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Published online before print May 15, 2008, 10.1148/radiol.2481071484
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(Radiology 2008;248:97-105.)
© RSNA, 2008

Contrast Media

Iso-Osmolality versus Low-Osmolality Iodinated Contrast Medium at Intravenous Contrast-enhanced CT: Effect on Kidney Function1

Shaun A. Nguyen, MD, MA, Pal Suranyi, MD, PhD, James G. Ravenel, MD, Patrick K. Randall, PhD, Peter B. Romano, MD, Kimberly A. Strom, RT, Philip Costello, MD, and U. Joseph Schoepf, MD

1 From the Department of Radiology (S.A.N., P.S., J.G.R., P.B.R., K.A.S., P.C., U.J.S.) and Center for Drug and Alcohol Programs (P.K.R.), Medical University of South Carolina, PO Box 250322, 169 Ashley Ave, Charleston, SC 29425. Received August 20, 2007; revision requested October 30; revision received January 3, 2007; accepted February 4; final version accepted February 11. Supported in part by GE Healthcare. Address correspondence to U.J.S. (e-mail: schoepf{at}musc.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Purpose: To determine the effects of iso-osmolality contrast medium compared with a low-osmolality agent on renal function (serum creatinine [SCr] and glomerular filtration rate [GFR]) in high-risk patients undergoing intravenous contrast material–enhanced CT.

Materials and Methods: This HIPAA-compliant study was IRB-approved; formal consent was obtained. One hundred seventeen patients (83 men, 34 women; mean age, 64.3 years; range, 18–86 years) with decreased renal function underwent contrast-enhanced CT with either iso-osmolality iodixanol (n = 61) or low-osmolality iopromide (n = 56). Outcome measures were of SCr increase or GFR decrease for 3 days after CT, a SCr increase (of ≥0.5 mg/dL [44.2 µmol/L, 25%] or ≥1.0 mg/dL [88.4 µmol/L, 50%]), a GFR reduction (of ≥5 mL/min), and patient outcome at 30- and 90-day follow-up.

Results: Iodixanol decreased SCr (mean ± standard deviation) from 1.77 mg/dL ± 0.24 (156.47 µmol/L ± 21.22) at baseline to 1.65 mg/dL ± 0.35 (145.86 µmol/L ± 30.94, P = .046) at day 1, 1.73 mg/dL ± 0.53 (152.93 µmol/L ± 46.85, not significant) at day 2, and 1.73 mg/dL ± 0.55 (152.93 µmol/L ± 48.62, not significant) at day 3 (not significant). Iopromide increased SCr from 1.75 mg/dL ± 0.32 (154.7 µmol/L ± 28.29) at baseline to 1.8 mg/dL ± 0.42 (159.12 µmol/L ± 15.59) at day 1, 1.77 mg/dL ± 0.49 (156.47 µmol/L ± 43.32) at day 2, and 1.77 mg/dL ± 0.62 (156.47 µmol/L ± 54.81) at day 3 (not significant). Iodixanol increased and iopromide decreased GFR on all 3 days after CT (not significant). Fewer patients in the iodixanol group (8.5%) than in the iopromide group (27.8%) had SCr increase 0.5 mg/dL or higher (≥25%, P = .012). Two patients in each group had SCr increase of 1.0 mg/dL or more (not significant). More patients in the iopromide group (42.3%) than in the iodoxanol group (24.1%) had a GFR reduction of 5 mL/min or higher (P = .0426). No patient had a contrast material–related adverse event at 30- or 90-day follow-up.

Conclusion: Intravenous contrast material application in high-risk patients is unlikely to be associated with permanent adverse outcomes. SCr levels after contrast material administration are lower in iodixanol than iopromide groups.

© RSNA, 2008


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Contrast medium–induced renal failure remains one of the most dreaded complications related to the use of iodinated contrast medium (1–4). To study the effect of contrast medium on renal function, contrast media–induced nephropathy (CIN) has been defined as an absolute increase in the serum creatinine (SCr) concentration of at least 0.5 mg/dL (44.2 µmol/L) or by a relative increase of at least 25% from the baseline value (5–8). In general, the SCr increase will peak 48–72 hours after contrast medium administration before returning to the baseline level. The incidence of CIN is low in the general population and has been calculated to be less than 2% regardless of the contrast medium used (7–11). Patients at increased risk include those with renal impairment and diabetes, especially in combination (5,8,12). In such patients, the incidence is significantly higher, in the range of 12%–50% (2,4,5,8,13–16).

The introduction of the currently used low-osmolality contrast agents for intraarterial applications substantially decreased the incidence of CIN in high-risk patients as compared with the previously used high-osmolality contrast media (6,8,15,17,18). However, it has been reported that in comparison with currently used low-osmolality agents, intraarterial application of iso-osmolality contrast medium causes an even lower incidence of CIN (19–21).

We hypothesized that the safety profile of iso-osmolality contrast medium should apply equally to intravenous contrast-enhanced computed tomographic (CT) examinations, which today are much more frequently performed than conventional angiography. We thus undertook a randomized prospective study to investigate the effects of iso-osmolality contrast medium compared with a low-osmolality agent on renal function (SCr and glomerular filtration rate [GFR]) in high-risk patients undergoing intravenous contrast-enhanced CT.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
This study was conducted in the Department of Radiology at the Medical University of South Carolina. The study was supported by a research grant provided by GE Healthcare (Princeton, NJ). Two authors (P.S., U.J.S.) are medical consultants for Bayer (Wayne, NJ); two authors (P.C., U.J.S.) are medical consultants for Bracco (Princeton, NJ); and one author (U.J.S.) is a medical consultant for GE Healthcare, Medrad (Indianola, Pa), Siemens (Malvern, Pa), and Tera Recon (San Mateo, Calif). Those authors who are not consultants for GE Healthcare had control of inclusion of any data and information that might present a conflict of interest.

Our institutional review board approved this investigation, and all patients provided written informed consent and release of their medical information for the purpose of this research, in compliance with Health Insurance Portability and Accountability Act requirements.

This investigation was a single-center, randomized, double-blind prospective study. Patients with impaired renal function undergoing CT were randomized by using the permuted block method to receive isoiodine (37 g) doses of 115 mL of dimeric, iso-osmolality iodixanol (320 mg per milliliter of iodine; Visipaque, GE Healthcare) or 100 mL of monomeric, low-osmolality iopromide (370 mg per milliliter of iodine; Ultravist, Bayer). Contrast-enhanced CT was performed according to standard of care practice at our institution. SCr was measured by using our clinical laboratory prior to contrast medium administration (baseline level), within 24 hours after contrast-enhanced CT (day 1), and on days 2 and 3 after the procedure.

The primary end point was the change in the SCr concentration between baseline and the subsequent maximum SCr attained on day 1, 2, or 3. Secondary end points were the number of patients with an increase of at least 0.5 mg/dL (44.2 µmol/L) or 1.0 mg/dL (88.4 µmol/L), as well as the change in SCr concentration from the baseline level through day 3 exceeding or equal to 25% or 50% of the baseline. In addition, data were analyzed to determine GFR changes (GFR was calculated by using the Cockcroft-Gault method) from baseline through day 3. A clinically important GFR reduction was defined as 5 mL/min or more (22).

Thirty-day and 90-day follow-up by using medical record review and phone calls to patients and referring physicians were conducted to record adverse events (death, myocardial infarction, revascularization, cerebral infarction, delayed allergoid reactions, dialysis after procedure, permanent renal failure) after the contrast-enhanced procedure.

Patients
Patients 18 years and older with impaired renal function (baseline SCr ≥1.5 mg/dL [132.6 µmol/L] or GFR <60 mL/min) who required clinically indicated contrast-enhanced CT were considered to be eligible to enroll in the clinical study. None of the CT studies were performed for mere research purposes. The use of protocols aimed at renal protection (hydration, acetylcysteine, sodium bicarbonate [21,23–25]) was left to the discretion of the referring physician requesting the CT scan. Patients from the outpatient clinics, emergency department, and inpatient units were screened from September 2004 through July 2006. Exclusion criteria were pregnancy; lactation; administration of iodinated contrast media within 7 days prior to study entry; history of anaphylaxis to iodinated contrast medium; acute renal failure; end-stage renal disease requiring dialysis; heart or kidney transplant or otherwise treated with cyclosporine or tacrolimus; patients receiving other potentially nephrotoxic drugs; administration of dopamine, mannitol, or theophylline 24 hours prior to enrollment; and administration of nonsteroidal antiinflammatory drugs other than aspirin within 48 hours prior to enrollment.

Statistical Analysis
All analyses and graphs were performed by using software (Sigma Stat 3.0, Sample Power 2.0, and Sigma Plot 8.0; SPSS, Chicago, Ill). All continuous variables were normal and distributed as determined by using the Kolmogorov-Smirnov test. Comparisons of baseline patient characteristics were performed by using the {chi}2 test with the Yates continuity correction (categoric variables) and the t test (continuous variables). The Fisher exact test (fewer than five expected observations in one or more group) was used to find significant differences between the two groups in the number of patients displaying clinically significant changes in SCr or GFR.

SCr and GFR values were analyzed as a mixed model by using software (Proc Mixed; SAS Institute, Cary, NC) with an unstructured variance-covariance matrix. This analysis is robust to noninformative missing data and does not have the more restrictive assumptions regarding the variance-covariance structure of the repeated measures. However, a more traditional mixed-model analysis with listwise deletion of subjects with any missing data, with an unstructured variance-covariance matrix (ie, with the fewest statistical assumptions) was also performed.

Power analysis was performed by using software (Sample Power, version 2.0; SPSS) by editing the actual data in matrix form. This provides power values for the full analysis of variance model by using the covariance structure of the actual experimental values from the study. When an analysis of variance model was found to indicate a significant difference (P < .05), individual post hoc comparisons were performed as Bonferroni-adjusted contrasts between contrast media within days and as a Dunnett test with contrast media across days. A P value of less than .05 was considered to indicate a significant difference for post hoc tests.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Patient Demographics and Disposition
Between September 2004 and July 2006, we screened a total of 393 patients with impaired renal function who were scheduled to undergo clinically indicated CT (Fig 1). One hundred twenty-six patients met all eligibility criteria and consented to be enrolled in the clinical study. The 126 patients were randomized to receive iodixanol (n = 65) or iopromide (n = 61). After exclusions because of protocol violations (n = 6) or patient withdrawals (n = 3) (Fig 1), 61 patients receiving iso-osmolality iodixanol and 56 patients receiving low-osmolality iopromide were included in the final analysis. Demographic and baseline data are provided in the Table. There were no significant differences between the two groups in age, weight, sex, race, baseline renal function, status as inpatient or outpatient, or use of reno-protective regimens. The prevalence of diabetes (P = .029) and of diabetes combined with hypertension (P = .029) was significantly greater in the iodixanol group. One hundred seventeen patients underwent contrast-enhanced CT scans of the head and/or neck (n = 11), chest (n = 33), abdomen and/or pelvis (n = 53), and combined scanning of the chest, abdomen, and pelvis (n = 20); all scans were performed with 115 mL of iodixanol or 100 mL of iopromide.


Figure 1
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  		Figure 1: Flowchart of study patients.

 

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  		Characteristics of the Study Population

 
In both groups, a minority of patients had missing values because of lost samples or missed follow-up appointments. From the iodixanol group, 24 (9.8%) data points were missing of 244 (four time points in 61 patients), and from the iopromide group, 25 (11.1%) data points were missing out of 224 (four time points in 56 patients). Thus, the missing number of data points was balanced between the two groups.

Changes in SCr from Baseline through Days 1–3
A mixed-model analysis found a significant difference in mean SCr levels between the two groups on day 1 (P = .048), but not on days 2 and 3 (Fig 2). The differential time-course in SCr across the two groups was confirmed with a significant group by using time interaction (P = .005), with significant variation across days only in the iodixanol group (P = .046). Iodixanol decreased SCr levels (measured as the mean ± standard deviation) from 1.77 mg/dL ± 0.24 (156.47 µmol/L ± 21.22) at baseline to 1.65 mg/dL ± 0.35 (145.8 µmol/L ± 30.94, P = .046) on day 1, 1.73 mg/dL ± 0.53 (152.93 µmol/L ± 46.85) on day 2 (not significant), and 1.73 mg/dL ± 0.55 (152.93 µmol/L ± 48.62) on day 3 (not significant). Iopromide increased SCr levels from 1.75 mg/dL ± 0.32 (154.7 µmol/L ± 28.32) at baseline to 1.80 mg/dL ± 0.42 (159.12 µmol/L ± 37.13) on day 1, 1.77 mg/dL ± 0.49 (156.47 µmol/L ± 43.32) on day 2, and 1.77 mg/dL ± 0.62 (156.47 µmol/L ± 54.81) on day 3 (not significant). The more traditional analysis, after exclusion of all patients with any missing values, confirmed the previous results, with a significance of interaction between contrast media and days (P = .003). Further analyses with a Bonferroni-Dunn correction yielded a significant difference between iodixanol (n = 48) and iopromide (n = 43) on day 1 after CT (P = .01), and a significant difference in the iodixanol group between baseline and day 1 after CT (P = .01).


Figure 2
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  		Figure 2: Change (defined as mean ± standard error) in SCr levels (milligram per decaliter; SI unit, micromol per liter) from baseline through days 1–3 after contrast material administration in patients receiving iodixanol and iopromide. * = SCr level on day 1 after CT was significantly lower than baseline in iodixanol group (P < .05). + = SCr level on day 1 after CT in iodixanol group was significantly lower than in iopromide group (P < .05).

 
The statistical power for detecting a clinically significant difference of 0.5 mg/dL was greater than 95% for both interaction power (between groups) and individual difference (within a group). The power analysis for the actual observed difference yielded a power of greater than 95% for interaction power and 67% for individual difference.

Three (5.1%) patients in the iodixanol group and 10 (18.5%) patients in the iopromide group had an SCr level increase of 0.5 mg/dL or higher (P = .037) (Fig 3) on at least one of the follow-up days. There was one patient in the iodixanol group and three patients in the iopromide group that had an elevated SCr level of more than 0.5 mg/dL on all 3 days after CT. For the remaining patients, the SCr returned to baseline level by day 3 after CT. An increase in SCr of 25% or more over baseline was found in five (8.5%) patients in the iodixanol group and in 15 (27.8%) patients in the iopromide group (P = .012) (Fig 4). Two patients in each group had an SCr level increase of 1.0 mg/dL or more (not significant) (Fig 3). One patient in the iodixanol group and three patients in the iopromide group showed an increase of 50% or more over baseline (not significant) (Fig 4).


Figure 3
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  		Figure 3: Incidence of SCr level increase of 0.5 mg/dL or more or 1.0 mg/dL or more for patients receiving iodixanol (black) and iopromide (gray). * = P < .05.

 

Figure 4
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  		Figure 4: Incidence of SCr level increase of 25% or more or 50% or more for patients receiving iodixanol (black) and iopromide (gray). * = P < .05.

 
Changes in GFR from Baseline through Days 1–3
The overall mixed model did not detect any main effect of interaction, though the interaction was suggestive (P = .083). Iodixanol increased GFR on all 3 days after CT from 51.8 mg/dL ± 16.58 (4579.12 µmol/L ± 139.67) at baseline to 55.48 mg/dL ± 23.19 (4904.43 µmol/L ± 2049.99) on day 1, 55.11 mg/dL ± 23.31 (4871.72 µmol/L ± 2060.6) on day 2, and 55.51 mg/dL ± 21.69 (4907.08 µmol/L ± 1917.4) on day 3 (not significant). Iopromide decreased the GFR from 52.98 mg/dL ± 26.02 (4683.43 µmol/L ± 2300.17) at baseline to 49.54 mg/dL ± 19.82 (4379.34 µmol/L ± 1752.09) on day 1, 48.65 mg/dL ± 25.60 (4300.66 µmol/L ± 2263.04) on day 2, and 50.17 mg/dL ± 24.68 (4435.03 µmol/L ± 2181.71) on day 3 (not significant) (Fig 5).


Figure 5
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  		Figure 5: Change (defined as mean ± standard error) in GFR (milliliter per minute) from baseline through days 1–3 in patients receiving iodixanol and iopromide. There was no significant reduction in GFR in either group.

 
A clinically significant (P = .0426) GFR reduction of 5 mL/min or more was found in significantly more patients in the iopromide group (22 patients, 42.3%) than in the iodixanol group (14 patients, 24.1%) (Fig 6).


Figure 6
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  		Figure 6: Incidence of clinically significant reduction of 5 mL/min or more in GFR in iodixanol (black) and iopromide (gray). * = P < .05.

 
The power to detect a GFR change of 5 mL/min on any day after contrast medium injection was calculated to be 61%. Thus, the power is lower with this clinical parameter, probably owing to slightly greater proportionate variance in the GFR values, relative to the difference used in the calculations. This would support the assumption that similar patterns prevail in SCr level and GFR that reach significance for SCr but not for GFR.

Changes in SCr in Patients on Reno-protective Regimens
Analysis of variance showed no significant difference in SCr (F(3,35) = 0.56713, P = .6427) (Fig 7) and GFR (F(3,35) = 0.14234, P = .9334) (Fig 8) between the iodixanol and iopromide groups in patients that received reno-protective regimens. Reno-protective regimens with acetylcysteine, hydration, and/or sodium bicarbonate were prescribed in only a small minority of study patients (eight in the iodixanol group, eight in the iopromide group).


Figure 7
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  		Figure 7: Change (defined as mean ± standard error) in SCr (milligram per decaliter; SI unit, micromol per liter) level from baseline through days 1–3 after contrast material administration in patients receiving reno-protective regimens. Two groups (iodixanol vs iopromide) x 4 days used to calculate repeated-measures analysis of variance (F(3,35) = 0.56713, P = .6427).

 

Figure 8
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  		Figure 8: Change (defined as mean ± standard error) in GFR (milliliter per minute) from baseline through days 1–3 after contrast material administration in patients receiving reno-protective regimens. Two groups (iodixanol vs iopromide) x 4 days used to calculate repeated-measures analysis of variance (F(3,35) = 0.14234, P = .9334).

 
Subgroup Analyses
The incidence of increase in SCr levels from baseline of 0.5 mg/dL or more and 1.0 mg/dL or more was significantly lower for diabetic patients in the iodixanol group (zero of 23) compared with patients in the iopromide group (three of 10) (P = .0401, Fisher test). However, the results from two analyses of variance (nondiabetic vs diabetic) x 4 (days) repeated measures (F(3,207) = 0.93218, P = .4268) indicated that there was no significant difference on the effects of iodixanol on SCr between nondiabetic (n = 38) and diabetic patients (n = 23) (Fig 9) across days. In addition, the effects of iopromide on SCr between nondiabetic (n = 46) and diabetic (n = 10) patients was also not significant (F(3,183) = 0.56229, P = .6408) (Fig 10).


Figure 9
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  		Figure 9: Change (defined as mean ± standard error) in SCr level (milligram per decaliter; SI unit, micromol per liter) from baseline through days 1–3 after contrast material administration in patients receiving iodixanol. Two groups (nondiabetics vs diabetics) x 4 days used to calculate repeated-measures analysis of variance (F(3,207) = 0.93218, P = .4268).

 

Figure 10
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  		Figure 10: Change (measured as mean ± standard error) in SCr level (milligram per decaliter; SI unit, micromol per liter) from baseline through days 1–3 after contrast material administration in patients receiving iopromide. Two groups (nondiabetics vs diabetics) x 4 days used to calculate repeated-measures analysis of variance (F(3,207) = 0.56229, P = .6408).

 
Patient Outcome
All patients were followed-up at 30 and 90 days after CT. Five patients in the study population had died at 30-day follow-up; all remaining patients were alive at 90-day follow-up. Of five deaths, three patients had received iodixanol and two had received iopromide. The causes of death for the five patients were heart failure (n = 3), peritoneal carcinomatosis (n = 1), and septicemia (n = 1). All deaths were investigated and adjudicated by an independent panel formed by our institutional review board and were deemed unrelated to contrast medium administration. No patient in either group had required dialysis, had suffered cerebral or myocardial ischemia or late allergoid reactions, or had undergone revascularization during the follow-up period.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
The results of our study suggest that the incidence of contrast medium–related permanent adverse outcomes with intravenous application of current iodinated contrast media in high-risk patients is low. In our investigation, none of the patients who received either low-osmolality or iso-osmolality contrast material suffered permanent contrast medium–related adverse events. Specifically, no instance of permanent contrast medium–induced renal failure was observed and no patient required dialysis. As implied by our results, SCr levels after contrast media administration are lower when iso-osmolality iodixanol is used, as compared with low-osmolality iopromide.

Our two randomized patient populations were extremely balanced in their demographics, with no significant differences in age, weight, race, sex, baseline SCr level, GFR, or use of reno-protective measures, although there was a significantly higher prevalence of diabetes and combined diabetes and hypertension in the iodixanol group, potentially increasing the a priori risk of this group. However, in our patient population, contrast-enhanced SCr patterns were not significantly different between diabetics and nondiabetic patients, suggesting that that the effects of the iso-osmolality agent are present in both the diabetic and nondiabetic populations.

We found a significant decrease in SCr level on the first day after contrast medium administration compared with the baseline when iodixanol was used. Also, SCr levels in the iodixanol group were significantly lower compared with the iopromide group on the same day. The incidence of SCr level increases of greater than 0.5 mg/dL or 25% over baseline during follow-up was significantly lower with iodixanol compared with iopromide.

Similar trends were observed for mean GFR on all 3 days after contrast medium administration, although these did not reach significance. However, a clinically significant GFR reduction of 5 mL/min or more was found in significantly more patients in the iopromide group than in the iodixanol group.

Most prior studies investigated the effect of intravascular iodinated contrast media on renal function during catheter-directed intraarterial application (5–8,15,20,26). The effect of intravenous application is less researched (27–31), although in current clinical practice, intravenous application occurs much more frequently and in ever increasing numbers compared with intraarterial injection, predominantly for the purpose of contrast-enhanced CT.

The pathophysiology of CIN is incompletely understood. Hemodynamic effects with decreased renal blood flow, direct tubular cell toxicity, and an increase in oxygen-free radicals and/or a decrease in antioxidant enzyme activity have been proposed as putative mechanisms (32,33). The effects of iodinated contrast media on all three pathways have been reported (34–36). The role of contrast media osmolality has been exhaustively documented (8,17,20). Explanations for the reported lower effect on renal function of iso-osmolality contrast media compared with low-osmolality agents have been sought in the greater osmotic diuresis induced by using low-osmolality contrast media with increased medullary work, hypoxia, and consequent activation of vasoregulatory hormones. Insufficient activation of compensatory vasoregulatory mechanisms in patients with renal impairment has been discussed as a potential factor in the development of CIN, which could serve to explain the reported lower effect of iso-osmolality contrast medium on renal function, which is isotonic to human plasma (20,37,38). In addition, iso-osmolality contrast medium was shown to have a less pronounced effect on renal nitric oxide production (35), whereas there are conflicting results regarding direct cytotoxicity (32,36).

Our results are in good agreement with previous investigations, demonstrating the general safety, low incidence of CIN and contrast medium–related adverse events of intravenously injected low-osmolality or iso-osmolality contrast agents in high-risk patients (28,29,31). One may hypothesize that greater dilution in the blood volume after intravenous injection may lessen the renal effect of contrast media, compared with the direct, more concentrated influx to the renal vasculature during intraarterial application.

Furthermore, as in previous investigations (19,20,26), our results confirm that SCr levels after contrast media administration tend to be lower when iso-osmolality contrast medium is used, as compared with low-osmolality contrast medium. However, in our study, the significant difference in mean SCr levels between the two groups on day 1 was partially related to a decrease in SCr level in the iodixanol group. To our knowledge, similar phenomena have not been described and future research appears warranted to better define this observation.

One prior investigation comparing the renal effects after intravenous administration of iodixanol versus iopromide for excretory urography reports no significant difference between the two agents (27) and development of CIN in only one patient. However, the patient population in this previous study was smaller and the volume of injected contrast medium was lower than those in our current investigation, which may explain these conflicting results. A prior systematic analysis (39) and two prospective studies (29,40) report no significant difference between the renal effects of intravenous (29) and intraarterial (39,40) iodixanol and the low-osmolality iopamidol. Our findings may not be directly comparable with these results, as a different low-osmolality agent was evaluated for intravenous injection at CT. Compared with the investigation involving intravenous application (29), however, our systematic serial assessment of SCr level and GFR over 3 days after contrast medium administration may have been more sensitive to detect SCr level changes compared with the single sampling at a variable interval (48–72 hours) after contrast medium administration (29) in the prior investigation. Considering that in most patients with decreased renal function the SCr will peak in the first 72 hours after contrast medium administration, multiple measures may provide greater accuracy regarding SCr dynamics.

A limitation of this study was its single-center design. Larger, longitudinal multicenter studies are desirable to further define our observations. However, we believe that the standard of patient care in our facility is fairly consistent with that of other medical communities. We did not attempt to control for the institution of reno-protective measures such as hydration, acetylcysteine, or sodium bicarbonate, as this would have created an artificial scenario relative to current patient care. However, the protective character of acetylcysteine and sodium bicarbonate is equivocal (24), and only a small minority of our patient population was treated in such a manner, likely reflecting clinical reality. Finally, the iodixanol group received 15% more contrast medium than did the iopromide group. This was an effect of equal iodine dosing owing to the variation in iodine concentration between the two products (320 mg of iodine per milliliter vs 370 mg of iodine per milliliter). An identifiable variable to minimize CIN is control of the volume of contrast medium administered (21). However, this would have limited the function of iodixanol to a greater degree.

In conclusion, the incidence of contrast medium–related permanent adverse outcomes with intravenous application of current iodinated contrast media in high-risk patients is low; SCr levels after contrast medium administration are lower when iso-osmolality iodixanol is used, as compared with low-osmolality iopromide.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
IMPLICATION FOR PATIENT CARE
 References
 


   IMPLICATION FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
References
 


   FOOTNOTES
 

Abbreviations: CIN = contrast medium–induced nephropathy • GFR = glomerular filtration rate • SCr = serum creatinine

See Materials and Methods for pertinent disclosures.

Author contributions: Guarantor of integrity of entire study, S.A.N.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, U.J.S.; clinical studies, S.A.N., J.G.R., P.R., P.C., U.J.S.; statistical analysis, S.A.N., P.S.; and manuscript editing, all authors


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 

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