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      Risk factors for exertional rhabdomyolysis with renal stress

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          Abstract

          Background

          Exercise-induced rhabdomyolysis denotes the exertional damage of myocytes with leakage of sarcoplasmic content into the circulation. The purpose of this study was to determine important risk factors for the development of exertional rhabdomyolysis in a temperate climate and to study the renal effects of myoglobinuria.

          Methods

          A cluster of eight military recruits was admitted to hospital due to exertional rhabdomyolysis with myoglobinuria. The patients were treated according to current guidelines with isotonic saline and alkalinisation of the urine. The eight patients were compared with a randomly selected control group of 26 healthy fellow recruits. All subjects responded to a standardised questionnaire.

          Results

          There were little differences in baseline characteristics between patients and controls. In the present study, exercise intensity, duration and type were all significant determinants of exertional rhabdomyolysis in univariate models. However, in a multivariate model, high exercise intensity on day −1 was the only significant predictor of rhabdomyolysis (p=0.02). All patients had a stable serum creatinine and cystatin C. There was a significant increase in serum neutrophil gelatinase-associated lipocalin (NGAL) in the patients, suggesting renal stress.

          Conclusions

          Sustained maximal intensity exercise is a crucial risk factor for rhabdomyolysis with gross pigmenturia. Elevated serum NGAL concentrations indicate the presence of renal stress. It appears to be possible to quantify the risk of rhabdomyolysis by means of a simple questionnaire. In the future, this may be used as a tool to prevent rhabdomyolysis.

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          Most cited references23

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          Dual action of neutrophil gelatinase-associated lipocalin.

          Neutrophil gelatinase-associated lipocalin (NGAL) is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL exerts bacteriostatic effects, which are explained by its ability to capture and deplete siderophores, small iron-binding molecules that are synthesized by certain bacteria as a means of iron acquisition. Consistently, NGAL deficiency in genetically modified mice leads to an increased growth of bacteria. However, growing evidence suggests effects of the protein beyond fighting microorganisms. NGAL acts as a growth and differentiation factor in multiple cell types, including developing and mature renal epithelia, and some of this activity is enhanced in the presence of siderophore:iron complexes. This has led to the hypothesis that eukaryotes might synthesize siderophore-like molecules that bind NGAL. Accordingly, NGAL-mediated iron shuttling between the extracellular and intracellular spaces may explain some of the biologic activities of the protein. Interest in NGAL has been sparked by the observation that NGAL is massively upregulated after renal tubular injury and may participate in limiting kidney damage. This review summarizes the current knowledge about the dual effects of NGAL as a siderophore:iron-binding protein and as a growth factor and examines the role of these effects in renal injury.
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            Creatine-Kinase- and Exercise-Related Muscle Damage Implications for Muscle Performance and Recovery

            The appearance of creatine kinase (CK) in blood has been generally considered to be an indirect marker of muscle damage, particularly for diagnosis of medical conditions such as myocardial infarction, muscular dystrophy, and cerebral diseases. However, there is controversy in the literature concerning its validity in reflecting muscle damage as a consequence of level and intensity of physical exercise. Nonmodifiable factors, for example, ethnicity, age, and gender, can also affect enzyme tissue activity and subsequent CK serum levels. The extent of effect suggests that acceptable upper limits of normal CK levels may need to be reset to recognise the impact of these factors. There is a need for standardisation of protocols and stronger guidelines which would facilitate greater scientific integrity. The purpose of this paper is to examine current evidence and opinion relating to the release of CK from skeletal muscle in response to physical activity and examine if elevated concentrations are a health concern.
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              Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin.

              Acute renal failure secondary to ischemic injury remains a common problem, with limited and unsatisfactory therapeutic options. Neutrophil gelatinase-associated lipocalin (NGAL) was recently shown to be one of the maximally induced genes early in the postischemic kidney. In this study, the role of NGAL in ischemic renal injury was explored. Intravenous administration of purified recombinant NGAL in mice resulted in a rapid uptake of the protein predominantly by proximal tubule cells. In an established murine model of renal ischemia-reperfusion injury, intravenous NGAL administered before, during, or after ischemia resulted in marked amelioration of the morphologic and functional consequences, as evidenced by a significant decrease in the histopathologic damage to tubules and in serum creatinine measurements. NGAL-treated animals also displayed a reduction in the number of apoptotic tubule cells and an increase in proliferating proximal tubule cells after ischemic injury. The results indicate that NGAL may represent a novel therapeutic intervention in ischemic acute renal failure, based at least in part on its ability to tilt the balance of tubule cell fate toward survival.
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                Author and article information

                Journal
                BMJ Open Sport Exerc Med
                BMJ Open Sport Exerc Med
                bmjosem
                bmjosem
                BMJ Open Sport — Exercise Medicine
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2055-7647
                2017
                6 July 2017
                : 3
                : 1
                : e000241
                Affiliations
                [1 ]departmentDepartment of Medicine , Stavanger University Hospital , Stavanger, Norway
                [2 ]departmentFSAN , Norwegian Armed Forces , Stavanger, Norway
                [3 ]Birkenes Medical Centre , Birkeland, Norway
                [4 ]departmentDepartment of Transplantation Medicine , Oslo University Hospital–Rikshospitalet , Oslo, Norway
                [5 ]Stavanger Emergency Medical Centre , Stavanger, Norway
                [6 ]departmentDepartment of Cardiology , Stavanger University Hospital , Stavanger, Norway
                Author notes
                [Correspondence to ] Dr Terje Apeland, terje.apeland@ 123456lyse.net
                Author information
                http://orcid.org/0000-0002-7150-9416
                Article
                bmjsem-2017-000241
                10.1136/bmjsem-2017-000241
                5680435
                43713ccc-98dc-4847-aa09-295f01a1a4a3
                © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 26 May 2017
                Categories
                Original Article
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                creatin kinase,cross-sectional study,myoglobin,neutrophil gelatinase-associated lipocalin.

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