Research Increase in circulating non-esterified fatty acids during the hemodialysis session: The role of cell starvation
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Research Increase in circulating non-esterified fatty acids during the hemodialysis session: The role of cell starvation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Research Increase in circulating non-esterified fatty acids during the hemodialysis session: The role of cell starvation Masako Fujiwara, Hiroyuki Terawaki, Itiro Ando, You Shishido, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6101055/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Although an increase in plasma levels of non-esterified fatty acids (NEFA) during hemodialysis (HD) is reported, the precise pathophysiology remains unclear. We hypothesized that an elevation in NEFA levels reflects “cell starvation” or sudden-onset catabolism caused primarily by a steep depletion of plasma insulin during the HD session. Materials and Methods We measured in five cases the circulating levels of NEFA and insulin during the HD session under conditions without and with intradialytic parenteral nutrition (IDPN) that can suppress cell starvation. Results Without IDPN, insulin decreased rapidly, and NEFA increased to abnormally high levels. Such a steep elevation in NEFA levels was clearly suppressed in the IDPN condition with maintained levels of insulin. Conclusions Our findings suggest that the main cause of the increase in NEFA during HD is cell starvation. cell starvation hemodialysis intradialytic parenteral nutrition insulin non-esterified fatty acids Figures Figure 1 Introduction The kidney is an organ that maintains the extracellular environment through functions such as the excretion of waste products (uremic toxins) concurrently with the re-absorbing of useful substances, the maintenance of the volume of body fluids, and the maintenance of extracellular electrolyte status including hydrogen ions (= pH). On the other hand, the nutritional extracellular environment including glucose, amino acids and fatty acids is handled not by the kidney, but by another organic system that consists of the liver, subcutaneous fat and muscle, which is conducted by catabolic hormones (e.g. glucagon) and anabolic hormones (mainly insulin). The progression of clinical medicine has allowed patients with end-stage kidney disease (ESKD) to live using renal replacement therapy (RRT), including kidney transplantation, peritoneal dialysis (PD), and hemodialysis (HD). Of these, HD is the leading RRT modality in the world and in Japan. On 31 December 2023, the number of Japanese patients with ESKD treated with PD is 10,585, while that treated with HD was 332,923 [ 1 ], which is greater than the total population of Fukushima city (271,689). HD or an artificial kidney mimics kidney function; HD adjusts the status of extracellular electrolytes and excretes uremic toxins and excess water. However, an artificial kidney also excretes nutrients, such as amino acids and plasma proteins, including peptide hormones such as insulin, which a real kidney does not excrete. Rapid excretion of amino acids and peptide hormones causes sudden onset catabolism or “cell starvation” [ 2 ] and thus can raise problems especially among ESKD patients with diabetes and/or aging, being on the edge of malnutrition and sarcopenia. Recently, Boss et al. reported a decrease in the binding and detoxification efficiency of fatty acids in serum albumin and a reciprocal increase in the plasma levels of non-esterified fatty acids (NEFA), suggesting its pathophysiology may be dysregulation of triglyceride breakdown via acceleration of lipoprotein lipase triggered by heparin used as an anticoagulant for hemodialysis (HD) sessions [ 3 ]. However, such elevation in NEFA levels might reflect cell starvation [ 2 ]. More precisely, our previous studies, which observed a reciprocal relationship between plasma amino acids (AA), insulin, ketone bodies, and other organic acids during HD sessions, indicated the catabolic nature of the HD procedure with the breakdown of muscle cells [ 4 , 5 ]. Consequently, the elevation of NEFA levels during HD sessions can directly reflect cell starvation, which induces catabolism including muscle proteolysis. The aim of this study is to prove whether HD-induced plasma NEFA elevation is due to cell starvation. To this end, we measured the circulating levels of NEFA during the HD session under different nutritional conditions, that is, without and with intradialytic parenteral nutrition (IDPN), including amino acid and glucose supplementation that can suppress cell starvation [ 2 , 4 , 5 ]. Materials and methods Patients and sample collection We recruited five patients for this study (Table 1) and compared their circulating levels of NEFA and insulin during HD between conditions without or with IDPN to suppress cell starvation. We used heparin as an anticoagulant during all HD sessions. All patients had a meal at home approximately 2 hours before HD; of these, two patients with diabetes (Cases 4 and 5) administered insulin subcutaneously just before meals as usual. IDPN in this study included continuous infusion of the AA formulation (Kidmin® 200 mL, Otsuka Pharmaceutical Co. Ltd, Tokyo. Japan), together with 200 mL of 50% glucose solution, including 3 units of regular insulin, in cases with diabetes (Cases 4 and 5) only. Blood samples were collected before each HD session and every hour until the end of the session. Table 1. Characteristics and nutritional indices before the start of the study Unit Mean ± SD Case 1 Case 2 Case 3 Case 4 Case 5 Primary disease Malignant hypertension Glomeruo nephritis Polycystic kidney Diabetic Kidney Disease Diabetic Kidney Disease Sex female male female male male Age years 71.6 ± 5.2 72 77 74 72 63 Dialysis vintage years 8.4 ± 2.3 11 6 6 9 10 BMI kg/m 2 24.2 ± 5.4 25 20 17.3 29.5 29 Weight kg 63.2 ± 15.4 56.3 51.5 48.6 80.5 79 Creatinine mg/dL 10.7 ± 1.9 9.4 12.8 10.8 12.3 8.4 Albumin g/dL 3.7 ± 0.1 3.7 3.6 3.5 3.7 3.9 Hemoglobin g/dL 10.1 ± 0.7 11 10.5 9.3 9.4 10.2 Hematocrit % 31.0 ± 1.2 32 32 29 31.2 31 Glucose mg/dL 130.2 ± 48.0 88 80 128 163 192 CRP ng/mL 0.2 ± 0.1 0.1 0.1 0.4 0.05 0.1 GNRI 94.0 ± 5.2 96.0 92.0 86.0 96.0 99.8 nPCR g/kg/day 1.0 ± 0.1 1.10 1.00 1.05 0.82 0.85 Glycoalbumin % - - - 17.0 18.5 Insulin therapy Rapid acting insulin E - - - - 9 - 0 - 6 Mix type insulin E - - - 5 - 0 - 6 - Long acting insulin E - - - - 0 - 0 - 4 HD/HDF HD HDF HD HDF HD Substitution fluid volume L - 60 - 60 - Kt/V-urea 1.8 ± 0.3 2.1 1.68 2.23 1.62 1.5 Blood flow rate mL/min 248.0 ± 4.5 250 250 240 250 250 Membrane matrix PS PS PS CTA PAN Membrane surface area m 2 1.9 ± 0.3 1.80 2.00 2.20 1.80 1.53 Heparin (unfractionated) priming dose U 680 ± 110 600 600 800 600 800 maintenance dose U/h 680 ± 110 600 600 800 600 800 Note. HD: hemodialysis, HDF: hemodiafiltration, CRP:C-reactive protein; nPCR; normalized protein catabolic rate; GA: gulicated albumine; GNRI: geriatric nutritional risk index,PS:polysulfone, CTA: cellulose triacetate, PAN, polyacrylonitrile, Dialysate fluid rates are 500 mL/min. Unfractionated Heparin (Hepafilled®; Otsuka Pharmaceutical Co.Ltd.,Tokyo Japan) are used. Sample analysis The levels of immunoreactive insulin (IRI, mU/L) and NEFA (mmol/L) were determined using enzymatic method and chemiluminescent enzyme immunoassays, respectively. Obtained IRI and NEFA levels (Table 2) are evaluated as values subtracted by their baseline level and are referred to as ΔIRI and ΔNEFA (mean ± standard error). Table 2. Plasma levels of IRI (mU/L) and NEFA (mmol/L) during HD Without IDPN Patient Case 1 Case 2 Case 3 Case 4 Case 5 IRI NEFA IRI NEFA IRI NEFA IRI NEFA IRI NEFA Baseline 22.5 1.84 16.9 2.21 22.7 1.92 35.7 0.75 45.9 2.05 1 h 6.00 2.85 2.90 3.48 12.1 3.26 18.5 2.30 30.6 3.32 2 h 3.80 3.10 2.60 3.92 9.30 3.29 12.8 2.61 26.1 3.41 3 h 2.90 3.22 2.50 4.45 5.40 3.35 7.70 2.84 21.2 3.93 4 h 1.90 3.22 3.10 4.00 5.40 3.30 6.10 3.05 16.0 4.49 5 h 2.50 3.46 3.70 4.03 2.50 3.05 6.20 3.12 12.0 4.24 With IDPN Patient Case 1 Case 2 Case 3 Case 4 Case 5 IRI NEFA IRI NEFA IRI NEFA IRI NEFA IRI NEFA Baseline 15.0 0.10 14.5 0.14 11.5 0.10 15.3 0.12 14.2 0.09 1 h 22.1 0.41 24.3 0.28 49.8 0.30 24.8 0.37 13.9 0.50 2 h 15.0 0.38 38.8 0.29 45.8 0.24 27.4 0.41 19.3 0.43 3 h 9.1 0.49 22.2 0.16 34.5 0.23 17.1 0.31 20.2 0.59 4 h 8.3 0.34 21.4 0.08 23.1 0.30 15.3 0.31 19.8 0.69 5 h 7.8 0.32 13.9 0.12 11.9 0.41 13.3 0.26 19.3 1.03 Statement of Ethics This study was approved by the Ethics Committee of Teikyo University (TU–20–194), and written informed consent was obtained from all patients. Statistical Analysis Statistical analyses were performed using EZR Version 1.33 (Saitama Medical Center, Jichi Medical University), which is a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria) [6]. EZR is a modified version of the R commander that is designed to add statistical functions that are frequently used in biostatistics. Significance of collected data was evaluated using univariate type III repeated analysis of variance (ANOVA) followed by paired t -test with Bonferroni correction (vs. “Baseline”). Differences were considered significant for values of p <0.05. Results Fig. 1 shows the chronological course of IRI and NEFA. Under conditions without IDPN (Fig. 1A), the changes in IRI and NEFA were symmetric: IRI decreased rapidly and significantly during the initial one hour, then gradually decreased towards the end of the session, as previously reported [2, 4, 5], and NEFA increased significantly from the beginning of the sessions and remained at higher levels towards the end of the session, keeping a significant difference with baseline value. However, under IDPN conditions (Fig. 1B), the time-courses of IRI and NEFA distinctly differ from those under the condition without IDPN: The IRI level was maintained throughout and no steep elevation of NEFA was observed under this condition. Specifically, although NEFA showed a slight and unsignificant increase during the initial hour, it remained constant thereafter. Discussion Our previous studies [ 2 , 4 , 5 ] have revealed the presence of “cell starvation”, an acute-onset starvation induced by an HD session via insulin depletion, suggesting a suspended TCA energy-producing cycle during HD [ 2 ]. Such cell starvation, or catabolic status including insulin insufficiency, can induce the release of NEFA through hydrolysis of triglycerides in adipose cells by hormone-sensitive lipase [ 7 ]. In contrast, sufficient insulin can inhibit the degradation of triglycerides into NEFA in adipose cells through its antilipolytic action [ 8 ], promoting the proper use of supplied amino acids. Frailty is a common and serious problem among patients treated with HD: Yamamoto et al. evaluated the relationship between dialysis history and frailty among patients treated with HD therapy using data from a nationwide Japanese cohort (n = 227,136) and found a significant relationship between a longer period of dialysis and a higher prevalence of frailty and bedridden status, even after adjusting for confounders including age [ 9 ]. This result suggests that the long-term repeat of the HD session per se can act as a profound exacerbator of frailty and highlights the importance of an effective approach in preventing frailty. Overall, present study proved that HD-induced plasma NEFA elevation is due to cell starvation including insulin depletion and thus is avoidable using proper IDPN. Not only being a surrogate marker of cell starvation, elevated plasma NEFA can also be involved in the pathogenesis of organic damage, including albumin function disorder [ 3 ] and atherosclerosis [ 10 ], and may play a role in the pathogenesis of frailty called malnutrition-inflammation-atherosclerosis syndrome (MIA syndrome) [ 11 ] among patients with ESKD treated with HD. Therefore, recognizing cell starvation can create a pathway to improve the prognosis of all patients treated with HD, all on the edge of frailty. Conclusion Our findings suggest that the main cause of the increase in NEFA during HD is not heparin action, but cell starvation. Declarations Ethics approval and consent to patients This study was approved by the Ethical Committee of Teikyo University (TU-20-194), and written informed consent for participation was obtained from the five patients. Consent for publication Written informed consent for publication was obtained from the five patients. Availability of data and material The dataset supporting the conclusion of this article is included within the article as Tables 1 and 2. Competing interests The authors have no conflicts of interest directly related to the content of this article. Funding None. Authors' contributions All authors contributed to the conception of the study. Masako Fujiwara, Itiro Ando and Hiroyuki Terawaki designed the study. You Shishido and Masako Fujiwara collected the data. Masako Fujiwara and Itiro Ando created the initial database, and Hiroyuki Terawaki performed the statistical analyses. Masako Fujiwara prepared the draft manuscript. Takafumi Ito supervised this study, reviewed the manuscript thoroughly and gave critical suggestions. All the authors reviewed the draft and critically revised the manuscript for intellectual content. All authors have read and approved the final manuscript, which was mainly modified by Hiroyuki Terawaki. Acknowledgements The authors thank Emeritus professor Yutaka Imai for critical review and advice. References Masaki T, Hanafusa N, Abe M, et al. 2023 annual dialysis data report, JSDT Renal Data Registry. Jpn J Dial Ther. 2024; 57(12): 543-620. (in Japanese) https://doi.org/10.4009/jsdt.57.543 Fujiwara M, Ando I, Satoh K, et al. Biochemical evidence of cell starvation in diabetic hemodialysis patients. PLOS ONE . 2018; 13(9): e0204406. https://doi.org/10.1371/journal.pone.0204406. Boss K, Waterstradt K, Schnurr K, et al. Binding and detoxification efficiency of albumin decline after haemodialysis. Nephrol Dial Transplant. 2024; 39(2): 215–21. https://doi.org/10.1093/ndt/gfad133. Fujiwara M, Ando I, Shishido Y, et al. An increase of circulating levels of branched-chain amino acids during hemodialysis with regard to protein breakdown: three case report. Ren Replace Ther . 2022; 8(1): 1. https://doi.org/10.1186/s41100-021-00391-3. Fujiwara M, Ando I, Shishido Y, et al. Amino acid availability enhanced through glucose coadministration of amino acid supplementation during hemodiafiltration: two case reports. Ren Replace Ther. 2022; 8(1): 28. https://doi.org/10.1186/s41100-022-00417-4. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant . 2013; 48: 452–8. https://doi.org:10.1038/bmt.2012.244. Holm C. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans. 2003; 31(6): 1120–4. https://doi.org/10.1042/bst0311120 Petersen MC, Shulman GI. Mechanism of insulin action and insulin resistance. Physiol Rev. 2018; 98(4): 2133–223. https://doi.org/10.1152/physrev.00063.2017 Yamamoto S, Niihata K, Toida T, et al. Frailty and duration of maintenance dialysis: A Japanese Nationwide Cross-Sectional Study. Am J Kidney Dis. 2024; 84(5): 601–12.e1. https://doi.org/10.1053/j.ajkd.2024.04.012 Carlsson M, Wessman Y, Almgren P, at al. High levels of nonesterified fatty acids are associated with increased familial risk of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2000; 20: 1588-94. https://doi.org/10.1161/01.ATV.20.6.1588 Stenvinkel P, Heimbürger O, Lindholm B, et al. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant. 2000; 15: 953-60. https://doi.org/10.1093/ndt/15.7.953 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6101055","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":424202045,"identity":"3311e40d-85a9-4bc6-926e-d89abcfc5c76","order_by":0,"name":"Masako Fujiwara","email":"","orcid":"","institution":"Teikyo University Chiba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Masako","middleName":"","lastName":"Fujiwara","suffix":""},{"id":424202046,"identity":"e30c89b8-9810-4fe3-8a59-b869a8fc921b","order_by":1,"name":"Hiroyuki Terawaki","email":"data:image/png;base64,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","orcid":"","institution":"Teikyo University Chiba Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Hiroyuki","middleName":"","lastName":"Terawaki","suffix":""},{"id":424202048,"identity":"a20e34d4-4a16-4061-bcb1-b2915a2316cd","order_by":2,"name":"Itiro Ando","email":"","orcid":"","institution":"Teikyo University Chiba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Itiro","middleName":"","lastName":"Ando","suffix":""},{"id":424202050,"identity":"cc4afeca-ef7b-4001-bc19-ab9b68316465","order_by":3,"name":"You Shishido","email":"","orcid":"","institution":"Midorinosato Clinic","correspondingAuthor":false,"prefix":"","firstName":"You","middleName":"","lastName":"Shishido","suffix":""},{"id":424202052,"identity":"285972b6-57a8-4e9f-b3ac-fec27c97b1bc","order_by":4,"name":"Takafumi Ito","email":"","orcid":"","institution":"Teikyo University Chiba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Takafumi","middleName":"","lastName":"Ito","suffix":""}],"badges":[],"createdAt":"2025-02-25 03:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6101055/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6101055/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78241005,"identity":"947b9371-cb55-43d1-bdcb-3e24368f3886","added_by":"auto","created_at":"2025-03-11 09:02:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":271552,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in time course of IRI and NEFA during HD session in without (A) and with concomitant IDPN treatment (B).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn both figures, IRI and NEFA are shown as means ± standard errors of changes from baseline (ΔIRI and ΔNEFA). IRI is illustrated by a dashed blue line and NEFA by a solid red line.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6101055/v1/8b5194552af830a24d535a4a.png"},{"id":89779871,"identity":"a4068e6a-a4e0-4db4-b5b2-caf86d827aa7","added_by":"auto","created_at":"2025-08-25 01:46:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":946019,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6101055/v1/cb9d5189-744e-4d4f-bdb4-75d9e9464df4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Research Increase in circulating non-esterified fatty acids during the hemodialysis session: The role of cell starvation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe kidney is an organ that maintains the extracellular environment through functions such as the excretion of waste products (uremic toxins) concurrently with the re-absorbing of useful substances, the maintenance of the volume of body fluids, and the maintenance of extracellular electrolyte status including hydrogen ions (=\u0026thinsp;pH). On the other hand, the nutritional extracellular environment including glucose, amino acids and fatty acids is handled not by the kidney, but by another organic system that consists of the liver, subcutaneous fat and muscle, which is conducted by catabolic hormones (e.g. glucagon) and anabolic hormones (mainly insulin).\u003c/p\u003e \u003cp\u003eThe progression of clinical medicine has allowed patients with end-stage kidney disease (ESKD) to live using renal replacement therapy (RRT), including kidney transplantation, peritoneal dialysis (PD), and hemodialysis (HD). Of these, HD is the leading RRT modality in the world and in Japan. On 31 December 2023, the number of Japanese patients with ESKD treated with PD is 10,585, while that treated with HD was 332,923 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], which is greater than the total population of Fukushima city (271,689). HD or an artificial kidney mimics kidney function; HD adjusts the status of extracellular electrolytes and excretes uremic toxins and excess water. However, an artificial kidney also excretes nutrients, such as amino acids and plasma proteins, including peptide hormones such as insulin, which a real kidney does not excrete. Rapid excretion of amino acids and peptide hormones causes sudden onset catabolism or \u0026ldquo;cell starvation\u0026rdquo; [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and thus can raise problems especially among ESKD patients with diabetes and/or aging, being on the edge of malnutrition and sarcopenia.\u003c/p\u003e \u003cp\u003eRecently, Boss et al. reported a decrease in the binding and detoxification efficiency of fatty acids in serum albumin and a reciprocal increase in the plasma levels of non-esterified fatty acids (NEFA), suggesting its pathophysiology may be dysregulation of triglyceride breakdown via acceleration of lipoprotein lipase triggered by heparin used as an anticoagulant for hemodialysis (HD) sessions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, such elevation in NEFA levels might reflect cell starvation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. More precisely, our previous studies, which observed a reciprocal relationship between plasma amino acids (AA), insulin, ketone bodies, and other organic acids during HD sessions, indicated the catabolic nature of the HD procedure with the breakdown of muscle cells [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Consequently, the elevation of NEFA levels during HD sessions can directly reflect cell starvation, which induces catabolism including muscle proteolysis.\u003c/p\u003e \u003cp\u003eThe aim of this study is to prove whether HD-induced plasma NEFA elevation is due to cell starvation. To this end, we measured the circulating levels of NEFA during the HD session under different nutritional conditions, that is, without and with intradialytic parenteral nutrition (IDPN), including amino acid and glucose supplementation that can suppress cell starvation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003ePatients and sample collection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe recruited five patients for this study (Table 1) and compared their circulating levels of NEFA and insulin during HD between conditions without or with IDPN to suppress cell starvation. We used heparin as an anticoagulant during all HD sessions. All patients had a meal at home approximately 2 hours before HD; of these, two patients with diabetes (Cases 4 and 5) administered insulin subcutaneously just before meals as usual. IDPN in this study included continuous infusion of the AA formulation (Kidmin\u0026reg; 200 mL, Otsuka Pharmaceutical Co. Ltd, Tokyo. Japan), together with 200 mL of 50% glucose solution, including 3 units of regular insulin, in cases with diabetes (Cases 4 and 5) only. Blood samples were collected before each HD session and every hour until the end of the session.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 100%;\" colspan=\"8\"\u003e\u003cstrong\u003eTable 1. Characteristics and nutritional indices before the start of the study\u003c/strong\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eUnit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eCase 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eCase 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eCase 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eCase 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eCase 5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003ePrimary disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eMalignant hypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eGlomeruo nephritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003ePolycystic kidney\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eDiabetic Kidney Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eDiabetic Kidney Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eyears\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e71.6 \u0026plusmn; 5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eDialysis vintage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eyears\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e8.4 \u0026plusmn; 2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003ekg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e24.2 \u0026plusmn; 5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e17.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e29.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eWeight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003ekg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e63.2 \u0026plusmn; 15.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e56.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e51.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e48.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e80.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eCreatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003emg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e10.7 \u0026plusmn; 1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e10.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eAlbumin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e3.7 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eHemoglobin\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e10.1 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e10.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eHematocrit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e31.0 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e31.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eGlucose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003emg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e130.2 \u0026plusmn; 48.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e192\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eCRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eng/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.2 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eGNRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e94.0 \u0026plusmn; 5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e96.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e92.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e86.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e96.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e99.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003enPCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eg/kg/day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.0 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.00\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eGlycoalbumin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e17.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eInsulin therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Rapid acting insulin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e9 - 0 - 6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Mix type insulin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e5 - 0 - 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Long acting insulin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0 - 0 - 4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eHD/HDF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eHDF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eHDF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eHD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eSubstitution fluid volume\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eKt/V-urea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.8 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e2.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eBlood flow rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003emL/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e248.0 \u0026plusmn; 4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eMembrane matrix\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003ePS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003ePS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003ePS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eCTA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003ePAN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eMembrane surface area\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003em\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.9 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.80\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e2.00\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e2.20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eHeparin (unfractionated)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp; priming dose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e680 \u0026plusmn; 110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e600\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e600\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e800\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e800\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e\u0026nbsp; maintenance dose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eU/h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e680 \u0026plusmn; 110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e800\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 609px;\"\u003e\n \u003cp\u003e\u003cem\u003eNote.\u003c/em\u003e HD: hemodialysis, HDF: hemodiafiltration, CRP:C-reactive protein; nPCR; normalized protein catabolic rate; GA: gulicated albumine; GNRI: geriatric nutritional risk index,PS:polysulfone, CTA: cellulose triacetate, PAN, polyacrylonitrile, Dialysate fluid rates are 500 mL/min. Unfractionated Heparin (Hepafilled\u0026reg;; Otsuka Pharmaceutical Co.Ltd.,Tokyo Japan) are used.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eSample analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe levels of immunoreactive insulin (IRI, mU/L) and NEFA (mmol/L) were determined using enzymatic method and chemiluminescent enzyme immunoassays, respectively. Obtained IRI and NEFA levels (Table 2) are evaluated as values subtracted by their baseline level and are referred to as \u0026Delta;IRI and \u0026Delta;NEFA (mean \u0026plusmn; standard error).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 2. Plasma levels of IRI (mU/L) and NEFA (mmol/L) during HD\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"549\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\" style=\"width: 99.6357%;\"\u003e\n \u003cp\u003eWithout IDPN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003ePatient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 86px;\"\u003e\n \u003cp\u003eCase 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 99px;\"\u003e\n \u003cp\u003eCase 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 99px;\"\u003e\n \u003cp\u003eCase 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 99px;\"\u003e\n \u003cp\u003eCase 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 99px;\"\u003e\n \u003cp\u003eCase 5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e22.5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e1.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e16.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e22.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e35.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e45.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e1 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e6.00\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.90\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e12.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e30.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e2 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e3.80\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.60\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e9.30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e26.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e3 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e2.90\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.50\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e4.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e5.40\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e7.70\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e21.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e4 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e1.90\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e4.00\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e5.40\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e6.10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e16.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e4.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e5 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e2.50\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.70\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e4.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e2.50\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e6.20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e3.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e12.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e4.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\" style=\"width: 99.6357%;\"\u003e\n \u003cp\u003eWith IDPN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003ePatient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 86px;\"\u003e\n \u003cp\u003eCase 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 99px;\"\u003e\n \u003cp\u003eCase 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 99px;\"\u003e\n \u003cp\u003eCase 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 99px;\"\u003e\n \u003cp\u003eCase 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 99px;\"\u003e\n \u003cp\u003eCase 5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eNEFA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e15.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e14.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e11.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e15.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e14.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e1 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e22.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e24.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e49.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e24.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e2 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37px;\"\u003e\n \u003cp\u003e15.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd 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style=\"width: 37px;\"\u003e\n \u003cp\u003e7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e19.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eStatement of Ethics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Teikyo University (TU\u0026ndash;20\u0026ndash;194), and written informed consent was obtained from all patients. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using EZR Version 1.33 (Saitama Medical Center, Jichi Medical University), which is a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria) [6]. EZR is a modified version of the R commander that is designed to add statistical functions that are frequently used in biostatistics.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSignificance of collected data was evaluated using univariate type III repeated analysis of variance (ANOVA) followed by paired \u003cem\u003et\u003c/em\u003e-test with Bonferroni correction (vs. \u0026ldquo;Baseline\u0026rdquo;). \u0026nbsp;Differences were considered significant for values of \u003cem\u003ep\u003c/em\u003e \u0026lt;0.05. \u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eFig. 1 shows the chronological course of IRI and NEFA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnder conditions without IDPN (Fig. 1A), the changes in IRI and NEFA were symmetric: IRI decreased rapidly and significantly during the initial one hour, then gradually decreased towards the end of the session, as previously reported [2, 4, 5], and NEFA increased significantly from the beginning of the sessions and remained at higher levels towards the end of the session, keeping a significant difference with baseline value.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHowever, under IDPN conditions (Fig. 1B), the time-courses of IRI and NEFA distinctly differ from those under the condition without IDPN: The IRI level was maintained throughout and no steep elevation of NEFA was observed under this condition. Specifically, although NEFA showed a slight and unsignificant increase during the initial hour, it remained constant thereafter.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur previous studies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] have revealed the presence of \u0026ldquo;cell starvation\u0026rdquo;, an acute-onset starvation induced by an HD session via insulin depletion, suggesting a suspended TCA energy-producing cycle during HD [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Such cell starvation, or catabolic status including insulin insufficiency, can induce the release of NEFA through hydrolysis of triglycerides in adipose cells by hormone-sensitive lipase [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In contrast, sufficient insulin can inhibit the degradation of triglycerides into NEFA in adipose cells through its antilipolytic action [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], promoting the proper use of supplied amino acids.\u003c/p\u003e \u003cp\u003eFrailty is a common and serious problem among patients treated with HD: Yamamoto et al. evaluated the relationship between dialysis history and frailty among patients treated with HD therapy using data from a nationwide Japanese cohort (n\u0026thinsp;=\u0026thinsp;227,136) and found a significant relationship between a longer period of dialysis and a higher prevalence of frailty and bedridden status, even after adjusting for confounders including age [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This result suggests that the long-term repeat of the HD session \u003cem\u003eper se\u003c/em\u003e can act as a profound exacerbator of frailty and highlights the importance of an effective approach in preventing frailty.\u003c/p\u003e \u003cp\u003eOverall, present study proved that HD-induced plasma NEFA elevation is due to cell starvation including insulin depletion and thus is avoidable using proper IDPN. Not only being a surrogate marker of cell starvation, elevated plasma NEFA can also be involved in the pathogenesis of organic damage, including albumin function disorder [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and atherosclerosis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and may play a role in the pathogenesis of frailty called malnutrition-inflammation-atherosclerosis syndrome (MIA syndrome) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] among patients with ESKD treated with HD. Therefore, recognizing cell starvation can create a pathway to improve the prognosis of all patients treated with HD, all on the edge of frailty.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur findings suggest that the main cause of the increase in NEFA during HD is not heparin action, but cell starvation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethical Committee of Teikyo University (TU-20-194), and written informed consent for participation was obtained from the five patients. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from the five patients.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset supporting the conclusion of this article is included within the article as Tables 1 and 2. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest directly related to the content of this article. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the conception of the study. Masako Fujiwara, Itiro Ando and Hiroyuki Terawaki designed the study. You Shishido and Masako Fujiwara collected the data. Masako Fujiwara and Itiro Ando created the initial database, and Hiroyuki Terawaki performed the statistical analyses. Masako Fujiwara prepared the draft manuscript. Takafumi Ito supervised this study, reviewed the manuscript thoroughly and gave critical suggestions. All the authors reviewed the draft and critically revised the manuscript for intellectual content. All authors have read and approved the final manuscript, which was mainly modified by Hiroyuki Terawaki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Emeritus professor Yutaka Imai for critical review and advice.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMasaki T, Hanafusa N, Abe M, et al. 2023 annual dialysis data report, JSDT Renal Data Registry. Jpn J Dial Ther. 2024; 57(12): 543-620. (in Japanese) https://doi.org/10.4009/jsdt.57.543 \u003c/li\u003e\n\u003cli\u003eFujiwara M, Ando I, Satoh K, et al. Biochemical evidence of cell starvation in diabetic hemodialysis patients. PLOS ONE\u003cem\u003e.\u003c/em\u003e 2018; 13(9): e0204406. https://doi.org/10.1371/journal.pone.0204406. \u003c/li\u003e\n\u003cli\u003eBoss K, Waterstradt K, Schnurr K, et al. Binding and detoxification efficiency of albumin decline after haemodialysis. Nephrol Dial Transplant. 2024; 39(2): 215\u0026ndash;21. https://doi.org/10.1093/ndt/gfad133. \u003c/li\u003e\n\u003cli\u003eFujiwara M, Ando I, Shishido Y, et al. An increase of circulating levels of branched-chain amino acids during hemodialysis with regard to protein breakdown: three case report. Ren Replace Ther\u003cem\u003e.\u003c/em\u003e 2022; 8(1): 1. https://doi.org/10.1186/s41100-021-00391-3. \u003c/li\u003e\n\u003cli\u003eFujiwara M, Ando I, Shishido Y, et al. Amino acid availability enhanced through glucose coadministration of amino acid supplementation during hemodiafiltration: two case reports. Ren Replace Ther. 2022; 8(1): 28. https://doi.org/10.1186/s41100-022-00417-4. \u003c/li\u003e\n\u003cli\u003eKanda Y. Investigation of the freely available easy-to-use software \u0026lsquo;EZR\u0026rsquo; for medical statistics. Bone Marrow Transplant\u003cem\u003e.\u003c/em\u003e 2013; 48: 452\u0026ndash;8. https://doi.org:10.1038/bmt.2012.244. \u003c/li\u003e\n\u003cli\u003eHolm C. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans. 2003; 31(6): 1120\u0026ndash;4. https://doi.org/10.1042/bst0311120 \u003c/li\u003e\n\u003cli\u003ePetersen MC, Shulman GI. Mechanism of insulin action and insulin resistance. Physiol Rev. 2018; 98(4): 2133\u0026ndash;223. https://doi.org/10.1152/physrev.00063.2017 \u003c/li\u003e\n\u003cli\u003eYamamoto S, Niihata K, Toida T, et al.\u003cem\u003e \u003c/em\u003eFrailty and duration of maintenance dialysis: A Japanese Nationwide Cross-Sectional Study. Am J Kidney Dis. 2024; 84(5): 601\u0026ndash;12.e1. https://doi.org/10.1053/j.ajkd.2024.04.012 \u003c/li\u003e\n\u003cli\u003eCarlsson M, Wessman Y, Almgren P, at al. High levels of nonesterified fatty acids are associated with increased familial risk of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2000; 20: 1588-94. https://doi.org/10.1161/01.ATV.20.6.1588 \u003c/li\u003e\n\u003cli\u003eStenvinkel P, Heimb\u0026uuml;rger O, Lindholm B, et al. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant. 2000; 15: 953-60. https://doi.org/10.1093/ndt/15.7.953 \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"cell starvation, hemodialysis, intradialytic parenteral nutrition, insulin, non-esterified fatty acids","lastPublishedDoi":"10.21203/rs.3.rs-6101055/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6101055/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAlthough an increase in plasma levels of non-esterified fatty acids (NEFA) during hemodialysis (HD) is reported, the precise pathophysiology remains unclear. We hypothesized that an elevation in NEFA levels reflects \u0026ldquo;cell starvation\u0026rdquo; or sudden-onset catabolism caused primarily by a steep depletion of plasma insulin during the HD session.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMaterials and Methods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe measured in five cases the circulating levels of NEFA and insulin during the HD session under conditions without and with intradialytic parenteral nutrition (IDPN) that can suppress cell starvation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWithout IDPN, insulin decreased rapidly, and NEFA increased to abnormally high levels. Such a steep elevation in NEFA levels was clearly suppressed in the IDPN condition with maintained levels of insulin.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eOur findings suggest that the main cause of the increase in NEFA during HD is cell starvation.\u003c/p\u003e","manuscriptTitle":"Research Increase in circulating non-esterified fatty acids during the hemodialysis session: The role of cell starvation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-11 09:02:01","doi":"10.21203/rs.3.rs-6101055/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"356afe04-94cb-4f32-bee0-963af1fd9331","owner":[],"postedDate":"March 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-25T01:38:29+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-11 09:02:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6101055","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6101055","identity":"rs-6101055","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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Source provenance
- europepmc
- last seen: 2026-05-20T01:45:00.602351+00:00