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      The effects of acute renal denervation on kidney perfusion and metabolism in experimental septic shock

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          Abstract

          Background

          Perfusion deficits likely play an important role in the development of renal dysfunction in sepsis. Renal denervation may improve kidney perfusion and metabolism.

          Methods

          We randomized 14 female sheep to undergo bilateral surgical renal denervation ( n = 7) or sham procedure ( n = 7) prior to induction of sepsis. Renal blood flow (RBF) was measured with a pre-calibrated flowprobe. Laser Doppler probes were implanted to measure cortical and medullary perfusion. Cortical glucose, lactate and pyruvate levels were measured using the microdialysis technique. Creatinine clearance was determined. Sepsis was induced by peritonitis and fluid resuscitation was provided to avoid hypovolemia.

          Results

          RBF and cortical perfusion were higher in the denervated group during the first 6 h after induction of sepsis ( P < 0.001 and P < 0.05, respectively), while medullary perfusion decreased similarly in both groups. After hypotension developed, RBF decreased to similar levels in both groups. Cortical pyruvate and lactate levels were lower in the denervated animals ( P < 0.001 and P < 0.001, respectively). There were no differences between groups in creatinine clearance, urine output or time to oliguria.

          Conclusion

          Denervation thus caused an early increase in RBF that was distributed towards the kidney cortex. Although associated with an attenuation of early cortical metabolic alterations, denervation failed to prevent the deterioration in renal function.

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          Most cited references55

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          Early acute kidney injury and sepsis: a multicentre evaluation

          Introduction We conducted a study to evaluate the incidence, risk factors and outcomes associated with early acute kidney injury (AKI) in sepsis. Methods The study was a retrospective interrogation of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were collected from 57 intensive care units (ICUs) across Australia. In total, 120,123 patients admitted to ICU for more than 24 hours from 1 January 2000 to 31 December 2005 were included in the analysis. The main outcome measures were clinical and laboratory data and outcomes. Results Of 120,123 patients admitted, 33,375 had a sepsis-related diagnosis (27.8%). Among septic patients, 14,039 (42.1%) had concomitant AKI (septic AKI). Sepsis accounted for 32.4% of all patients with AKI. For septic AKI stratified by RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease) category, 38.5% of patients belonged to the risk category, 38.8% to the injury category and 22.7% to the failure category. Septic AKI patients had greater acuity of illness (P < 0.0001), lower blood pressure (P < 0.0001), higher heart rates (P < 0.0001), worse pulmonary function measures by arterial oxygen tension/fraction of inspired oxygen ratio (P < 0.0001), greater acidaemia (P < 0.0001) and higher white cell counts (P < 0.0001) compared with patients with nonseptic AKI. Septic AKI was also associated with greater severity of AKI (RIFLE category injury or failure) compared with nonseptic AKI. Septic AKI was associated with a significantly higher crude and co-variate adjusted mortality in the ICU (19.8% versus 13.4%; odds ratio 1.60, 95% confidence interval 1.5 to 1.7; P < 0.001) and in hospital (29.7% versus 21.6%; odds ratio 1.53, 95% confidence interval 1.46 to 1.60; P < 0.001) compared with nonseptic AKI. Septic AKI was associated with higher ICU and hospital mortality across all strata of RIFLE categories. Septic AKI patients had longer durations of stay in both ICU and hospital across all strata of RIFLE categories. Conclusion Septic AKI is common during the first 24 hours after ICU admission. Patients with septic AKI are generally sicker, with a higher burden of illness, and have greater abnormalities in acute physiology compared with patients with nonseptic AKI. Moreover, septic AKI is independently associated with higher odds of death and longer duration of hospitalization.
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            Sympathetic nervous system overactivity and its role in the development of cardiovascular disease.

            This review examines how the sympathetic nervous system plays a major role in the regulation of cardiovascular function over multiple time scales. This is achieved through differential regulation of sympathetic outflow to a variety of organs. This differential control is a product of the topographical organization of the central nervous system and a myriad of afferent inputs. Together this organization produces sympathetic responses tailored to match stimuli. The long-term control of sympathetic nerve activity (SNA) is an area of considerable interest and involves a variety of mediators acting in a quite distinct fashion. These mediators include arterial baroreflexes, angiotensin II, blood volume and osmolarity, and a host of humoral factors. A key feature of many cardiovascular diseases is increased SNA. However, rather than there being a generalized increase in SNA, it is organ specific, in particular to the heart and kidneys. These increases in regional SNA are associated with increased mortality. Understanding the regulation of organ-specific SNA is likely to offer new targets for drug therapy. There is a need for the research community to develop better animal models and technologies that reflect the disease progression seen in humans. A particular focus is required on models in which SNA is chronically elevated.
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              Lactate and shock state: the metabolic view.

              Bruno Levy (2006)
              The conventional view in severe sepsis or septic shock is that most of the lactate that accumulates in the circulation is due to cellular hypoxia and the onset of anaerobic glycolysis. A number of papers have suggested that lactate formation during sepsis is not due to hypoxia. I discuss this hypothesis and outline the recent advances in the understanding of lactate metabolism in shock. Numerous experimental data have demonstrated that stimulation of aerobic glycolysis - that is, glycolysis not attributable to oxygen deficiency - and glycogenolysis occurs not only in resting, well-oxygenated skeletal muscles but also during experimental haemorrhagic shock and experimental sepsis, and is closely linked to stimulation of sarcolemmal Na+/K+ -ATPase under epinephrine stimulation. A human study of hyperkinetic septic shock demonstrated that skeletal muscle is a leading source of lactate production by exaggerated aerobic glycolysis through Na+/K+ -ATPase stimulation. There is increasing evidence that sepsis is accompanied by a hypermetabolic state, with enhanced glycolysis and hyperlactataemia. This should not be rigorously interpreted as an indication of hypoxia. It now appears, at least in the hyperkinetic state, that increased lactate production and concentration as a result of hypoxia are often the exception rather than the rule.
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                Author and article information

                Contributors
                elmar.hendrik.post@ulb.ac.be
                fuhongsu@yahoo.com
                khosok@gmail.com
                ftaccone@ulb.ac.be
                antoineherpain@mac.com
                Jacques.Creteur@erasme.ulb.ac.be
                ddeback@ulb.ac.be
                jlvincent@intensive.org
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                31 May 2017
                31 May 2017
                2017
                : 18
                : 182
                Affiliations
                Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium
                Article
                586
                10.1186/s12882-017-0586-6
                5452298
                f2a938de-a1c7-4b45-a3c3-27286a537ae0
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 November 2016
                : 16 May 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Nephrology
                acute kidney injury,sepsis,septic shock,renal blood flow,renal function
                Nephrology
                acute kidney injury, sepsis, septic shock, renal blood flow, renal function

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