The delayed diagnosis of acute kidney injury (AKI) episodes and the lack of specificity of current single AKI biomarkers hamper its management. Urinary peptidome analysis may help to identify early ...molecular changes in AKI and grasp its complexity to identify potential targetable molecular pathways.
In derivation and validation cohorts totalizing 1170 major cardiac bypass surgery patients and in an external cohort of 1569 intensive care unit (ICU) patients, a peptide-based score predictive of AKI (7-day KDIGO classification) was developed, validated, and compared to the reference biomarker urinary NGAL and NephroCheck and clinical scores.
A set of 204 urinary peptides derived from 48 proteins related to hemolysis, inflammation, immune cells trafficking, innate immunity, and cell growth and survival was identified and validated for the early discrimination (< 4 h) of patients according to their risk to develop AKI (OR 6.13 3.96-9.59, p < 0.001) outperforming reference biomarkers (urinary NGAL and IGFBP7.TIMP2 product) and clinical scores. In an external cohort of 1569 ICU patients, performances of the signature were similar (OR 5.92 4.73-7.45, p < 0.001), and it was also associated with the in-hospital mortality (OR 2.62 2.05-3.38, p < 0.001).
An overarching AKI physiopathology-driven urinary peptide signature shows significant promise for identifying, at an early stage, patients who will progress to AKI and thus to develop tailored treatments for this frequent and life-threatening condition. Performance of the urine peptide signature is as high as or higher than that of single biomarkers but adds mechanistic information that may help to discriminate sub-phenotypes of AKI offering new therapeutic avenues.
Because the pharmacological effects of ACEI therapy are partly mediated by bradykinin B2 receptor (B2R) activation, we hypothesized that acute B2R blockade would be beneficial in this setting. ...the ...mean arterial blood pressures during shock in the ACEI group were significantly lower compared to the control and ACEI group treated with icatibant (25 25-75% interquartile range (IQR), 21-29 mmHg vs 38 25-75% IQR, 33-43 mmHg and 36 25-75% IQR, 35-38 mmHg, respectively; p?<?0.001). ...we showed that survival in the control and ACEI groups treated with icatibant was significantly higher (81.8 and 90.9%, respectively) than in the ACEI group (36.4%) (p?<?0.01).
Spontaneous pneumothorax is a frequent situation in respiratory medicine, and its treatment is based on conservative treatment or pleural drainage. Reexpansion pulmonary edema (REPE) is often a mild ...complication following pneumothorax drainage. We report here a severe case of unilateral REPE following spontaneous pneumothorax drainage associated with major pulmonary plasmatic leakage. The clinical presentation was severe and sudden with respiratory and circulatory failures. Initial resuscitation was mostly based on prone and head-down positioning in association to fluid expansion and mechanical ventilation. On the basis of this clinical case report, we strongly suggest to think about severe pulmonary reexpansion edema when respiratory and hemodynamic failures occur few hours after pneumothorax-related efficient pleural tube drainage.
ABSTRACT
Background
Down-regulation of the enzymes involved in tryptophan-derived nicotinamide (NAM) adenine dinucleotide (NAD+) production was identified after acute kidney injury (AKI), leading to ...the hypothesis that supplementation with NAM may increase the kidney NAD+ content, rescuing tryptophan pathways and subsequently improving kidney outcomes.
Methods
Urinary measurement of tryptophan and kynurenin using liquid chromatography–mass spectrometry metabolomics was used in a cohort of 167 cardiac bypass surgery patients along with tests for correlation to the development of postoperative AKI. A mouse model of ischaemic AKI using ischaemia–reperfusion injury (bilateral clamping of renal arteries for 25 min) was also used.
Results
We identified a significant decrease in urinary tryptophan and kynurenin in patients developing AKI, irrespective of the Kidney Disease: Improving Global Outcomes (KDIGO) stage. Although a significant difference was observed, tryptophan and kynurenin moderately discriminated for the development of all AKI KDIGO stages {area under the curve AUC 0.82 95% confidence interval (CI) 0.75–0.88 and 0.75 0.68–0.83, respectively} and severe KDIGO Stages 2–3 AKI AUC 0.71 (95% CI 0.6–0.81) and 0.66 (0.55–0.77), respectively. Sparked by this confirmation in humans, we aimed to confirm the potential preventive effect of NAM supplementation in wild-type male and female C57BL/6 mice subjected to ischaemic AKI. NAM supplementation had no effect on renal function (blood urea nitrogen at Day 1, sinistrin–fluorescein isothiocyanate glomerular filtration rate), architecture (periodic acid–Schiff staining) and injury or inflammation (kidney injury molecule 1 and IL18 messenger RNA expression). In addition, NAM supplementation did not increase post-AKI NAD+ kidney content.
Conclusion
Notwithstanding the potential role of NAM supplementation in the setting of basal NAD+ deficiency, our findings in mice and the reanalysis of published data do not confirm that NAM supplementation can actually improve renal outcomes after ischaemic AKI in unselected animals and probably patients.
OBJECTIVE:Sparse data are available on renal consequences of hemorrhagic shock in mice. This study aimed to extend the current knowledge on functional and morphologic renal impact of hemorrhagic ...shock in mice and to determine its ability to stand as an accurate model of acute kidney injury.
DESIGN:In vivo study.
SETTING:University research unit.
SUBJECTS:C57/Bl6 mice.
INTERVENTIONS:A model of controlled hemorrhagic shock was adapted to determine the renal impact of hemorrhagic shock in mice.
MEASUREMENTS AND MAIN RESULTS:Renal functions and kidney morphology were followed up from 3 hrs to 21 days after hemorrhagic shock. When prolonged up to 2 hrs, hypotension (35 mm Hg mean arterial blood pressure) induced by temporary blood removal was responsible for an early and lasting increase in hypoxia-inducible factor-1α and kidney-inducible molecule-1 gene expression that paralleled acute tubular necrosis and renal failure. Two-hr hypotension induced an important but reversible decrease in glomerular filtration rate up to 6 days after hemorrhagic shock. Other renal dysfunctions included a renal loss of sodium, assessed by the increase in sodium excretion, and a decrease in urine concentration that persists up to day 21. Tissular damages prevailed in the outer medulla 2 days after hemorrhagic shock, being maximal at day 6. At day 21, renal healing was associated with epithelial recovery and a significant interstitial fibrosis.
CONCLUSIONS:Our data indicate that apparent recovery of renal function after acute kidney injury can mask persisting dysfunctions and tissular damages that could predispose to chronic kidney disease. Prolonged hemorrhagic shock in mice closely mimics renal effects induced by similar situation in humans, thus providing a useful tool to investigate pathophysiological mechanisms and protection strategies against acute kidney injury in situations such as hemorrhagic shock.
Anaemia and iron deficiency are frequent in patients scheduled for cardiac surgery. Perioperative patient blood management (PBM) is widely recommended in current practice guidelines. The aim of this ...protocol is to analyse the effect of a global perioperative PBM programme on the red blood cell (RBC) transfusion ratio, morbidities and rehabilitation score in elective cardiac surgery.
This study is a prospective, single-centre trial with a 2-step protocol, A and B, as follows: A: non-drug intervention: the caregiver is given a blood management educational programme; B: drug intervention: systematic correction of perioperative iron, vitamin deficiencies, and anaemia. This study was designed to enrol 900 patients (500 in group A and 400 in group B) in a rolling period starting at anaesthesia consultation and ending 3 months after surgery. The primary objective was a 20% reduction in RBC transfusion after implementation of PBM programmes (protocol A + B) when compared to our previous transfusion ratio in the first half of 2018 (30.4% vs 38%). The secondary objectives were to evaluate the impact for each step of the study on the RBC transfusion rate, morbidity and the quality of postoperative rehabilitation.
The strength of this study is its evaluation of the effect of a global PBM programme on RBC transfusion in cardiac surgery through a 2-step protocol. We aim to assess for the first time the impact of non-drug and drug interventions on RBC transfusion, comorbidities and delayed rehabilitation parameters.
ClinicalTrials.gov, NCT04040023: registered 29 July 2019.
Abstract Viral infections are frequent and severe in lung transplant recipients. They frequently occur during the first year after transplantation. We report on a rare case of bilateral adenovirus ...necrotizing pneumonia with a diffuse alveolar hemorrhage, 4 years after bilateral lung transplantation. The medical evolution was lethal in 72 hours because of respiratory, renal, and cardiac failure. Considering this case and the growing evidence on the severity of adenoviral infections, we call for controlled studies and therapeutic recommendations.
We report on a 62-year-old man referred to the cardiac intensive care unit less than 24 hours after anterior ST-segment elevated myocardial infarction. The patient developed cardiogenic shock ...requiring elective intubation, vasopressor, and inotropic support. Emergency coronary angiography, revascularization, and insertion of an intraaortic balloon pump were performed. Nevertheless, the hemodynamic situation remained unstable, and a left ventricular assist device (LVAD) was inserted. Severe hypoxemia occurred several minutes after initiating the Impella Recover LD/LP 5.0 (Abiomed, Danvers, MA). Transesophageal echocardiography allowed diagnosis of patent foramen ovale. The shunt resulted from abnormal left-to-right pressure gradient due to left ventricular unloading and increased right ventricular afterload induced by mechanical ventilation. Transesophageal echocardiography was used to regulate both LVAD output and positive end-expiratory pressure settings to optimize oxygen transport. Because patent foramen ovale is common in humans, transesophageal echocardiography should be performed systematically after LVAD insertion.
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