Multi-detector row CT angiography of pulmonary circulation with gadolinium-based contrast agents: prospective evaluation in 60 patients.

PURPOSE: To prospectively evaluate gadolinium dose safety and effectiveness for 16-detector pulmonary computed tomographic (CT) angiography. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Sixty patients with contraindications to iodine underwent CT of the pulmonary circulation with 0.5 mmol/L gadolinium chelate given at either 0.3 (n = 29, group A) or 0.4 (n = 31, group B) mmol/kg; clinical and biologic tolerances were evaluated. Enhancement of central and segmental pulmonary arteries was measured (poor enhancement, <100 HU; good, 100-150 HU; excellent, >150 HU). Subsegmental artery enhancement was assessed as similar or inferior to that of segmental arteries. Confidence in analysis of the pulmonary arterial bed was graded according to arterial enhancement: Grades 1-3, diagnostic images; grade 4, nondiagnostic. The main effectiveness parameter for comparison between groups A and B was diagnostic value of CT angiograms. Nonparametric statistics were used to analyze results. RESULTS: The mean (+/- standard deviation) contrast material volume was 50.09 mL +/- 8.45 (all patients: range, 30-64 mL; group A: 46.54 mL +/- 8.59; group B: 53.42 mL +/- 6.92). Diagnostic images were obtained in 55 (92%) patients, and confident analysis of pulmonary arteries to the subsegmental level was achieved in 26 (grade 1, 44%) and to the segmental level, in 21 (grade 2, 35%). Mean attenuation was higher in group B than in group A in central (180.61 HU +/- 53.85 vs 148.14 HU +/- 52.61; P = .04) and segmental (201.59 HU +/- 54.70 vs 164.73 HU +/- 59.26; P = .03) arteries. Number of diagnostic CT angiograms was higher (P = .02) in group B (n = 31 [100%]) than in group A (n = 24 [83%]). In both groups, mean enhancement of pulmonary arteries was significantly higher at 80 or 100 kV than at 120 kV. Renal function was impaired in two group A patients. CONCLUSION: Gadolinium chelates may be used as an alternative CT contrast agent in patients who cannot receive iodine.

Effect of iodinated contrast agents on residual renal function in PD patients.

BACKGROUND: Residual renal function (RRF) is an important predictor of outcome in peritoneal dialysis (PD) patients. Although increasing emphasis has been placed on preserving RRF, the nephrotoxicity associated with contrast medium administration in PD patients remains a controversial issue. In the present prospective study, we evaluated the evolution of RRF 2 weeks after iodinated contrast medium administration (ICMA) in a group of stable PD patients, and compared it with that in a non-treated control group of stable PD subjects. METHODS: The study was conducted from January 2003 to October 2004. RRF was quantified by the average of 24 h urinary urea and creatinine clearance and peritoneal creatinine clearance (PcrCl) were analyzed, the levels of which were analysed prior to and 2 weeks following ICMA in 36 PD patients and also assessed at the same time points in a group of 36 PD non-ICMA control subjects, matched according to RRF characteristics. Two weeks following ICMA, the values for RRF, daily urine volume and PcrCl were assessed against those at baseline, and the evolution of RRF was compared between the two groups. In the ICMA group, this study was performed with adequate pre-hydration and a minimum dose of contrast medium. RESULTS: Compared with baseline values, RRF, daily urine volume and PcrCl were not found to be significantly different 2 weeks after ICMA (7.0+/-4.3 vs 7.2+/-4.3 ml/min/1.73 m(2), P = 0.12; 1324+/-696 vs 1360+/-755 ml/day, P = 0.5; and 41.1+/-9 vs 40.6+/-9 l/week/1.73 m(2), P = 0.6, respectively). Following ICMA, variations in RRF and daily urine volume were found to be comparable with those of the control group (0.1+/-0.5 vs 0.1+/-0.5 ml/min/1.73 m(2), P = 0.9; 36+/-440 vs 40+/-493 ml/day, P = 0.8, respectively). CONCLUSION: In this study, 2 weeks following ICMA, no accelerated decline in RRF was determined in stable PD patients with adequate pre-hydration, i.e. subjects treated under optimal circumstances compared with the control group.

[Glycation, glycoxidation and diabetes mellitus]. / Glycation, glycoxydation et diabète.

Advanced glycation end-products (AGEs) result from a reaction between carbohydrates and the free amino groups of proteins, lipids, and DNA. Non enzymatic glycation, glycoxidation with glucose auto-oxidation and the polyol pathway are involved in glycated protein formation. AGEs also named glycotoxins are found in excess in pathological situations such as diabetes mellitus, renal failure, and aging or after absorption of food containing glycated products. Three major pathophysiological mechanisms are described to explain AGE toxicity, first AGEs can accumulate in the vessel wall and in collagen of different tissues; second in situ glycation is possible; third, AGEs bind to cell receptors inducing deleterious consequences. AGE receptor RAGE is a multiligand member of the immunoglobulin superfamily of cell surface molecules. AGE-receptor interaction can alter, macrophage, endothelial cell, mesangial and mesothelial cell functions and can induce inflammation. Oxidant stress, vascular hyperpermeability, vascular cell adhesion molecule-1 (VCAM-1) overexpression and monocytes chemotactic Protein-1 (MCP-1) production have been observed after cell activation by AGEs. AGEs appear to be involved in the genesis of diabetic macro but also microangiopathy such as retinopathy and glomerulosclerosis. New drugs are tested to prevent or break the AGE-protein cross-linkage, or to control the AGE-receptor interaction and their consequences. Dietary treatment, strict glycemic control and preservation of renal function remain the best approach for preventing AGE formation and limiting their deleterious effects.

Safety and effectiveness of gadolinium-enhanced multi-detector row spiral CT angiography of the chest: preliminary results in 37 patients with contraindications to iodinated contrast agents.

PURPOSE: To prospectively evaluate the safety and effectiveness of gadolinium-enhanced multi-detector row spiral computed tomographic (CT) angiography of the pulmonary circulation by using two gadolinium doses in patients with contraindications to iodinated contrast agents. MATERIALS AND METHODS: Study was approved by the Ethics Committee, and written informed consent was obtained. Thirty-seven patients (20 men, 17 women) with contraindications to iodinated contrast agents (allergic reactions, n = 27; impaired renal function, n = 10) underwent CT angiography of the pulmonary circulation in search of acute pulmonary embolism (n = 28) or for management of tumoral disease (n = 9). CT angiography was performed (a) with four-detector row (n = 19) or 16-detector row (n = 18) scanners; (b) at randomly assigned gadolinium doses of either 0.3 mmol per kilogram of body weight (n = 19) or 0.4 mmol/kg (n = 18); and (c) with a systematic evaluation of clinical and biologic tolerance of gadolinium. Comparison of percentages between group 1 and group 2 scans was performed with the chi2 or the Fisher exact test. An unpaired Wilcoxon rank sum test was used for numeric variables. P < .05 was considered to indicate a significant difference. RESULTS: The mean (+/- standard deviation) volume of gadopentetate dimeglumine administered in the overall study group was 48 mL +/- 9.6 (range, 29-65 mL). The level of maximal enhancement in the pulmonary arteries was significantly higher in group 2 than in group 1 (215.8 HU +/- 95 vs 141.3 HU +/- 44) (P = .02) and was maintained throughout the entire region of interest in a greater number of examinations in group 2 than in group 1 (n = 16 [89%] vs n = 2 [10.5%]) (P < .0001). The number of diagnostic CT angiograms was significantly higher in group 2 than in group 1 (n = 17 [94%] vs n = 13 [68%]) (P = .007). Significant but transient reduction of creatinine clearance was observed in one patient with preexisting moderate chronic renal failure (0.3 mmol/kg gadolinium dose). CONCLUSION: High-quality gadolinium-enhanced CT angiograms require the use of 16-detector row CT technology; the doses administered did not alter the renal function except transiently in one patient.

AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression.

BACKGROUND: Excess advanced glycation end-products (AGEs) are formed during renal failure, and AGE formation also may be connected with the high glucose concentration of peritoneal dialysis (PD) fluids. To determine the effect of human peritoneal mesothelial cell (HPMC) exposure to glycated proteins, we studied the HPMC receptor of AGE expression (RAGE), and analyzed the results of AGE-RAGE interaction on adhesion molecule expression and leukocyte binding. METHODS: RAGE was detected by FACS analysis, and RAGE mRNA by reverse transcription-polymerase chain reaction (RT-PCR). Vascular and intercellular cell adhesion molecule (VCAM-1 and ICAM-1) expression was measured by a known radiometric technique under basal conditions, after the addition of an AGE-specific compound, Nepsilon-carboxylmethyllysine (CML-albumin). Leukocyte adhesion on HPMC was analyzed by videomicroscopy after HPMC stimulation. RESULTS: RAGE protein was detected on HPMC, and RAGE mRNA was evidenced by RT-PCR. VCAM-1 expression was stimulated by CML-albumin (P < 0.01), while ICAM-1 was unchanged. By blocking the AGE-RAGE interaction, anti-RAGE antibodies or recombinant RAGE inhibited the increase in VCAM-1 expression. CML-albumin stimulation potentiated leukocyte adhesion to HPMC (P < 0.001). This effect was prevented by the incubation of leukocytes with recombinant VCAM-1 (P < 0.001). CONCLUSIONS: AGE binding to RAGE stimulated mesothelial cell activity, and resulted in the overexpression of VCAM-1, a structure for leukocyte adhesion. The AGE-RAGE interaction resulted in HPMC activation, which may promote local inflammation, and thus is implicated in the peritoneal injury found in long-term PD patients.