bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0875INFLUENCE OF CHRONIC KIDNEY DISEASE AND LEFT VENTRICULAR HYPERTROPHY ON CHANGE IN FGF23 AND RENIN-ANGIOTENSIN-ALDOSTERONE-SYSTEM
Authors: Okamoto Kohei , Fujii Hideki , Goto Shunsuke , Kono Keiji , Watanabe Kentaro , NOSE YUMA , Nishi Shinichi 
Published: June 2020

Abstract

Background and Aims
Left ventricular hypertrophy (LVH) is a clinically important risk factor for mortality and often observed in patients with chronic kidney disease (CKD). Serum FGF23 levels are elevated in CKD patients, and the relationship between elevated FGF23 and LVH has been reported in the previous studies. However, whether elevated FGF23 is a cause or result of LVH and whether FGF23 directly or indirectly affects LVH remain unclear. Therefore, we investigated changes in heart weight, CKD-mineral and bone disorder (MBD) parameters, including FGF23, and renin-angiotensin-aldosterone system (RAAS) related-factors in the setting of LVH and CKD using a mouse model.

Method
In the present study, twenty-four C57BL/6J mice were used and divided into 4 groups; control group (N=6), CKD group (N=6), LVH group (N=6), and LVH+CKD group (N=6). The mice in the CKD group underwent left 2/3 nephrectomy at 11 weeks of age and right nephrectomy at 12 weeks of age. Those in the LVH group underwent transverse aortic constriction (TAC) at 10 weeks of age. Those in the LVH+CKD group, TAC at 10 weeks of age, and left 2/3 nephrectomy at 11 weeks of age, and right nephrectomy at 12 weeks of age were performed. At 16 weeks of age, echocardiography was performed for all the mice, and they were sacrificed for blood and urine analysis, histopathological analysis and evaluating mRNA expressions of CKD-MBD- and RAAS-related factors in the heart.

Results
The systolic blood pressure was significantly higher in the LVH+CKD group and the CKD group than in the control group. The heart weight/body weight ratio in the LVH+CKD group was the highest, and that in the LVH was higher than that in the CKD group. Although serum creatinine and phosphate levels increased in CKD condition, those were comparable between the CKD and LVH+CKD groups. The urinary albumin excretion also increased in the CKD and LVH+CKD groups compared to the LVH and control groups. Serum FGF23 levels increased in the LVH and CKD group compared to the control group, and those in the LVH+CKD group were the highest among all the study groups. The cardiac mRNA expressions of FGF23, angiotensinogen (ANG), angiotensin type 1 receptor (AT1R), and angiotensin-converting enzyme (ACE) were also increased by induction of LVH and CKD, and those in the LVH+CKD group significantly increased compared to other groups. Heart weight/body weight ratio was significantly correlated with serum FGF23 levels and mRNA expression of FGF23, ANG, AT1R, ACE. In addition, significant correlations of serum FGF23 levels and cardiac mRNA expression of FGF23 with cardiac mRNA expressions of RAAS-related factors were observed.

Conclusion
Our results suggest that serum FGF23 levels and cardiac mRNA expression of FGF23 increase with the development of LVH and CKD and the changes is possibly enhanced through the colocalized activation of RAAS.
P1311IMPORTANCE OF FISTULA POSITION FOR DETECTING STENOSIS WITH VASCULAR ACCESS BLOOD FLOW MEASUREMENT
Authors: Rikker Csaba , Juhász Edina , Gáspár Renáta , Haraszti Maria , Rikker Bálint , Vizi Ildikó 
Published: June 2020

Abstract

Background and Aims
Surveillance of vascular access function in patients on chronic hemodialysis (HD) by measuring the access blood flow rate (Qa) is a widely accepted method for early detection of dysfunction. Qa threshold can be lower in the more distal accesses than in the more proximal accesses. However, cut-off values of Qa in different access positions have not yet been established. The aim of our study is to determine the critical values of Qa indicative of stenosis in different access sites.

Method
Between July 2012 and July 2019, we performed 5798 Qa measurements of native arteriovenous fistulas (AVFs) (wrist [w]: 2932, forearm [fa]: 2035 and elbow/upper arm [e/ua]: 731) in 242 chronic HD patients using Fresenius 5008 and 5008 S blood temperature monitors (BTMs) at the beginning of HD sessions. As reference we performed 512 colour duplex ultrasonographies (CDUSs) and 205 angiographies (ANGs). CDUS was performed as surveillance method independently from the BTM, or at the presence of low Qa and/or clinical signs of access failure. ANG was performed only in CDUS positive cases or at clinical signs of access failure. We performed percutaneous transluminal angioplasty (PTA) in 174 cases and stent implantation in 2 cases. New AVFs were created in 25 cases. The results were evaluated retrospectively according to access positions using Receiver Operating Characteristic (ROC) curve analysis.

Results
The number of true positive (TP), true negative (TN), false positive (FP), false negative (FN) cases, sensitivity (SENS) and specificity (SPEC) in different AVF sites and Qas are summarised in table below.

Conclusion
In order to prevent the fistula occlusion, the cut-off Qas can be different in various access positions. Based on our results we suggest 600-650 mL/min for w AVFs, 650-700 mL/min for fa AVFs and 750-800 mL/min for e/ua AVFs as cut-off values.
P1316PREDICTORS OF ARTERIO-VENOUS FISTULA FAILURE: A POST-HOC ANALYSIS OF THE FAVOURED STUDY
Authors: See Yong Pey , Viecelli Andrea , Voss David , Mori Trevor , Kerr Peter , Paul-Brent Peta-Anne , Cho Yeoungjee , Johnson David W , Hawley Carmel , Pascoe Elaine M 
Published: June 2020

Abstract

Background and Aims
An autologous arteriovenous fistula (AVF) is the preferred haemodialysis vascular access but successful creation is hampered by high rates of AVF failure. This study aimed to evaluate patient and surgical factors associated with AVF failure to improve vascular access selection and outcomes.

Method
This is a post-hoc analysis of all participants of FAVOURED, a multi-centre, double-blind, multinational, randomized placebo-controlled trial evaluating the effect of fish oil and/or aspirin in preventing AVF failure in patients receiving haemodialysis. The primary outcome of AVF failure was a composite of fistula thrombosis and/or abandonment and/or cannulation failure at 12 months post AVF creation and secondary outcomes included individual outcome components. Patient data (demographics, comorbidities, medications and laboratory data) and surgical factors (surgical expertise, anaesthetic, intraoperative heparin use) were examined using multivariable logistic regression analyses to evaluate associations with AVF failure.

Results
Of 536 participants, 253 patients (47%) experienced AVF failure during the study period. The mean age was 55 ± 14.4 years, 64% were male, 45% were diabetic and 4% had peripheral vascular disease. Factors associated with AVF failure included female sex (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.20-2.67), lower diastolic blood pressure (DBP; OR for higher DBP 0.98, 95% CI 0.97-0.99), presence of central venous catheter (OR 1.50, 95% CI 1.02-2.20, p=0.04) and aspirin requirement (OR 1.61, 95% CI 1.01-2.57).

Conclusion
Female sex, requirement for aspirin therapy, requiring haemodialysis via a central venous catheter and lower diastolic blood pressure were factors associated with higher odds of AVF failure. These associations have potential implications for vascular access planning and warrant further studies.
P1619OUTCOME OF HIGH DONOR-RECIPIENT AGE GAP IN LIVE-DONOR RENAL TRANSPLANTS IN TACROLIMUS ERA
Authors: Ali Hatem Kaies Ibrahim Elsayed , Daoud Ahmed , Soliman Karim , Mohamed Mahmoud , Murtaza Asam 
Published: June 2020

Abstract

Background and Aims
High donor-recipient age gap among deceased-donor renal transplant patients leads to worse outcomes. However, the impact of this gap among live-donor renal transplants is unclear. The aim of this study is to assess the effect of this age gap on graft survival and acute rejection rates among renal transplants in tacrolimus era.

Method
14390 live-donor renal transplant patients who received a single organ transplant, had no previous renal transplants, discharged on tacrolimus-based immunotherapy and were registered in the Organ Procurement Transplantation Network from January 2000 till June 2017 were included in the study. Donor–recipient age difference was divided into 5 groups; group A (difference &lt;−10,n=4375), group B (difference from -10 to 10,n=7229), group C (difference between 10-20, n=861), group D ( difference between 20–29, n=1406) and group E (difference ≥30 years, n=519). Poisson regression analysis was used to assess effect of age gap on acute rejection rates. Kaplan-Meier survival curves and Cox hazard regression analysis were used to assess this effect on graft survival.

Results
Regarding graft survival, groups with age difference ≥30 years and between 20-29 years showed a significantly higher risk of graft loss when compared to group with age difference &lt;−10 (HR equals 4.6 and 3.8 respectively). Groups with age difference between 10 to 20 years and between -10 to 10 years showed no significant difference in graft survival when compared to same group (HR equals 1.03 and 0.95 respectively). Groups B,C,D,E were not associated with increased risk of acute rejection episodes when compared to group A (IRR=1.001, 1.001, 1.022, 1.027 respectively).

Conclusion
Donor-recipient age difference up to 20 years has similar renal transplant outcomes to those receiving kidneys from younger donors and therefore, should not be precluded from paired kidney donation programs. The donor-recipient age difference above 20 years is associated with worse outcomes in terms of graft survival.
P0045GENETIC ABLATION OF NFAT5 IN THE PRINCIPAL CELLS OF THE COLLECTING DUCT LEADS TO A WATER HANDLING DEFECT
Authors: Petrillo Federica , Fischer Annika , Chernyakov Dmitry , Esteva Font Cristina , Poulsen Søren B , Krogager Toke P , Edemir Bayram , Fenton Robert A 
Published: June 2020

Abstract

Background and Aims
Nuclear Factor of Activated T-Cells 5 (NFAT5), also called TonEBP/OREBP, helps protecting kidney cells from the stress of extracellular hypertonic challenge. In response to hypertonicity, NFAT5 rapidly translocates into the nucleus and enhances the transcription of osmoprotective genes. Mice lacking NFAT5 have embryonic lethality, with those surviving having severe renal atrophy and hydronephrosis. Overexpression of a dominant-negative NFAT5 in all epithelial cells of the thick ascending limb, distal tubule and collecting duct (CD) leads to an impairment in the urine concentration, with reduced expression of AQP2 and urea transporters UT-A1 and UT-A2. Here, we generated a novel mouse model to assess the role of NFAT5 in the water transporting principal cells of the CD.

Method
The mouse model was generated by breeding floxed NFAT5 mice with mice specifically expressing Cre recombinase in AQP2 expressing cells (NFAT5f/f-AQP2cre+/-). AQP2cre+/- mice served as controls. For renal function analysis, mice were kept in metabolic cages for 5 days and water intake, urinary volume, osmolality, and serum and urine electrolytes were evaluated. Mice were euthanized and the kidneys were used for western blot analysis.

Results
NFAT5f/f-AQP2cre+/- mice show a significant increase of 24 hour urine output compared to the control (KO: 6.267 ± 0.9367 µl/h/g BW vs WT: 0.9593 ± 0.0796 µl/h/g BW), a decrease in the urine osmolality (KO: 505.6 ± 107.6 mOsm/Kg H2O vs WT: 6205 ± 752.7 mOsm/Kg H2O) and urea concentration. After 3h and half intraperitoneal injection of dDAVP (1ug/kg) the osmolality was still significantly low in NFAT5f/f-AQP2cre+/- mice (KO: 743.7 ± 81.77 vs WT: 3342 ± 80.14 mOsm/Kg H2O), as well as after 8h water restriction (KO: 732.8 ± 24.90 vs WT: 3784 ± 450.9 mOsm/Kg H2O). Immunoblotting demonstrated a significant decrease in AQP2, AQP3 and AQP4 abundance in cortical kidney fractions and inner medulla. There were no differences in vasopressin V2 receptor (V2R) and AVP-regulated transporters NKCC2, ROMK and alpha-ENaC.

Conclusion
We demonstrate that NFAT5 ablation from AQP2-expressing cells results in a urinary concentration defect. NFAT5f/f-AQP2cre+/- mice have a hypoosmotic polyuria, without major effects on the AVP-V2R axis, suggesting Nephrogenic Diabetes Insipidus.
P0149PREVALENCE OF MASKED HYPERTENSION IN HEMODIALYSIS PATIENTS
Authors: Borodulina Ekaterina , Shutov Alexander M 
Published: June 2020

Abstract

Background and Aims
Arterial hypertension is main cause of left ventricular hypertrophy (LVH) in hemodialysis patients. Masked hypertension is associated with asymptomatic organ damage, including the development of LVH. The aim of this study was to investigate the prevalence of white-coat hypertension and masked hypertension in hemodialysis patients.

Method
Hemodialysis patients (n=88; 42 males, 46 females, mean age was 51.7±13.3 years) were studied. Office blood pressure measurements were performed before and after hemodialysis within 30 days. Home Blood Pressure Measurements (HBPM) was collected in the morning and in the evening during 4 weeks including hemodialysis session days. 24 hours blood pressure monitoring (ABPM) was performed in the next day after hemodialysis. Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) were analyzed. White-coat hypertension was diagnosed when blood pressure elevated in the office, but was normal when was measured by ABPM, HBPM, or both. Masked hypertension was determined when blood pressure was normal in the office, but increased when was measured by HBPM or ABPM. The definitions of the European Society of Cardiology (2018 ESC/ESH Guidelines for the management of arterial hypertension) were used for the diagnosis of hypertension according to office, ambulatory, and home blood pressure levels. Echocardiographic evaluation was performed on the day after dialysis and left ventricular mass index (LVMI) was calculated.

Results
Arterial hypertension was diagnosed by office blood pressure measurements in 39 (44.3%) patients. Arterial hypertension was defined by ABPM (mean 24h BP &gt; or = 130 and 80 mmHg) in 48 (54.5%) patients. The number of non-dipper patients was 59 (67.0%). According to HBPM arterial hypertension was observed in 61 (69.3%) patients. Left ventricular hypertrophy was detected in 71 (80.7%) patients. Mean LVMI was 140.5±43.0 g/m2. According to the results of three methods of blood pressure measuring arterial hypertension was diagnosed in 53 (60.2%) patients, white-coat hypertension was observed in 5 (5.7%) patients, masked hypertension – in 19 (21.6%) patients.

Conclusion
According to office blood pressure measurements arterial hypertension was diagnosed in 44.3% hemodialysis patients. Masked hypertension was often observed in hemodialysis patients and when using not only ABPM, but also HBPM was detected in 21.6% of patients. The results indicate the importance of using not only ABPM, but also HBPM in hemodialysis patients.
P0337PROTEOME CHANGES IN TUBULOINTERSTITIAL TISSUE OF PROGRESSIVE VS NON-PROGRESSIVE IGAN
Authors: Paunas Flavia Teodora , Finne Kenneth , Leh Sabine , Marti Hans-Peter , Vikse Bjørn Egil 
Published: June 2020

Abstract

Background and Aims
IgA nephropathy (IgAN), a common glomerulonephritis worldwide, is associated with a significant risk of progression to end-stage renal failure. In the Oxford classification, tubular atrophy is an established important risk factor for the risk of progression but few studies have investigated possible tubulointerstitial markers and the mechanisms of progression in IgAN. The present study investigated changes in the tubulointerstitial proteome from patients with IgAN.

Method
Based on data from the Norwegian Kidney Biopsy Registry and the Norwegian Renal Registry, two groups were included: IgAN patients with (n=9) or without (n=16) progression to ESRD during 10 years. Tubulointerstitial tissue without discernible interstitial expansion or pronounced tubular alterations were microdissected, proteome was analysed using mass spectrometry and protein abundances were compared between groups.
Results: Proteomic analyses quantified 2562 proteins with 2 or more unique peptides . Of these, 201 proteins had significant different abundance between progressive and non-progressive IgAN patients, 96 were more abundant and 105 less abundant. Periostin was the protein with the highest fold change between progressive and non progressive IgAN (fc 9.59, p&lt;0.05). Proteins related to inflammation were more abundant and proteins involved in the aerobic energy metabolism and energy demanding ion channels were significantly less abundant in progressive vs non-progressive patients.

Conclusion
Our study describes extensive proteome changes of tubulo-interstitial tissue in patients with progressive IgAN and indicates several proteins and pathways that are important in the progression of the disease.
P0968THE INFLUENCE OF ALPHA KLOTHO ON NPP1 ACTIVITY IN CULTURED RAT PODOCYTES
Authors: Piwkowska Agnieszka , Audzeyenka Irena , Rogacka Dorota 
Published: June 2020

Abstract

Background and Aims
Kidney is the principal contributor to circulating αKlotho (αKL), and simultaneously, constitutes the major organ where circulating αKlotho is taken up from the circulation. Klotho is mainly expressed in proximal renal tubule and in distal tubular epithelium. In the kidney soluble αKlotho acts from the urinary luminal side as an autocrine or paracrine enzyme to regulate transporters and ion channels. Recently, it has been demonstrated that the glomerulus is another source of αKlotho production.
NPP1 is the best characterized nucleotide pyrophosphatases/phosphodiesterases (NPP) family member, encoded by the ENPP1 gene, and is a type II transmembrane glycoprotein that forms disulfide-bonded homodimers in the plasma membrane and in the mineral-depositing matrix vesicles. The major function of NPP1 is generation of PPi from adenosine triphosphate (ATP). Recently, we demonstrated that extracellular nucleotides stimulate an increase in glomerular albumin permeability, in part due to glomerular NO production and actin reorganization in podocytes . Furthermore, both αKlotho and NPP1 regulate insulin-dependent signaling. Thus, a key aim of this study is to fully examine the role of αKlotho on NPP1 function and its role in the protection of glomerular filtration barrier and podocyte function in diabetes.

Method
We measured glomerular permeability to albumin (Palb) in a single isolated rat glomerulus based on the video-microscopy method and permeability to albumin across the podocyte monolayer. Expression of αKlotho and NPP1 was confirmed in podocytes using Western blotting and immunofluorescence. Ecto-nucleotide pyrophosphatase/phosphodiesterase activity in podocytes was assessed using p-nitrophenyl-5′-thymidine monophosphate (p-Nph-5′-TMP) as a substrate. The ATP concentration was measured using luciferin-luciferase reaction.

Results
Since NPP1 and Klotho regulate insulin-dependent signaling we investigated the role of Klotho on NPP1 dimerization and NPPs activity. Podocyte treatment withαKlotho (0.5 nM, 30 min) in non-reducing conditions (maleimide, 100 mM) increased the disulfide bond formation of NPP1 (Fig. 1A). The percentage of dimerized (260 kDa) NPP1 increased approximately by 45%. This effect was abolished in the presence of ATP (100 µM, 30 min). As a positive control, we used hydrogen peroxide (100 μM, 5 min) which induces oxidative disulfide bond formation (Fig. 1A). We also demonstrated time-dependent decrease of NPPs activity in the presence of αKL (Fig. 1B). Klotho also induces an increase of extracellular ATP concentration by 76% (from 3.19±0.01 to 5.62±0.43, n=6, P&lt;0.05). Moreover, we confirmed the role of soluble αKlotho in ATP-evoked increases of glomerular and podocyte albumin permeability.

Conclusion
Summarizing, we have clearly demonstrated an interaction between αKL and NPP1 in podocytes. Moreover, we observed the protective role of αKlotho in podocyte permeability to albumin.
P1233M2 MACROPHAGES PROMOTE MOUSE AORTIC SMOOTH MUSCLE CELLS CALCIFICATION BY SGK1-TGFB1 AXIS
Authors: Wu Beibei , Zhang Xiaodong , Liu Yuqiu , Zhang Xiao liang 
Published: June 2020

Abstract

Background and Aims
Vascular calcification is an independent risk factor for all-cause mortality in patients with CKD. Macrophages play an important role in vascular calcification, which involve in the osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Recent research shows SGK1 is a highly attractive candidate for developing VSMCs calcification. Previous studies indicated that TGFβ1 induces vascular calcification by regulating osteo-/chondrogenic transdifferentiation of VSMCs. This study focus on the effects of macrophages-derived SGK1 on VSMCs transdifferentiation via regulating TGFβ1 expression.

Method
Before induced into M2 phenotype with IL-4, RAW 264.7 cells were treated with SGK1 inhibitor EMD638683 for 24 hours to reduce SGK1 expression. The above cells were grouped as: M0, M2, M2+EMD to explore the expression of SGK1 and TGFβ1 by using western blot, qRT-PCR and immunofluorescence staining, respectively. The culture medium (CM) of the above group macrophages was collected. Then mouse aortic smooth muscle cells (MAoSMCs ) were cultured in these supernatants with normal medium or osteogenic medium (OM) with or without TGFβ1 receptor inhibitor SB-431542 for 3 weeks to explore the transdifferentiation and calcification of MOVAS by using western blot, RT-qPCR, immunofluorescence staining, calcium quantification, Alizarin Red and Von Kossa Staining.

Results
As Alizarin Red and Von Kossa Staining shown, MAoSMCs contained more calcium deposits in the M2-CM group compared with either in the group of NC nor M0-CM. Consistent with the above results, We also found that M2-CM promoted MAoSMCs transdifferentiation, which was characterized by markedly increase of expression of osteo-/chondrogenic markers (Runx2, ALPL, FGF23) and decrease of the MAoSMCs marker (SM22α). Exploring the mechanism of the above phenomenon we found the expression of SGK1 and TGFβ1 were significantly increased in M2 group compared with M0 group. Interestingly, both SGK1 inhibitor EMD638683 which reduced TGFβ1 expression in M2 and TGFβ1 receptor inhibitor SB-431542 could partially blocked MAoSMCs osteo-/chondrogenic transdifferentiation and calcification. Furthermore, recombinant mouse TGFβ1 Protein increased calcium content in MAoSMCs by using calcium quantification, Alizarin Red and Von Kossa Staining and promoted MAoSMCs osteo-/chondrogenic transdifferentiation, which was characterized by markedly increase of expression of osteo-/chondrogenic markers (Runx2, ALPL, FGF23) and decrease of the MAoSMCs marker (SM22α).

Conclusion
Our findings shed light M2 macrophages promotes MAoSMCs osteo-/chondrogenic transdifferentiation and calcification by up-regulating TGFβ1 expression.