and blood pressure to improve vessel contrast and varied from 15 to 30 ml per series with a flow rate ranging from 10 to 20 ml/s. The first injection, which always was performed immediately above the renal arteries, continuously had a volume of 15 ml at a constant flow rate of 20 ml/s. Contrast medium injection was performed automatically by use of a contrast medium injector (Angiomat 6000, Liebel-Flarsheim, Cincinnatti, USA).

The mean total volume of the contrast medium injected was 145 ml (110–200 ml) for the LOCM group and 153.8 ml (100–200 ml) for the IOCM group. Accordingly, the mean iodine concentration in relation to the body weight was 566.4 mg/kg for the LOCM group and 628.6 mg/kg for the IOCM group. The mean duration of contrast-enhanced DSA was 12.4 min for the control group and 13.3 min for the study group (Table 1). These differences in contrast media volumes, iodine concentration and duration of the examinations between both groups were statistically not significant (P = 0.437, P = 0.602 and P = 0.371, respectively).

All angiographic images were processed later and digitally stored in a picture archiving and communication system (IMPAX® R4.1, AGFA Gevaert GmbH, Cologne, Germany) for further evaluation.

Colour-coded duplex sonography
CCDS was performed by a nephrologist experienced in this examination technique using a multi-purpose ultrasound unit (Sonoline Elegra, Siemens Medical AG). The examiner was blinded to the type of contrast medium used to avoid as much bias as possible. The imaging and Doppler systems were operated at 3.5 MHz with a sample Doppler volume of 5 mm and an image rate of 20/s. The patients were examined in the supine position using a lateral or postero-lateral approach. In all patients, the right kidney was examined. In the B-mode examination prior to DSA, no morphological abnormalities of the renal arteries were detected in any patient. Under imaging guidance of the colour signal, the sample Doppler volume was directed towards a segmental or interlobar artery.

Measurement of the RRI and HR
The Doppler signals were registered for at least four systolic phases. Using the Doppler flow curves, the following data were measured: maximum systolic blood flow rate (Vmax systolic), maximum end-diastolic blood flow rate (Vmax end-diastolic) and HR. The RRI was calculated from these values according to the following equation:

RRI = Vmax systolic Vmax end-diastolic/Vmax systolic

Five measurements of the RRI and the HR were performed 15, 10, 5, 2 and 0 min before the injection of contrast medium in order to calculate their baseline values. The baseline values of the RRI and the HR of each patient were calculated as the mean of these five measurements for each patient. After the start of the contrast injection, up to 25 measurements, each 1 min apart, were performed. On average, 20 measurements of the RRI and HR were obtained according to the duration of the angiographic examination. After the completion of the contrast-enhanced DSA, the RRI and HR were measured for additional 30 min: the first 10 min with intervals of 1 min, and after that with intervals of 5 min. Therefore, the mean overall observation period of the RRI and HR was 65 min (±5 min).

Statistical analysis
For statistical analysis, the statistical package for the social sciences (SPSS) 15.0.1® software was used (SPSS Inc., Chicago, IL, USA). The statistical significance of changes in RRI, HR and SCR levels after intra-arterial injection of either iopamidol or iodixanol in comparison to a baseline value prior to DSA was calculated by the two-tailed Student's t-test for paired samples. A P-value <0.05 was considered statistically significant.



   Results
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 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 References
 
Renal resistance index
The results of the measurements of the RRI are shown in Table 2 and depicted graphically in Figure 1. The mean basic value of the RRI was 0.69 in the LOCM group and 0.71 in the IOCM group (Table 1). After intra-arterial administration of LOCM, a statistically significant increase of the RRI was found within 1 min after the start of the contrast injection (delta RRI +0.03 on average, P < 0.001), which increased for 15 min (delta RRI +0.05 on average, P < 0.002) and returned back to pre-contrast values after 30 min (± 2.3 min). Intra-arterial administration of IOCM did not result in a change of the RRI during the entire observation period of 50 min (delta RRI ± 0.00 on average, P-values >0.078).


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  		Table 2 Results for the baseline measurements of the renal resistance index (RRI), and its changes after intra-arterial administration of low-osmolar (LOCM; iopamidol) or isosmotic contrast medium (IOCM; iodixanol)

 

Figure 1
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  		Fig. 1 Changes in the renal resistance index (RRI) after intra-arterial administration of iopamidol and iodixanol. Following iopamidol, a statistically significant increase was observed in the RRI 1 min after the start of the injection, which returned to the basic value after 30 min (± 2.3) on average. Administration of iodixanol did not result in renal vasoconstriction, as expressed by constant values of the RRI.

 
HRs
The results of the measurements of the HRs are shown in Table 3. The mean basic value of the HR was almost identical in both groups (Table 1). Neither LOCM nor IOCM had any significant influence on the HR during the whole observation period (mean delta HR is 2.58 for LOCM and 0.35 for IOCM, P-values >0.069).


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  		Table 3 Results for the baseline measurements of the heart rate (HR), and its changes after intra-arterial administration of low-osmolar (LOCM; iopamidol) or isosmotic contrast medium (IOCM; iodixanol)

 
SCR levels
SCR levels were taken in all patients from 1 day before until 4 days after intra-arterial contrast media administration. The results are shown in Table 4. The maximum increase of SCR was 0.08 mg/dl for LOCM and 0.04 mg/dl for IOCM (Table 4; P-values >0.075). No patient developed a CIN.


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  		Table 4 Changes in serum creatinine levels after intra-arterial administration of low-osmolar contrast media (LOCM; iopamidol) and isosmotic contrast medium (IOCM; iodixanol) from 1 day before until 4 days after injection

 


   Discussion
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
References
 
CIN is still one of the leading causes of hospital-acquired acute renal deterioration, especially in diabetic patients with renal insufficiency [15,16]. For that reason, the administration of iodinated contrast media for DSA or computed tomography (CT) always requires special diligence and a strong clinical indication. However, with advanced imaging techniques such as whole body examinations, coronary CT and CT angiography, the clinical indications for contrast-enhanced imaging and the use of iodinated contrast media continue to increase. Up to now, patients with renal insufficiency were rather referred to magnetic resonance imaging (MRI), when applicable, because the gadolinium contrast media used for MRI were believed to be generally safe and not nephrotoxic. However, patients with renal insufficiency are at risk of developing potentially lethal nephrogenic systemic fibrosis [17,18]. Therefore, there is an increasing demand for less or non-nephrotoxic iodinated contrast media, especially for this growing subgroup of patients.

Contrast media are classified according to their osmolality. In the middle of the last century, only high-osmolar contrast media like diatrizoate were available. Their osmolality averaged at values of 2000 mOsm/kg and was about five to eight times greater than that of plasma [19]. In the following three decades, contrast medium osmolality was decreased to values only two to three times greater than that of plasma. Important representatives of this group of low-osmolar contrast media with a mean osmolality of 600–700 mOsm/kg are iohexol, iopamidol and ioxaglate [19]. Iodixanol, which was introduced in the 1990s, is the only iodinated contrast medium available with the same physiologic osmolality as that of blood at 290 mOsm/kg.

Several studies indicate that contrast medium osmolality rather than viscosity or ionicity is a predisposing factor for CIN [20,21]. It was shown that the contrast media of higher osmolality induce red blood cell deformation, systemic vasodilatation, intrarenal vasoconstriction and direct renal tubular toxicity more often than low- or isosmotic contrast media [19].

However, the pathogenesis of contrast media-associated nephrotoxicity is not yet fully understood [7]. In general, contrast media are believed to result in both a change of renal haemodynamics and a direct tubulotoxic effect. In cell cultures and animal studies, an ischaemic necrosis in the ascending Henle loop was found with high-osmolar contrast media but not with low- or isosmotic substances [4]. On the other hand, as shown in cell cultures, isosmotic contrast media induced a reversible vacuolization of epithelial tubular cells, which is not considered to contribute to renal toxicity [4]. The administration of high- or low-osmolar contrast media causes a very short period of vasodilatation followed by a prolonged vasoconstriction in the renal medulla through the activation of vasoactive substances like endothelin and adenosine, thereby leading to medullary ischaemia [4,22]. In addition, an interaction with the tubular water and sodium transporters results in osmotic diuresis and natriuresis and increases the metabolic activity and oxygen consumption in the distal nephron, which also contributes to medullary hypoxia [22,23]. The extent of these interactions directly correlates with contrast medium osmolality. Isosmotic contrast media like iodixanol will, therefore, induce less diuresis and natriuresis. However, whether they will induce a reduction of RBF is still unexplored.

The impact of contrast media on RBF was extensively examined in the 1960s and 1970s. In 1968, Talner and Davidson published their experiments on the effect of contrast medium injection into a renal artery on the RBF in dogs. Different high-osmolar test substances and contrast media were used, and all resulted in a reduction of RBF between 10 and 20% after 1–13 min [8]. In a similar experiment using an electromagnetic flow meter placed inside the renal artery, Caldicott et al. found a biphasic reaction of the RBF in response to the contrast medium injection with an initial increase of 36% that lasted <30 s, followed by a decrease of 26% for an average of 45 s after injection [10]. Between 2 and 15 min after injection, a second and smaller flow decrease was observed [10].

So far, data on changes of RBF and the RRI, which is a major indicator of RBF, are mostly based on animal experiments and low-osmolar contrast media typically injected intra-venously. One of the first human in vivo studies dealing with this issue was published in 2001 by Hetzel et al. [7]. They used CCDS for transcutaneous measurements of the RRI after intra-venous administration of the low-osmolar contrast medium iopamidol and observed a significant rise in the RRI 2 min after the injection of iopamidol, followed by a return to pre-injection values ~10–15 min later. These in vivo experiments for the first time indicated that even in humans, low-osmolar contrast media may have a major impact on RBF by increasing renal vascular resistance.

In our study, we evaluated the direct effect of an intra-arterial injection of typical diagnostic volumes of the isosmotic contrast medium iodixanol and the low-osmolar contrast medium iopamidol on the RBF. According to the study protocol of Hetzel et al., we used transcutaneous CCDS for repeated measurements of the RRI. This technique is well established and scientifically accepted [7,24]. The patient groups were selected according to the strict inclusion and exclusion criteria. Patients with pre-existing renal failure were not enrolled in this trial since any of these conditions might impede intrarenal vasomotor changes. As shown in Table 1, both groups were comparable and differences for SCR levels and GFR rates were statistically not significant. Furthermore, the basic value of the RRI, averaged from five measurements before contrast medium administration, was almost identical for both groups (0.69 versus 0.71), and we assume that the vasomotor potential of both groups was identical too.

This study confirms the results of Hetzel et al. After intra-arterial injection of iopamidol, a statistically significant increase of the RRI by ± 0.05, beginning 1 min after the first injection, with a maximum after 15 min and a return to the basic value after 30 min, was observed. In contrast, intra-arterial injection of iodixanol had no significant influence on the RRI. The RRI may be influenced by cardiovascular parameters such as HR and blood pressure. Therefore, the HR was measured simultaneously with the RRI measurements but no significant changes were observed in either group. The amount of contrast medium applied and the corresponding iodine concentration in relation to the body weight of the patients were comparable, and the difference was statistically not significant. We therefore can preclude systematic errors like different amounts of contrast medium or iodine as well as changes in the HR or cardiac output being the cause for the effects on the RRI we observed.

We followed up SCR levels of all patients for at least 4 days, and none of the patients in either group experienced the development of CIN (Table 4). There was no statistically significant increase of SCR levels in both groups, but it regularly returned to the basic value by Day 4.

To our knowledge, this is the first in vivo study on humans demonstrating that the intra-arterial injection of the isosmotic contrast medium iodixanol does not alter the RRI. However, as shown by clinical trials like the Cardiac Angiography in Renally Impaired Patients (CARE) trial, which was recently published by Solomon et al. [25], and other trials [21,26,27], iodixanol still has a nephrotoxic potential. The reported rate of CIN after administration of iodixanol ranged between 0% and 11%. For most low-osmolar contrast media examined, the reported rate of CIN varied between 6.2% and 26.2% [28]. The only exception is represented by the low-osmolar contrast medium iopamidol, which exhibited also a low rate of CIN (6.2–11.2%) comparable to that of iodixanol for non-risk patients without renal insufficiency [25,29]. Therefore, the nephrotoxic potential of contrast media may still not be explained by their osmolality alone.

In 2005, Heinrich et al. incubated LLC-PK1 cells with several contrast media of different osmolality such as iomeprol, iodixanol and iotrolan. They discovered that the dimeric isosmotic contrast medium iodixanol produced significantly more direct cytotoxic effects in this experimental renal tubular cell line [30] than the monomeric low-osmolar contrast media examined. Therefore, some authors hypothesize that the reason for the remaining nephrotoxic potential of iodixanol lies in its increased viscosity, which leads to extended retention periods within the tubular system, and an increase of direct toxic effects on tubular cells [4]. However, our study strongly focussed on the physiologic effects of contrast media on renal resistance, and therefore no final conclusion regarding the renal toxicity of either substance can be drawn, especially since no patient in either group developed a CIN. Contrast media-induced alterations of RBF may substantially contribute to its nephrotoxic potential, and our data indicate that this effect can be reduced by decreasing contrast media osmolality.

The small number of patients within this study is a potential limitation that we have to address. It was caused by the strong inclusion and exclusion criteria, especially regarding patients’ medication. We strongly focussed on patients not suffering from hypertension and not receiving any medication potentially altering renal vasomotor changes, in order to reduce the systematic error and bias as much as possible, and to produce a highly realistic test scenario for contrast media-induced renal vasomotor changes. However, our data are concordant with all published animal experiments on this topic [8–10], and to the findings of Hetzel et al. [7], who, too, demonstrated an increase of the RRI after intra-arterial injection of iopamidol in humans. At least, partially different results were published by Möckel et al. They measured the RBF within one renal artery during cardiac intervention in a small group of patients by an intra-arterial placed Doppler probe, and compared the effects of the contrast media iopramide and iodixanol [31]. In contrast to our results, they found a delayed decrease in RBF during the course of cardiac intervention for both substances, which was, nevertheless, lower for iodixanol. To our opinion, their study is not comparable to ours and their results could be biased by several unknown factors. In contrast to our study, Möckel et al. included only patients with a reduced renal function and significantly increased SCR levels (1.3–3.7 mg/dl), possibly influencing the renal potential for any changes in the intrarenal vascular tone. In addition, almost all patients in their study were suffering from diabetes. They, too, did hydrate the patients prior to angiography, but, in contrast, appliedacetylcysteine. Most importantly, they do not state whether they excluded patients receiving drugs potentially influencing renal vasomotor changes as in our study. Other differences between both studies include the fact that Möckel et al. injected significant larger amounts of contrast medium but over a significant longer period of time than we did (volumes ranging from 120 to 440 ml, duration of the examinations ranging from 27 to 150 min). Therefore, the volume of each single injection as well as the bolus concentration of the contrast media was significantly lower than in our study.

Another potential limitation might be the fact that changes in the systemic blood pressure and cardiac output were not registered during the examination. We therefore, basically, cannot rule out an influence of the systemic blood pressure on the demonstrated changes in the RRI. However, to our knowledge there are no reports on significant changes in the systemic blood pressure caused by the intra-arterial injection of contrast media. Since the changes in the RRI occurred very fast and early after contrast injection, we hypothesize that we indeed demonstrated a direct effect of the contrast medium on the renal vascular tone. In the case of an increase of the renal vascular resistance due to changes of the systemic blood pressure or cardiac output, we would have expected a much more delayed reaction. Furthermore, we could show that the HR remained stable during the whole examination in both groups (see Table 3), which enforces our thesis that the changes in renal vascular tone we observed were not influenced by the cardiac output.

Finally, we have to state that a remarkable amount of the contrast medium was injected solely into the legs after retraction of the catheter tip to the aortic bifurcation. For that reason, the contrast medium injected during this second part of the examination would have reached the kidneys after passing through the lung first, and therefore again the cardiac output could have had a major impact. As we already stated, the HR remained stable during the whole examination for both groups and the main effect on the RRI occurred immediately after the first bolus injection. But we cannot rule out that the changes of the RRI we observed could have been much more pronounced if the total amount of contrast medium were injected above the renal arteries, since the passage through the lung circulation causes a significant dilution of the contrast medium. However, even when concerning the potential limitations of this study we still assume that the different effects of both contrast media are not due to a sample error, since our data are still concordant to the findings of Hetzel et al. [7]. Nevertheless, additional studies with larger patient collectives will be required to confirm these observations.

In conclusion, we have shown that the intra-arterial injection of the isosmotic contrast medium iodixanol did not alter RBF. The low-osmolar contrast medium iopamidol resulted in a significant reduction of RBF. Since contrast media-induced alterations of RBF may substantially contribute to its nephrotoxic potential, our data indicate that this effect can be reduced by decreasing contrast media osmolality.

Conflict of interest Statement. There are no conflicts of interests for any of the authors.



   References
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 

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Received for publication: 9. 1.08
Accepted in revised form: 22.10.08


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