bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO003ADHERENCE TO DIETARY GUIDELINES IN ADULTS UNDERGOING MAINTAINANCE HAEMODIALYSIS: THE DIET-HD STUDY
Authors: Saglimbene Valeria , Su Guobin , Ruospo Marinella , Carrero Juan Jesus , Strippoli Giovanni 
Published: June 2020

Abstract

Background and Aims
While clinical guidelines emphasize dietary modifications as a cornerstone component in the management of patients undergoing dialysis, the adherence to these recommendations has been poorly quantified. The aim of this study is to evaluate the extent of adherence to diet guidelines for adults treated with long-term haemodialysis within the European patients included in the multinational cohort of the “DIETary intake, death and hospitalization in adult with ESKD treated with Haemodialysis” (DIET-HD) study.

Method
Cross-sectional analysis of the DIET-HD study in 6906 adults undergoing haemodialysis in 10 European countries. Patients responded to the Global Allergy and Asthma European Network (GA2LEN) Food Frequency Questionnaire, and dietary intakes were estimated to evaluate the adherence to the European Best Practice Guidelines nutritional recommendations.

Results
Patients showed low adherence to the daily recommended intake of phosphorous (&lt;1000mg, met by 25% of participants) and potassium (&lt;2730mg, met by 28% of participants). Almost half the participants achieved targets for energy (&gt;30 kcal/kg, 45% of participants) and calcium (&lt;800mg/day, 53% of participants) intake, while the recommended sodium (&lt;2300mg/day) and proteins intake (≥1.1g/kg) was achieved in 85% and 67% of participants, respectively. Adherence to renal guidelines varied across participating countries, but followed the same pattern. Only 1% of patients adhered to all six recommendations at the same time.

Conclusion
Adherence to dietary guideline recommendations is poor, particularly regarding phosphorus, potassium, calcium and energy intake.
MO056MODIFICATION OF P16, P21 AND NRF2 EXPRESSION IN A MODEL OF UREMIC VASCULAR CALCIFICATION
Authors: LAGET JONAS , HOBSON SAM , JOVER BERNARD , MUYOR KAREN , Duranton Flore , Kublickiene Karolina , LAJOIX ANNE DOMINIQUE , Stenvinkel Peter , Argiles Ciscart Angel , Gayrard Nathalie 
Published: June 2020

Abstract

Background and Aims
Vascular calcification (VC) is a consequence of ageing that confers development of future cardiovascular events. Accumulation of senescent cells can lead to structural and functional abnormalities in vessel wall towards increased stiffness, reduced compliance and impaired contractile and dilatory capacity. Thus, accumulation of senescent cells in the arterial wall could also contribute to the pathophysiology of VC. To test this hypothesis, the presence of cellular markers of senescence, p16, p21 and NRF2, was assessed in aorta from rat model of VC associated with chronic kidney disease (CKD).

Method
Six-week-old Sprague-Dawley rats underwent 5/6th subtotal nephrectomy (SNx, n=6) or no surgery (Control, n=1). After 8 weeks of renal failure, the regular chow was supplemented with high phosphate (1.2%) and vitamin D (1 µg/day, 5 days per week) for 1 or 4 weeks to initiate vascular calcification (SNx-VC group). At the end of the protocol (Figure 1), blood pressure was measured, and thoracic aorta was taken for determination of calcification by Von Kossa staining, and protein and gene expressions of p16, p21, and NRF2 by immunostaining and qPCR, respectively.

Results
After 4 weeks of dietary intervention, SNx rats showed an increase in pulse pressure (88±15mmHg vs 35 mmHg for the control). Marked VC was also observed in these animals, 17% of calcified area vs &lt;1 % in the control rat. Calcification was focal giving strong and no calcified areas on the same aorta. Expressions of p16, p21and NRF2 proteins were enhanced at the site of calcification in the SNx-VC 4-week (4W) group whereas it was unchanged in aortic media without calcification compared to the control rat (Figure 2). In SNx-VC 1-week (1W) rats, no change in pulse pressure or vascular calcification was observed without obvious changes for staining patterns of selected markers. Using qPCR we found p16 gene expression to be higher in the most calcified aortas (4W) (fold-change = 4.32 vs 1W) and p21 gene expression to be slightly increased (fold-change = 0.53 vs 1W). NRF2 gene expression was enhanced in 1W group compared to control, but decreased in the most calcified samples (4W).

Conclusion
This pilot study suggests that uraemia-induced cellular senescence accompanies VCs, as suggested by the modified expression of p16 or NRF2 genes. Our observations deserve exploration in larger studies using additional senescence markers for validation. If so, cellular senescence kinetics will be evaluated in order to test whether senolytics compounds could be a therapeutic option to arrest VC in CKD.
MO057HYPOXIA AS INDUCER OF FIBROBLAST GROWTH FACTOR 23 IN OSTEOCYTES
Authors: Bonnemaijer Josephine , Koolwijk Pieter , Bravenboer Nathalie , Van Essen Huib , Vervloet Marc 
Published: June 2020

Abstract

Background and Aims
Cardiovascular disease accounts for a major proportion of deaths among chronic kidney disease (CKD) patients. Fibroblast Growth Factor 23 (FGF23), a key regulator in phosphate homeostasis and mainly produced by osteocytes, is associated with CKD progression and cardiovascular mortality. FGF23 is involved in the development of left ventricular hypertrophy that can lead to congestive heart failure. Dysfunction of the heart causes tissue malperfusion, for instance in bones, inducing the hypoxia-inducible signaling pathway. Recently, the hypoxia-inducible factor-1α (HIF-1α) has been suggested as inducer of FGF23. Therefore, we investigated whether hypoxia in osteocytes induces FGF23 production mediated by the stabilization of HIFs.

Method
Human sarcoma osteogenic cells (SaOS2 cell line) and primary human osteocytes were cultured and exposed to hypoxic conditions (1% and 5% O2) and normoxic condition (20% O2) for 24 hours. qPCR was performed to investigate the expression of HIFs and FGF23 mRNA in these cells. HIFs protein expression was also evaluated by Western Blot analysis.

Results
Our data show that HIF-1α, and not HIF-2α, protein increases in SaOS2 cells and primary osteocytes under hypoxic conditions as compared to normoxic condition. In addition, we found that FGF23 mRNA expression is elevated in SaOS2 cells in these hypoxic conditions compared to normoxic condition (Fig.1). This increase was significant in SaOS2 cells exposed to 1% O2 (p &lt;0.05). Preliminary data of primary osteocytes show that FGF23 mRNA is not expressed in hypoxic conditions compared with normoxic conditions (Fig.1).

Conclusion
HIF-1α protein was increased in both SaOS2 cells and primary osteocytes exposed to 1% O2. Hypoxic conditions upregulated FGF23 mRNA in SaOS2 cells. Taken together, these findings suggest that bone malperfusion upregulates FGF23 by stabilizing HIF-1α. This could then close a vicious circle where FGF23 induces cardiovascular disease, and circulatory failure upregulates FGF23.
MO069HIF-1Α C-TERMINAL TRANSCRIPTIONAL ACTIVATION DOMAIN MEDIATED KLF5 SIGNALING DRIVES AKI TO CKD PROGRESSION
Authors: Li Zuolin , Ji Jia-ling , Lv Linli , Yang Yan , Tang Tao-tao , Wang Bin , Liu Bicheng 
Published: June 2020

Abstract

Background and Aims
Acute kidney injury (AKI) is increasingly recognized as a major risk factor for progression to CKD. However, the mechanisms governing AKI to CKD progression are poorly understood. Hypoxia is a key player in the pathophysiology of the AKI to CKD transition. Thus, we aimed to investigate the exact mechanisms of AKI to CKD progression mediated by hypoxia.

Method
Mild ischemic injury and severe ischemic injury (AKI-to-CKD transition) were established by clamping renal pedicle for 30 and 40 minutes, respectively. Meanwhile, the mice model of AKI-to-CKD transition was treated with HIF-1α inhibitor, PX-478. In vitro, PHD inhibition and combined PHD with FIH inhibition mimic the HIF-1α activation caused by mild or severe hypoxia, respectively. Besides the human proximal tubular epithelial cell line HK-2, tubular cells were isolated from mice for primary culture. KLF5 knockdown, FIH and HIF-1α C-terminal transcriptional activation domain (C-TAD) overexpression in tubular cells were achieved by Lentiviral transfection. Immunocoprecipitation was used to explore the relationship between the HIF-1α and FIH-1. Luciferase reporter assay was used to investigate whether KLF5 was regulated transcriptionally by HIF-1α C-TAD. To explore the roles of FIH-1 and HIF-1α C-TAD in vivo, FIH-1 and HIF-1α C-TAD overexpression (Lentivirus-mediated) was given after severe ischemic injury or mild ischemic injury via tail vein injection, respectively.

Results
AKI to CKD progression was highly associated with the time-course expression of tubular HIF-1α in severe ischemia/reperfusion injury. Interestingly, ameliorated AKI-to-CKD transition was observed by treating PX-478, which destabilized HIF-1α. In vitro, fibrogenesis could be induced by combined PHD with FIH inhibitor treatment in TEC. More interestingly, alleviated fibrogenesis could be achieved by knockdown of KLF5 and overexpression of FIH, respectively, while HIF-1α C-TAD overexpression promoted fibrogenesis in tubular cells. Immunocoprecipitation results indicated that HIF-1α and FIH-1 are interactive. Furthermore, we demonstrated that KLF5 could be regulated transcriptionally by HIF-1α C-TAD by luciferase reporter assay. In vivo, AKI to CKD progression was ameliorated significantly when mice model of AKI-to-CKD transition intervened with FIH-1 overexpression (Lentivirus-mediated). However, treatment of HIF-1α C-TAD (Lentivirus-mediated) in mild ischemic injury model could promote progression of CKD significantly.

Conclusion
FIH-1 mediated HIF-1α C-TAD activation was the key mechanism of AKI to CKD transition by transcriptionally regulating the KLF5 pathway in tubules. Blockade of FIH-1 mediated HIF-1α C-TAD in tubules may serve as a novel therapeutic approach to ameliorate AKI to CKD progression.
MO072LONGITUDINAL SERUM BICARBONATE MEASUREMENTS AND RISK OF CHRONIC KIDNEY DISEASE PROGRESSION AND MORTALITY: INSIGHTS FROM THE CKD-REIN COHORT
Authors: Prezelin-Reydit Mathilde , Combe Christian , Harambat Jerome , Massy Ziad , Metzger Marie , Lange Céline , Lambert Oriane , Stengel Benedicte , Leffondré Karen 
Published: June 2020

Abstract

Background and Aims
Metabolic acidosis is a common complication of CKD and may contribute to CKD progression. However, the association between serum bicarbonate and CKD progression has not yet been investigated using longitudinal measurements.

Method
We used data from CKD-REIN, a prospective cohort study conducted in 40 representative French nephrology clinics which included 3033 patients with CKD stages 3 to 5 between 2013 and 2016. Patients who had no serum bicarbonate or no creatinine measure at within 6 months of their inclusion date in the CKD-REIN study were excluded. All serum bicarbonate measurements were taken into account, from inclusion to the occurrence of renal replacement therapy (RRT), death, or end of follow-up, whichever came first. We used a shared random-effect model for the joint analysis of individual trajectories of serum bicarbonate and the hazard of the composite outcome (RRT or death before RRT) and each specific event separately. Hazard ratio were adjusted (aHR) for age, sex, primary kidney disease, metabolic syndrome, cardiovascular disease, proteinuria (&lt; 30, 30-300, &gt; 300 mg/day), and the CKD-EPI estimated glomerular filtration rate (eGFR) at baseline.

Results
A total of 2977 patients (65.4% men, median age 69 years) were included. At baseline, the median eGFR was 31.8 mL/min/1.73m2 and the median bicarbonate concentration was 25 mmol/L. During a median follow-up of 4.5 years, 615 patients received RRT and 378 died before RRT. At any time of follow-up, a decrease of 1 mmol/l of the current level of serum bicarbonate was associated with a significantly increased hazard of RRT or death before RRT (aHR 1.05, 95%CI 1.02-1.08). The estimated effect was stronger on death before RRT (aHR 1.05, 95% CI 1.00-1.09) than on RRT (aHR 1.02, 95% CI 0.99-1.06).

Conclusion
A lower current level of serum bicarbonate is associated with an increased mortality in patients with CKD stage 3 to 5.
MO077TEN YEAR TRENDS IN PAEDIATRIC RENAL REPLACEMENT THERAPY IN EUROPE: DATA FROM THE ESPN/ERA-EDTA REGISTRY
Authors: Bonthuis Marjolein , Harambat Jerome , Vidal Enrico , Jager Kitty J 
Published: June 2020

Abstract

Background and Aims
The ESPN/ERA-EDTA Registry includes data on children with end-stage kidney disease receiving renal replacement therapy (RRT) in Europe for 10 consecutive years. We examined time trends in incidence, prevalence and patient survival for paediatric RRT in Europe.

Method
We included all children aged &lt; 15 years starting RRT in 22 European countries from 2007 to 2016. General population statistics were derived from Eurostat. Incidence and prevalence were expressed per million age related population (pmarp) and time trends were studied with Joinpoint regression. We analyzed patient survival using Cox regression.

Results
The incidence of children commencing RRT &lt; 15 years remained stable over the past ten years, varying between 5.5 pmarp to 6.5 pmarp. The incidence by treatment modality did not change over time: 2.0 to 3.0 pmarp for haemodialysis (HD) and peritoneal dialysis (PD) and 1.0 pmarp for transplantation. Overall prevalence rose by 2% annually (95% CI: 1.5-2.3%) from 29.5 pmarp in 2007 to 35.6 pmarp in 2016.
The increase in prevalence was observed in all age categories, but was strongest among children older than 5 years at RRT initiation. The prevalence of patients on all treatment modalities increased during the study period: from 4.5 to 5.4 pmarp for HD, from 4.9 pmarp to 6.0 pmarp for PD and from 19.6 to 23.9 pmarp for transplantation (Figure).
Four-year adjusted patient survival on RRT was around 96% and similar for those initiating from 2007-2009 and from 2010-2012 (adjusted HR: 0.97, 95% CI: 0.69-1.36).

Conclusion
Over the past decade we found a stable incidence and an increasing prevalence of European children on RRT. Four-year patient survival was good, and did not change over time. These data are important to inform patients and healthcare providers and to aid health policy makers on future resource planning of pediatric RRT in Europe.
TO014COMPARISON BETWEEN HIGH FLUX-HD AND OL-HDF ON SURVIVAL AND ADEQUACY: TEN YEARS EXPERIENCE
Authors: Terlizzi Vincenzo , Lucca Bernardo , Manenti Chiara , Gaggia Paola , Zubani Roberto , Sandrini Massimo , Movilli Ezio , Scolari Francesco 
Published: June 2020

Abstract

Background and Aims
Four RCTs have been published that compared on-line HDF (Ol-HDF) with HD. However, to date, an indisputable answer in determining whether patients treated with Ol-HDF had a better survival than those treated with high-flux HD (Hf-HD) has not been reached. The aim of our study was to retrospectively evaluate the impact of the dialysis modality (Hf-HD, Ol-HDF or acetate-free biofiltration AFB) on patient survival and dialysis adequacy.

Methods
We retrospectively evaluated all the incident patients that started dialysis due to uremia from 01-01-2008 to 31-12-2018 at the U.O. Nephrology ASST Spedali Civili of Brescia. Exclusion criteria were: duration of dialysis treatment less than 3 months, and previous dialytic treatment or kidney transplantation. The dialysis modality performed (Hf-HD vs Ol-HDF), the modality of infusion (pre-dilution or post-dilution) and mean total convective volume (replacement fluid volume + ultrafiltration) during last year’s dialysis session in Ol-HDF were analyzed for each patient.

Results
During observation 677 patients started HD treatment. 70 patients were excluded due to less than 3 months HD treatment. 607 patients (male 390, 64%) were analyzed. 467 pts (77%) were treated with Hf-HD, 103 pts (17%) with Ol-HDF, 36 pts (6%) with AFB. Median duration of HD treatment was 2.6 years (IQR 1.3; 4.7). Ol-HDF was performed in post-dilution mode in 60% of cases (total convective volume 25±4 L); pre-dilution mode was used in 40% of the cases (total convective volume 51±18 L). Patients in the Ol-HDF group were significantly younger than those in Hf-HD and AFB groups (respectively 59±15 years vs 71±15 vs 78±9, p &lt;0.05), and had less diabetes, hypertension and ischemic heart disease (p&lt;0.05) while presenting similar prevalence of cirrhosis (p=0.93) and peripheral vascular disease (p=0.09). Adequacy indices were similar between groups (eKt/V 1.39±0.02 vs 1.41±0.01 vs 1.44±0.04, p=0.47) as well as the protein intake (PCRn 0.92±0.01 vs 0.93±0.01 vs 0.90±0.03 g/Kg/d, p=0.69) and residual renal function (1.5±0.3 vs 1.6±0.1 vs 0.8±0.4 ml/min, p=0.20). Patients on Ol-HDF more frequently had an AV fistula (71% vs 58% vs 59%, p&lt;0.05). At the end of follow-up, 12% of patients had undergone kidney transplantation, 42% continued dialytic treatment while 43% died. Univariate analysis showed a better survival for Ol-HDF patients (Figure 1) (p &lt;0.05). This benefit was confirmed in multivariate analysis (Figure 2) showing that older age, cirrhosis and ischemic heart disease negatively affect survival, while a high protein intake, use of an AV fistula and Ol-HDF (HR 0.43[0.30-0.61]) are protective.

Conclusions
The use of Ol-HDF is associated with better survival compared to Hf-HD. This is confirmed after adjustment for demographic and comorbidities of the patients, characterizing Ol-HDF as an independent predictor of better survival.
P0007EFFECT OF SODIUM BICARBONATE LOAD ON URIC ACID LEVELS IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND METABOLIC ACIDOSIS: PRELIMINARY RESULTS OF THE SOBIC-STUDY
Authors: Repitz Alexandra , Aigner Christof , Sunder-Plassmann Gere , Gaggl Martina 
Published: June 2020

Abstract

Introduction and Aims
Sodium bicarbonate is a commonly used drug that balances metabolic acidosis in patients with chronic kidney disease (CKD) and is said to delay disease progression. Elevated serum uric acid levels are frequently seen in CKD and the prevalence of gout disease in CKD patients is higher than in the normal population. Animal studies suggest that excessive sodium bicarbonate intake may increase uric acid levels, and in Korean Native Broilers led to visceral and articular gout. In turn, individuals with Gitelman/Bartter tubulopathy present alkemic and also show increased gout prevalence. The aim of the study was to evaluate the effect of oral sodium bicarbonate supplementation on uric acid levels after 20 weeks of treatment in patients with CKD and metabolic acidosis.

Methods
Patients with CKD stage 3 and 4 and HCO3- &lt; 21mmol/l enrolled in the ongoing randomized controlled SoBic-study (since 2013) were randomized into the intervention group (target HCO3- 24±1mmol/l) or the rescue group (target HCO3- 20±1mmol/l). Baseline serum uric acid levels were determined prior to sodium bicarbonate supplementation and after 20 weeks. We used Spearman’s correlation and regression analysis to detect a possible association between the amount of sodium bicarbonate intake (milligrams per day) and the alteration of uric acid in patients using a significance level of p=0.05.

Results
Forty-five patients were included in the study until January 2019 (23 intervention group, 22 rescue group) and demographic data is given in table 1. Of the total patient population 24.4% were already affected by hyperuricemia (serum uric acid ≥6.5mg/dl) before participating in the study (47.8% of the intervention group, 13.6% of the rescue-group). During the study period, none of the patients showed symptoms of gout. The mean uric acid level at baseline was 7.3(±1.3) and 7.4(±1.6) after 20 weeks. The median uric acid increased by 0.1 in the intervention group (p=0.651) and decreased by 0.1 in the rescue group (p=0.889) from baseline until 20 weeks. Serum bicarbonate levels and uric acid were not correlated (rs=0.201, p=0.185). The regression analysis showed no association between the uric acid level and the total daily intake of sodium bicarbonate over 20 weeks.

Conclusions
In patients with CKD and metabolic acidosis the treatment with oral sodium bicarbonate for 20 weeks hat no adverse effect on the uric acid level.
P0016EFFECT OF GEMFIBROZIL ON KYNURENINE AMINOTRANSFERASE ACTIVITY AND KYNURENIC ACID PRODUCTION IN RAT KIDNEY
Authors: Zakrocka Izabela , Targowska-Duda Katarzyna , Wnorowski Artur , Kocki Tomasz , Jóźwiak Krzysztof , Turski Waldemar , Załuska Wojciech 
Published: June 2020

Abstract

Background and Aims
Hypertriglyceridemia is the most common lipid disorder in chronic kidney disease. Lifestyle changes and fibrates administration are main methods of lowering triglycerides’ level. PPARα (peroxisome proliferator-activated receptor-α) activation is the primary mechanism of action of fibrates.
A tryptophan metabolite, kynurenic acid (KYNA), is produced from L-kynurenine (L-KYN) by kynurenine aminotransferases (KATs). KAT I and KAT II isoenzymes are the best analyzed KATs. KYNA acts predominantly as a nonselective antagonist of ionotropic glutamatergic receptors, particularly N-methyl-D-aspartate (NMDA) type, which are highly expressed in the kidney. Natriuretic and hypotensive effects of KYNA are well described. Diet rich in fatty acids was reported to elevate central and peripheral KYNA level.
The goal of presented study was to analyze the influence of gemfibrozil, one of the fibrates given to treat hypertriglyceridemia, on KYNA production and the activity of KAT isoenzymes: KAT I and KAT II, in rat kidney in vitro. Additionally, the molecular docking of gemfibrozil to KAT I and KAT II structures was performed to study drug-enzyme interaction. On the final step the microarray datamining was carried out to investigate whether gemfibrozil affects the expression of KAT-coding genes.

Method
The effect of gemfibrozil on KYNA synthesis together with KAT I and KAT II activity was tested in rat kidney homogenates in vitro after 2 hours incubation in the presence of L-KYN and gemfibrozil. The drug was examined at the concentration of 1 µM, 10 µM, 50 µM, 100 µM, 500 µM and 1 mM. Production of KYNA was analyzed using the high performance liquid chromatography (HPLC) with fluorometric detector.

Results
Gemfibrozil at 100 µM, 500 µM and 1 mM decreased KYNA production in kidney homogenates in vitro to 66% (P &lt; 0.05), 58% (P &lt; 0.01) and 41% (P &lt; 0.01) of control value, respectively. At 100 µM, 500 µM and 1 mM concentration gemfibrozil lowered renal KAT I activity in vitro to 68% (P &lt; 0.05), 56% (P &lt; 0.01) and 52% (P &lt; 0.01) of control value, respectively. Moreover, gemfibrozil at 500 µM and 1 mM concentration decreased kidney KAT II activity in vitro to 47% (P &lt; 0.001) and 26% (P &lt; 0.001) of control value, respectively. Results of the molecular docking suggested that gemfibrozil may affect the active site of both KAT I and KAT II. Publicly available microarray datasets suggested that the expression of KAT-coding genes does not change after gemfibrozil administration.

Conclusion
Gemfibrozil decreases KYNA production in rat kidney in vitro through inhibition of KAT I and KAT II isoenzymes. Presented results indicate a novel mechanism of gemfibrozil’s action in the kidney. Its potential role in nephrotoxicity needs verification in upcoming studies.