Contrast Medium-induced Acute Kidney Injury Research Articles

Remote ischemic preconditioning for prevention of contrast-medium-induced nephropathy: (RenoProtection-trial)

BackgroundContrast-medium-induced acute kidney injury is associated with substantial morbidity and mortality. The underlying mechanism has been partially attributed to ischemic kidney injury. The aim of this randomized, double-blind, sham-controlled trial was to assess the impact of remote ischemic preconditioning on contrast-medium-induced acute kidney injury. MethodsPatients with impaired renal function (serum creatinine >1.4mg/dL and/or estimated glomerular filtration rate <60mL/min/1.73m2) undergoing elective coronary angiography were randomized in a 1:1 ratio to standard care with (n=50) or without ischemic preconditioning (n=50; intermittent arm ischemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Overall, both study groups were at high risk to develop contrast-medium-induced acute kidney injury using Mehran risk score. The primary endpoint was the incidence of contrast-medium-induced kidney injury, defined as an increase of serum creatinine ≥25% and/or ≥0.5mg/dL above baseline at 48h after contrast-medium exposure. ResultsContrast-medium-induced acute kidney injury occurred in 26 patients (26%), 20 (40%) in the control group and 6 (12%) in the remote ischemic preconditioning group (OR 0.21; 95% CI 0.07–0.57; P=0.002). No major adverse events were related to remote ischemic preconditioning. ConclusionsRemote ischemic preconditioning before contrast-medium use prevents contrast medium-induced acute kidney injury in high risk patients. Our findings merit a larger trial to establish remote ischemic preconditioning on clinical outcomes.

The Preinterventional Cystatin-Creatinine-Ratio: A Prognostic Marker for Contrast Medium-Induced Acute Kidney Injury and Long-Term All-Cause Mortality

Background/Aims: Contrast medium-induced acute kidney injury (CI-AKI) is an important iatrogenic complication following the injection of iodinated contrast media. The level of serum creatinine (SCr) is the currently accepted ‘gold standard' to diagnose CI-AKI. Cystatin C (CyC) has been detected as a more sensitive marker for renal dysfunction. Both have their limitations. Methods: The role of the preinterventional CyC-SCr ratio for evaluating the risk for CI-AKI and long-term all-cause mortality was retrospectively analyzed in the prospective single-center ‘Dialysis-versus-Diuresis trial'. CI-AKI was defined and staged according to the Acute Kidney Injury Network classification. Results: Three hundred and seventy-three patients were included (average age 67.4 ± 10.2 years, 16.4% women, 29.2% with diabetes mellitus, mean baseline glomerular filtration rate 56.3 ± 20.2 ml/min/1.73 m² [as estimated by Chronic Kidney Disease Epidemiology Collaboration Serum Creatinine Cystatin C equation], 5.1% ejection fraction <35%). A total of 79 patients (21.2%) developed CI-AKI after elective heart catheterization, and 65 patients (17.4%) died during follow-up. Multivariate analyses by logistic regression confirmed that the preinterventional CyC-SCr ratio is independently associated with CI-AKI (OR 9.423, 95% CI 1.494-59.436, p = 0.017). Also, the Cox regression model found a high significant association between preinterventional CyC-SCr ratio and long-term all-cause mortality (mean follow-up 649 days, hazards ratio 4.096, 95% CI 1.625-10.329, p = 0.003). Conclusion: The preinterventional CyC-SCr ratio is independently associated with CI-AKI and highly significant associated with long-term mortality after heart catheterization.

Estimating GFR prior to contrast medium examinations--what the radiologist needs to know!

Creatinine-based equations to estimate glomerular filtration rate (GFR) are increasingly used in radiological practice and in studies on contrast medium-induced acute kidney injury (CIAKI). Their use is recommended in guidelines and contrast medium textbooks to identify patients at risk of CIAKI or nephrogenic systemic fibrosis. There is also an increased interest in cystatin C-based equations. Adopting GFR equations requires local creatinine and cystatin C assay calibrations to equal those used in developing the equations to avoid overestimation or underestimation of renal function. Methods should preferably be traceable to international standards, and assay traceability should be defined in CIAKI studies. Absolute GFR (mL/min) should be used when dosing contrast media and relating the dose to CIAKI instead of commonly used relative GFR (mL/min/1.73 m(2)) estimates. Accuracy of creatinine and cystatin C equations (percentage of GFR estimates within 30% of measured GFR) ranges between 75% and 85%. Equations combining creatinine and cystatin C may reach 90%, an accuracy similar to clearance methods (used as a reference test when developing and validating equations) when compared to the gold standard, renal clearance of inulin. The local laboratory or nephrology experts should be consulted in matters of method calibration and choice of GFR equation. • Traceability of creatinine/cystatin C assays used in GFR equations must be defined. • Absolute, not relative, GFR should be used when dosing contrast media. • Consult the local laboratory or nephrologist to choose the proper GFR equation.

Long-Term Follow-Up of Patients at High Risk for Nephropathy After Contrast Exposure.

Contrast medium-induced acute kidney injury (CI-AKI) is associated with morbidity and mortality, but the long-term outcomes of patients who do not develop CI-AKI remain unknown. We assessed clinical end points during long-term follow-up in patients at high risk for nephropathy who did not develop CI-AKI. Patients (n = 135) with impaired renal function (estimated glomerular filtration rate: 30-60 mL/min/1.73 m(2)) were divided into 2 groups according to contrast media (CM) exposure. The primary end point of this study was a composite outcome measure of death or renal failure requiring dialysis. Multivariate analyses identified CM exposure to be independently associated with major adverse long-term outcomes (hazard ratio: 2.3; 95% confidence interval, 1.34-6.52; P = .018). Even when CM exposure does not cause CI-AKI in patients with impaired renal function, in the long term, primary end points occur more frequently in patients exposed to CM than in those with no CM exposure.

Contrast-induced acute kidney injury after computed tomography prior to transcatheter aortic valve implantation

To identify independent predictors of contrast medium-induced acute kidney injury (CI-AKI) after enhanced multidetector-row computed tomography (MDCT) prior to transcatheter aortic valve implantation (TAVI) in high-risk patients. The present single-centre study analysed retrospectively 361 patients who were assessed using MDCT prior to TAVI. CI-AKI was defined as an increase in serum creatinine (SCr) of ≥ 25% or ≥ 0.5 mg/dl in at least one sample over baseline (24 h before MDCT) and at 24, 48, and 72 h after MDCT. A total of 38 patients (10.5%) experienced CI-AKI. As compared to patients without CI-AKI, they presented more frequently with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2), (81.6% versus 64.4%, p = 0.045) and tended to receive higher volumes of iodinated contrast media (ICM; 55.3% versus 39%, p = 0.057). There was a significant interaction between baseline eGFR and the amount of intravenous ICM administered (pfor interaction = <0.001) identifying the amount of ICM >90 ml as independent predictive factor of CI-AKI only in patients with baseline eGFR <60 ml/min/1.73m(2) (OR 2.615; 95% CI: 1.21-5.64). One in ten elderly patients with aortic stenosis undergoing MDCT to plan a TAVI procedure experienced CI-AKI after intravenous ICM injection. Intravenous administration of <90 ml of ICM reduces this risk in patients with or without pre-existing impaired renal function. However, in the majority of patients renal function recovers before the TAVI procedure.

Association Between Contrast Media Volume-Glomerular Filtration Rate Ratio and Contrast-Induced Acute Kidney Injury After Primary Percutaneous Coronary Intervention.

We hypothesized that contrast media volume-estimated glomerular filtration rate (CV-e-GFR) ratio may be a predictor of contrast media-induced acute kidney injury (CI-AKI). We investigated the associations between CV-e-GFR ratio and CI-AKI in 597 patients undergoing primary percutaneous coronary intervention (pPCI). An absolute ≥0.3 mg/dL increase in serum creatinine compared with baseline levels within 48 hours after the procedure was considered as CI-AKI; 78 (13.1%) of the 597 patients experienced CI-AKI. The amount of contrast during procedure was higher in the CI-AKI group than in those without CI-AKI (153 vs 135 mL, P = .003). The CV-e-GFR ratio was significantly higher in patients with CI-AKI than without (2.3 vs 1.5, P < .001). In multivariate analysis, independent predictors of CI-AKI were low left ventricular ejection fraction (P = .018, odds ratio [OR] = 0.966), e-GFR <60 mL/min (P = .012, OR = 2.558), and CV-e-GFR >2 (P < .001, OR = 5.917). In conclusion, CV-e-GFR ratio is significantly associated with CI-AKI after pPCI.

Effect of renin-angiotensin-system blockers on contrast-medium-induced acute kidney injury after coronary angiography.

Background/AimsWith the increasing incidence of cardiovascular disease, angiocardiography using contrast-enhancing media has become an essential diagnostic and therapeutic tool, despite the risk of contrast-medium-induced acute kidney injury (CIAKI). CIAKI may be exacerbated by renin-angiotensin-system (RAS) blockers, which are also used in a variety of cardiovascular disorders. This study evaluated the effects of RAS blockade on CIAKI after coronary angiography.MethodsPatients who underwent coronary angiography in our hospital between May 2009 and July 2011 were reviewed. Serum creatinine levels before and after coronary angiography were recorded. CIAKI was diagnosed according to an increase in serum creatinine > 0.5 mg/dL or 25% above baseline.ResultsA total of 1,472 subjects were included in this study. Patients taking RAS blockers were older, had a higher baseline creatinine level, lower estimated glomerular filtration rate (eGFR), and had received a greater volume of contrast medium. After propensity score matching, no difference was observed between the RAS (+) and RAS (.) groups. Multiple logistic regression identified RAS blockade, age, severe heart failure, contrast volume used, hemoglobin level, and eGFR as predictors of CIAKI. Multiple logistic regression after propensity matching showed that RAS blockade was associated with CIAKI (odds ratio, 1.552; p = 0.026).ConclusionsThis study showed that the incidence of CIAKI was increased in patients treated with RAS blockers.

Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in diabetic rats via suppression of Rho-kinase pathway

Contrast medium-induced acute kidney injury (CI-AKI) remains a leading cause of iatrogenic, drug-induced acute renal failure. This study aimed to investigate the protective effects of atorvastatin against renal tubular cell apoptosis in diabetic rats and the related mechanisms. CI-AKI was induced by intravenous administration of iopromide (12ml/kg) in streptozotocin-induced diabetic rats. Atorvastatin (ATO) was administered intragastrically at the dose of 5, 10 and 30mg/kg/d in different groups, respectively, for 5 days before iopromide injection. Renal function parameters, kidney histology, renal tubular cell apoptosis, the expression of apoptosis regulatory proteins, caspase-3 and Rho-associated protein kinase 1 (ROCK-1), and the phosphorylation of myosin phosphatase target subunit -1 (MYPT-1), were determined. Atorvastatin was shown to notably ameliorate contrast medium induced medullary damage, restore renal function, and suppress renal tubular apoptosis. Meanwhile, atorvastatin up-regulated the expression of Bcl-2, down-regulated the expression of Bax, caspase-3 and ROCK-1, restored the ratio of Bcl-2/Bax, and suppressed the phosphorylation of MYPT-1 in a dose-dependent manner. Thus, atorvastatin pretreatment could dose-dependently ameliorate the development of CI-AKI, which was partly attributed to its suppression of renal tubular cell apoptosis by inhibiting the Rho/ROCK pathway.

Response to Letter Regarding Article, “Ischemic Preconditioning for Prevention of Contrast Medium–Induced Nephropathy: Randomized Pilot RenPro-Trial (Renal Protection Trial)”

We thank the authors for their interest in our study on the impact of remote ischemic preconditioning on contrast medium–induced acute kidney injury (CI-AKI).1 The incidence of CI-AKI varies substantially among several studies because of the lack of a uniform definition of CI-AKI.2 Rates of CI-AKI may be as high as 50% or even higher, depending on the presence of risk factors such as chronic renal insufficiency and diabetes mellitus. Although the definition of CI-AKI varies across the trials, the most commonly used definition includes an absolute increase in serum creatinine of 0.5 mg/dL or a 25% relative increase in …

Impact of Peripheral Arterial Occlusive Disease on the Development of Contrast Medium-Induced Acute Kidney Injury

Background/Aims: Contrast medium-induced acute kidney injury (CI-AKI) is an important complication following the use of iodinated contrast media. It accounts for a significant number of hospital-acquired acute kidney injuries and is associated with increased in-hospital and long-term mortality and immense health care costs. We evaluated whether the presence of peripheral arterial occlusive disease (PAD) affects the incidence of CI-AKI following heart catheterization. Methods: The impact of PAD on the frequency of CI-AKI after heart catheterization was analysed in the prospective single-centre Dialysis-versus-Diuresis trial (January 2001 to July 2004). The patients were retrospectively divided into 3 subgroups: patients with coronary heart disease (CHD), patients with PAD and patients without PAD or CHD. Results: 412 patients were included (83.5% men, 29.1% diabetes mellitus, 4.9% ejection fraction <35%). Of these, 251 (60.9%) suffered from CHD but not from PAD, 77 (18.7%) from PAD and 84 (20.4%) had neither CHD nor PAD. After heart catheterization, 49 (11.9 %) patients developed CI-AKI. Patients with PAD suffered significantly more often from CI-AKI than those without PAD (32.7 vs. 16.8%, p = 0.008). Multivariate analyses by logistic regression confirmed PAD to be an independent predictor of a CI-AKI (odds ratio 2.013, 95% confidence interval 1.009-4.016, p = 0.047). The CHD was not significantly associated with CI-AKI. Conclusion: Patients with PAD significantly more often develop a CI-AKI after heart catheterization than those without PAD.

Endothelial dysfunction in the outer medullary vasa recta as a key to contrast media-induced nephropathy

THE ROLE OF THE ENDOTHELIUM in the adverse reaction of blood vessels to contrast media imaging agents, and in particular the sensitivity of the kidney, has been a subject of interest dating back to 1964 (2). The renal vasculature seems particularly sensitive to the influence of endothelium-derived nitric oxide vasodilation (7) and its buffering of endogenous vasoconstrictors. Thus the possible interaction between contrast agents and renal vascular resistance has become a subject of intense interest, in particular regarding the possible role of endothelial dysfunction in contrast media-induced nephropathy. Several particular points regarding contrast agent toxicity have been established. First, all contrast media are cytotoxic (5), and virtually all cells may be subject to this cytotoxicity to some extent. This may be compounded by the nature of the specific contrast media, such as its ionic strength, osmolality, or viscosity (4). Contrast media have been reported to induce necrosis and apoptosis in renal tubular cells (3), and disrupt nitric oxide-mediated vasodilation without altering anatomic integrity in systemic and renal cortical endothelia (9). These detrimental interactions may be particularly important in the kidney due to the particularly increased sensitivity of the renal endothelium in maintaining renal perfusion (7) and the fact that the content of the renal tubules and postglomerular juxtamedullary capillaries (vasa recta) becomes more concentrated as they descend into the medulla (4), strengthening the potential toxicity of the contrast media. While medullary blood flow accounts for only 20% of total renal blood flow, perfusion of this anatomic region is critical for the concentrating mechanisms of the kidney, as well as regulated sodium reabsorption and its potential involvement in sodium-induced hypertension. The outer medullary vasa recta are particularly suited for regulating medullary perfusion as they are simple vessels composed of an endothelial lining surrounded by constrictor pericytes. The deep medullary vasa recta become little more than an endothelial sleeve which is unlikely to regulate perfusion, although it may play a role in endothelium-mediated selective permeability of the deep vessel. Cao et al. (1) have documented that endothelium-derived nitric oxide is a critical vasodilatory regulator of descending vasa recta perfusion, which acts in juxtaposition to the constrictor action of endogenous superoxide. Nitric oxide synthase inhibition reduces (total kidney) renal blood flow some 35%, with coupled decreases in glomerular filtration rate (GFR) and increased renal vascular resistance, and these changes have been shown to be directly linked to the endogenous levels of the renin-angiotensin system (1). Because the medullary vasa recta are in series and downstream from the afferent and efferent resistance vessels, changes in vascular resistance may be even more amplified in the medulla if endothelial integrity is compromised. The importance of this topic is underlined by the disproportionately high number of review articles addressing the subject. With all of these potential problems pointing to an exaggerated vulnerability of the medullary circulation to compromised endothelial function, in an issue of the American Journal of Physiology-Renal Physiology Sendeski et al. (6) from the Berlin group (which includes some of the major contributors to this field) have provided a series of integrated protocols that demonstrate just how important the outer medullary vasa recta endothelium is in contrast media-induced acute kidney injury. First, they tested the perfusion of both viable human and rat isolated, perfused renal medullary descending vasa recta and found that exposure to contrast media resulted in significant pericyte-mediated vasoconstriction to a luminal diameter smaller than that of a red blood cell. They found that angio

Iodinated Contrast Media Differentially Affect Afferent and Efferent Arteriolar Tone and Reactivity in Mice: A Possible Explanation for Reduced Glomerular Filtration Rate

To determine the effect of the iodinated contrast medium iodixanol on arteriolar tone in afferent and efferent arterioles of the glomerulus and the functional interactions with the major modulators of arteriolar tone, angiotensin II and nitric oxide, in mice. Animal handling conformed to the ethics guidelines of the Office for Health and Social Matters of Berlin. Arterioles were isolated from 136 C57BL/6 mice, perfused with either vehicle solution or iodixanol (23 mg of iodine per milliliter) for 20 minutes, followed by angiotensin II administration. Fluorescence of 3-amino-4-(N-methylamino)-2',7'-difluorofluorescein (DAF-FM) and dihydroethidium (DHE) were used for quantification of nitric oxide bioavailability and superoxide concentration, respectively. Statistical analysis of time- and dose-dependent data was performed by using the nonparametric test for repeated measurements. With iodixanol, afferent arteriole diameters were significantly reduced from 9.2 µm to 8.3 µm; in control group, the diameters were increased from 8.7 µm to 9.3 µm (P = .008). Nitric oxide synthase inhibition augmented iodixanol-induced constriction, with diameters reduced from 9.9 µm to 5.8 µm (P < .0001). DAF-FM fluorescence increased less during iodixanol treatment and nitric oxide synthase inhibition (3.6% and 3.7% vs 10.7% in control group, P = .009 and P = .049, respectively), indicating impaired nitric oxide bioavailability. With iodixanol, DHE fluorescence ratio was increased by 12% (P < .0001). Angiotensin II responses were enhanced by iodixanol and by nitric oxide synthase inhibition after perfusion with iodixanol (3.3 µm and 4.3 µm vs 7.5 µm [control group] with 1 × 10(-6)/mol/L angiotensin II, P = .03 for both). In contrast, in efferent arterioles, neither their basal diameters nor the responses to angiotensin II were significantly affected by iodixanol. A more pronounced effect of iodixanol on afferent than on efferent arterioles may contribute to the reduction of glomerular filtration rate in contrast medium-induced acute kidney injury. Decreased nitric oxide bioavailability and increased concentration of superoxide explain the increased tone and reactivity in afferent arterioles perfused with iodixanol.

Abstractss “From Qatar to the World”

The utilization of coronary angiography and percutaneous coronary intervention in the routine care for patients with acute coronary syndromes (ACS) has resulted in significant improvement in their prognosis. Consequently, recommendations on the use of these management strategies are reflected in the ACC/AHA guidelines for the management of patients with unstable angina and myocardial infarction. However, among other causes, the 'phobia' of nephrotoxicity of iodinated contrast media (ICM) in chronic kidney disease (CKD) patients and its claimed adverse effect on shortterm and longterm survival has led to a worryingly low use of ICM-based diagnostic and therapeutic interventions in patients with CKD. We argue that the fear of iodinated contrast media-induced acute kidney injury (ICI-AKI) is not a valid reason to avoid ICMbased investigations/interventions in CKD patients with ACS; the risks of myocardial infarction and death greatly outweigh the risk of ICI-AKI in most of these patients and hence they should always be considered for myocardial revascularization.

Management of Acute Coronary Syndrome in Patients with Chronic Kidney Disease: If We Don’t Risk Anything, We Risk Even More

The utilization of coronary angiography and percutaneous coronary intervention in the routine care for patients with acute coronary syndromes (ACS) has resulted in significant improvement in their prognosis. Consequently, recommendations on the use of these management strategies are reflected in the ACC/AHA guidelines for the management of patients with unstable angina and myocardial infarction. However, among other causes, the ‘phobia’ of nephrotoxicity of iodinated contrast media (ICM) in chronic kidney disease (CKD) patients and its claimed adverse effect on short-term and long-term survival has led to a worryingly low use of ICM-based diagnostic and therapeutic interventions in patients with CKD. We argue that the fear of iodinated contrast media-induced acute kidney injury (ICI-AKI) is not a valid reason to avoid ICM-based investigations/interventions in CKD patients with ACS; the risks of myocardial infarction and death greatly outweigh the risk of ICI-AKI in most of these patients and hence they should always be considered for myocardial revascularization.

Urinary L-type fatty acid-binding protein as a new renal biomarker in critical care

Acute kidney injury (AKI) remarkably increases the mortality of critically ill patients treated in ICUs. Recently, several renal biomarkers have been developed for the early detection of AKI. We review the potential of urinary L-type fatty acid-binding protein (L-FABP) as a new renal biomarker for AKI diagnosis in critical care. In the kidney, L-FABP is expressed in renal proximal tubular epithelial cells and shed into urine rapidly in response to renal insults. By using human L-FABP transgenic mice, we reported that urinary L-FABP can detect AKI sensitively and reflect its severity accurately in animal models of AKI and sepsis. In clinical evaluations, the good performance of urinary L-FABP was demonstrated not only in pediatric postcardiopulmonary bypass surgery AKI and contrast media-induced AKI but also in septic shock patients complicated with AKI. Recent data suggest that urinary L-FABP can contribute to the development of new AKI diagnostic tools in critical care. Combining with other renal markers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), optimal threshold determination for distinguishing AKI from chronic renal failure should be explored before translation to the clinical.

Increasing evidence base for sodium bicarbonate therapy to prevent contrast media-induced acute kidney injury: little role of unpublished studies

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Prophylaxe des kontrastmittelinduzierten Nierenversagens

The increasing use of iodine-based contrast media for diagnostic and therapeutic interventions is associated with the risk of contrast media-induced acute kidney injury with a significant impact on patient morbidity and mortality as well as healthcare expenditure. To reduce patient risk, strict indications as well as the assessment of individual risk profiles and the use of effective renoprotective regimen are required. Reducing contast media exposure, the use of low-osmolar agents, hydration with isotonic saline and N-acetylcysteine have proven effective in the prevention of contrast media-induced acute kidney injury. In contrast, postinterventional hemodialysis for removal of contrast media from the circulation has been without benefit regarding renal and patient outcome and is not generally recommended. An algorithm for assessment of individual patient risk and a summary of current concepts in the prevention of contrast media-induced acute kidney injury is provided.