bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO058INHIBITION OF OSTEOCLAST DIFFERENTIATION BY 1.25-D AND THE CALCIMIMETIC KP2326 REVEALS 1.25-D RESISTANCE IN ADVANCED CKD
Authors: Bernardor Julie , Flammier Sacha , Ranchin Bruno , Gaillard Segolene , Platel Diane , Peyruchaud Olivier , Machuca-Gayet Irma , Bacchetta Justine 
Published: June 2020

Abstract

Background and Aims
Active vitamin D analogs and calcimimetics are cornerstones for managing secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). Their direct effects on bone cells remain to be determined.

Method
Peripheral blood mononuclear cells (PBMCs) of 19 pediatric CKD patients and 6 healthy donors (HD) were differentiated into osteoclasts in presence of M-CSF and RANKL. Effect of combined or single treatment with active vitamin D (1.25-D) and/or the calcimimetic KP2326 were evaluated onto osteoclast differentiation and osteoclast mediated bone resorption.

Results
1.25-D inhibited osteoclastic differentiation, a significant resistance to 1.25-D was observed when CKD worsens. A significant albeit less important inhibitory effect of KP2326 on osteoclastic differentiation was also found both in cells derived from HD and CKD patients, through an activation of the Erk pathway. This inhibitory effect was not modified by CKD stage. Combinatorial treatment with 1.25-D and KP2326 did not result in synergistic effects. Last, KP2326 significantly inhibited human osteoclast-mediated bone resorption.

Conclusion
Both 1.25-D and KP2326 inhibit osteoclastic differentiation, however to a different extent. Whilst 1.25-D has no significant effect on bone resorption, KP2326 inhibits bone resorption. Recent data showed that calcimimetics also have a direct anabolic effect on bone, through the stimulation of osteoblastic differentiation and mineralization in human mesenchymal stem cells in vitro. All these results provide a strong rationale for a global positive effect of calcimimetics on bone remodeling. Calcimimetics also significantly decrease FGF23 levels. In the setting of global systematic deleterious effects of high FGF23 levels in CKD, and keeping in mind that active vitamin D analogs stimulate FGF 23 production, all these data could favor the use of decreased doses of 1.25-D with low-doses of calcimimetics in SHPT in dialysis, the combination of these two therapies already being proposed in the 2017 K-DIGO guidelines.
MO063CHRONIC INTERSTITIAL NEPHRITIS IN AGRICULTURAL COMMUNITIES IS A TOXIN-INDUCED PROXIMAL TUBULAR NEPHROPATHY
Authors: Vervaet Benjamin , Nast Cynthia , Jayasumana Channa , Schreurs Gerd , Roels Frank , Herath Chula , Kojc Nika , Samaee Vahid , Rodrigo Sonali , Gowrishankar Swarnalata , Mousson Christiane , Dassanayake Rajeewa , Orantes Carlos , Vuiblet Vincent , Rigothier Claire , D'Haese Patrick , De Broe Marc 
Published: June 2020

Abstract

Background and Aims
30 years after the detection of CINAC, there is no consensus on its etiology. Heat stress/dehydration and toxic exposure are the two most likely etiologies. There are no diagnostic criteria that can directly identify CINAC patients.

Method
Renal biopsies (RB) (18 Sri Lanka, 10 El Salvador, 1 India, 3 France) of patients with CINAC (CKD2-3) were examined by light (LM) and electron microscopy (EM) in comparison to RB of normal kidneys at implantation and 6 and 12 months of calcineurin inhibitor (CNI) therapy, transplant patients on CNI with indication biopsies (n=24), proteinuric nephropathies (n=15), light chain disease (n=4), cases on nephrotoxic drugs (lomustine, clomiphene, lithium, tenofovir, cisplatinum) and CKD of various causes (n=20). A rat study was conducted comparing histopathology of heat stress/dehydration with cyclosporine nephrotoxicity.

Results
In addition to previously described histopathological changes, there was a unique constellation of proximal tubular cell (PTC) findings: cellular/tubular atrophy, cell fragment shedding, weak to non-proliferative capacity of the PTC and dysmorphic lysosomes increased in size and number with a light-medium electron-dense matrix containing dispersed dark electron-dense non-membrane bound “aggregates”. Identical renal lesions were observed in 55-80% of renal transplant protocol biopsies taken after 6 and 12 months of calcineurin inhibitor (CNI) therapy and in indication biopsies, in implantation biopsies the prevalence was 6%. Several cases of nephrotoxic drugs (lomustine, clomiphene, lithium) and a subset of patients with light chain disease, all conditions that can be linked to CNI, presented the same lesion. Control RBs (n=66) of normal kidney, toxic nephropathies (tenofovir, cisplatinum), and overt proteinuric patients of different etiology to some extent could demonstrate the tubular cell changes observed by LM, but not or very rarely those that were observed by EM. Rats treated with cyclosporine for 4 weeks developed similar PTC lysosomal alterations, absent in a dehydration group.

Conclusion
A sensitive constellation of renal PTC lesions was detected associated with CINAC and CNI nephrotoxicity in several countries, suggesting a common new paradigm where CINAC patients are experiencing a tubulotoxic mechanism similar to CNI nephrotoxicity, the latter also being known as a direct or suggested indirect effect of pesticides.
MO070APPROPRIATE INTERVAL BETWEEN TWO EGFR MEASUREMENTS FOR THE EVALUATION OF THE ASSOCIATION OF EGFR SLOPE WITH INCIDENCE OF RENAL EVENTS
Authors: Kokubu Maiko , MATSUI MASARU , Uemura Takayuki , Tsuruya Kazuhiko 
Published: June 2020

Abstract

Background and Aims
In recent years, growing evidence has shown the prognostic utility of eGFR slope for the risk of end-staging renal disease (ESRD). Previous observational studies have assessed the association between renal events and eGFR slopes estimated by two measurements of eGFR but had great differences in the interval between two eGFR measurements. In this study, we thus aimed to determine the appropriate interval between two eGFR measurements to evaluate the association of eGFR slope with incidence of renal events.

Method
This is a retrospective cohort study in 203 chronic kidney disease (CKD) patients who visited Nara Prefecture General Medical Center, Japan between 1 January 2013 and 31 December 2016 and in whom two or more than two measurements of eGFR levels were confirmed in medical records. eGFR slopes were estimated by using two measurements of eGFR at baseline and 0.5, 1, 1.5, 2, or 3 years. We excluded patients with acute kidney injury, urologic malignancies, nephrotic syndrome with steroid treatment or collagen diseases. Outcome was renal events defined as a composite of ESRD and eGFR decline of &gt; 30%. C statistics were used to evaluate the association between eGFR slope and incidence of renal events.

Results
The median (interquartile range) age of study participants was 67 (56-77) years and 71 (37%) were male. The median (interquartile range) levels of baseline eGFR were 34 (21-48) mL/min/1.73m2 and diabetes was present in 80 (39%) participants. During the median follow-up period of 38 months, renal events occurred in 52 participants. Medial levels of eGFR slopes0.5, 1, 1,5, 2 and 3yr were -7.8, -3.6, -2.9, -0.9, -1.5 mL/min/1.73m2, respectively. C-statistics of eGFR slopes0.5, 1, 1,5, 2 and 3yr for renal events were 0.622, 0.691, 0.797, 0.858, 0.806, respectively (shown in Figure 1), and that of eGFR slope1.5yr was significantly higher than that of eGFR slope0.5yr and eGFR slope1yr (p&lt;0.001 and p=0.001, respectively). In stratified analysis, eGFR slope1.5yr had higher prognostic ability of renal events in patients with versus without diabetes, advanced CKD and proteinuria. C-statistics of renal events when considering baseline eGFR alone was 0.853 but combination use of baseline eGFR and eGFR slope1.5yr significantly increased c-statistics, to 0.913 (p=0.01).

Conclusion
eGFR slope for high prognostic ability of renal events may be needed to be calculated by at least 1.5-year interval between two eGFR measurements.
MO079SECURITY OF THERAPEUTIC APHERESIS IN PEDIATRICS. PROSPECTIVE STUDY DURING 2018 IN 171 APHERESIS SESSSIONS
Authors: López Baez Víctor , Arango Sancho Pedro , Calzada Baños Yolanda , Codina Sampera Elena , Vinuesa Jaca Ana , Hernández Zúñiga Lina , Madrid Aris Álvaro 
Published: June 2020

Abstract

Background and Aims
Identify hypocalcemia and hemodynamic disorders related to apheresis in pediatrics either complications in vascular access or related to anticoagulation and adverse reactions with replacement fluid.

Method
Prospective and descriptive study of 171 sessions for therapeutic apheresis in pediatrics during 2018. Inclusion criteria was based on the 2016 Clinical-Practice-of-Therapeutic-Apheresis-guidelines(ASFA). The apheresis technique was selected also based on the 2016 ASFA Guidelines and the expertise in our center.

Results
The 171 sessions were distributed as follows: 73% were immunoadsorption(IA), 12% were cytoapheresis, 10.5% were LDL-apheresis and 4.5% therapeutic plasma exchange(TPE). The average age was 9 years and 58% were women. 50, 33 and 17% were due to Nephrological, Neurological and Digestive pathology respectively. 83% of the nephrological indications correspond to a category I of the ASFA Guidelines, as well as 25% of the neurological indications and all indications of Digestive pathology correspond to a category II. 58, 25 and 17% used temporary catheter, permanent catheter and needles respectively. Only one patient is accidentally removed from the temporary jugular catheter and it has not been related to vascular access or by the apheresis technique itself. Sixty-six percent had individual anticoagulation with citrate/calcium plus heparin and the remaining 33%, only once. Any case of bleeding related to catheter or others. Only 3 sessions of IA in the hypocalcemia objective, being symptomatic in only one of them. Of all 8 sessions of TPE, we performed 6 with frozen fresh plasma as replacement fluid with no adverse reactions.

Conclusion
The apheresis techniques in pediatrics had been presented with few complications in our center, none derived from vascular access, anticoagulation, infections or adverse effects due to use of replacement fluid. The training of medical and nursing staff is essential to identify risk situations. The use of protocols and international guidelines ensure safety in pediatrics.
TO005OPERATIONAL TOLERANCE IN KIDNEY TRANSPLANT RECIPIENTS: TOMOGRAM TRANSCRIPTOMIC STUDY
Authors: Viklicky Ondrej , Klema Jiri , Mrazova Petra , Abramowicz Daniel , Abramowicz Marc , Massart Annick , Hruba Petra , Study Group TOMOGRAM 
Published: June 2020

Abstract

Background and Aims
TOMOGRAM, multicenter study founded by DESCARTES ERA/EDTA WG, aims to identify transcriptomic and genomic signatures of operational tolerance (OT) in recently identified cohort of OT kidney transplant recipients.

Method
RNA sequencing of peripheral blood was evaluated in 15 OT patients recently identified by TOMOGRAM consortium in 8 European countries, 23 stable patients (≥ 15 years on immunosuppression, STA), 14 CABMR patients (≥ 1 year, CR), 14 non-transplant CNI-treated patients and 14 healthy controls (HC). Differential expression was performed using DESEq2 and gene annotation analysis using Enrichr. Besides immunosuppression unadjusted model, robust negative-binomial regression model was created to adjust for immunosuppression intake. The models was trained on homogeneous group of STA patients.

Results
Using model unadjusted for immunosuppression, no differences in transcriptomic profiles between OT, STA and HC groups were identified. Nine transcripts were upregulated and 2 downregulated in OT compared CR group. The number of deregulated transcripts substantially increased when the model was adjusted for immunosuppression. Gene annotation analysis of top ranked deregulated 1109 transcripts (FC&gt;2, adjusted p value &lt;0.0001) showed deregulation of biological processes related to interferon-γ-mediated signaling pathway (p=1.4*10-5), response to cytokine (p=1.5*10-5), type I interferon signaling pathway (p=0.00036), regulation of I-kappaB kinase/NF-kappaB signaling (p=0.0021), cytokine-mediated signaling pathway (p=0.019) and neutrophil mediated immunity (p=0.033). While interferon-γ-mediated and type I interferon signaling were related to transcripts increased in CR, neutrophils associated transcripts were increased in OT. Analysis of cell types transcripts showed enrichment of CD19 B cells (p=1.6*10-9) in CR, while CD56NK cells (p=2.5*10-11) and CD8 T cells (p=1.6*10-11) transcripts predominated in OT. To reveal probability of operational tolerance inside STA group, 13 transcripts able to discriminate OT and CR cohorts with high AUC (&gt;0.89) were used in PCA analysis (ADGRG3, ATG2A, GDPD5, IL16, MX2, SLA2, PRKD2, SLIRP, GNLY, SRCAP, ARGHAP9, IGHM, CD5). The high probability of OT signature was found in a single STA patient.

Conclusion
Contrary to previous reports which pointed out towards naïve B cell signatures, unique OT patients exhibit other specific immunosuppression-independent transcriptomic profiles.
TO012HOW DIFFERENT IS THE CLEARANCE OF LARGE MIDDLE MOLECULES AND INFLAMMATORY MARKERS FROM EXPANDED HEMODIALYSIS THERAPY COMPARED TO ONLINE HEMODIAFILTRATION?
Authors: Hadad Arrascue Fernando , Nilsson Lars-Göran , Bernardo Angelito , Rivera Angela , Guardiola Belmonte, Lourdes , Rosique Florentina , Andreu Muñoz Alberto , Perez Perez Antonio , Cabezuelo-Romero Juan 
Published: June 2020

Abstract

Background and Aims
Expanded hemodialysis (HDx) with a medium cut-off dialyzer, Theranova® 500, can achieve a middle molecule clearance but its efficacy or comparison with HDF is still unknown. It is still unknown on how large middle molecules and inflammation markers are affected over time with a medium cut-off dialyzer. This study compared the purifying effectiveness of Theranova® 500 dialyzer with respect to online Hemodiafiltration (OL-HDF).

Method
Sixty-three patients who were already receiving HDF were evaluated and 43 were randomized by residual renal function. Twenty-one patients received treatment with HDx using Theranova® 500 and 22 patients remained in HDF in post-dilution mode, using a high-flux dialyzer, Polyflux® 170H, for up to 24 weeks. The dialysis time and the adequacy parameters for both arms were the same. Large middle molecules were measured (kappa immunoglobulin free light chains [κ-FLC], lambda immunoglobulin free light chains [λ-FLC], chitinase-3-like protein 1 [YKL-40], fibroblast growth factor 23 [FGF-23] and serum beta-2 microglobulin [β2M]), ; and inflammatory markers (high sensitivity C-reactive protein [hs-CRP], pentraxin - 3 [PTX-3], interleukin-6 [IL-6], interleukin-10 [IL-10]) at 12 weeks of treatment; and its change from baseline to weeks 12 and 24 in mid-week pre-dialysis. The method of measurement was the immunoassay. Siemens immunoassay was used for FLCs.

Results
HDx with Theranova® 500 demonstrated comparable results to OL-HDF with convective volume 24.4±3.2 L in terms of reduction rate (RR) of middle molecules (κ-FLC, λ-FLC, FGF-23 and β2M) at 12 weeks of treatment. HDx demonstrated similar performance to HDF in mid-week pre-dialysis plasma levels of middle molecules from baseline, at 12 and 24 weeks of treatment. Greater RR of YKL-40 at 12 weeks of treatment was seen in HDx group when compared to HDF (58.1% vs 42.4%; p≤0.0001), and there was a difference in the pre-dialysis β2M change from Baseline values between the groups (-0.60 for HDx arm and +3.28 for HDF arm, p=0.46). HDx with Theranova® 500 demonstrated comparable results to HDF in terms of reduction rate (RR) of inflammatory markers (hs-CRP, PTX-3, IL-6 and IL-10) at 12 weeks of treatment.
There were no differences in the parameters of adequacy of dialysis between both arms. Both treatments were effective in maintaining pre-dialysis albumin and fibrinogen levels throughout the study. There were no significant adverse events related to the safety of Theranova.

Conclusion
HDx with Theranova® 500 is an emergent, effective and safe hemodialysis therapy that showed a purifying efficacy at least comparable to OL-HDF.
TO015INTRADIALYTIC ON-LINE MULTICOMPONENT TOTAL REMOVED SOLUTE MONITORING IN SPENT DIALYSATE BY A NOVEL MINIATURIZED OPTICAL SENSOR
Authors: Adoberg Annika , Paats Joosep , Arund Jürgen , Leis Liisi , Pilt Kristjan , Fridolin Ivo , Luman Merike 
Published: June 2020

Abstract

Background and Aims
Urea is the most commonly exploited marker of dialysis adequacy. Plenty of other uremic retention solutes with a deleterious effect on morbidity and mortality of uremic patients accumulate in ESKD patients [1]. Commonly, the uremic solutes are divided into three physicochemical types [2] with the representative markers urea, uric acid (UA),indoxyl sulfate (IS), and β2-Microglobulin (B2M). Optical monitoring of the uremic marker molecules has been proposed [3]. Despite being cumbersome as a clinical routine, direct dialysis quantification from total dialysate collection (TDC) is as the ‘gold standard’ for measuring the total amount of uremic solutes removed [4]. A robust and compact optical on-line dialysis monitoring device is a step closer to automatic assessment of removal of uremic toxins in dialysis.
The aim of this study was to evaluate intradialytic on-line multicomponent Total Removed Solute (TRS) monitoring in the spent dialysate by a novel miniaturized optical sensor during hemodialysis (HD) and hemodiafiltration (HDF) with different settings.

Method
Ten ESKD patients (6 male and 4 female, 60.2±16.8 years) on chronic HDF were enrolled into the study (fistula N=9, graft N=1). For each patient 5 midweek dialysis sessions (length 240min, HD: N=1, Qb=200ml/min, Qd=300ml/min, 1,5m2; HDF: N=4, Qb≥300ml/min, Qd≥500ml/min, Vsubst≥15l, 1,8m2 and 2,2m2) were included. Spent dialysate from the drain was monitored on-line by a miniaturized sensor prototype (Optofluid Technologies OÜ, Estonia). For the reference, the samples from the spent dialysate drain tube of the HD machine were taken as 7, 60, 120 and 180min after the start and at the end of the session (240min). The concentrations of urea and B2M in dialysate were determined in the clinical laboratory. Concentration of IS and UA was determined utilizing the HPLC. TRS values were calculated using the tank weight and the lab or optical tank solute concentrations. t-test was used to determine significant differences between the methods (P≤0.05).

Results
The laboratory and optical TRS values were 489±112mM and 512±87mM for urea (R2=0.870), 4232±712µM and 4331±756µM for UA (R2=0.985), 230±47mg and 231±40mg for B2M (R2=0.906), 606±339µM and 616±321µM for IS (R2=0.969) (Fig. 1), being not statistically different for any uremic solutes. The reason for higher correlation for UA and IS is direct measurements of UA and IS by the optical sensor whereas urea and B2M are estimated indirectly.

Conclusion
Novel miniaturized optical sensor successfully carried out intradialytic on-line multicomponent TRS monitoring for the uremic solutes urea, UA, B2M and IS in the spent dialysate.
P0005TIME-VARYING DIALYSATE BICARBONATE CONCENTRATIONS CAN REDUCE PEAK INTRADIALTIC SERUM BICARBONATE CONCENTRATIONS
Authors: Ebinger Anna , Waniewski Jacek , Malyszko Jolanta , Wieliczko Monika , Mauro Pietribiasi , Leypoldt John (Ken) 
Published: June 2020

Abstract

Background and Aims
Hemodialysis (HD) treatments using bicarbonate-containing dialysis solutions can result in large intradialytic increases in serum bicarbonate concentration, potentially inducing intradialytic alkalemia. It has been suggested that a time-varying, compared with a constant, dialysate bicarbonate concentration may limit the intradialytic increase in serum bicarbonate concentration (Tobvin & Sherman, Semin Dial 2016). We tested this hypothesis using a mathematical model of bicarbonate transport during HD.

Method
We used the H+ mobilization model describing bicarbonate transport during HD (Sargent et al, Semin Dial 2018) to compare intradialytic serum bicarbonate concentrations when using constant or time-varying dialysate bicarbonate concentrations that deliver the same total amount of buffer base to the patient during the HD treatment. We employed this model to evaluate different time-varying dialysate bicarbonate concentration profiles that started at a high value and then decreased as a step function with a 10-minute timing resolution. Dialysis time was 210 minutes, dialysis solutions were assumed to contain acetate at 3 mEq/L, and all kinetic parameters were assumed to be identical to those reported by Sargent et al (Semin Dial 2018). All results with time-varying dialysate bicarbonate concentrations were compared to a constant dialysate concentration of 32 mEq/L.

Results
Example results comparing time-varying (36.0 mEq/L for the initial 40 min, 31.2 mEq/L thereafter) and constant (32 mEq/L) dialysate bicarbonate concentrations are shown in the figure. The time-varying dialysate bicarbonate concentration lowered the peak intradialytic serum bicarbonate by 0.4 mEq/L for approximately one-half of the treatment. Similar reductions in the peak intradialytic serum bicarbonate concentration could be achieved if the initial high dialysate bicarbonate concentration was 37.6 mEq/L for 30 min or 40.8 for 20 min. The optimal initial high dialysate bicarbonate concentrations and the reduction in the peak intradialytic serum bicarbonate concentrations were somewhat dependent on the assumed patient-dependent H+ mobilization coefficient.

Conclusion
We conclude that a time-varying dialysate bicarbonate concentration can lower the peak intradialytic serum bicarbonate concentrations while delivering the same total amount of buffer base to the patient. Whether this approach will yield improved patient outcomes requires further evaluation.