Comparison of Contrast-Induced Nephrotoxicity of Iodixanol and Iopromide in Patients With Renal Insufficiency Undergoing Coronary Angiography

doi:10.1016/j.amjcard.2011.03.019

The American Journal of Cardiology

Volume 108, Issue 2, 15 July 2011, Pages 189-194

https://doi.org/10.1016/j.amjcard.2011.03.019 Get rights and content

This prospective, randomized, double-blind study was performed to compare the incidence of contrast-induced nephropathy (CIN) after the administration of the iso-osmolar contrast medium iodixanol to the low-osmolar contrast medium iopromide during coronary angiography in patients with impaired renal function. Patients with creatinine clearance (CrCl) <60 ml/min who underwent coronary angiography and/or percutaneous coronary intervention were randomized to receive either iodixanol (n = 215) or iopromide (n = 205). The primary study end point was the incidence of CIN, which was defined as an absolute increase in serum creatinine (SCr) ≥0.5 mg/dl (44.2 mol/L) or a relative increase ≥25% compared to baseline SCr. The secondary end points were the proportion of patients with increases in SCr ≥0.5 mg/dl, the proportion with SCr increases ≥1.0 mg/dl (88.4 mol/L), and the peak increase in SCr. Age, the presence of diabetes mellitus, mean baseline SCr, CrCl, the use of N-acetylcysteine, contrast volume, and the predicted risk score for CIN were similar in the 2 groups. CIN developed in 39 patients (9.3%); there was no significant difference between the iodixanol and iopromide groups (10.7% and 7.8%, respectively; absolute difference 2.9%, 95% confidence interval −3.1% to 8.9%, p = 0.394). The proportions of patients with SCr increases ≥0.5 mg/dl (6.5% vs 6.3%) and ≥1.0 mg/dl (2.8% vs 2.9%) were similar in the 2 groups. There was a tendency for more patients with relative increases ≥25% (10.2% vs 6.8%) and greater peak increases in SCr (0.037 ± 0.375 vs 0.029 ± 0.351 mg/dl) to be in the iodixanol group, but these differences were not statistically significant. In conclusion, the incidences of CIN after coronary angiography did not significantly differ between the iodixanol and iopromide groups in patients with impaired renal function.

Section snippets

Methods

Consecutive patients scheduled for CAG were screened from February 2009 through May 2010 regardless of percutaneous coronary intervention. Patients aged >19 years with creatinine clearance (CrCl) <60 ml/min were eligible for enrollment. The exclusion criteria were pregnancy, lactation, having received contrast media <7 days before the procedure, emergent CAG in which sufficient preprocedural hydration was unavailable, acute renal failure, end-stage renal disease requiring dialysis, history of

Results

Among the 429 patients, 218 received iodixanol and 211 received iopromide (Figure 1). Nine patients were excluded because of inappropriate inclusion or insufficient SCr follow-up; the final group available for analysis included 420 patients, 215 in the iodixanol group and 205 in the iopromide group.

The baseline characteristics of the 2 groups were similar, as listed in Table 1. CIN developed in 39 patients (9.3%), of whom 23 (10.7%) were in the iodixanol group and 16 (7.8%) in the iopromide

Discussion

The goal of this study was to compare iodixanol to iopromide with regard to the incidence of CIN after CAG in patients with impaired renal function. There was no significant difference in the incidences of CIN or the safety outcomes.

The results of the comparison of IOCM to LOCM have been inconclusive to date; there are contradicting reports on outcomes. Early studies reported that IOCM is less likely to result in CIN than other types of LOCM, such as iohexol or ioxaglate.4, 5 However,

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Contrast media use in patients with chronic kidney disease undergoing coronary angiography: A systematic review and meta-analysis of randomized trials
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Citation Excerpt :
In this study of 146 patients, there was no reduction in renal deterioration with IOCM [26]. Shin et al. compared iodixanol with iopromide in 420 patients with CKD and showed no statistically significant difference in the incidence of CIN (P = 0.394) [27]. Osmotic diuresis has been hypothesized to contribute to the process of CIN as it enhances distal sodium delivery, thus increasing medullary work and inducing hypoxia or volume depletion, with consequent activation of vasoregulatory hormones.
Patients with chronic kidney disease (CKD) undergoing coronary angiography (CA), adequate hydration and minimizing volume of contrast media (CM) are class 1b recommendations for preventing contrast induced nephropathy (CIN). Current data are insufficient to justify specific recommendations about isoosmolar vs. low-osmolar contrast media by the ACCF/AHA/SCAI guidelines.
Randomized trials comparing IOCM to LOCM in CKD stage 3 and above patients undergoing CA, and reporting incidence of CIN (defined by a rise in creatinine of 25% from baseline) were included in the analysis. The secondary outcome of the study was the incidence of serum creatinine increase by > 1 mg/dl.
A total of 2839 patients were included in 10 trials, in which 1430 patients received IOCM and 1393 received LOCM. When compared to LOCM, IOCM was not associated with significant benefit in preventing CIN (OR = 0.72, [CI: 0.50–1.04], P = 0.08, I2 = 59%). Subgroup analysis revealed non-significant difference in incidence of CIN based on baseline use of N-acetylcystine (NAC), diabetes status, ejection fraction, and whether percutaneous coronary intervention vs coronary angiography alone was performed. The difference between IOCM and LOCM was further attenuated when restricted to studies with larger sample size (> 250 patients) (OR = 0.93; [CI: 0.66–1.30]) or when compared with non-ionic LOCM (OR = 0.79, [CI: 0.52–1.21]).
In patients with CKD stage 3 and above undergoing coronary angiography, use of IOCM showed overall non-significant difference in incidence of CIN compared to LOCM. The difference was further attenuated when IOCM was compared with non-ionic LOCM.
Radiological contrast agents and radiopharmaceuticals
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The difference in the incidence of contrast-induced nephropathy between low-osmolar and iso-osmolar agents has been studied, without definite conclusions. In a study in which contrast-induced nephropathy was studied in 584 patients with renal impairment undergoing coronary angiography, low-osmolar and iso-osmolar agents were compared [13C]. The incidences of contrast-induced nephropathy were 7.8% and 11 respectively.
The Side Effects of Drugs Annuals form a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the 2011 publications on radiological contrast agents and radiopharmaceuticals covers iodinated water-soluble contrast media (diatrizoate, iotalamic acid, ioxitalamic acid, metrizoate, ioxaglic acid, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, metrizamide, iodixanol, iosimenol, and iotrolan), gadolinium salts (gadobenic acid, gadobutrol, gadocoletic acid, gadodenterate, gadodiamide, gadofosveset, gadomelitol, gadopenamide, gadopentetic acid, gadoteric acid, gadoteridol, gadoversetamide, and gadoxetic acid), superparamagnetic iron oxide (SPIO) MRI contrast agents (ferucarbotran, feruglose, ferumoxide, ferumoxtran, and ferumoxytol), ultrasound contrast agents, and anti-[¹⁸F]FACBC. It includes a special review on iodinated radiocontrast-induced nephropathy.
Reading between the (guide)lines - The KDIGO practice guideline on acute kidney injury in the individual patient
2014, Kidney International
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Animal models of CI-AKI have shown that sodium delivery to the kidney and increasing urinary flow rate reduce renal tubular toxicity, as does alkalinization of the urine. Thus, normal saline (0.9%) was reported to reduce CI-AKI compared with 0.45% saline.55 More recently, the debate has centered on whether isotonic sodium bicarbonate offers additional benefit over 0.9% saline.56
The KDIGO guidelines for acute kidney injury (AKI) are designed to assist health-care providers around the world in managing patients with AKI. Clinical guidelines are intended to help the clinician make an informed decision based on review of the currently available evidence. Due to the generic nature of guidelines, it is sometimes difficult to translate a guideline for a particular individual patient who may have specific clinical circumstances. To illustrate this point, we have discussed the interpretation of the KDIGO guideline in patients who have subtleties in their clinical presentation, which may make treatment decisions less than straightforward.
Coronary vascular dysfunction and prognosis in patients with chronic kidney disease
2012, JACC: Cardiovascular Imaging
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The potential impact of CFR on risk stratification was assessed by net reclassification improvement (NRI) (22) at 2 years using threshold annual rates of cardiac mortality of 2% and 4%. These thresholds were selected to be slightly higher than American College of Cardiology/American Heart Association guidelines for management of chronic stable angina (23) because of the higher periprocedural morbidity and mortality of coronary angiography and revascularization in patients with moderate to severe renal impairment (3–7). Reclassification metrics using guideline-derived (23) 1% and 3% thresholds were also computed as a secondary analysis.
This study sought to evaluate whether impaired vasodilator function, an early manifestation of coronary artery disease, which precedes angiographic stenosis, accounts for increased risk among patients with moderate to severe renal dysfunction.
Patients with renal dysfunction are at increased risk of adverse cardiac outcomes, even in the absence of overt myocardial ischemia or infarction.
We included 866 consecutive patients with moderate to severe renal dysfunction referred for rest and stress myocardial perfusion positron emission tomography and followed them for a median of 1.28 years (interquartile range: 0.64 to 2.34). Regional myocardial perfusion abnormalities were assessed by semiquantitative visual analysis of positron emission tomography images. Rest and stress myocardial blood flow were calculated using factor analysis and a 2-compartment kinetic model; they were also used to compute coronary flow reserve (stress/rest myocardial blood flow). The primary endpoint was cardiac death.
Overall, 3-year cardiac mortality was 16.2%. After adjusting for clinical risk, left ventricular ejection fraction, as well as the magnitude of scar and/or ischemia, coronary flow reserve below the median (<1.5) was associated with a 2.1-fold increase in the risk of cardiac death (95% confidence interval [CI]: 1.3 to 3.5, p = 0.004). Incorporation of coronary flow reserve into cardiac death risk assessment models resulted in an increase in the C-index from 0.75 to 0.77 (p = 0.05) and in a net reclassification improvement of 0.142 (95% CI: 0.076 to 0.219). Among patients at intermediate risk based on all data other than coronary flow reserve, the net reclassification improvement was 0.489 (95% CI: 0.192 to 0.836). Corresponding improvements in risk assessment for mortality from any cause were also demonstrated.
The presence of coronary vascular dysfunction in patients with moderate to severe renal dysfunction, as assessed by positron emission tomography, is a powerful, independent predictor of cardiac mortality and provides meaningful incremental risk stratification over conventional markers of clinical risk.
Contrast induced acute kidney injury in interventional cardiology: An update and key guidance for clinicians
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^†: Drs. Shin and Choi contributed equally to this article.

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Coronary artery diseaseComparison of Contrast-Induced Nephrotoxicity of Iodixanol and Iopromide in Patients With Renal Insufficiency Undergoing Coronary Angiography

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

Kidney Int Suppl

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

Kidney Int

JACC Cardiovasc Interv

Kidney Int

Kidney Int Suppl

Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies

Circulation

Nephrotoxic effects in high-risk patients undergoing angiography

N Engl J Med

Coronary artery disease
Comparison of Contrast-Induced Nephrotoxicity of Iodixanol and Iopromide in Patients With Renal Insufficiency Undergoing Coronary Angiography