DIALYSIS. PROTEIN ENERGY WASTING, INFLAMMATION AND OXIDATIVE STRESS FP716 EFFICACY OF LEVOCARNITINE SUPPLEMENTATION IN IMPROVING LEAN BODY MASS AND PHYSICAL FUNCTION IN PATIENTS ON HEMODIALYSIS: A RANDOMIZED CONTROLLED TRIAL Masanori Abe 1 , Takashi Maruyama 1 , Noriaki Maruyama 1 , Seishirou Baba 1 , Hiroyuki Takashima 1 , Tomoyasu Otsuki 1 , Terumi Higuchi 2 1 Nihon University School of Medicine, Itabashi-ku, Japan and 2 Keiai Hospital, Tokyo, Japan, Japan INTRODUCTION: Patients on hemodialysis (HD) are known to develop carnitine deficiency. This may contribute to a number of clinical disorders, including cachexia, dyslipidemia, erythropoiesis stimulating agent-resistant anemia, insulin resistance and glucose intolerance, muscle weakness, and myopathy, as well as intradialytic symptoms, including muscle cramps, hypotension, and cardiac arrhythmias. However, the efficacy of levocarnitine (L-carnitine) supplementation on lean body mass (LBM) and physical function have not been studied and remain unclear. This study aimed to determine the effect of L-carnitine supplementation on physical and nutritional status in patients undergoing hemodialysis. METHODS: In this multicenter, prospective, open-label, parallel, randomized, controlled trial, patients on maintenance hemodialysis who developed carnitine deficiency were randomly assigned to receive injections of L-carnitine 1,000 mg 3 times weekly after hemodialysis sessions (L-carnitine group) or no injections (control group) with monitoring for 12 months. All eligible participants were required to undergo dual-energy X-ray absorptiometry (DXA) scans to determine their LBM, fat mass, and skeletal muscle mass. The primary efficacy endpoints were physical function-related parameters, including dry weight, body mass index (BMI), mid-upper arm muscle area (AMA), hand grip strength, and LBM, which were measured as the magnitude of change from baseline and compared between the two groups. The secondary endpoints were the differences in magnitude of change from baseline in clinical parameters between the two groups. RESULTS: Data for 84 of the 91 patients were available for analysis (L-carnitine group, n = 42; control group, n = 42). Dry weight and BMI did not significantly change in the L-carnitine group, but significantly decreased in the control group. AMA did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean AMA between the groups was 6.22% (95% confidence interval [CI] 1.90–10.5; P = 0.037). Hand grip strength did not change significantly in the L-carnitine group, but decreased significantly in the control group. The difference in change in hand grip strength between the groups was 4.27% (95% CI 0.42–8.12; P = 0.030). Furthermore, LBM did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean LBM between the groups was 2.95% (95% CI 1.28–4.61; P = 0.0007). CONCLUSIONS: Our findings showed the utility of L-carnitine injection for prevention of muscle weakness in patients who develop carnitine deficiency while on HD. The benefits of L-carnitine supplementation in these patients include maintenance of both physical function and LBM. Further large-scale clinical studies would be needed to establish L-carnitine supplementation significantly influences mortality rates for dialysis patients. FP717 DECIPHERING NEUTROPHIL DYSFUNCTION IN HEMODIALYSIS PATIENTS Adi Litmanovich 1 , Khaled Khazim 1 , Kamal Hassan 2 , Idan Cohen 2 , Talal Salti 1 , Batya Kristal 1 1 Bar Ilan University, School Of Medicine, Safed, Israel and 2 Galilee Medical Center, Nahariya, Israel INTRODUCTION: Neutrophils serve as the first line of defense against infections. They fight pathogens intracellularly via phagocytosis or extracellularly via NETosis. The latter is a mechanism where batches of DNA and proteins are released into the extracellular space in response to bacteria, trapping and localizing the infection. NETosis is activated through NADPH oxidase (NOX)-dependent and/or NOX- independent pathways. Reactive oxygen species (ROS) are involved in both phagocytosis and NETosis. HD neutrophils show altered ROS signaling and impaired bacterial killing, contributing to these patients’ increased susceptibility to infections, in an underlying mechanism not yet fully understood. To date, defective NETosis was only described in several human congenital mutations. We hypothesize that HD-induced impaired ROS signaling results not only in damaging HD neutrophils&#39; ability to digest and kill bacteria intracellularly, as previously described, but also impairs NET formation. In this research, we aim to molecularly characterize the impaired bacterial killing of HD patients&#39; neutrophils in both intracellular and extracellular pathways, to gain a better understanding of the relations between the two, and try to restore it as a possible future therapeutic approach. METHODS: Highly purified neutrophils were isolated from HC (healthy controls) and HD patients using negative selection cell sorting. NETosis was triggered in vitro on isolated neutrophils using calcium ionophore and PMA stimuli. NETs were quantified both visually under the microscope using immunofluorescence and by measuring their media-secreted cell-free DNA levels. Bacterial killing was assessed in both pathways using bacterial stimuli and NETosis inhibitor DNase I. ROS levels were measured by chemiluminescence and hydrogen peroxide (H2O2) was added as an end-product of the ROS signaling cascade in order to test its ability to restore NETosis in the patients&#39; group. RESULTS: HD patients&#39; neutrophils exhibit more than a 40% decrease in NOX- independent NETosis and a substantial decrease in the NOX-dependent pathway compared with HCs. Intracellular levels of superoxide ions were found elevated in HDs neutrophils, but H2O2 levels were decreased. Finally, we were successful in restoring NET formation in HD patients&#39; neutrophils with the addition of exogenous H2O2. CONCLUSIONS: Neutrophils of HD patients suffer from an impaired capacity to engage in both extracellular and intracellular bacterial killing, possibly through a defective common pathway, which can be bypassed with the addition of exogenous H2O2 for successful NET formation. Deciphering and restoring neutrophil dysfunction may be a crucial step in improving the innate immunity of HD patients and reducing morbidity and mortality rates due to infections in this population. FP718 DIABETES AND MALNUTRITION RISK IN HEMODIALYSIS PATIENT Vitor Martins 1 , Leila Aguiar 1 , Catarina Dias 1 , Pedro Lourenc ¸o 1 , Tatiana Pinheiro 1 , Br  ıgida Velez 1 , Rita Birne 1 , Nuno Borges 2 , Teresa Adrag~ ao 1 , Conceic ¸ ~ ao Calhau 3 , Fernando Mac ario 1 1 Diaverum, Sintra, Portugal, 2 Universidade do Porto, Porto, Portugal and 3 Faculdade de Ci ^ encias Me ´dicas da Universidade Nova de Lisboa, Lisboa, Portugal INTRODUCTION: Diabetes is highly prevalent in hemodialysis (HD) patients (pts) as well as malnutrition. Due to the diabetes onset, pathological and metabolic nature, it would be expected to have a high impact on chronic pts’ nutritional risk. We aim to analyze the association of diabetes, namely non-insulin treated (NIT) vs insulin treated (INS), with malnutrition risk in HD pts. METHODS: Cross sectional analysis of 2975 HD patients (25% of Portuguese pts in HD), assessed between September 15th 2015 and January 31st 2016. Nutritional risk was assessed with the malnutrition-inflammation score (MIS) and when >5 indicates increased risk. RESULTS: 1758 male (59.1%) pts; 622 (21%) pts on hemodiafiltration and 2353 (79%) on High-flux HD. All diabetic pts, 984 (33.1%), were treated, 756(25.4%) INS and 228 (7.7%) NIT. In univariate analysis diabetes was not associated with a MIS>5 (p=0.094) but ROC Curve Analysis identified the association of a MIS>6 with diabetes (AUC= 0.51760.01; 95%CI 0.49-0.53; Sensitivity 41%; Specificity 63%). Diabetic vs non-Diabetic pts were older (70.2611 vs 64.9615, p<0.001), with lower nPCR (1.0760.27 vs 1.1060.18, p=0.008), lower Ca (9.260.7 vs 9.360.7, p=0.014), lower P (4.0561.2 vs 4.261.3, p=0.01), lower CaXP (37.8610.9 vs 38.8612.4, p=0.001) lower PCreat (8.661.5 vs 9.161.3, 6.666.8, p<0.001), lower EPO res index (6.866.8 vs 7.568.3, p=0.032), lower Kt/V (1.860.34 vs 1.960.39, p<0.001), lower PTH (3896262 vs 4486393, p<0.001), lower URR (0.77860.08 vs 0.79660.55,p<0.001) and lower weekly treatment duration (743688 vs 7966114, p=0.002). INS vs NIT pts were younger (69.7611.4 vs 71.7610, p<0.001), with lower nPCR (1.0660.27 vs 1.1060.27, p=0.008), lower EPO Res index (6.566.6 vs 7.767.9, p=0.036), higher Htc (34.164.4 vs 33.465.2, p<0.001), lower Kt/V (1.8460.32 vs 1.8560.31, p<0.001), and lower CRP (11.8620.9 vs 17.7632.4, p=0.027). MIS>6 was associated with older age (70.1614.3 vs 63.9614.9, p<0.001), higher prevalence of female gender (44% vs 34%, p<0.001), diabetes (41% vs 37%, p=0.023), lower P (3.861.2 vs 4.31.2, p<0.001), higher Ca (9.360.65 vs 9.260.62, p<0.001), lower nPCR (1.0160.28 vs 1.1360.26, p<0.001), higher EPO Res index (8.769.2 vs 6.366.7, p<0.001), higher Kt/V (1.960.3 vs 1.8 60.3, p<0.001), higher URR (0.7960.6 vs 0.78606, p<0.001), higher CRP (15.7625 vs 9.7616.8p<0.001), lower prevalence of HDF (31% vs 41%, p<0.001). Analyzing separately INS and NIT pts, only INS pts had higher prevalence of MIS>6 (42% vs 37%, p=0.014). V C The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. Nephrology Dialysis Transplantation 34 (Supplement 1): i292–i304, 2019 doi:10.1093/ndt/gfz106 Downloaded from https://academic.oup.com/ndt/article/34/Supplement_1/gfz106.FP718/5515152 by guest on 08 March 2022