Design and protocol of a comprehensive multicentre biobank for abdominal aortic aneurysms.

INTRODUCTION: The pathophysiology and natural course of abdominal aortic aneurysms (AAAs) are insufficiently understood. In order to improve our understanding, it is imperative to carry out longitudinal research that combines biomarkers with clinical and imaging data measured over multiple time points. Therefore, a multicentre biobank, databank and imagebank has been established in the Netherlands: the 'Pearl Abdominal Aortic Aneurysm' (AAA bank). METHODS AND ANALYSIS: The AAA bank is a prospective multicentre observational biobank, databank and imagebank of patients with an AAA. It is embedded within the framework of the Parelsnoer Institute, which facilitates uniform biobanking in all university medical centres (UMCs) in the Netherlands. The AAA bank has been initiated by the two UMCs of Amsterdam UMC and by Leiden University Medical Center. Participants will be followed during AAA follow-up. Clinical data are collected every patient contact. Three types of biomaterials are collected at baseline and during follow-up: blood (including DNA and RNA), urine and AAA tissue if open surgical repair is performed. Imaging data that are obtained as part of clinical care are stored in the imagebank. All data and biomaterials are processed and stored in a standardised manner. AAA growth will be based on multiple measurements and will be analysed with a repeated measures analysis. Potential associations between AAA growth and risk factors that are also measured on multiple time points can be assessed with multivariable mixed-effects models, while potential associations between AAA rupture and risk factors can be tested with a conditional dynamic prediction model with landmarking or with joint models in which linear mixed-effects models are combined with Cox regression. ETHICS AND DISSEMINATION: The AAA bank is approved by the Medical Ethics Board of the Amsterdam UMC (University of Amsterdam). TRIAL REGISTRATION NUMBER: NCT03320408.

Urine neutrophil gelatinase-associated lipocalin predicts outcome and renal failure in open and endovascular thoracic abdominal aortic aneurysm surgery.

Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been evaluated as a biomarker for AKI detection and adverse outcome in open and endovascular thoracoabdominal aortic aneurysm surgery. This observational, retrospective study included 52 patients. UNGAL was measured peri-operatively (48 h) and correlated with AKI requiring dialysis, tracheotomy and adverse outcome. Mean patients' age was 64.5 years. A total of 26.9% (n = 14) developed AKI, and 21.1% (n = 11) required dialysis, tracheotomy rate was 19.2% (n = 10) and in-hospital mortality rate was 7.6% (n = 4). uNGAL levels were related to AKI requiring dialysis at ICU (p = 0.0002), need for tracheotomy at baseline and admission on ICU (p = 0.0222, p = 0.0028, respectively), as well as adverse discharge modality (p = 0.0051, p = 0.0048, respectively). Diagnostic quality was good for uNGAL levels at admission to ICU regarding AKI requiring dialysis (sensitivity: 81.8% [48.2-97.7]; specificity: 87.8% [73.8-95.9]; area under the curve (AUC): 0.874 [0.752-0.949]). The diagnostic quality of uNGAL was favorable for the prediction of tracheotomy (sensitivity: 70.0% [34.8-93.3]; specificity: 83.3% [68.6-93.0]; AUC: 0.807 [0.674-0.903]) and adverse discharge (sensitivity: 77.8% [40.0-97.2]; specificity: 83.7% [69.3-93.2]; AUC: 0.817 [0.685-0.910]). uNGAL may be valuable as an post-operative predictor of AKI and adverse outcome after open and endovascular TAAA repair.

Leukotrienes biosynthesis in vascular surgery patients during perioperative period.

Leukotrienes (LTs), highly bioactive lipid mediators play a major role in inflammation, wound healing and in the development of atherosclerosis. LTs biosynthesis have been suggested to be increased in myocardial infarction (MI) and in surgical patients with abdominal aortic aneurysms. Among LTs, Cysteinyl-LTs have the most potent biological properties and their production is well reflected by LTE4 concentration in urine (uLTE4). Aim of the study was to evaluate perioperative biosynthesis of uLTE4 in noncardiac vascular surgery patients, and its impact on patients' outcomes. Twenty eight consecutive patients aged 61.5 (59.0-72.5) that undergone an elective surgery for abdominal aortic aneurysm (AAA; n=6) or peripheral artery disease (PAD; n=22) were studied. uLTE4 was measured in urine samples using ELISA: before surgery (LT0), 6 hours postoperatively (LT1), and on three following days (LT2-LT4), and the results were adjusted for the urinary creatinine concentration. Patients were followed-up for 30-days for cardio-vascular complications including myocardial infarction (MI) with active post-surgery troponin T screening. One way analysis of variance (ANOVA) for repeated measurements and logistic regression tests were used to analyse the data with P<05 considered significant. Excretion of uLTE4 raised in the first two urine sample (LT1 and LT2) after surgery as compared to preoperative baseline value (LT0) (P=0.008) and returned to normal values on the second day (LT3). Patients that suffered MI during postoperative period had increased uLTE4 levels when compared to the no-MI patients (P=0.006). In conclusion we state that uLTE4 biosynthesis is increased shortly after surgery and returns to the preoperative level on the second day. The increase in uLTE4 biosynthesis is higher in patients that suffer MI after surgery, however this warrants further investigations.

Neutrophil gelatinase-associated lipocalin (NGAL) and endothelial progenitor cells (EPCs) evaluation in aortic aneurysm repair.

BACKGROUND: Acute kidney injury (AKI) develops in 10% of patients after surgical abdominal aortic aneurysm (AAA) repair. Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of AKI and Endothelial Progenitor Cells (EPCs) represent a potential repair mechanism for vascular lesions. We evaluated the diagnostic power of serum (s) and urine (u) NGAL in detecting a possible event of AKI in patients undergoing surgical treatment for AAA repair. We also investigated the influence of vascular injury on EPCs. METHODS: We examined 50 patients who underwent open AAA repair. Blood and urine was collected preoperatively and every hour after surgery until 8 h to quantify sNGAL, uNGAL and circulating EPCs. AKI, was defined as a ≥25% decrease in eGFR compared with baseline values. RESULTS: There was an inverse correlation between eGFR, sNGAL and uNGAL, while a direct correlation between sNGAL APACHE II Score and EPCs was found. At receiver operating characteristic (ROC) analysis, sNGAL and uNGAL showed a very good diagnostic profile. Kaplan Meier curves showed that NGAL is a highly sensitive predictor of incidence of AKI. Univariate followed by multivariate Cox proportional hazard regression analysis showed that uNGAL and sNGAL predicted AKI independently of other potential confounders, including eGFR and APACHE II Score. Patients had at baseline and after surgical stress a significantly higher number of EPCs than control group. CONCLUSIONS: NGAL represents an independent renal predictor of incidence of AKI. EPCs reflect the degree of vascular damage and could be considered as an indicator of disease with a reparative-regenerative vascular-endothelial function.

Fibrinogen excretion in the urine and immunoreactivity in the kidney serves as a translational biomarker for acute kidney injury.

Fibrinogen (Fg) is significantly up-regulated in the kidney after acute kidney injury (AKI). We evaluated the performance of Fg as a biomarker for early detection of AKI. In rats and mice with kidney tubular damage induced by ischemia/reperfusion (I/R) or cisplatin administration, respectively; kidney tissue and urinary Fg increased significantly and correlated with histopathological injury, urinary kidney injury molecule-1 (KIM-1) and N-acetyl glucosaminidase (NAG) corresponding to the progression and regression of injury temporally. In a longitudinal follow-up of 31 patients who underwent surgical repair of abdominal aortic aneurysm, urinary Fg increased earlier than SCr in patients who developed postoperative AKI (AUC-ROC = 0.72). Furthermore, in a cohort of patients with biopsy-proven AKI (n = 53), Fg immunoreactivity in the tubules and interstitium increased remarkably and was able to distinguish patients with AKI from those without AKI (n = 59). These results suggest that immunoreactivity of Fg in the kidney, as well as urinary excretion of Fg, serves as a sensitive and early diagnostic translational biomarker for detection of AKI.

Tratamento endovascular dos aneurismas da aorta abdominal com anatomia com anatomia complexa: resultados preliminares com a segunda geração de endoprótese com arcabouço metálico circular / Endovascular treatmente of abdominal aortic aneurysms with complex anatomy: preliminary results of the second generation stent graft with a dual-ring design

Introdução: O tratamento endovascular dos aneurismas da aorta abdominal tem revolucionado o tratamento dessa afecção, em decorrência das baixas taxas de morbidade e mortalidade.Apesar dos avanços tecnológicos ocorridos nas endopróteses, ainda existem limitações anatômicas para o emprego da técnica. Este estudo teve por objetivo avaliar os resultados imediatos do tratamento de pacientes portadores de aneurisma da aortaabdominal com anatomia complexa com uma endoprótese de segunda geração. Métodos: Estudo observacional, prospectivo, não-randomizado, realizado em um único centro, em uma série de pacientes submetidos a tratamento endovascular de aneurismas da aorta abdominal infrarrenais complexos, comprótese com arcabouço metálico disposta em anéis (AnacondaTM– Vascutek, Terumo, Inchinnan, Escócia). Foram avaliados as características clínicas e angiográficas, o sucesso técnico, o sucesso terapêutico, a morbidade e a mortalidade, e a taxa de reintervenção perioperatória. Resultados: Foram analisados, no período de fevereiro de 2010 a dezembro de 2011, 108pacientes consecutivos portadores de aneurisma da aorta, dos quais 16 eram portadores de aneurisma da aorta abdominal com anatomia complexa tratados com a prótese AnacondaTM.A média de idade foi de 76 + 7 anos e 75% eram do sexo masculino. Houve sucesso técnico em 94% e êxito terapêutico em 75% dos casos. Ocorreu um óbito no pós-operatório. Ascomplicações perioperatórias mais prevalentes foram sangramento da ferida operatória (2/16) e embolia periférica (2/16). Foram necessárias reintervenções em 12,5% dos pacientes durante o seguimento. Conclusões: Neste estudo, a segunda geração da endoprótese AnacondaTM foi efetiva e apresenta resultados imediatos satisfatórios no tratamento do aneurisma da aorta abdominal infrarrenal de anatomia complexa.

Does N-acetylcysteine prevent contrast-induced nephropathy during endovascular AAA repair? A randomized controlled pilot study.

PURPOSE: To examine if N-acetylcysteine (NAC) reduces the incidence of contrast nephropathy during endovascular abdominal aortic aneurysm repair (EVAR) as evidenced by changes in markers of renal function. METHODS: Twenty consecutive men (mean age 72 years, range 65-79) undergoing EVAR were randomized to receive standard intravenous fluid hydration or standard fluid hydration and NAC (600 mg BID orally, 4 doses). Venous blood and urine were collected prior to the procedure and for 5 postoperative days and analyzed blindly for serum creatinine, urinary retinol-binding protein (RBP), and albumin/creatinine ratio (ACR). RESULTS: There were no significant differences in baseline demographics between the groups. No patient developed acute renal failure. In both groups, urinary RBP rose significantly from baseline (median 15 microg/mmol to peak 699 microg/mmol in controls versus 17 to 648 microg/mmol in the treatment group, p<0.003). There were similar significant rises in ACR (p<0.02). There was, however, no significant difference in the postoperative RBP or ACR between the groups at any time point. CONCLUSION: EVAR causes significant acute renal injury in most patients. This was not attenuated by N-acetylcysteine. The causes of renal injury are probably multifactorial, the long-term clinical significance of which is unclear.

Incidence and effect of bare suprarenal stent struts crossing renal ostia following EVAR.

OBJECTIVES: The incidence and effect of bare stent struts crossing the renal ostia following endovascular aortic aneurysm repair with the Talent stent-graft is not known. The study aims to establish the incidence in which bare stent struts cross the renal ostia and to assess any associated effects on renal function. METHODS: Fifty-five patients (51 men, mean age 73 years, range 57-90) who had endovascular repair of their abdominal aortic aneurysms with a Talent suprarenal stent-graft were included in the study. Patients were scanned at a variety of follow-up periods (median 24 months, range 3-102). The relationship between the bare stent struts and the renal ostia, together with renal function were retrospectively recorded. The presence and location of the bare stent struts was assessed using CT virtual intravascular endoscopy (CT VIE). Struts were defined as being absent, peripherally located or in the central channel of the renal ostia. Renal function was assessed from glomerular filtration rates (GFR) derived from serum creatinine levels and the Cockcroft and Gault formula. RESULTS: A total of 109 renal ostia were evaluated by CT VIE with one patient having a previous nephrectomy. Bare stent struts crossed 1 renal ostium in 22 (40%) patients and bilateral ostia in 5 (9%) patients. Of the 109 ostia assessed, 15 (14%) ostia were crossed centrally and 17 (16%) had struts crossing the ostium peripherally. There were no statistically significant differences in the change between pre-operative GFR and latest GFR in the group without any strut involvement (6 mLs/min +/- 7 mLs/min) and the group with struts crossing one or both renal ostia (2 mLs/min +/- 9 mLs/min; p > .05). CONCLUSION: Peripheral or central coverage of renal ostia by bare stent struts occurs in a third of all renal arteries following EVAR. Crossing of renal ostia by bare stent struts does not affect follow-up GFR.

The mid-term effect of bare metal suprarenal fixation on renal function following endovascular abdominal aortic aneurysm repair.

OBJECTIVE: The aim of this study was to assess the mid term effect of proximal bare metal fixation design on renal function in patients undergoing endovascular repair (EVR) of abdominal aortic aneurysm (AAA). METHODS: Consecutive EVR patients for AAA from December 1995-2001 were included and grouped to either infrarenal (Group 1) or uncovered suprarenal (Group 2) fixation. Peri-operative renal function and at 6, 12 and 24 months was determined by serum creatinine (sCr mmol l(-1)) and Cockroft-Gault creatinine clearance (CrC ml min(-1)). Changes in renal function were compared using non-parametric analysis. RESULTS: Of the 179 EVR procedures during this six-year period, paired renal data was available for 135 patients at a minimal follow-up of 6 months (Gp1, n = 63; Gp2, n = 72). Median pre-EVR sCr and CrC were 113, 57 in Group 1 and 108, 58 in Group 2, p = NS. There was no significant deterioration in renal function within or between either group at 2 years post-EVR: median sCr, CrC values were 118, 56 (Group 1) and 111, 56 (Group 2), all p = NS. CONCLUSION: This study suggests mid-term renal function remains unaffected following EVR of AAA, irrespective of proximal fixation type. Designs to improve stent durability and EVR applicability do not appear to compromise renal function.