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      Pulmonary function and exercise tolerance are related to disease severity in pre-dialytic patients with chronic kidney disease: a cross-sectional study

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          Abstract

          Background

          Chronic kidney disease (CKD) involves a progressive, irreversible loss of kidney function. While early-stage CKD patients may show changes in pulmonary function and lowered exercise tolerance, the role of the estimated glomerular filtration rate (eGFR) in these patterns remains unknown. The aim of this study was to investigated pulmonary function and exercise tolerance in pre-dialytic CKD patients.

          Methods

          A cross-sectional study was carried out with 38 adult volunteers divided into a control group (CG), consisting of 9 healthy adults, and 29 pre-dialytic CKD patients in stages 3 (G3), 4 (G4), and 5 (G5). All participants underwent spirometric and manovacuometric tests, a cardiopulmonary exercise test (CPET), a 6-minute walk test (6MWT), and laboratory tests.

          Results

          The significant differences was observed in maximal exercise tolerance, measured as peak oxygen consumption percentage (VO 2peak) (mL/kg/min) (CG = 28.9 ± 7.8, G3 = 23.3 ± 5.6, G4 = 21.4 ± 5.2, G5 = 20.2 ± 6.9; p = 0.03), and submaximal exercise tolerance, measured by 6MWT (m) (CG = 627.6 ± 37.8, G3 = 577.4 ± 66.1, G4 = 542.7 ± 57.3, G5 = 531.5 ± 84.2, p = 0.01). The eGFR was associated with pulmonary function-forced expiratory volume in the first second percentage (FEV 1) (%) (r = 0.34, p = 0.02) and maximum inspiratory pressure (PImax) (r = 0.41, p = 0.02) - and exercise tolerance - VO 2peak (mL/kg/min) (r = 0.43, p = 0.01) and 6MWT distance (m) (r = 0.55, p < 0.01).

          Conclusion

          Pre-dialytic CKD patients showed lower maximal and submaximal exercise tolerances than healthy individuals.

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          Most cited references28

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          Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation.

          The strength of the respiratory muscles can be evaluated from static measurements (maximal inspiratory and expiratory pressures, MIP and MEP) or inferred from dynamic maneuvers (maximal voluntary ventilation, MVV). Although these data could be suitable for a number of clinical and research applications, no previous studies have provided reference values for such tests using a healthy, randomly selected sample of the adult Brazilian population. With this main purpose, we prospectively evaluated 100 non-smoking subjects (50 males and 50 females), 20 to 80 years old, selected from more than 8,000 individuals. Gender-specific linear prediction equations for MIP, MEP and MVV were developed by multiple regression analysis: age and, secondarily, anthropometric measurements explained up to 56% of the variability of the dependent variables. The most cited previous studies using either Caucasian or non-Caucasian samples systematically underestimated the observed values of MIP (P < 0.05). Interestingly, the self-reported level of regular physical activity and maximum aerobic power correlates strongly with both respiratory and peripheral muscular strength (knee extensor peak torque) (P < 0.01). Our results, therefore, provide a new frame of reference to evaluate the normalcy of some useful indexes of respiratory muscle strength in Brazilian males and females aged 20 to 80.
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            Exercise in the end-stage renal disease population.

            Many of the known benefits of exercise in the general population are of particular relevance to the ESRD population. In addition, the poor physical functioning that is experienced by patients who are on dialysis is potentially addressable through exercise interventions. The study of exercise in the ESRD population dates back almost 30 yr, and numerous interventions, including aerobic training, resistance exercise training, and combined training programs, have reported beneficial effects. Recently, interventions during hemodialysis sessions have become more popular and have been shown to be safe. The risks of exercise in this population have not been rigorously studied, but there have been no reports of serious injury as a result of participation in an exercise training program. It is time that we incorporate exercise into the routine care of patients who are on dialysis, but identification of an optimal training regimen or regimens, according to patient characteristics or needs, is still needed to facilitate implementation of exercise programs.
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              Review of muscle wasting associated with chronic kidney disease.

              Muscle wasting increases the morbidity and mortality associated with chronic kidney disease (CKD) and has been attributed to malnutrition. In most patients, this is an incorrect diagnosis because simply feeding more protein aggravates uremia. Instead, there are complex mechanisms that stimulate loss of skeletal muscle, involving activation of mediators that stimulate the ATP-dependent ubiquitin-proteasome system (UPS). Identified mediators of muscle protein breakdown include inflammation, metabolic acidosis, angiotensin II, and neural and hormonal factors that cause defects in insulin/insulin-like growth factor I (IFG-I) intracellular signaling processes. Abnormalities in insulin/IGF-I signaling activate muscle protein degradation in the UPS and caspase-3, a protease that disrupts the complex structure of muscle proteins to provide substrates for the UPS. During the cleavage of muscle proteins, caspase-3 leaves behind a characteristic 14-kD actin fragment in the insoluble fraction of muscle, and characterization of this fragment identifies the presence of muscle catabolism. Thus, it could become a marker of excessive muscle wasting, providing a method for early detection of muscle wasting. Another consequence of activation of caspase-3 in muscle is stimulation of the activity of the proteasome, which increases the degradation of muscle proteins. Treatment strategies for blocking muscle wasting include correction of metabolic acidosis, which can suppress muscle protein losses in patients with CKD who are or are not being treated by dialysis. Correcting acidosis also improves bone metabolism in CKD and hence should be a goal of therapy. Exercise training is a potentially beneficial approach, but more information is needed to optimize exercise regimens. Replacing testosterone deficits can improve muscle mass in men, but dosing and side effects in women have not been adequately tested. Although insulin resistance occurs early in the course of CKD, there are no effective means of correcting it. Consequently, new therapies that can safely suppress muscle wasting are needed.
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                Author and article information

                Contributors
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central
                1471-2369
                2013
                4 September 2013
                : 14
                : 184
                Affiliations
                [1 ]Interdisciplinary Nucleus of Study, Research and Treatment in Nephrology (NIEPEN), Federal University of Juiz de Fora, José Lourenço Kelmer, 1300, São Pedro, 36036-330 Juiz de Fora, Minas Gerais, Brazil
                [2 ]Department of Medicine, Campus Universitário, Federal University of Juiz de Fora, Martelos, 36016-970 Juiz de Fora, Minas Gerais, Brazil
                [3 ]Division of Pneumology, University Hospital of Federal University of Juiz de Fora, Rua Catulo Breviglieri, Santa Catarina, 36036110 Juiz de Fora, Minas Gerais, Brazil
                Article
                1471-2369-14-184
                10.1186/1471-2369-14-184
                3847184
                24007403
                c7b3c7c3-3555-4734-8056-56d6cd669ad4
                Copyright © 2013 Faria et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 March 2012
                : 8 July 2013
                Categories
                Research Article

                Nephrology
                respiratory function tests,exercise tolerance,physical fitness,kidney failure chronic

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