Postconditioning with cyclosporine a reduces early renal dysfunction by inhibiting mitochondrial permeability transition

International audienceBACKGROUND: Ischemia-reperfusion (IR) injury leads to mitochondrial permeability transition pore opening, which contributes to cell death. The aim of this study is to determine whether ischemic or pharmacological postconditioning with cyclosporine A (CsA) might protect the kidney from lethal reperfusion injury. METHODS: Male mice underwent a unilateral (right) nephrectomy followed by 30 minutes of contralateral (left) clamping of the renal artery. We studied 4 groups at 20 minutes and 24 hours of reperfusion: a sham group (n = 4), an ischemic group (n = 6), CsA-postconditioned group (postcond-CsA, injection of 3 mg/kg of CsA 5 minutes before the end of ischemia, (n = 6), and an ischemic postconditioning (IPC) group (n = 6), consisting of 3 cycles of 30 seconds of renal ischemia with 30 seconds intervening reperfusion. After 24 hours of reperfusion, we measured plasma creatinine, urea, and histological kidney injury. The kidney mitochondria were isolated to assess the mitochondria calcium retention capacity and oxidative phosphorylation. RESULTS: At 24 hours after reperfusion, serum creatinine decreased in postcond-CsA and IPC compared to ischemic group. The histological score was also significantly improved with postcond-CsA and IPC. At 20 minutes and 24 hours of reperfusion, calcium retention capacity was decreased significantly in the ischemic group. The mitochondrial respiration stay decreased in the ischemic group at 24 hours of reperfusion, whereas the respiration was improved significantly in the postcond-CsA and IPC group. Bax and cleaved caspase 3 decreased in PostCsA and IPC group. CONCLUSIONS: Our results suggest that IPC and CsA, administered immediately before reperfusion, protect the kidney from lethal injury

Creatinine- versus cystatine C-based equations in assessing the renal function of candidates for liver transplantation with cirrhosis

International audienceRenal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFR-predicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI-CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4- and 6-variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR-predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score \textless/= or \textgreater15 and KDOQI stages, respectively). In the whole population, CystC-based equations showed a better performance than Pcr-based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR \textless60 mL/min/1.73 m(2)). CONCLUSION: Pcr-based GFR predicting equations are not reliable in pre-OLT patients even when an IDMS-traceable enzymatic Pcr assay is used. Whenever a CystC-assay traceable to primary reference materials is performed and when a true measurement of GFR is not possible, CystC-based equations, especially CKD-EPI-CystC, may be recommended to evaluate renal function and for KDOQI staging

Towards Industry 4.0: The Future Automated Aircraft Assembly Demonstrator

Part 4: Digital Technologies and Industry 4.0 ApplicationsInternational audienceAs part of the Future Automated Aircraft Assembly Demonstrator developed by the University of Nottingham, this paper presents a new flexible production environment for the complete manufacturing of high-accuracy high-complexity low-volume aerospace products. The aim is to design a product-independent manufacturing and assembly system that can react to fluctuating product specifications and demands through self-reconfiguration. This environment features a flexible, holistic, and context-aware solution that includes automated positioning, drilling and fastening processes, and is suitable for different aircraft structures with scope to address other manufacturing domains in the future (e.g. automotive, naval and energy). The assembly cell features industrial robots for the handling of aircraft components, while intelligent metrology and control systems monitor the cell to ensure that the assembly process is safe and the target tolerances are met. These three modules are integrated into a single standardized interface, requiring only one operator to control the cell. Performance analyses have shown that, using the reconfigurable production environment described hereafter, a positioning accuracy better than ±0.1 mm can be achieved for large airframe components

The Chronic Kidney Disease Epidemiology Collaboration equation outperforms the Modification of Diet in Renal Disease equation for estimating glomerular filtration rate in chronic systolic heart failure

Aims The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula estimates glomerular filtration rate (GFR) better than the simplified Modification of Diet in Renal Disease (sMDRD) formula in numerous populations. It has not previously been validated in heart failure patients. Methods and results The GFR was measured in 120 patients with chronic systolic heart failure (CHF) using [I-125]iothalamate clearance (GFR(IOTH)) and estimated using the sMDRD and CKD-EPI equations. Accuracy, bias, and prognostic performance were compared. Cockcroft-Gault, CKD-EPI serum cystatin C, and CKD-EPI creatinine-serum cystatin C equations were compared in secondary analyses. Mean age was 59 +/- 12 years, 80% were male. Mean LVEF was 29 +/- 10%. Mean GFR(IOTH) was 74 +/- 27 mL/min/1.73 m(2), and mean estimated GFR was 66 +/- 23 mL/min/1.73 m(2) (CKD-EPI) and 63 +/- 21 mL/min/1.73m(2) (sMDRD). CKD-EPI showed less bias than sMDRD (-8 +/- 15 vs. -11 +/- 16 mL/min/1.73 m(2), P <0.001). Both equations underestimate at higher and overestimate at lower GFR(IOTH). Eleven patients (9%) were accurately reclassified into lower CKD classes with CKD-EPI. Cockcroft-Gault showed lower bias (-3 +/- 16 mL/min/1.73 m(2)) but worse precision and accuracy. Cystatin C-based estimation showed the lowest bias (-3 +/- 14 mL/min/1.73 m(2)) and the best precision and accuracy. Prognostic value did not differ between all GFR estimates Conclusion The CKD-EPI equation more accurately estimates measured GFR than the sMDRD equation in CHF patients, with less bias and greater accuracy and precision. The prognostic power of all GFR assessments was equivalent. Based on better performance and equal risk prediction, we believe the CKI-EPI equation should be the preferred creatinine-based GFR estimation method in heart failure patients, particularly those with preserved or moderately impaired renal function

Renovascular hypertension: screening and modern management

The diagnosis and management of patients with renovascular disease and hypertension continue to elude healthcare providers. The advent of novel imaging and interventional techniques, and increased understanding of the pathways leading to irreversible renal injury and renovascular hypertension, have ushered in commendable attempts to optimize and finetune strategies to preserve or restore renal function and control blood pressure. Large randomized clinical trials that compare different forms of therapy, and smaller trials that test novel experimental treatments, will hopefully help formulate innovative concepts and tools to manage the patient population with atherosclerotic renovascular disease