Refining the assessment of contrast-induced acute kidney injury: the load-to-damage relationship.

AIMS: Comparing the nephrotoxicity of individual contrast agents is challenging, as contrast-induced acute kidney injury (CI-AKI), a widely used trial endpoint, is unable to discriminate between contrast-related and contrast-unrelated causes of renal damage. We established a quantitative method to selectively evaluate the dose-dependent nephrotoxic effect of different contrast agents. METHODS: We randomized 113 patients undergoing coronary procedures to either iodixanol 320 mg/ml or iobitridol 350 mg/ml. We calculated baseline creatinine clearance (CrCl) and postprocedural change in serum creatinine. We then calculated the regression of the individual iodine load against the creatinine maximum change [load-to-damage relationship (LDR)]. We assumed that its R estimates the predictive accuracy of contrast dose-dependent effects on renal function changes, and that the slope of the LDR characterizes the intrinsic nephrotoxicity of the contrast. We also performed a semi-quantitative evaluation of procedural complexity to assess its complementary role in postprocedural AKI. RESULTS: We found significant correlations between contrast load and creatinine changes for both iobitridol (R: 0.29; P <0.0001) and iodixanol (R: 0.15; P = 0.00028). The LDR slope was, however, significantly steeper for iobitridol compared with iodixanol (19.03 ±â€Š4.02 vs. 14.50 ±â€Š4.63 Cr*CrCl/I; P <0.001) and in diabetic compared with nondiabetic patients (24.35 ±â€Š4.96 vs. 4.59 ±â€Š3.25 Cr*CrCl/I; P <0.001). Adding the procedural complexity score to the contrast load significantly increased the predictive ability of the regression model for postprocedural renal function changes (P < 0.02 for the R increase in overall population), suggesting a role for procedural complexity in postprocedural renal function damage. CONCLUSION: The LDR slope is a promising method to evaluate the specific contrast-related fraction of postprocedural AKI.

The contrast media and nephrotoxicity following coronary revascularization by primary angioplasty for acute myocardial infarction study: design and rationale of the CONTRAST-AMI study.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a complex syndrome of acute renal failure occurring after the administration of contrast media and contributing to prolonged hospital stay and mortality. The risk of CI-AKI is higher among patients undergoing primary percutaneous coronary interventions for acute myocardial infarction (AMI), but its clinical relevance in such setting has only been evaluated by small sample size single-center studies and retrospective or observational analyses. Furthermore, whereas high-osmolar contrast media was shown to have direct nephrotoxicity, the role of low-osmolar and iso-osmolar agents is still debated. STUDY DESIGN: The CONTRAST-AMI study is a prospective, multicenter, controlled, randomized, single-blind, parallel-group trial, designed to show the noninferiority of the effects of iopromide (low-osmolar) compared with iodixanol (iso-osmolar) contrast media on the incidence of CI-AKI and tissue-level perfusion in patients with AMI. All consecutive patients admitted to participating centers for ST-segment elevation AMI undergoing primary percutaneous coronary intervention will be enrolled. All patients will be treated with high-dose N-acetylcysteine (1200 mg intravenously during the procedure and 1200 mg orally two times daily for the next 48 h after percutaneous coronary intervention) and hydration according to a standardized protocol. The primary endpoint is the proportion of patients with a relative increase in serum creatinine (sCr) of at least 25% from baseline to 72 h after agent administration. The secondary endpoints are absolute and relative increases in sCr of at least 50%, thrombolysis in myocardial infarction (TIMI) perfusion grade, and major adverse cardiac events at 1, 6, and 12 months. CONCLUSION: The CONTRAST-AMI study will provide information on the effects of iodixanol and iopromide on the incidence of CI-AKI and tissue-level perfusion in patients with AMI.

Analysis of RR variability in drug-resistant epilepsy patients chronically treated with vagus nerve stimulation.

Vagus nerve stimulation (VNS) has been suggested as an adjunctive treatment for drug-resistant epilepsy when surgery is inadvisable. The overall safety profile of VNS seems to be favorable as only minor adverse effects have been described. The purpose of this study was to determine if cardiac vagal tone is eventually modified by short- and long-term VNS. The effects of short- and long-term VNS were evaluated in seven subjects with intractable epilepsy. Autonomic cardiac function has been carried out by means of a 24-h analysis of RR variability at baseline (t(0)), 1 month (t(1), short-term VNS) and 36 months after VNS initiation (t(2), long-term VNS). Frequency- and time-domain parameters were calculated. Periodic cardiological and neurological evaluations were performed.Clinically relevant cardiac effects were not observed throughout the study. Despite the limited number of patients and the variety of data among them, for all the patients, a common trend towards a nocturnal decrease in the high-frequency (HF) component of the spectrum was observed after long-term VNS (mean+/-S.D.: 40+/-18 normalized units (nu) at t(0), 38+/-17 nu at t(1), 18+/-10 nu at t(2); p<0.05 of t(2) vs. either t(0) or t(1)). The day-to-night changes in the power of low-frequency (LF) and HF components were significantly blunted after long-term VNS (LF day-to-night change: +16+/-13 nu at t(0) and +15+/-8 nu at t(1) vs. +3+/-13 nu at t(2), p<0.02; HF day-to-night change: -18+/-13 nu at t(0) and -13+/-11 nu at t(1) vs. +3+/-12 nu at t(2), p<0.003). No significant changes were observed with regard to the time-domain parameters of the heart rate variability. Throughout the neurological follow-up, one subject became seizure-free, three experienced a seizure reduction of >50%, two patients of <50% and one had no changes in his seizure frequency. Our findings suggest that long-term VNS might slightly affect cardiac autonomic function with a reduction of the HF component of the spectrum during night and a flattening of sympathovagal circadian changes, not inducing, however, clinically relevant cardiac side effects.

Vasomotor effects of iodinated contrast media: just side effects?

Routinely used iodinated contrast media have complex vasomotor effects on several arterial districts. All classes of iodinated radiographic contrast media are vasoactive, with iso-osmolar dimers inducing the smallest changes in vascular tone. The mechanisms responsible for contrast-induced vasomotor changes are not fully elucidated and are likely to be multifactorial. Although contrast-induced vasomotility is usually considered as an unwanted "side effect", recent findings suggest that it might indeed be useful in exploring the functional integrity of the vessel wall. We found that atherosclerosis has an impact on the type of the contrast-induced coronary vasomotor reaction. In fact, angiographically normal coronary segments show divergent vasomotor reactions to iodixanol or iopromide according to the presence/absence of, and distance from, a coronary atherosclerotic lesion located in their proximity. The mechanism responsible for this vasomotor effect does not apparently involve flow-mediated vasodilatation or endothelial nitric oxide synthesis. On the other hand, a cyclooxygenase product may be, at least in part, responsible for the vasodilating effect of non-ionic agents on epicardial coronary arteries, since contrast-induced vasodilatation is strongly inhibited in the presence of indomethacin. These findings have potential clinical implications, since the analysis of contrast-induced coronary vasomotion might result in a new test capable of evaluating vascular functional integrity. Such a test might be alternative or complementary to the tests based on muscarinic agonists (acetylcholine) or serotonin, which are known to evaluate the nitric oxide pathway.