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AbstractObjectiveTo determine agreement in oxygen consumption (VO2) values calculated using Sykes’ formula VO2 = (FIO2 – Fe′O2 ) X V?E (where FI and FE are the inspired and end-tidal fractional concentrations of O2 respectively and VM = minute volume; ADDIN EN.CITE <EndNote><Cite><Author>Sykes</Author><Year>2010</Year><IDText>Oxygen monitoring during low flow anaesthesia</IDText><DisplayText>(Sykes, 2010)</DisplayText><record><dates><pub-dates><date>2010//</date></pub-dates><year>2010</year></dates><urls><related-urls><url> monitoring during low flow anaesthesia</title><secondary-title>Journal of Clinical Monitoring and Computing</secondary-title></titles><pages>141-141</pages><number>2</number><contributors><authors><author>Sykes, Oliver</author></authors></contributors><added-date format="utc">1489502591</added-date><ref-type name="Journal Article">17</ref-type><rec-number>185</rec-number><last-updated-date format="utc">1489502591</last-updated-date><electronic-resource-num>10.1007/s10877-010-9222-8</electronic-resource-num><volume>24</volume></record></Cite></EndNote>(Sykes, 2010)) with values derived using Brody’s formula (VO2 = 10kg3/4; ADDIN EN.CITE <EndNote><Cite><Author>Brody</Author><Year>1945</Year><IDText>Bioenergetics and growth: with special reference to the efficiency complex in domestic animals</IDText><DisplayText>(Brody, 1945)</DisplayText><record><titles><title>Bioenergetics and growth: with special reference to the efficiency complex in domestic animals</title><secondary-title>Bioenergetics and growth: with special reference to the efficiency complex in domestic animals.</secondary-title></titles><contributors><authors><author>Brody, Samuel</author></authors></contributors><added-date format="utc">1489502686</added-date><ref-type name="Journal Article">17</ref-type><dates><year>1945</year></dates><rec-number>186</rec-number><publisher>New York: Reinhold Publishing Corporation</publisher><last-updated-date format="utc">1489502686</last-updated-date></record></Cite></EndNote>(Brody, 1945)). It was hypothesized that the two methods would not yield statistically significant differences in calculated values.Study DesignProspective, clinical, pilot study.AnimalsTwenty-two client-owned dogs.MethodsThe minute volume of ventilation (Vm), FIO2 and Fe′O2 were measured during positive pressure ventilation of the lungs (Vt: 10 mL kg-1; fr: 8–12 breaths minute-1) in dogs undergoing surgery anaesthetized with either isoflurane or sevoflurane. Oesophageal temperature was maintained between 37.0 and 38.5 ?C. Values for VO2 derived by Sykes’ and Brody’s methods were compared and agreement determined using Bland-Altman analysis.ResultsMean VO2, calculated using Brody’s formula, was 4.67 (±0.51) mL kg -1 min-1 whilst the mean value using Sykes’ equation was 5.32 (±1.69) mL kg -1 min-1. There was greater variability in the values obtained from Sykes’ equation. The Bland-Altman plot revealed a proportional error with correlation but poor agreement between values. Conclusion and clinical relevanceBoth methods yielded VO2 values of approximately 5 mL kg-1min-1 with no statistically significant differences between the two methods. IntroductionOxygen consumption (VO2) - the volume of O2 used per unit time - depends on factors including basal metabolic rate, body temperature, body composition, gender and age. When oxygen delivery per unit time (DO2) falls below VO2, anaerobiosis occurs. Brody (1945) proposed oxygen consumption (VO2) in conscious homeotherms could be estimated by the equation: VO2 = 10 BW (body weight)3/4 mL minute-1. Whilst VO2 is normally reduced during anaesthesia, anaesthetics may reduce DO2 in a disproportionally greater manner, especially when factors limiting DO2 are present, or VO2 is elevated, e.g. in pregnancy, during surgical stimulation, hyperthyroidism, and malignant hyperthermia. For any values of VO2, O2 delivery into breathing systems must ensure that the inspired gas composition does not become a factor limiting DO2. This can be assured by measuring – and increasing when necessary - the fractional concentration of inspired O2 (FiO2).Based as it is on body mass alone, Brody’s law is unlikely to provide adequately accurate estimates of VO2 in anaesthetized, sick subjects. In these, application of the Fick principle is more appropriate, i.e.VO2 = Qt X C(a-v)O2wWhere Qt = cardiac output, and C(a-v)O2 is the arteriovenous O2 content difference.However, Fick’s method requires pulmonary arterial catheterisation so may be unjustifiably invasive and costly. An alternative method involves measuring VO2 under anaesthesia using the formula:VO2 = (FIO2 - Fe/O2) X V?E. (Sykes, 2010) where VO2 = oxygen consumption, FIO2 = fraction of inspired oxygen, Fe/O2 = end tidal fraction of oxygen and V?E = minute volume.This method is non-invasive, achievable using widely available technology and enables the frequent adjustment of oxygen flows by a simple calculation in real time. The objective of this study was to compare the values for VO2 in anaesthetized dogs calculated using Sykes’ formula with those derived using Brody’s equation. The null hypothesis was that the two methods would not yield statistically significant differences in calculated values.Material and MaterialsThe study received ethical approval from the veterinary ethical review committee of the XXXXX. Dogs of either gender, and all ages and habitus, scoring 1, 2 or 3 on the American Society of Anaesthesiologists physical status scale ADDIN EN.CITE <EndNote><Cite><Author>New Classification of Physical</Author><Year>1963</Year><IDText>American Society of Anaesthesiologists</IDText><DisplayText>(New Classification of Physical, 1963)</DisplayText><record><titles><title>American Society of Anaesthesiologists</title><secondary-title>Anaesthesiology</secondary-title></titles><contributors><authors><author>New Classification of Physical, status</author></authors></contributors><added-date format="utc">1537195240</added-date><ref-type name="Journal Article">17</ref-type><dates><year>1963</year></dates><rec-number>296</rec-number><last-updated-date format="utc">1537195240</last-updated-date><volume>24</volume></record></Cite></EndNote>(New Classification of Physical, 1963) and admitted to the XXXX hospital to undergo orthopaedic and soft tissue surgery under general anaesthesia were studied. In all cases the animals’ body mass was measured using a Marsden V-150 veterinary scale (Marsden, Rotherham, UK) no more than 12 hours before anaesthesia. Body condition score was recorded ADDIN EN.CITE <EndNote><Cite><Author>Laflamme</Author><Year>1997</Year><IDText>Development and validation of a body condition score system for dogs</IDText><DisplayText>(Laflamme, 1997)</DisplayText><record><dates><pub-dates><date>1997</date></pub-dates><year>1997</year></dates><urls><related-urls><url> and validation of a body condition score system for dogs</title><secondary-title>Canine Pract.</secondary-title></titles><pages>10-15</pages><contributors><authors><author>Laflamme, D.</author></authors></contributors><added-date format="utc">1510828941</added-date><ref-type name="Journal Article">17</ref-type><rec-number>258</rec-number><last-updated-date format="utc">1510828941</last-updated-date><volume>22</volume></record></Cite></EndNote>(Laflamme, 1997). Pre-anaesthetic medication and induction agents were selected by individual anaesthetists based on animal and operative requirements. However, in all cases, the trachea was intubated, the lungs were ventilated, and anaesthesia was maintained with either isoflurane or sevoflurane delivered in oxygen. Physiological monitoring consisted of capnography, electrocardiography, non-invasive arterial blood pressure, oesophageal temperature and pulse oximetry. The lungs of all animals were mechanically ventilated using a Datex Smartvent (Ohmeda 7900,?Datex-Ohmeda, GE Healthcare, UK) and V?E, FIO2 and Fe/O2 were recorded using a Datex S5 monitor and pitot tube spirometry. The same anaesthetic machine and monitor wereas used for all animals. Initially, a tidal volume of 10 mL kg -1 was delivered at an fR of 12 breaths per minute. The fR was adjusted to maintain end-tidal CO2 (Fe/CO2) values of 5.2 - 5.4 kPa (39 - 42 mm Hg). Oesophageal body temperature was measured using a Datex S5 K-type thermistor and maintained between 37.0 and 38.5?C using blankets, bubble wrap, minimal clipping and a 3M Bair Hugger. Baseline values for V?E, FiO2 and Fe/O2 were recorded once a surgical plane of anaesthesia had been achieved (as indicated by ocular position, palpebral areflexia and other signs of cranial nerve inactivity including jaw tone) but before surgery began. Values for VO2 using Sykes’ formula were compared with values using Brody’s formula. Consequently 22 pairs of VO2 values were obtained. Statistical AnalysisOxygen consumption data are shown as mean and standard deviation (± SD). Using MedCalc () a Bland & Altman plot (1986) was used to assess agreement between VO2 from Sykes’ formula and Brody’s formula (Figure 1). The difference in VO2 was calculated using (Sykes’ – Brody). Limits of agreement and bias are plotted on the graph. The plot was examined for evidence of bias or proportional error. In case of proportional error a regression line was drawn. Statistical significance was set at p < 0.05. Results A total of 22 dogs were studied. Body weight and ASA classification values are detailed in Table 1. Median body weight was 23.2 kg (range of 7.2 to 40 kg). Most dogs (15/22) were scored as body condition score 2-6. Mean VO2, calculated using Brody’s formula, was 4.67 (±0.51) mL kg -1 minute-1 whilst the mean measured value using Sykes’ formula was 5.32 (±1.69) mL kg -1 minute-1. There was no statistically significant difference between the values for oxygen consumption usding the different formulae. A Bland and Altman plot (Figure 1) revealed a bias of 0.6518 and limits of agreement were -2.487 and 3.79. There was a proportional error with correlation but poor agreement between values. The regression line did not demonstrate statistical significance. The plot showed decreased agreement at higher values of oxygen consumption. DiscussionThe measured mean value for VO2 using Sykes' formula was not significantly different from that using Brody’s formula which was unexpectedexpected and therefore supported our hypothesis.: The limits of agreement for the formulae were wide and as values of oxygen consumption increased the difference between the two methods became greater. The wide limits of agreement are unacceptable in a clinical context and this demonstrates that the two methods are not interchangeable. Brody’s formula was based on values obtained in conscious animals, while isoflurane anaesthesia causes a 15% reduction in metabolic rate - and, therefore, VO2 ADDIN EN.CITE <EndNote><Cite><Author>Rolly</Author><Year>1984</Year><IDText>Cardiovascular, metabolic and hormonal changes during isoflurane N2O anaesthesia</IDText><DisplayText>(Rolly et al., 1984)</DisplayText><record><dates><pub-dates><date>Dec</date></pub-dates><year>1984</year></dates><keywords><keyword>Adult</keyword><keyword>*Anesthesia, Inhalation</keyword><keyword>Blood Glucose/metabolism</keyword><keyword>Blood Pressure/drug effects</keyword><keyword>Carbon Dioxide/blood</keyword><keyword>Cardiac Output/drug effects</keyword><keyword>Epinephrine/blood</keyword><keyword>Female</keyword><keyword>Heart Rate/drug effects</keyword><keyword>Hemodynamics/*drug effects</keyword><keyword>Hormones/*blood</keyword><keyword>Humans</keyword><keyword>Hydrocortisone/blood</keyword><keyword>Hysterectomy</keyword><keyword>Isoflurane/*pharmacology</keyword><keyword>Methyl Ethers/*pharmacology</keyword><keyword>Middle Aged</keyword><keyword>Nitrous Oxide</keyword><keyword>Norepinephrine/blood</keyword><keyword>Oxygen/blood</keyword><keyword>Oxygen Consumption/*drug effects</keyword><keyword>Prolactin/blood</keyword><keyword>Stroke Volume/drug effects</keyword></keywords><isbn>0265-0215 (Print)
0265-0215</isbn><titles><title>Cardiovascular, metabolic and hormonal changes during isoflurane N2O anaesthesia</title><secondary-title>Eur J Anaesthesiol</secondary-title><alt-title>European journal of anaesthesiology</alt-title></titles><pages>327-34</pages><number>4</number><contributors><authors><author>Rolly, G.</author><author>Versichelen, L.</author><author>Moerman, E.</author></authors></contributors><edition>1984/12/01</edition><language>eng</language><added-date format="utc">1510080844</added-date><ref-type name="Journal Article">17</ref-type><remote-database-provider>NLM</remote-database-provider><rec-number>251</rec-number><last-updated-date format="utc">1510080844</last-updated-date><accession-num>6443092</accession-num><volume>1</volume></record></Cite></EndNote>(Rolly et al., 1984). Furthermore, mechanical ventilation reduces oxygen requirements beyond the reductions caused by anaesthesia ADDIN EN.CITE <EndNote><Cite><Author>Aubier</Author><Year>1982</Year><IDText>Respiratory muscle contribution to lactic acidosis in low cardiac output</IDText><DisplayText>(Aubier et al., 1982)</DisplayText><record><dates><pub-dates><date>Oct</date></pub-dates><year>1982</year></dates><keywords><keyword>Abdominal Muscles/metabolism</keyword><keyword>Acidosis/complications/*metabolism</keyword><keyword>Animals</keyword><keyword>Cardiac Output, Low/complications/*metabolism</keyword><keyword>Diaphragm/metabolism</keyword><keyword>Dogs</keyword><keyword>Glycogen/metabolism</keyword><keyword>Intercostal Muscles/metabolism</keyword><keyword>Lactates/*metabolism</keyword><keyword>Muscles/*metabolism</keyword><keyword>*Respiration</keyword><keyword>Shock, Cardiogenic/metabolism</keyword></keywords><isbn>0003-0805 (Print)
0003-0805</isbn><titles><title>Respiratory muscle contribution to lactic acidosis in low cardiac output</title><secondary-title>Am Rev Respir Dis</secondary-title><alt-title>The American review of respiratory disease</alt-title></titles><pages>648-52</pages><number>4</number><contributors><authors><author>Aubier, M.</author><author>Viires, N.</author><author>Syllie, G.</author><author>Mozes, R.</author><author>Roussos, C.</author></authors></contributors><edition>1982/10/01</edition><language>eng</language><added-date format="utc">1510082491</added-date><ref-type name="Journal Article">17</ref-type><remote-database-provider>NLM</remote-database-provider><rec-number>252</rec-number><last-updated-date format="utc">1510082491</last-updated-date><accession-num>6214978</accession-num><electronic-resource-num>10.1164/arrd.1982.126.4.648</electronic-resource-num><volume>126</volume></record></Cite></EndNote>(Aubier et al., 1982). These reducing effects are offset during surgery by the associated stress response. However, the values obtained in the current study were recorded before surgery began, so a straightforward explanation is not forthcoming. The differences in oxygen consumption were not statistically significant and both mean values were approximately 5mL kg-1 minute-1. This is considerably less than the oxygen flow recommendations for a circle breathing system (10 mL kg-1 minute-1) ADDIN EN.CITE <EndNote><Cite><Author>Duke-Novakovski</Author><Year>2016</Year><IDText>BSAVA manual of canine and feline anaesthesia and analgesia</IDText><DisplayText>(Duke-Novakovski, 2016)</DisplayText><record><isbn>1905319614</isbn><titles><title>BSAVA manual of canine and feline anaesthesia and analgesia</title></titles><contributors><authors><author>Duke-Novakovski, Tanya</author></authors></contributors><added-date format="utc">1528964155</added-date><ref-type name="Book">6</ref-type><dates><year>2016</year></dates><rec-number>285</rec-number><publisher>John Wiley & Sons</publisher><last-updated-date format="utc">1528964155</last-updated-date></record></Cite></EndNote>(Duke-Novakovski, 2016). The limits of agreement for the formulae were wide and as values of oxygen consumption increased the difference between the two methods became greater. The wide limits of agreement are unacceptable in a clinical context and this demonstrates that the two methods are not interchangeable.Factors affecting metabolic rate and therefore VO2 include alterations in body temperature, the subject’s tissue composition, disease, the drugs used for sedation and anaesthesia and activation of a stress response. These may be secondary to - amongst other things - tracheal intubation and surgery PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaW5nPC9BdXRob3I+PFllYXI+MTk1MTwvWWVhcj48SURU
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ADDIN EN.CITE.DATA (King et al., 1951, Robinson et al., 1983). Brody’s formula excludes these factors whilst Sykes’ method does not, explaining the greater variability between VO2 values obtained with the latter method. Every effort was made to reduce heat loss in the dogs studied but temperatures as low as 37°C were recorded in some dogs. This represents mild hypothermia and can be attributed to abolished behavioural responses, increased heat loss, the cooling effect of anaesthetic gases and vapours and reduced heat production due to decreased muscle activity and brain metabolism. In humans, hypothermia decreases cerebral metabolic rate by approximately 8% for each degree Celsius below normal. Given that the brain accounts for 25% of total body oxygen consumption, hypothermia may alter VO2 considerably. However, in the current study, reduced core temperatures were not associated with lower measured VO2 values, which means other, unidentified factors were present. It is known that some types of neoplasia and renal disease can lead to increased VO2 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYW5ha2E8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxJ
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ADDIN EN.CITE.DATA (Tanaka and Nangaku, 2010, Macbeth and Bekesi, 1962). Brody’s formula was proposed using data from presumably healthy animals and so this might have accounted for some of the differences encountered in the current study. Furthermore Brody studied a large number of different animals and the value is likely to be an average from different species. A previous study by Haskins et al., (2005), which collated cardiopulmonary variables from unsedated, instrumented dogs, found a VO2 of 6.0 ± 2.6 mL kg -1 minute-1 ADDIN EN.CITE <EndNote><Cite><Author>Haskins</Author><Year>2005</Year><IDText>Reference Cardiopulmonary Values in Normal Dogs</IDText><DisplayText>(Haskins et al., 2005)</DisplayText><record><dates><pub-dates><date>//</date></pub-dates><year>2005</year></dates><urls><related-urls><url> Cardiopulmonary Values in Normal Dogs</title><secondary-title>Comparative Medicine</secondary-title></titles><pages>156-161</pages><number>2</number><contributors><authors><author>Haskins, Steve</author><author>Pascoe, Peter J.</author><author>Ilkiw, Jan E.</author><author>Fudge, James</author><author>Hopper, Kate</author><author>Aldrich, Janet</author></authors></contributors><added-date format="utc">1528904166</added-date><ref-type name="Journal Article">17</ref-type><rec-number>284</rec-number><last-updated-date format="utc">1528904166</last-updated-date><volume>55</volume></record></Cite></EndNote>(Haskins et al., 2005). This suggests that dogs may have a higher VO2 than previously indicated suggested by Brody’s formula.There were several limitations to the study. Body condition and ASA physical status scores were not taken into account. Preferably, In addition, body temperature would should have been maintained within normal physiological limits (38.3-38.9 °C). It is possible that the useing of a range of anaesthetic techniques in the current study increased variance in the data recorded. However, the clinical nature of the study rendered the use of a standardised protocol infeasible. One further major limitation was the lack of calibration of the spirometer. While the anaesthetic machine we used hads been recently purchased and commissioned check by the manufacturer, no calibration was done at the time of the study. Further work would include standardising the anaesthetic protocol and reducing pathophysiological variation by only including ASA 1 or 2 animals would limit some of the variability inherent in our study. In addition, segregating data according to body condition score, fitness and age categories may allow further insight into how VO2 varies with body composition. Obese dogs with higher proportions of adipose tissue compared with normal dogs may account for alterations in VO2 and this may be an area for further study. Research in humans suggests that oxygen consumption decreases with the degree of obesity ADDIN EN.CITE <EndNote><Cite><Author>Hallgren</Author><Year>1989</Year><IDText>Influence of age, fat cell weight, and obesity on O2 consumption of human adipose tissue</IDText><DisplayText>(Hallgren et al., 1989)</DisplayText><record><dates><pub-dates><date>Apr</date></pub-dates><year>1989</year></dates><keywords><keyword>Adipose Tissue/*metabolism/pathology</keyword><keyword>Adult</keyword><keyword>Aging/*metabolism</keyword><keyword>Body Composition</keyword><keyword>Body Height</keyword><keyword>Body Weight</keyword><keyword>Carbon Dioxide/metabolism</keyword><keyword>Child, Preschool</keyword><keyword>Energy Metabolism</keyword><keyword>Female</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Obesity/*metabolism/pathology</keyword><keyword>*Oxygen Consumption</keyword><keyword>Triglycerides/metabolism</keyword><keyword>Weight Loss</keyword></keywords><isbn>0002-9513 (Print)
0002-9513</isbn><titles><title>Influence of age, fat cell weight, and obesity on O2 consumption of human adipose tissue</title><secondary-title>Am J Physiol</secondary-title><alt-title>The American journal of physiology</alt-title></titles><pages>E467-74</pages><number>4 Pt 1</number><contributors><authors><author>Hallgren, P.</author><author>Sjostrom, L.</author><author>Hedlund, H.</author><author>Lundell, L.</author><author>Olbe, L.</author></authors></contributors><edition>1989/04/01</edition><language>eng</language><added-date format="utc">1517490638</added-date><ref-type name="Journal Article">17</ref-type><auth-address>Department of Medicine, Sahlgren's Hospital, Goteborg, Sweden.</auth-address><remote-database-provider>NLM</remote-database-provider><rec-number>262</rec-number><last-updated-date format="utc">1517490638</last-updated-date><accession-num>2495730</accession-num><electronic-resource-num>10.1152/ajpendo.1989.256.4.E467</electronic-resource-num><volume>256</volume></record></Cite></EndNote>(Hallgren et al., 1989). In conclusion, values for VO2 calculated using two methods produced results which were not statistically significantly different from one another. However, VO2 values calculated using Sykes’ formula were more variable and unexpectedly higher than that calculated using Brody’s equation. Overall, O2 flows recommended for use in rebreathing systems appear to be in excess of requirements. Using the simple formula proposed by Sykes may enable lower flows to be used safely, minimising environmental pollution and cost.References ADDIN EN.REFLIST Aubier, M., Viires, N., Syllie, G., Mozes, R. and Roussos, C. (1982) 'Respiratory muscle contribution to lactic acidosis in low cardiac output', Am Rev Respir Dis, 126(4), pp. 648-52.Brody, S. (1945) 'Bioenergetics and growth: with special reference to the efficiency complex in domestic animals', Bioenergetics and growth: with special reference to the efficiency complex in domestic animals.Duke-Novakovski, T. (2016) BSAVA manual of canine and feline anaesthesia and analgesia. John Wiley & Sons.Hallgren, P., Sjostrom, L., Hedlund, H., Lundell, L. and Olbe, L. (1989) 'Influence of age, fat cell weight, and obesity on O2 consumption of human adipose tissue', Am J Physiol, 256(4 Pt 1), pp. E467-74.Haskins, S., Pascoe, P. J., Ilkiw, J. E., Fudge, J., Hopper, K. and Aldrich, J. (2005) 'Reference Cardiopulmonary Values in Normal Dogs', Comparative Medicine, 55(2), pp. 156-161.King, B. D., Harris, L. C., Jr., Greifenstein, F. E., Elder, J. D., Jr. and Dripps, R. D. (1951) 'Reflex circulatory responses to direct laryngoscopy and tracheal intubation performed during general anesthesia', Anesthesiology, 12(5), pp. 556-66.Laflamme, D. (1997) 'Development and validation of a body condition score system for dogs', Canine Pract., 22, pp. 10-15.Macbeth, R. A. L. and Bekesi, J. G. (1962) 'Oxygen Consumption and Anaerobic Glycolysis of Human Malignant and Normal Tissue', Cancer Research, 22(2), pp. 244.New Classification of Physical, s. (1963) 'American Society of Anaesthesiologists', Anaesthesiology, 24.Robinson, W. R., Peters, R. H. and Zimmermann, J. (1983) 'The effects of body size and temperature on metabolic rate of organisms', Canadian Journal of Zoology, 61(2), pp. 281-288.Rolly, G., Versichelen, L. and Moerman, E. (1984) 'Cardiovascular, metabolic and hormonal changes during isoflurane N2O anaesthesia', Eur J Anaesthesiol, 1(4), pp. 327-34.Sykes, O. (2010) 'Oxygen monitoring during low flow anaesthesia', Journal of Clinical Monitoring and Computing, 24(2), pp. 141-141.Tanaka, T. and Nangaku, M. (2010) 'The role of hypoxia, increased oxygen consumption, and hypoxia-inducible factor-1 alpha in progression of chronic kidney disease', Curr Opin Nephrol Hypertens, 19(1), pp. 43-50. ................
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