RenalGuard system in high-risk patients for contrast-induced acute kidney injury.

BACKGROUND: High urine flow rate (UFR) has been suggested as a target for effective prevention of contrast-induced acute kidney injury (CI-AKI). The RenalGuard therapy (saline infusion plus furosemide controlled by the RenalGuard system) facilitates the achievement of this target. METHODS: Four hundred consecutive patients with an estimated glomerular filtration rate ≤30 mL/min per 1.73 m(2) and/or a high predicted risk (according to the Mehran score ≥11 and/or the Gurm score >7%) treated by the RenalGuard therapy were analyzed. The primary end points were (1) the relationship between CI-AKI and UFR during preprocedural, intraprocedural, and postprocedural phases of the RenalGuard therapy and (2) the rate of acute pulmonary edema and impairment in electrolytes balance. RESULTS: Urine flow rate was significantly lower in the patients with CI-AKI in the preprocedural phase (208 ± 117 vs 283 ± 160 mL/h, P 0.32 mg/kg (HR 5.03, 95% CI 2.33-10.87, P < .001) were independent predictors of CI-AKI. Pulmonary edema occurred in 4 patients (1%). Potassium replacement was required in 16 patients (4%). No patients developed severe hypomagnesemia, hyponatremia, or hypernatremia. CONCLUSIONS: RenalGuard therapy is safe and effective in reaching high UFR. Mean intraprocedural UFR ≥450 mL/h should be the target for optimal CI-AKI prevention

A spotlight on the role of copper in the epithelial to mesenchymal transition

The complex process known as epithelial to mesenchymal transition (EMT) plays a fundamental role in several biological settings, encompassing embryonic development, wound healing, and pathological conditions such as cancer and fibrosis. In recent years, a bulk of research has brought to light the key role of copper, a trace element with essential functions in cellular metabolism, cancer initiation and progression. Indeed, copper, besides functioning as cofactor of enzymes required for essential cellular processes, such as energy production and oxidation reactions, has emerged as an allosteric regulator of kinases whose activity is required to fulfill cancer dissemination through the EMT. In this comprehensive review, we try to describe the intricate relationship between the transition metal copper and EMT, spanning from the earliest foundational studies to the latest advancements. Our aim is to shed light on the multifaceted roles undertaken by copper in EMT in cancer and to unveil the diverse mechanisms by which copper homeostasis exerts its influence over EMT regulators, signaling pathways, cell metabolic reprogramming and transcription factors ultimately contributing to the spread of cancer. Therefore, this review not only may contribute to a deeper comprehension of copper-mediated mechanisms in EMT but also supports the hypothesis that targeting copper may contribute to counteract the progression of EMT-associated pathologies

The Avantgarde Carbostent in Patients Scheduled for Undelayable Noncardiac Surgery

Background. Treatment of patients who need coronary revascularization before undelayable non-cardiac surgery is challenging. Methods. We assessed the safety and efficacy of percutaneous coronary interventions (PCI) using the Avantgarde TM Carbostent (CID, Italy) in patients undergoing PCI before undelayable non-cardiac surgery. The Multiplate analyzer point-of-care was used to assess residual platelet reactivity. One major cardiac events (MACE, defined as death, myocardial infarction, and stent thrombosis and major bleeding) were assessed. Results. 42 consecutive patients were analyzed. Total stent length ≥25 mm was observed in 16 (37%) patients. Multivessel stenting was performed in 11 (31.5%) patients. Clopidogrel was interrupted 5 days before surgery in 35 patients, whereas it was stopped the day of the surgery in 7 patients. Surgery was performed after 27 ± 9 (7–42) days from PCI. MACE occurred in one patient (2.4%; 95% confidence interval: 0.01–13%), who had fatal acute myocardial infarction 3 days after abdominal aortic aneurysm surgery and 12 days after stent implantation. No case of major bleeding in the postoperative phase was observed. Conclusions. The present pilot study suggests that, although at least 10–14 days of dual antiplatelet therapy remain mandatory, the Avantgarde TM stent seems to have a role in patients requiring undelayable surgery

RenalGuard system in high-risk patients for contrast-induced acute kidney injury.

Background High urine flow rate (UFR) has been suggested as a target for effective prevention of contrast-induced acute kidney injury (CI-AKI). The RenalGuard therapy (saline infusion plus furosemide controlled by the RenalGuard system) facilitates the achievement of this target. Methods Four hundred consecutive patients with an estimated glomerular filtration rate ≤30 mL/min per 1.73 m 2 and/or a high predicted risk (according to the Mehran score ≥11 and/or the Gurm score >7%) treated by the RenalGuard therapy were analyzed. The primary end points were (1) the relationship between CI-AKI and UFR during preprocedural, intraprocedural, and postprocedural phases of the RenalGuard therapy and (2) the rate of acute pulmonary edema and impairment in electrolytes balance. Results Urine flow rate was significantly lower in the patients with CI-AKI in the preprocedural phase (208 ± 117 vs 283 ± 160 mL/h, P P = .009). The best threshold for CI-AKI prevention was a mean intraprocedural phase UFR ≥450 mL/h (area under curve 0.62, P = .009, sensitivity 80%, specificity 46%). Performance of percutaneous coronary intervention (hazard ratio [HR] 4.13, 95% CI 1.81-9.10, P P = .012), and total furosemide dose >0.32 mg/kg (HR 5.03, 95% CI 2.33-10.87, P Conclusions RenalGuard therapy is safe and effective in reaching high UFR. Mean intraprocedural UFR ≥450 mL/h should be the target for optimal CI-AKI prevention

Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure

AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene-related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two incremental doses of AM5 (10 and 100 ng/min per kg of body weight each for 90 min) into eight sheep with pacing-induced HF. Compared with time-matched vehicle control infusions, AM5 produced progressive and dose-dependent increases in left ventricular dP/dt(max) [LD (low dose), +56 mmHg/s and HD (high dose), +152 mmHg/s] and cardiac output (+0.83 l/min and +1.81 l/min), together with decrements in calculated total peripheral resistance (−9.4 mmHg/min per litre and −14.7 mmHg/min per litre), mean arterial pressure (−2.8 mmHg and −8.4 mmHg) and LAP (left atrial pressure; −2.6 mmHg and −5.6 mmHg) (all P<0.001). HD AM5 significantly raised PRA (plasma renin activity) (3.5-fold increment, P<0.001), whereas plasma aldosterone levels were unchanged over the intra-infusion period and actually fell in the post-infusion period (70% decrement, P<0.01), resulting in a marked decrease in the aldosterone/PRA ratio (P<0.01). Despite falls in LAP, plasma atrial natriuretic peptide and B-type natriuretic peptide concentrations were maintained relative to controls. AM5 infusion also induced significant increases in urine volume (HD 2-fold increment, P<0.05) and urine sodium (2.7-fold increment, P<0.01), potassium (1.7-fold increment, P<0.05) and creatinine (1.4-fold increment, P<0.05) excretion and creatinine clearance (60% increment, P<0.05). In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest that AM5 may have potential as a therapeutic agent in human HF

Cardio-renal syndromes: report from the consensus conference of the Acute Dialysis Quality Initiative

A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI). The following topics were matter of discussion after a systematic literature review and the appraisal of the best available evidence: definition/classification system; epidemiology; diagnostic criteria and biomarkers; prevention/protection strategies; management and therapy. The umbrella term CRS was used to identify a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Different syndromes were identified and classified into five subtypes. Acute CRS (type 1): acute worsening of heart function (AHF–ACS) leading to kidney injury and/or dysfunction. Chronic cardio-renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD) leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type 3): acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5): systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Consensus statements concerning epidemiology, diagnosis, prevention, and management strategies are discussed in the paper for each of the syndromes