Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with a significant risk of postoperative renal dysfunction. We studied the utility of a novel biomarker in predicting acute kidney injury (AKI) in adult patients undergoing cardiac surgery. METHODS AND RESULTS: Blood and urine were obtained from 50 patients undergoing CPB-requiring surgery. Patients were divided into group A (n=41) with normal creatinine pre-bypass and post-bypass and group B (n=9) who developed an increase in serum creatinine of >0.5 mg/dL within the first 48 hours post CPB. Plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL) was determined at baseline and 2 hours after CPB.Plasma levels of NGAL were higher in patients who developed AKI [214+/-16.7 ng/mL (95% CI 176.9-252.9)] compared with those who did not [149.5+/-13.5 ng/mL (95% CI 122.1-175.7); P=0.035]. Two hours after CPB, there was a significant increase (P=0.0003) in NGAL levels, greater in those patients who developed AKI [476.1+/-41.1 ng/mL (95% CI 380.6-571.6); P=0.0003] compared with those who did not [278.4+/-22 ng/mL (95% CI 233.9-323.0)]. In the AKI group, urinary NGAL increased from 7.13+/-2.30 ng/mL (95% CI 2.5-11.8) to 2924+/-786 ng/mL (95% CI 1110-4739). In the non-AKI group, there was an increase from 1.6+/-0.6 (95% CI 0.3-3.0) to 749+/-179 ng/mL (95% CI 386-1113). The post-CPB levels of urinary NGAL were significantly different in the AKI group (P<0.0001) such that a suitable threshold for use as a diagnostic test could be determined. Receiver operating characteristics were determined for plasma and urinary NGAL with area under the curve (AUC) of 0.80 and 0.96, respectively. For a threshold of 433 ng/mmol creatinine, the test had 90% sensitivity and 78% specificity for the detection of post-CPB renal dysfunction. CONCLUSIONS: Measurement of this novel biomarker in the urine or plasma of patients in the first hours after CPB is predictive of subsequent renal injury. Although the AUC for plasma NGAL seemed inferior to urine, even an AUC of 0.8 as reported compares very favorably to that for other "outstanding" biomarkers (eg, AUCs in the 0.7 range for troponin).

Drug-eluting balloons with provisional bail-out or adjunctive stenting in de novo coronary artery lesions-a systematic review and meta-analysis.

BACKGROUND: Efficacy of drug-eluting balloons (DEB) for treatment of de novo coronary lesions remains controversial. The present systematic review and meta-analysis of randomised controlled trials assessed DEB with bare-metal stents (BMS) and also DEB with provisional bail-out stents ('DEB-only' strategy), to other conventional options: plain-old balloon angioplasty (POBA), BMS and drug-eluting stents (DES). METHODS: A systematic literature search from January 2000 until May 2017 was conducted. Primary outcome measure, late lumen loss (LLL); and secondary outcomes; binary restenosis, major adverse cardiac events (MACE), target lesion revascularization (TLR), myocardial infarction (MI), cardiovascular death and stent thrombosis were analysed. RESULTS: Seventeen RCTs were included with 2,616 patients. Several comparative groups showed significant differences. DEB with BMS were inferior to DES for LLL [mean difference (MD) =0.12 mm; 95% confidence interval (CI), 0.03 to 0.22; P=0.01]; and binary restenosis [risk ratio (RR) =1.89; (CI, 1.13 to 3.18); P=0.02]. DEB with BMS was superior to BMS for LLL [MD =-0.27 mm; (-0.45 to -0.10); P=0.002]; and MACE [RR =0.64; (0.46 to 0.90); P=0.010]. Finally, DEB alone was superior to POBA for LLL [MD =-0.39 mm; (-0.67 to -0.11); P=0.006] and binary restenosis [RR =0.20; (0.05 to 0.85); P=0.03] in bifurcation lesions. CONCLUSIONS: The results of this meta-analysis showed that whilst DEB with BMS is superior to BMS alone, the combination is inferior to DES for treatment of de novo coronary lesions. Thus, DEB + BMS should not be applied in de novo lesions unless in patients who have absolute contraindications to DES. DEB alone, however, should be considered for relative contraindications to DES such as small vessel disease and bifurcation lesions.

Drug-Coated Balloon-Only Percutaneous Coronary Intervention for the Treatment of De Novo Coronary Artery Disease: A Systematic Review.

Percutaneous coronary intervention (PCI) with a drug coated balloon (DCB) is a novel treatment which seeks to acutely dilate a coronary stenosis and deliver an anti-proliferative drug to the vessel wall (reducing the risk of re-stenosis), without implanting a drug eluting stent (DES). In this study, we performed a systematic review of stentless DCB-only angioplasty in de novo coronary artery disease. We identified 41 studies examining the effects of DCB-only PCI in a variety of clinical scenarios including small vessels, bifurcations, calcified lesions, and primary PCI. DCB-only PCI appears to be associated with comparable clinical outcomes to DESs and superior angiographic outcomes to plain-old balloon angioplasty. Although current data are promising, there is still a need for further long-term randomized control trial data comparing a DCB-only approach specifically against a second- or third-generation DES. A 4-week period of dual antiplatelet therapy provides a real advantage for the DCB-only PCI approach, which is not possible with most DESs. Since rates of adverse clinical outcomes are very low for all PCI procedures attention should be turned to the development of robust endpoints with which to compare DCB-only PCI approaches to the standard treatment with a DES.

Regulation of chemokine expression in atherosclerosis.

(1) Chemokines play a central role in the pathogenesis of atherosclerosis, contributing to leukocyte recruitment, angiogenesis and also proliferation and migration of smooth muscle cells into atherosclerotic plaques. (2) Leukocytes and endothelial cells are an important source of chemokines, and many of the risk factors associated with atherosclerosis increase chemokine expression. There is now a body of evidence to suggest that interactions between cells such as leukocytes and endothelial cells amplify chemokine release, and this may contribute to sustained chemokine generation in inflammatory conditions. (3) This article summarises, briefly, what is currently known about chemokines release. A number of important pharmacological strategies used in the treatment of atherosclerosis inhibit chemokine release and the extent to which this may contribute to their therapeutic effect will be discussed. Understanding the mechanisms controlling chemokine expression is essential for the design of specific therapeutic interventions in atherosclerosis.