in even excellently designed randomized crossover trials the increase of potassium with various treatment regimens was only mild and rarely within normal range. These findings question the role of potassium level as the ideal marker of potassium hoemostasis in SLT and underline the need for new treatment targets, preferably related to increased QoL. The aim of this prospectively cross-sectional study was to define a surrogate endpoint for future treatment trials in SLT through evaluation of the biochemical parameters most relevant to domains of QoL and cardiac abnormalities. We speculated that higher aldosterone activity may be related to worse QoL parameters and increased risk for cardial arrhythmia. This hypothesis was evaluated using the transtubular potassium gradient (TTKG) as a previously described surrogate of aldosterone activity. METHODS: We included 11 prevalent subjects with SLT in two centers (Medical University of Vienna and Klinikum Klagenfurt). We assessed in a cross-sectional design the biochemical, clinical and cardiological parameters and their relationship with QoL. The primary hypothesis was that higher aldosterone activity, assessed by the TTKG reflects QoL more accurately. Secondary endpoints were the presence of cardiac arrhythmia in 24h ECG and cardiac abnormalities via ultrasound (US). Single domains of QoL were evaluated with the standardized RAND 36-Questionnaire including calculation of sum scores for physical and mental health. RESULTS: The cohort were of mainly female sex with a mean age of 34 years. The mean K+ was 3.3 mmol/l, mean Mg++ 0.67 mmol/l and mean TTKG 10.3. While dimensions of mental health were mostly reflected by Mg++ (r=0.68, p=0.04) and K+ (r=0.55, p=0.08) better physical health was associated with lower aldosterone levels (r=0.61, p=0.06). Of note, TTKG did not reflect aldosterone activity and was not related to QoL. In detail K+ was significantly related to the domain emotional well-being (r=0.70, p=0.01) and showed a trend for general health (r=0.54, p=0.09) and energy/fatigue (r=0.56, p=0.07) The lower aldosterone the less role limitations due to physical health (RP) were observed (-0.74, p=0.02). Mg++ correlated significantly with RP (r=0.65, p=0.06) and social functioning (SF, r=0.74, p=0.02). No relevant abnormalities were observed in either 24h ECG or cardiac US. CONCLUSIONS: Hyperaldosteronism, K+ and Mg++ are the most important parameters of QoL in SLT. TTKG is not a suitable marker for hyperaldosteronism in SLT or QoL. Future treatment trials in SLT should include QOL assessment as well aldosteron, K+ and Mg++ assessment. SP020 SCREENING OF FABRY DISEASE IN THE SLOVAK KIDNEY POPULATION Sara Maria Fellegi-Majernikova 1 , Agata Argalasova 2 , Jaroslav Rosenberger 3 1 Gymnazium, Kosice, Slovakia, 2 FMC-Dialysis services Slovakia, Bratislava, Slovakia and 3 Faculty of Medicine, Safarik University, Kosice, Slovakia INTRODUCTION: Fabry disease is an X-linked inherited disorder of glycosphingolipid metabolism based on a pathogenic mutation in the GLA gene (Xq21.3-q22). Encoding of the alpha-galactosidase A enzyme caused by deficient or absent lysosomal a-galactosidase A activity leads to the accumulation of globotriaosylceramide (Gb3) within the lysosomes and is believed to trigger a cascade of cellular events inside the cells. This might then manifest progressively in many specific systemic forms. One of the symptoms is chronic kidney disease (CKD), which leads to a need for renal replacement therapy. Early diagnosis and consecutive enzyme replacement therapy by recombinant a-galactosidase A might prevent morbidity and mortality. The aim of the study was to determine the prevalence of Fabry disease in the Slovak kidney population. METHODS: A cross-sectional epidemiology study was performed on 6088 consecutive patients between 2015 and 2018 to determine the prevalence of Fabry disease in Slovakia. Data collection and sample analysis in the pre-dialyzed group (G4-G5 CKD) occurred between 2016 and 2018, in the dialyzed population between 2015 and 2016, and in transplanted patients in 2017. Sub-cohorts consist of 1659 (RR=100%) patients in the G4-5 CKD, 3107 (RR=86.7%) on dialysis and 1322 (RR=80.7%) after kidney transplantation. Screening was based on the dried blood spot test by determination of a-galactosidase A activity, lyso-Gb3 values and GLA gene mutations. Laboratory tests were carried out at Metabolic Laboratory in Hamburg, ARCHIMED Life Science GmbH in Vienna and Centrogene AG in Rostock. Data collection and sample analyses were supported by the Genzyme and Shire companies. The Institutional Ethics Committee of the Slovak Nephrology Society approved the study. All data and information from the documentation were used in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. RESULTS: Summary, deficient activity of lysosomal a-galactosidase A was demonstrated in 64 respondents (1.1%): 21 (1.3%) of them were pre-dialyzed, 37 (1.2%) dialyzed and 22 (1.7%) transplanted patients. The polymorphism was shown in 17 pre-dialyzed, 8 dialyzed and 0 transplanted patients. The mutation in the GLA gene was shown in 16 cases (0.26%): 7 (4 male) of which were pre-dialyzed (4x: c.427G>A; 3x: c.352C>T); 9 (2 male) dialyzed (1x: c.765T>A; 1x: c.937G>T; 1x: c.427G>A; 3x: c.637G+6A>C; 3x: c.937G>T) and 0 after kidney transplantation. CONCLUSIONS: A national screening program among the Slovak kidney population including pre-dialyzed, dialyzed as well as transplanted patients confirmed 0.26% prevalence of a pathogenic mutation in the GLA gene. Surprisingly, these findings do not correspond with other national registry data. No confirmed positive patient has undergone enzyme replacement therapy yet. Active searching for Fabry disease with subsequent early treatment would slow down chronic kidney disease progression and decrease morbidity and even mortality. SP021 IDENTIFICATION AND PHENOTYPING OF A HEALTHY HUMAN DEFICIENT IN HAO1 SUPPORTS GLYCOLATE OXIDASE KNOCKDOWN AS A POTENTIAL APPROACH TO THERAPY FOR PRIMARY HYPEROXALURIA TYPE 1 Tracy L Mcgregor 1 , Karen A Hunt 2 , Paul Nioi 1 , John Wright 3 , David Erbe 1 , David Van Heel 2 1 Alnylam Pharmaceuticals, Cambridge, United States of America, 2 Queen Mary University of London, London, United Kingdom and 3 Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom INTRODUCTION: Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by persistent hepatic overproduction of oxalate, a renally excreted metabolite. Oxalate crystalizes with calcium and leads to serious disease manifestations including recurrent kidney stones, nephrocalcinosis, progressive renal failure, and multiorgan damage from systemic oxalosis once the disease advances. A therapeutic specifically designed to reduce the substrate needed for oxalate production could potentially halt or prevent disease progression. Glycolate oxidase (GO) is a liver- specific enzyme encoded by HAO1 that converts glycolate to glyoxylate, the major substrate required for oxalate production; thus, reducing GO could reduce the production of oxalate. The aim here is to further understand potential consequences of chronic GO reduction in humans. METHODS: A large population sequencing and health records program (Narasimhan, V. M. et al. Science. 2016) identified an adult woman with homozygous mutations in HAO1 predicted to be deleterious. Medical history, detailed phenotyping and biochemical investigation was completed for this individual. RESULTS: The identified individual was a healthy female in her 5th decade. Her homozygous HAO1 genotype was confirmed via Sanger sequencing of saliva DNA. As expected, her plasma glycolate levels were notably elevated at 171 nmol/mL, 12 times the upper limit of normal in reference individuals (<14 nmol/mL), while her urinary glycolate levels were 309 mg/g Cr, 6 times the upper limit of normal (<50 mg/g Cr). These results provide support for confirmation of the loss-of-function phenotype and are consistent with <2% remaining GO activity in this individual. Plasma and urine oxalate levels were normal. Primary care and hospital health records confirmed no remarkable clinical events. Liver function, transaminases, renal function, and renal ultrasound were normal and she had a history of three successful pregnancies. CONCLUSIONS: An individual with homozygous loss of function mutations in HAO1 is predicted to be very rare in the general population (1 in 30 million) but was identified through a focused effort to identify homozygous deleterious mutations. This case report of a healthy mother of three provides evidence that very low or absent levels of glycolate oxidase function is well tolerated with no apparent clinical consequences over the course of decades. These data support the approach of HAO1 silencing, which is the mechanism of lumasiran, an investigational RNA interference therapeutic in development for adults and children with PH1. SP022 IMPAIRED ENDOTHELIAL CELL MIGRATION: NEW INSIGHTS INTO THE MECHANISMS OF COMPLEMENT-MEDIATED ENDOTHELIAL CELL INJURY Valentina Bruno 1 , Magdalena Riedl 2 , Chia Wei Teoh 2 , Carmine Pecoraro 1 , Christoph Licht 2 1 Santobono-Pausilipon Children’s Hospital, Naples, Italy and 2 The Hospital for Sick Children, Toronto, Canada INTRODUCTION: Recent evidence suggests impairment of cell migration as a new mechanism of complement-mediated endothelial cell (EC) injury leading to thrombotic microangiopathy (TMA). We aimed to evaluate whether complement activation affects EC migration. METHODS: Healthy donor blood outgrowth endothelial cells (BOECs) were sensitized with anti-CD59 antibody and exposed to 50% Normal Human Serum (50% NHS). As controls, BOECs were exposed to 50% NHS without sensitization with anti- CD59 or to 50% Heat Inactivated Serum (50% HIS, complement inactive). A cell viability/proliferation assay was performed to evaluate the percentage of necrosis/ apoptosis and proliferation. A scratch wound assay was used to study cell migration RESULTS: We found significant differences (p<0.001) in wound closure between BOECs exposed to complement or not. Compared to controls, wound closure was reduced in BOECs after 4, 6, 8 and 10 hours of complement activation (11.59% vs 22.95% after 4 hours; 19.99% vs 38.27% after 6 hours; 31.99% vs 53.03% after 8 hours; 43.20% vs 67.43% after 10 hours. Figure). Cell death was excluded as cause for the defective wound closure (no significant difference in the rate of proliferation/viability compared to controls). We also found that impairment of BOEC migration was reversible after a short complement exposure (2-4 hours). doi:10.1093/ndt/gfz103 | i369 Nephrology Dialysis Transplantation Abstracts Downloaded from https://academic.oup.com/ndt/article/34/Supplement_1/gfz103.SP022/5516261 by guest on 03 December 2021