bluuebunny/crossref_metadata_2025 huggingface dataset:
P1857SALT CONSUMPTION, LIFESTYLE AND PROTEINURIA IN A HETEROGENEOUS YOUNG POPULATION
Authors: Zullo Claudia , Dallari Lorenzo , Bagalà Alfredo , Somma Chiara , Ferro Giuseppe , Burgio Lorenzo , Dattolo Pietro
Published: June 2020

Background and Aims

Obesity, hypertension, smoke, high dietary salt intake and physical inactivity are the main modifiable risk factors for chronic kidney disease, that affects about 9-10% of Italian people. About daily salt intake, the World Health Organization recommends a maximum consumption of 5 grams of salt per day. In Italy, most people consume too much salt – on average 8-10 grams per day or around twice the recommended maximum level of intake. Aim of this study was to investigate dietary habits and lifestyle of the heterogeneous students population of “Scuola Carabinieri di Firenze” (attended by people coming from all Italian regions) and their relations with urinary abnormalities.

Method

from November 2018 to March 2019 we collected anamnestic and anthropometric data, blood pressure measurements and body cellular mass (BCM) of 257 young subjects (152 males, 105 females; mean age 32 + 11 yy).

We determinated sodium, chlorine and protein excretion on a spot urine sample in addition to plasma creatinine levels. Statistical analyses were performed using SPSS.

Results

We analyzed preliminary data of urinary sodium excretion (UNa), proteinuria (Up) and hematuria (Urbc) of all the subjects. Fifty-five percent of them had a UNa higher than 100 mmol/L (approximately equivalent to a dietary salt intake of 6 grams/day). In these subjects with higher salt consumption, Up and Urbc, measured by urine dipstick, were detectable in 32% and 21% respectively. In subjects with lower salt intake (less than 6 grams/day), Up and Urbc were 0% and 5% respectively.

To determine if there was an association between our variables, we used Pearson correlation coefficient. We found that UNa was directly related to Up (r 0.26, p 0.002), age (r 0.22 p 0.011) and diastolic blood pressure (DBP, r 0.22, p 0.012). We also found that poor exercise (r -0.15, p 0.7) and low lean body mass percentage (r -0.15, p 0.7) were inversely related to UNa.

Conclusion

high dietary salt intake is associated with elevated blood pressure and proteinuria in a young and “healthy” population. Hypertension and proteinuria are both known risk factors for the development of chronic kidney disease. Wrong dietary habits and lifestyles must be detected and corrected in order to prevent nephropathy onset.
P0030MIR-182 INHIBITS KIDNEY FIBROSIS BY REGULATING TGF-Β1/SMAD3 PATHWAY IN ADPKD
Authors: Sun Liping , Zhang Xinzhou
Published: June 2020

Background and Aims

The aim of the present study was to investigate the molecular mechanism of miR-182 in kidney fibrosis in polycystic kidney disease (PKD).

Method

We measured the expression of miR-182 in kidney tissue of autosomal dominant polycystic kidney disease (ADPKD). Additionally, we investigated the relationship between miR-182 and fibrotic protein by transfecting miR-182 mimics and miR-182 inhibitor into polycystic kidney cyst-lined epithelial cells, respectively. Furthermore, we observed the interaction between TGF-β1 and miR-182 and fibrinogen factors of cyst-lined epithelial cells after TGF-β1 intervention, and measured the expression of Smad2, 3 protein.

Results

(1) MiR-182 was positively correlated with fibrosis of cyst-lined epithelial cells; (2) TGF-β1 could induce fibrosis of cyst-lined epithelial cells; (3) the expression of miR-182 had an remarkably impact on the fibrosis induced by TGF-β1, but had little effect on the expression of TGF-β1; (4) the expression of Smad3 protein in TGF-β1 induce- cyst-lined epithelial cells were increased.

Conclusion

TGF-β and miR-182 promoting the fibrosis of polycystic kidney cyst -lined epithelial cells may be mediated by the TGF-β/Smad3 signaling pathway, of which Smad3 was an important regulator.
P0767INTRAUTERINE GROWTH RESTRICTION AND RISK OF KIDNEY DISEASE DURING THE FIRST 50 YEARS OF LIFE
Authors: Gjerde Anna , Reisater Anna Varberg , Skrunes Rannveig , Marti Hans-Peter , Vikse Bjørn Egil
Published: June 2020

Background and Aims

Previous studies have shown that Low Birth Weight (LBW) and small for gestational age (SGA) are associated with increased risk of end-stage renal disease. Few population-based studies have however investigated risk of less severe kidney disease and in the present study, we investigate risk of chronic kidney disease and other kidney disease diagnoses.

Method

The Norwegian Patient Registry (NPR) has registered ICD diagnostic codes for all admissions and outpatient visits to Norwegian hospitals since 2008 (available for 2008-2016 in this study). The Norwegian Medical Birth Registry (MBR) has registered birth weight, gestational age and several other data on maternal and offspring health for all birth in Norway since 1967. Data from these registries were linked and risk of chronic kidney disease (CKD) and other groups of kidney disease were analyzed with logistic regression statistics. LBW (less than the 10th percentile), SGA (less than the 10th percentile) and preterm birth (less than 37 weeks) were analyzed as risk markers. Adjusted analyses were performed for the main analyses by including birth year, gender, maternal disease, maternal preeclampsia, maternal marital status and malformations in the newborn.

Results

Of the 2,663,010 included individuals, 4,495 had been diagnosed with CKD and 12,818 with acute kidney disease, glomerulonephritis, hereditary kidney disease or kidney disease due to kidney or urinary tract malformations. LBW was associated with an adjusted odds ratio (aOR) for CKD of 1.61 (1.48-1.74), SGA with an aOR of 1.51 (1.39-1.63) and preterm birth with an aOR of 1.47 (1.31-1.66). As compared to subjects with none of these risk factors (LBW, SGA or preterm birth), subjects with only one risk factor had an aOR of 1.49 (1.35-1.66), subjects with 2 risk factors had adjusted aOR of 1.72 (1.57-1.88) and subjects with 3 risk factors had aOR of 2.56(1.99-3.29). Analyses of chronic kidney disease stage 3, 4 and 5 showed similar results. There were no significant gender differences. We further analysed aOR for other groups of kidney disease and found that LBW was associated with aOR of 1.52 (1.40-1.65) for acute kidney disease, 1.26 (1.16-1.38) for glomerulonephritis, 1.55 (1.34-1.80) for hereditary kidney disease and 1.38 (1.27-1.49) for kidney disease due to kidney or urinary tract malformations; analyses for the other risk factors showed similar results.

Conclusion

LBW and SGA are strong risk factors for diagnosis of all stages of CKD during the first 50 years of life and the risks seem to be increased also for other groups of kidney disease. Our results underline the public health importance of LBW and SGA.
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

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

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

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

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 <−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 <−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

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

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 > 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

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<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

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<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

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.
P1234SNF472 IMPROVES LIMB BLOOD PERFUSION AND WALKING ABILITY IN A PERIPHERAL ARTERY DISEASE VASCULAR CALCIFICATION RAT MODEL
Authors: Bassissi Firas , Ferrer Reynes Miguel David , Pérez M Mar , Perelló Joan , Salcedo Carolina
Published: June 2020

Background and Aims

Peripheral Artery disease (PAD) is a common vascular disease associated with functional impairment and increased risk of cardiovascular events in End Stage Kidney Disease (ESKD) patients undergoing dialysis. Poor limb salvage outcomes and high post-amputation mortality in hemodialysis (HD) patients highlight the need for earlier medical therapies. Cilostazol and pentoxifylline are approved for PAD. Their use in HD patients stays limited and cilostazol use requires caution in this population. Clinical studies demonstrate associations between arterial calcification and adverse outcomes in PAD patients. SNF472, a selective calcification inhibitor that interferes in the formation and growth of hydroxyapatite, is in Phase 3 for calciphylaxis treatment. This study aims to evaluate the effects of SNF472 on limb functional recovery and blood perfusion in a Vitamin D3 (VitD)-induced arterial calcification rat model.

Method

Arterial calcification was induced in 32 Sprague Dawley rats by 3 consecutive daily s.c. doses of 120 kIU/kg VitD. Rats were divided into four groups and treated during 12 days by: placebo s.c, placebo p.o, SNF472 (20 mg/kg/day, s.c.) or cilostazol (20 mg/kg/day, p.o.). An additional group of 8 rats without VitD received vehicle only (sham). Efficacy was evaluated at day 12 and 17 (5 days after treatment stop). Posterior limb blood perfusion was measured using Laser Doppler Imaging and limb walking ability was evaluated by measuring Maximum Walking Distance (MWD) and Maximum Walking Time (MWT) using a treadmill. Rats were sacrificed at day 26 (14 days after treatment stop), and aortas were collected for calcium analysis.

Results

VitD-induced arterial calcification was associated with decreased blood perfusion and impairment of limb walking ability (MWT and MWD) compared to sham. SNF472 reduced aorta calcification by 41% compared to placebo. No effects of cilostazol on vascular calcification were observed. The inhibition of calcification in SNF472-treated animals was associated with significant higher limb blood perfusion compared to placebo or Cilostazol (1.28 and 1.37-fold higher, respectively at day 12: p< 0.001) and it was translated into a significant improvement in walking ability compared to placebo (515±114 meters vs 334±187 meters, respectively: p<0.05).

Conclusion

SNF472 shows improvements in vascular calcification, blood perfusion and a functional parameter like walking distance in a PAD vascular calcification rat model. These results suggest that SNF472 may represent a new therapeutic approach for the treatment of PAD associated with high vascular calcification such as in renal disease.
P1235THE IMPACT OF SPIRONOLACTONE ON DIASTOLIC FUNCTION IN HEMODIALYSIS PATIENTS - THE MIRENDA RCT
Authors: Hauser Tobias Gregor , Dornberger Vivien , Malzahn Uwe , Liu Dan , Störk Stefan , Nauck Matthias , Friedrich Nele , Wanner Christoph , Krane Vera , Hammer Fabian
Published: June 2020

Background and Aims

Patients on maintenance hemodialysis (HD) treatment are particularly prone to develop cardiovascular disease. Heart failure with preserved ejection fraction (HFpEF) characterized by diastolic dysfunction (DD) is highly prevalent and lacks an effective treatment to date. We investigated the effect of the mineralocorticoid receptor antagonist spironolactone compared to placebo on diastolic function in maintenance HD patients.

Method

The MiREnDa trial was a multicenter randomized-controlled trial that recruited 97 HD patients without previous spironolactone treatment. Participants were randomized 1:1 to spironolactone 50 mg once daily (n=50) or placebo (n=47). Changes in parameters of diastolic function were secondary endpoints of the trial whereas the primary endpoint was change in left ventricular mass index (LVMi). At baseline and after 40 weeks, subjects underwent echocardiography and biomarker testing. DD was defined according to the American Society of Echocardiography 2016 guidelines.

Results

At baseline, mean age was 58.3 ± 13.0 years, 13 subjects were female and 28 presented with NYHA grade II or higher. Median serum level of NT-proBNP was 2,803 (quartiles: 1,060; 10,676) pg/ml, median previous time on dialysis was 45.0 (quartiles: 21.0; 79.0) months. 28 patients (45.9%) had normal diastolic function, 16 (26.2%) were diagnosed with grade 1 DD, 15 (24.6%) with grade 2 DD and 2 (3.3%) with grade 3 DD. In the remaining cases, the grade of DD was rated indeterminate. There were no significant disparities between the placebo and spironolactone group regarding baseline characteristics.

At follow-up, diastolic function improved in two and deteriorated in three subjects on spironolactone treatment, whereas in the placebo group, diastolic function improved in three and deteriorated in two patients. No change in diastolic function was observed in 14 individuals on spironolactone treatment and in 10 receiving placebo (Pearson’s Χ: p=0.87). According to the diagnostic algorithm proposed by the American society of Echocardiography 2016 guideline, 18 patients (11 on spironolactone; 7 on placebo) could no longer be allocated to a distinct group of DD. These patients needed to be classified as indeterminate, even though they only showed mild alterations in diastolic function parameters.

Conclusion

In this randomized, placebo-controlled trial, 40 weeks of spironolactone treatment did not change diastolic function in HD patients.
P1432THE PRE-DIALYSIS CARE TRAJECTORIES OF ESRD PATIENTS: WHAT TYPES AND WHAT FACTORS OF EMERGENCY DIALYSIS START?
Authors: Raffray Maxime , Pladys Adélaïde , Gao Fei , Couchoud Cécile , Vigneau Cécile , Bayat Sahar
Published: June 2020

Background and Aims

According to the REIN registry, in France in 2017, 30% of incident end-stage renal disease (ESRD) patients started dialysis in emergency. Emergency dialysis start (ES) is associated with higher risks of morbidity and mortality as well as a decreased quality of life for patients. The objectives were to describe groups of patients with similar care trajectories (or “types”) and identify the factors associated with ES.

Method

Data from the French REIN registry linked with the French national health insurance database (SNDS) were used. Patients aged 18 years old and older who started dialysis in 2015 in France were included. The 2 years pre-dialysis care trajectory was defined using 8 key components of ambulatory and hospital CKD care consumption. Multiple Correspondence Analysis (MCA) on these components was performed before a Hierarchical Clustering on Principal Components (HCPC) in order to identify types of care trajectories. Logistic regression models including both patients’ characteristics and the key CKD healthcare consumption were used to identify factors associated with ES.

Results

Among the 8856 patients included, 2681 (30.3%) started dialysis in emergency. The HCPC identified 6 types of pre-dialysis care trajectories. ES rate ranged from 11% to 62% depending on the type. Patient’s profiles were also different between types of trajectories, including age and comorbidities (diabetes prevalence ranged from 22% to 56%). For example, the 5th and 6th types of pre-dialysis care trajectories with high ES rates were characterized by low and absent CKD healthcare consumption respectively. They were shared by younger and less comorbid patients (26.7% and 25.7% aged < 45 years old, 66.5% and 59.4% without any cardiovascular diseases respectively). Conversely to the absence of nephrologist follow-up, the absence of general practitioner follow-up was not significantly associated with ES (OR=1.83, CI 95% [1.58-2.13] and OR=0.79, CI 95% [0.61-1.04] respectively).

Conclusion

Exploiting the strength of the combined use of clinical and healthcare consumption data, our study shows the diversity of pre-dialysis care trajectories of CKD patients. While some of these types of trajectories can be explained by patients’ clinical and demographic characteristics, complementary qualitative approaches are required to fully understand ES. Some types, as well as ES associated factors, highlight the need for earlier CKD screening and nephrologist referral.
P1433VALIDATION OF A SERUM CALCIFICATION PROPENSITY TEST FOR THE PREDICTION OF ALL-CAUSE MORTALITY AMONG DIALYSIS PATIENTS
Authors: Ramos Sanchez Rosa , Zawada Adam , Wolf Melanie , Rincon Bello Abraham , Masso Jimenez Elisabet , Hurtado Munoz Sara , Ribera Tello Laura , Mora-Macia Josep , Stuard Stefano , Stauss-Grabo Manuela , Winter Anke , Canaud Bernard
Published: June 2020

Background and Aims

Vascular calcification as cause of vascular stiffness is a major contributor to the high cardiac burden among stage 5 chronic kidney disease dialysis (CKD5HD) patients. Early identification of patients with high calcification propensity is crucial for proper risk stratification and management of these patients. Recently, a novel in vitro test (T50-test) was developed which determines calcification propensity of human serum and predicts mortality among ND-CKD (non-dialysis chronic kidney disease) patients, kidney transplant recipients and CKD5HD patients suffering from secondary hyperparathyroidism. We now evaluated whether these results can be confirmed in an unselected cohort of CKD5HD patients and can be used in the future for improving care of these patients.

Method

This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 Fresenius Medical Care NephroCare centers in Cataluña (Spain). T50 was determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database (EuCliD®). After their baseline T50 measurement, patients were followed for two years for the occurrence of the primary endpoint all-cause mortality. The association between T50 and all-cause mortality was examined by using proportional subdistribution hazards regression modelling accounting for kidney transplantation as competing event. In sensitivity analyses we adjusted for age, sex, vascular access (fistula/graft, catheter), treatment modality (HD, HDF), Charlson comorbidity index and dialysis vintage.

Results

Mean age of the study population was 72.2 years and 63.8% were male. 42.5% had diabetes and 55.0% past history of cardiovascular disease. Mean T50 was 283.4 min among the total cohort. During follow-up, 185 (23.8%) patients died. Patients who reached the endpoint had a significantly lower T50 at baseline as compared to those who survived during follow-up (269.6 vs 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained a significant predictor of all-cause mortality after adjusting for relevant confounding in sensitivity analyses.

Conclusion

In this prospective study, we confirmed that T50 is an independent predictor of all-cause mortality among a large unselected cohort of hemodialysis patients. T50 may be used to identify patients with high vascular calcification propensity and mortality risks and may help physicians to implement a personalized and more precise renal replacement therapy option.
Association between health insurance status and malignant glioma
Authors: Fischer Igor , Mijderwijk Hendrik-Jan , Kahlert Ulf D , Rapp Marion , Sabel Michael , Hänggi Daniel , Steiger Hans-Jakob , Forster Marie-Therese , Kamp Marcel A
Published: June 2020

Background

Prior studies have suggested an association between patient socioeconomic status and brain tumors. In the present study we attempt to indirectly validate the findings, using health insurance status as a proxy for socioeconomic status.

Methods

There are 2 types of health insurance in Germany: statutory and private. Owing to regulations, low- and middle-income residents are typically statutory insured, whereas high-income residents have the option of choosing a private insurance. We compared the frequencies of privately insured patients suffering from malignant neoplasms of the brain with the corresponding frequencies among other neurosurgical patients at our hospital and among the German population. To correct for age, sex, and distance from the hospital, we included these variables as predictors in logistic and binomial regression.

Results

A significant association (odds ratio [OR] = 1.59, CI = 1.45-1.74, P < .001) between health insurance status and brain tumors was found. The association is independent of patients’ sex or age. Whereas privately insured patients generally tend to come from farther away, such a relationship was not observed for patients suffering from brain tumors. Comparing the out of house and in-house brain tumor patients showed no selection bias on our side.

Conclusion

Previous studies have found that people with a higher income, level of education, or socioeconomic status are more likely to suffer from malignant brain tumors. Our findings are in line with these studies. Although the reason behind the association remains unclear, the probability that our results are due to some random effect in the data is extremely low.
Class Status and Social Mobility on Tobacco Smoking in Post-Reform China Between 1991 and 2011
Authors: Yang Xiaozhao Yousef
Published: June 2020

Introduction

There is growing attention to social mobility’s impact on tobacco use, but few studies have differentiated the two conceptually distinct mechanisms through which changes in social class can affect tobacco smoking: the class status effect and the mobility effect.

Aims and Methods

I applied Diagonal Reference Modeling to smoking and heavy smoking among respondents of the 1991 China Health and Nutrition Survey who were revisited two decades later in 2011 (n = 3841, 49% male, baseline mean age was 38 years). I divided the sample into six social classes (non-employment, self-employed, owners, workers, farmers, and retirees) and measured social mobility by changes in income and occupational prestige.

Results

About 61.7% of men were smokers and those from the classes of workers, owners, and self-employees consumed more cigarettes compared to the unemployed, but women smokers (3.7%) tend to be from the lower classes (unemployed and farmers). Controlling for social class, each 1000 Yuan increase in annual income led to smoking 0.03 more cigarettes (p < .05) and 1% increase (p < .05) in the likelihood of heavy smoking among men, but the income effect is null for women. Upwardly mobile men (a 10-points surge in occupational prestige) smoked like their destination class (weight = 78%), whereas men with downward mobility were more similar to peers in the original class (weight = 60%).

Conclusions

Contrary to the social gradient in smoking in other industrial countries, higher class status and upward mobility are each associated with more smoking among Chinese men, but not among women.

Implications

Tobacco control policies should prioritize male smoking at workplaces and the instrumental purposes of using tobacco as gifts and social lubricant. Taxation may counter the surge in smoking brought by individuals’ income increase after upward mobility. Caution should be paid to women joining the similar social gradient in smoking as they gain foothold in the labor market.
Utilizing Behavioral Science to Improve Antibiotic Prescribing in Rural Urgent Care Settings
Authors: Cummings Patricia L , Alajajian Rita , May Larissa S , Grant Russel , Greer Hailey , Sontz Jordan , Dezfuli Massoud
Published: June 2020

Background

Antibiotic-inappropriate prescribing for acute respiratory tract infections (ARTI) is 45% among urgent care centers (UCCs) in the United States. Locally in our UCCs, antibiotic-inappropriate prescribing for ARTI is higher—over 70%.

Methods

We used a quasi-experimental design to implement 3 behavioral interventions targeting antibiotic-inappropriate/non-guideline-concordant prescribing for ARTI at 3 high-volume rural UCCs and analyzed prescribing rates pre- and post-intervention. The 3 interventions were (1) staff/patient education, (2) public commitment, and (3) peer comparison. For peer comparison, providers were sent feedback emails with their prescribing data during the intervention period and a blinded ranking email comparing them with their peers. Providers were categorized as “low prescribers” (ie,  ≤23% antibiotic-inappropriate prescriptions based off the US National Action Plan for Combating Antibiotic Resistant Bacteria 2020 goal) or “high prescribers” (ie,  ≥45%—the national average of antibiotic-inappropriate prescribing for ARTI). An interrupted time series (ITS) analysis compared prescribing for ARTI (the primary outcome) over a 16-month period before the intervention and during the 6-month intervention period, for a total of 22 months, across the 3 UCCs.

Results

Fewer antibiotic-inappropriate prescriptions were written during the intervention period (57.7%) compared with the pre-intervention period (72.6%) in the 3 UCCs, resulting in a 14.9% absolute decrease in percentage of antibiotic-inappropriate prescriptions. The ITS analysis revealed that the rate of antibiotic-inappropriate prescribing was statistically significantly different pre-intervention compared with the intervention period (95% confidence interval, –4.59 to –0.59; P = .014).

Conclusions

In this sample of rural UCCs, we reduced antibiotic-inappropriate prescribing for ARTI using 3 behavioral interventions.