Richard Solomon

Contrast-Induced Nephropathy and Long-Term Adverse Events: Cause and Effect?

BACKGROUND AND OBJECTIVES The relationship of contrast-induced nephropathy (CIN) to long-term adverse events (AEs) is controversial. Although an association with AEs has been previously reported, it is unclear whether CIN is causally related to these AEs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We obtained long-term (> or =1 yr) follow-up on 294 patients who participated in a randomized, double-blind comparison of two prevention strategies for CIN (iopamidol versus iodixanol). A difference in the incidence of AEs between patients who had developed CIN and those who had not was performed using a chi(2) test and Poisson regression analysis. A similar statistical approach was used for the differences in AEs between those who received iopamidol or iodixanol. Multiple definitions of CIN were used to strengthen and validate the results and conclusions. RESULTS The rate of long-term AEs was higher in individuals with CIN (all definitions of CIN). After adjustment for baseline comorbidities and risk factors, the adjusted incidence rate ratio for AEs was twice as high in those with CIN. Randomization to iopamidol reduced both the incidence of CIN and AEs. CONCLUSIONS The parallel decrease in the incidence of CIN and AEs in one arm of this randomized trial supports a causal role for CIN.

Contrast-Induced Acute Kidney Injury

Case Presentation : A 63-year-old man with prior mitral valve repair, hyperlipidemia, hypertension, and mild chronic renal insufficiency (creatinine 1 year earlier, 1.2 mg/dL) presents to the emergency department with progressive dyspnea on exertion and new anterior T-wave inversions. Subsequent laboratory testing confirms a myocardial infarction (troponin I, 11.0 ng/mL) and worsening renal insufficiency in the setting of recently being started on chlorthalidone for hypertension (creatinine, 2.7 mg/dL). Diuretics are discontinued; intravenous fluids are infused; and therapy for an acute coronary syndrome, including aspirin, clopidogrel, nitrates, and intravenous unfractionated heparin, is initiated. After 48 hours, creatinine improves to 1.8 mg/dL (estimated glomerular filtration rate, 46 mL/min), and the patient undergoes cardiac catheterization with iopamidol (Isovue, Bracco Diagnostics Inc, Princeton, NJ) contrast after receiving 1 hour of prophylactic sodium bicarbonate infusion. A complex bifurcation lesion of the left anterior descending artery/first diagonal branch is identified (Figure 1A). What is this patients risk of contrast-induced acute kidney injury (CI-AKI), and which measures may modify that risk significantly? This Clinician Update reviews the recent literature on the acute kidney injury that follows the administration of iodinated contrast medium. Figure 1. A, A complex culprit lesion in the left anterior descending artery (LAD) and first diagonal branch (D1). B, After 250 cm3 iopamidol contrast dye, successful drug-eluting stent placement in the LAD-D1 bifurcation lesion. Patients at risk for CI-AKI have comorbidities that will exacerbate the primary pathogenesis of the injury: contrast-induced vasoconstriction leading to diminished blood flow to the renal medulla. These comorbidities include diabetes mellitus, congestive heart failure, acute hypotension (requiring pressors or intra-aortic balloon pump), ST-elevation myocardial infarction, and volume depletion. Patients with chronic kidney disease are also at risk for contrast-induced acute kidney injury because compensatory mechanisms to maintain filtration function are diminished, and a smaller number of nephrons must excrete …

Contrast media and nephropathy: findings from systematic analysis and Food and Drug Administration reports of adverse effects.

Context:Recent studies suggest differences in the incidence of contrast-induced nephropathy (CIN) among contrast media (CM). Objective:To determine whether there are significant differences among low-osmolality CM (LOCM) in the incidence of contrast-induced nephropathy (CIN), we reviewed published studies of CIN in renally impaired patients and conducted statistical data mining using databases of adverse events maintained by the U.S. Food and Drug Administration (FDA). Data Sources:A systematic literature search was performed for prospective, controlled, English language studies published in peer-reviewed journals that reported CIN rates in renally impaired patients after a specific LOCM. Databases searched were EMBASE, MEDLINE, Biosis Previews, Derwent Drug File, Pascal, and SciScearch Cited Ref Sci. For the FDA analysis, we used the SRS and AERS databases. Data Selection:Twenty-two studies reporting data in 3112 patients with renal impairment met the inclusion criteria. Most studies reported on the use of a pharmacologic intervention to prevent CIN. From the FDA databases, we evaluated 18 adverse event terms associated with renal injury or dysfunction after CM use. Data Extraction:Data from 22 studies were entered into a database. A meta-regression analysis using a mixed effect model was performed. CM effect was adjusted by the following covariates: baseline patient characteristics (mean age, gender distribution) and risk factors (prevalence of diabetes mellitus, degree of renal impairment, CM volume), and the use of prophylactic drug treatments. Multiple disproportionality analyses (adjusted odds ratio, adjusted empirical Bayesian estimate, or Bayesian logistic regression) were performed on the FDA databases to estimate associations between 4 CM and 18 AE terms related to CIN. Data Synthesis:Systematic analysis of clinical trials suggest the highest incidence of CIN occurs in patients receiving iohexol and the lowest incidence in patients receiving iopamidol, even when corrected for other CIN risk factors. Statistical data mining of FDA data also showed the highest association of CIN for iohexol and the lowest for iopamidol. Conclusions:The risk of CIN was higher in patients receiving iohexol compared with patients receiving iopamidol. No significant differences were found comparing iohexol to other LOCMs, including iodixanol.

Does Safe Dosing of Iodinated Contrast Prevent Contrast-Induced Acute Kidney Injury?

Background—Previous work on contrast-induced acute kidney injury (CI-AKI) has identified contrast volume as a risk factor and suggested that there is a maximum allowable contrast dose (MACD) above which the risk of CI-AKI is markedly increased. We hypothesized that there is a relationship between contrast volume and CI-AKI and that there might be reason to track incremental contrast volumes above and below the MACD limit. Methods and Results—Consecutive patients undergoing percutaneous coronary intervention (PCI) were prospectively enrolled from 2000 to 2008 (n=10 065). Patients on dialysis before PCI were excluded (n=155). MACD was defined as (5 mL×body weight [kg])/baseline serum creatinine [mg/dL]) and divided into categories in which 1.0 reflects the MACD limit: ⩽MACD ratios (<0.5, 0.5 to 0.75, and 0.75 to 1.0) and >MACD (1.0 to 1.5, 1.5 to 2.0, and >2.0). CI-AKI was defined as a ≥0.3 (mg/dL) or ≥50% increase in serum creatinine from baseline or new dialysis. Multivariable regression was conducted to evaluate the effect of exceeding the MACD on CI-AKI. Twenty percent of patients exceeded the MACD. Risk-adjusted CI-AKI increased by an average of 45% for each category exceeding the MACD (odds ratio, 1.45; 95% confidence interval, 1.29 to 1.62) Adjusted odds ratios for each category exceeding the MACD were 1.60 (95% confidence interval, 1.29 to 1.97), 2.02 (95% confidence interval, 1.45 to 2.81), and 2.94 (95% confidence interval, 1.93 to 4.48). CI-AKI for contrast dose <MACD showed no statistical difference (P=0.5). Conclusions—Contrast volume is a key risk factor for CI-AKI and matters the most in the highest-risk patient. The incremental use of contrast beyond the MACD is associated with an increased risk of CI-AKI.

Defining acute kidney injury: what is the most appropriate metric?

Glomerular filtration rate (GFR) is the most widely accepted measure of kidney function. Acute kidney injury (AKI) is defined as a reduction in GFR. GFR is, however, rarely measured in clinical practice; instead, serum markers (primarily creatinine) are used to define AKI. Because serum creatinine level is not linearly related to GFR, the performance of this marker is associated with ascertainment bias and poor sensitivity. In this article we discuss the limitations and pitfalls of using serum markers to define AKI, and offer some suggestions for the future.

Contrast-Induced Acute Kidney Injury (CIAKI)

Injury to the kidney continues to occur following the administration of intravascular iodinated contrast media. In this article, the author reviews the pathophysiology of contrast-induced acute kidney injury (CIAKI), the relationship of CIAKI to long-term adverse outcomes, what type of patients are at risk of CIAKI, and how the diagnosis is made. After discussion of the reported incidence of CIAKI, an approach to prevention is briefly reviewed.

Reducing Contrast-Induced Acute Kidney Injury Using a Regional Multicenter Quality Improvement Intervention

Background—Contrast-induced acute kidney injury (CI-AKI) is associated with increased morbidity and mortality after percutaneous coronary interventions and is a patient safety objective of the National Quality Forum. However, no formal quality improvement program to prevent CI-AKI has been conducted. Therefore, we sought to determine whether a 6-year regional multicenter quality improvement intervention could reduce CI-AKI after percutaneous coronary interventions. Methods and Results—We conducted a prospective multicenter quality improvement study to prevent CI-AKI (serum creatinine increase ≥0.3 mg/dL within 48 hours or ≥50% during hospitalization) among 21 067 nonemergent patients undergoing percutaneous coronary interventions at 10 hospitals between 2007 and 2012. Six intervention hospitals participated in the quality improvement intervention. Two hospitals with significantly lower baseline rates of CI-AKI, which served as benchmark sites and were used to develop the intervention, and 2 hospitals not receiving the intervention were used as controls. Using time series analysis and multilevel poisson regression clustering to the hospital level, we calculated adjusted risk ratios for CI-AKI comparing the intervention period to baseline. Adjusted rates of CI-AKI were significantly reduced in hospitals receiving the intervention by 21% (risk ratio, 0.79; 95% confidence interval: 0.67–0.93; P=0.005) for all patients and by 28% in patients with baseline estimated glomerular filtration rate <60 mL/min per 1.73 m2 (risk ratio, 0.72; 95% confidence interval: 0.56–0.91; P=0.007). Benchmark hospitals had no significant changes in CI-AKI. Key qualitative system factors associated with improvement included multidisciplinary teams, limiting contrast volume, standardized fluid orders, intravenous fluid bolus, and patient education about oral hydration. Conclusions—Simple cost-effective quality improvement interventions can prevent ⩽1 in 5 CI-AKI events in patients with undergoing nonemergent percutaneous coronary interventions.

Intrarenal oxygenation by blood oxygenation level-dependent MRI in contrast nephropathy model: effect of the viscosity and dose.

To compare the effects of osmolality versus viscosity of radio‐contrast media on intra‐renal oxygenation as determined by blood oxygenation level‐dependent (BOLD) MRI in a model of contrast induced nephropathy (CIN).

Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging.

ObjectivesThe objectives of this study were to evaluate differences in intrarenal oxygenation as assessed by blood oxygen level–dependent (BOLD) magnetic resonance imaging in contrast-induced acute kidney injury (CIAKI)–susceptible rats when using 4 contrast media with different physicochemical properties and to demonstrate the feasibility of acquiring urinary neutrophil gelatinase–associated lipocalin (NGAL) levels as a marker of CIAKI in this model. Materials and MethodsOur institutional animal care and use committee approved the study. Sixty-six Sprague-Dawley rats were divided into CIAKI-susceptible groups (received nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester [10 mg/kg] and cycloxygenase inhibitor indomethacin [10mg/kg]) and control groups (received saline instead). One of the 4 iodinated contrast agents (iothalamate, iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram of body weight). Multiple blood oxygen level–dependent magnetic resonance images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after N-nitro-L-arginine methyl ester (or saline), indomethacin (or saline), and iodinated contrast agent (or placebo). R2* (R2* = 1/T2*) maps were generated inline on the scanner. A mixed-effects growth curve model with first-order autoregressive variance-covariance was used to analyze the temporal data. Urinary NGAL, a marker of kidney injury (unlike serum creatinine), was measured 4 hours after contrast injection in the 2 subgroups. ResultsDifferences in blood oxygen level–dependent magnetic resonance imaging results between the contrast media were observed in all 4 renal regions. However, the inner stripe of the outer medulla (ISOM) showed the most pronounced changes in the CIAKI-susceptible group and R2* increased significantly (P < 0.01) over time with all 4 contrast media. In the control groups, only iodixanol showed an increase in R2* (P < 0.05) over time. There was an agreement between increases in NGAL and R2* values in ISOM. ConclusionsIn rats susceptible to CIAKI, those receiving contrast media had significant increases in R2* in renal ISOM compared with those receiving placebo. The agreement between NGAL and R2* values in the ISOM suggests that the observed immediate increase in R2* after contrast injection may be the earliest biomarker of renal injury. Further studies are necessary to establish threshold values of R2* associated with acute kidney injury and address the specificity of R2* to renal oxygenation status.

Forced diuresis with the RenalGuard system: Impact on contrast induced acute kidney injury

Kidney injury following the administration of iodinated contrast media occurs particularly in patients with reduced kidney and cardiac function and when large doses of contrast are used. There is little compelling evidence that vasodilators and anti-oxidants prevent this injury. Most prevention trials have employed intravenous volume loading as a central strategy. However, the success of this approach depends upon maintaining euvolemia while producing a vigorous diuresis. A novel strategy for maintaining euvolemia and inducing a vigorous diuresis has been developed using the RenalGuard system. In this review; the mechanism of protective action is reviewed. The trials of the RenalGuard device are reviewed and future uses of the device are discussed.