bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0866EVALUATION OF ERYPTOSIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: GÖK Mehmet Gökhan , Paydas Saime , Kaya Bülent , Onan Engin , Boral Barış 
Published: June 2020

Abstract

Background and Aims
One of the many factors in the pathogenesis of renal anaemia, is eryptosis. The aim of this study is to evaluate eryptosis in patients with chronic renal disease stage 3-5 and 5 dialysis (5D).

Method
Patients with CKD who were monitored in our nephrology department were included in the study. The age range of the patient groups was 18-80 years and haemoglobin levels were &lt;13 g / dl in men and &lt;12 g / dl in women. As parameters of eryptosis, flow cytometric annexin V binding and intracellular calcium, and superoxide dismutase (SOD) activity with ELISA method were measured in 59 predialysis patient (eGFR&lt;60 mL / min 1.73 m2), 26 haemodialysis patient, 21 peritoneal dialysis patient and 29 healthy volunteers with similar age (control). Haematological and biochemical tests including complete blood count(CBC), erythrocyte sedimentation rate (ESR), Parathormone (PTH), 25-OH vit D3, Blood urea nitrogen (BUN), Creatinine (Cr), C-reactive protein (CRP), Na, K, phosphor (P), ionized and total Calcium, Ferritin, B12 and Folate, were performed. IBM SPSS Statistics Version 20.0 was used for statistical analysis of the data

Results
The amount of intracellular calcium were 3.05 ± 1.66 in predialysis group, 2.24 ± 0.99 in haemodialysis group, 2.38 ± 0.87 in peritoneal dialysis group and 1.71 ± 0.46 in control group. For intracellular calcium there was statistically significant difference only between predialysis group and control group (p &lt;0. 000). Annexin V binding were calculated as 1.05 ± 0.99 in predialysis group, 1.15 ± 0.56 in haemodialysis group, 1.06 ± 0.87 in peritoneal dialysis group and 0.88 ± 0.86 in control group. Comparing to control group annexin V binding in predialysis, haemodialysis and peritoneal dialysis groups, were statistically significantly increased (for all p &lt;0.000). SOD activity was 0.07 ± 0.07 in predialysis group, 0.13 ± 0.08 in haemodialysis group, 0.14 ± 0.07 in peritoneal dialysis group and 0.03 ± 0.01 in control group. The difference between the control group and dialysis group was statistically significant (p &lt;0. 00). Comparing to nonusers; patients using calcium channel blockers (CCB) had low annexin V binding level (p = 0.013). Patients using erythropoietin (EPO) had elevated annexin V binding level (p &lt;0.000) and lower intracellular calcium (p = 0.014) according to non- users.

Conclusion
We determined increased eryptosis in patients with CKD stage 3-5 and 5D in our study. Inflammation and elevated parathormone were also associated with increased eryptosis. Therefore, eryptosis may be an important factor in the pathogenesis of renal anaemia. Inflammation associated CKD may increase eryptosis. In addition, this effect can be taken into consideration in the planning of treatment because of the lower incidence of eryptosis in patients using calcium channel blocker and EPO.
P0881ANEMIA SIGNIFICANTLY INCREASES RISK OF OSTEOPOROSIS IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE
Authors: Lee Seonyeong , Nam Yooju , Kim Hyung Woo , Chang Jae Hyun , Yoo Tae-Hyun 
Published: June 2020

Abstract

Background and Aims
Anemia was frequently observed in chronic renal failure patients. The risk of osteoporosis is higher in patients with chronic anemia. Chronic anemia also showed a close relationship with bone mineral density. However, few studies have been done whether anemia affects bone mineral density with chronic kidney disease(CKD) patient. Therefore, the aim of our study is to evaluate the relationship between anemia and bone mineral density(BMD) in a large sample of non-dialysis CKD cohort.

Method
We performed an observational study in 2,089 patients who measured hemoglobin and BMD with non-dialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Anemia was defined as hemoglobin(Hb) levels of &lt; 13.0 g/dL for males and 12.0 g/dL for females, respectively. BMD was estimated by dual energy x-ray absorptiometry system. The observed variable was decline of BMD during follow up.

Results
The mean age was 53.6 ± 12.2 years and 1,292(61.1%) patients were males. The BMD score was positively correlated with hemoglobin levels (β, 0.007; 95% CI, 0.003-0.012; P 0.002), but inversely with prevalence of anemia (β, -0.03; 95% CI, -0.042--0.008; P 0.004). In the multivariable logistic regression model, the prevalence of osteoporosis was significantly higher in the anemia group than that in the normal hemoglobin levels (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.11-2.51, P=0.014). Among 881 patients except unavailable following BMD, 396 (19.7%) patients developed the decline of BMD during a median follow-up duration of 48 (interquartile range, 46-49) months. In the fully adjusted multivariable Cox models, risk of developing the decline of BMD was significantly higher in the anemia group (HR, 1.38; 95% CI, 1.02-1.87; P= 0.036) as compared to normal hemoglobin group.

Conclusion
We found that anemia is independently and significantly correlated with an increased risk of osteoporosis with non-dialysis CKD. Our study suggests that prompt correction of anemia in CKD patients could be beneficial to preserving bone mineral density.
P0884MYO-INOSITOL HEXAPHOSPHATE PEGYLATION IMPROVES BIOAVAILABILITY BUT REDUCES ITS ANTI-VASCULAR CALCIFICATION EFFECT IN RATS
Authors: Pérez M Mar , Ferrer Reynes Miguel David , Ortega-Castro Joaquín , Bassissi Firas , Perelló Joan , Salcedo Carolina 
Published: June 2020

Abstract

Background and Aims
Vascular calcification (VC) is a major contributor to increased morbidity and mortality in End Stage Kidney Disease (ESKD) patients undergoing dialysis. SNF472, a salt of inositol hexaphosphate (InsP6), is a selective calcification inhibitor that interferes in the formation and growth of ectopic hydroxyapatite (HAP). SNF472 is currently in Phase 3 clinical trials for the treatment of calciphylaxis in ESKD patients on dialysis. Inositol-1,2,3,5-tetraphosphate-4,6-bisPEG100 (InsP4bisPEG or INS3001) results from the PEGylation of inositol tetraphosphate (InsP4) with polyethylene glycol (PEG) 100. Our aim was to compare the relative bioavailability of SNF472 and InsP4bisPEG and their efficacy in the inhibition of calcification in silico, in vitro and in vivo.

Method
Subcutaneous (10 mg/kg) pharmacokinetics of InsP4bisPEG and SNF472 were assessed in Sprague Dawley (SD) rats. To evaluate the adsorption binding affinity (Eads) of SNF472, InsP4bisPEG and other inositol phosphates to the HAP crystal surface, computational studies were performed using Density Functional Theory calculations with DMOL3 (MS2016). The in vitro efficacy of the compounds was evaluated using a pharmacodynamic assay to measure the calcification potential of human plasma. An in vivo efficacy study (calcification induced by 3 consecutives daily s.c. administrations of 150 kIU/kg vitamin D3) was performed with SD rats receiving s.c. vehicle, or equimolar doses (36 µmol/kg) of SNF472 or InsP4bisPEG once daily.

Results
The PEGylation of inositol tetraphosphate in positions 4 and 6 increased the exposure and t1/2 of the compound when given subcutaneously compared to SNF472. Molecular modelling revealed that SNF472 binds to the HAP surface with higher affinity than InsP4bisPEG and INSP4 (ΔEads=-352 kcal/mol for SNF472, ΔEads=-177 kcal/mol for InsP4bisPEG and ΔEads=-146 Kcal/mol for InsP4, taking inositol as reference). These results were correlated with the inhibition of calcium phosphate crystallization in plasma in vitro. SNF472 treated animals presented significantly lower calcium levels in aorta, which were 38% and 55% lower than placebo and InsP4bisPEG treated animals, respectively.

Conclusion
The differential pharmacokinetic profile of InsP4bisPEG (INS3001) does not translate into higher, but lower, efficacy than SNF472 against vascular calcification when comparing equimolar doses.
P0885THE RELATIONSHIP BETWEEN BONE REGULATORY MARKERS AND BONE TURNOVER IN RENAL OSTEODYSTROPHY
Authors: Salam Syazrah , Gallagher Orla , Gossiel Fatma , Khwaja Arif , Eastell Richard 
Published: June 2020

Abstract

Background and Aims
Renal osteodystrophy is common in advanced chronic kidney disease (CKD) patients and is characterized by abnormal bone turnover and mineralization. Parathyroid hormone (PTH) increases bone turnover through osteoblast and osteoclast activation. Osteoprotegerin (OPG) is a decoy receptor of receptor activator of nuclear factor kappa-β ligand and thus, inhibits osteoclast maturation. Meanwhile, sclerostin is an inhibitor of the Wnt signalling pathway and thus, inhibits osteoblast maturation. We aimed to assess the relationship between these bone regulatory markers and bone turnover as assessed by bone histomorphometry and bone turnover markers (BTMs).

Method
We recruited 43 CKD patients with eGFR&lt;30ml/min/1.73m2 or on dialysis. Fasting serum samples were analysed using Immunodiagnostic Systems automated assays (Boldon, UK) for intact PTH (iPTH) and BTMs such as bone alkaline phosphatase (bALP) and intact procollagen type 1 N-terminal propeptide (intact PINP) which are bone formation markers, and tartrate-resistant acid phosphatase 5b (TRAP5b) which is a bone resorption marker. OPG and sclerostin were analysed using manual ELISA by Biomedica (Vienna, Austria). Trans-iliac bone biopsy was performed after tetracycline labelling. Bone samples were analysed using quantitative histomorphometry. Normal bone turnover was defined as bone formation rate/bone surface (BFR/BS) of 18 - 38µm3/µm2/year. Spearman rank correlation was used to test the relationship between the variables.

Results
Median BFR/BS was 32.12 (IQR 17.76 – 48.25) um3/um2/year. 26% of patients had low and 40% had high bone turnover. iPTH and OPG were positively correlated with BFR/BS (rho = 0.42, p&lt;0.01 and rho = 0.36, p&lt;0.05 respectively). Sclerostin was not correlated with BFR/BS. Furthermore, sclerostin did not correlate with bALP and intact PINP whereas OPG correlated with TRAP5b (rho = 0.43, p&lt;0.01). iPTH correlated with bALP (rho = 0.62, p&lt;0.001), intact PINP (rho = 0.62, p&lt;0.001) and TRAP5b (rho = 0.50, p = 0.001).

Conclusion
Circulating levels of iPTH and OPG were modestly associated with bone turnover but sclerostin was not. There are likely to be bone regulators other than iPTH, OPG and sclerostin which regulate bone turnover in renal osteodystrophy.
P0888FIBROBLAST GROWTH FACTOR 23 PRODUCES ARTERIAL STIFFNESS THROUGH CHANGES IN VASCULAR SMOOTH MUSCLE CELL PHENOTYPE
Authors: Muñoz-Castañeda Juan R , Rodelo-Haad Cristian , Pendon-Ruiz de Mier M Victoria , Vergara Noemi , Revilla-Gonzalez Gonzalo , Diaz-Tocados Juan Migueo , Membrives Cristina , Lopez-Baltanas Rodrigo , Soriano Cabrera Sagrario , Martin-Malo Alejandro , Ureña Juan , Santamaria Rafael , Rodriguez Mariano 
Published: June 2020

Abstract

Background and Aims
In patients with chronic kidney disease (CKD), high levels of c-terminal fibroblast growth factor 23 (FGF23) are associated with cardiovascular disease and mortality. Vascular smooth muscle cells (VSMC) may present two clearly differentiated functional phenotypes, contractile and synthetic. The abundance of synthetic phenotype is associated with vascular dysfunction and it is unknown whether in FGF23 may promote transition from a contractile to a synthetic phenotype in VSMC causing vascular stiffness. The present study was conducted to evaluate whether FGF23 affects VSMC phenotype and arterial stiffness.

Method and Results
High levels of FGF23 promoted VSMC transition from a contractile to a synthetic phenotype. These effects were mediated through FGFR1 and Ras/MAPK signaling activation. Inhibition of both pathways enhanced contractile phenotype of VSMC. The pro-contractile microRNAs, miR-221 and miR-222 were reduced by FGF23 and miR-221 transfection recovered the contractile phenotype of VSMC decreased by FGF23. In experimental rats, exogenous infusion of FGF23 produced an increase in vascular wall thickness with VSMC exhibiting synthetic phenotype and reduction of plasma levels of miR-221. Functional studies performed on aortic arterial rings revealed that passive and active forces were altered in rats treated with FGF23. In a group of CKD stage 2-3 patients with rather high levels of FGF23 it was observed an increased in pulse pressure reflecting vascular stiffness together with low plasma levels of miR-221 and miR-222.

Conclusion
FGF23 favors the transition of VSMC from contractile to synthetic phenotype causing vascular dysfunction and arterial stiffness; this may be a mechanism by which FGF23 contribute directly to the development of vascular disease in CKD patients.
P0897RISK FACTORS FOR AVASCULAR BONE NECROSIS IN PATIENTS WITH LUPUS NEPHRITIS
Authors: Monova Daniela , Monov Simeon , Kamenov Assen , Milenova Vladislava 
Published: June 2020

Abstract

Background and Aims
Avascular necrosis of bone (AVN) is an important complication of systemic lupus erythematosus (SLE) and often causes serious physical disability. The aim of this study was to investigate the risk factors for symptomatic avascular necrosis of bone (AVN) in lupus nephritis (LN) patients.

Method
The records of 374 patients (43 males, 331 females) with kidney biopsy-proven LN were reviewed retrospectively. Symptomatic AVN cases were defined as those with at least one diagnosis of AVN. The patients with LN who did not have AVN were evaluated as a control group. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression.

Results
Symptomatic AVN was present in 17 patients (4 males, 13 females, mean age of 27,4±6,7 years). Among the 17 patients, 28 joints presented AVN. 12 occurred in hips (2 bilateral), 6-in ankles, 4-in knees, 3-in shoulders and 1- in lumbar spine. In 9 patients AVN involved 2 or more joints. 14 patients were on steroids at the time of presentation of AVN. 2 patients were not on CS and 1 patient did not has documentation of steroid use. Meta-analysis demonstrates a significant increased risk of AVN in patients with high disease activity and class IV LN (p&lt;0,005). LN patients with AVN showed an earlier onset age (p&lt;0,05) and received significantly higher total cumulative corticosteroid dose. AVN was not significantly associated with use of immunosuppressive agents. Serositis, coagulation disorders, vasculitis, cigarette smoking were higher incidence in male with LN and AVN. Raynaud‘s phenomenon, autoimmune thyroiditis, arthritis, Sjögren’s syndrome, IgM anticardiolipin antibodies, antiphospholipid syndrome, Cushingoid body habitus were higher incidence in female with LN and AVN.

Conclusion
Many risk factors have been involved in the development of AVN in LN patients. AVN is prevalent in class IV LN and in younger patients. Since asymptomatic osteonecrosis may remain undetected, its true prevalence could be much higher than we reported. Multifocal lesions involving more than three anatomical sites are unusual. Corticosteroids are the principal risk factor, although some cases of AVN occur in relatively steroid naïve patients. Early detection of AVN is important because the prognosis depends of the stage and location of the lesion. An individual risk assessment for AVN development should be made prior to and during treatment for LN, especially in patients high dose corticosteroids.
P0900EXPLORE THE MECHANISM OF BEAUVERICIN ON THE OSTEOBLAST CELLS
Authors: Lu Chien-Lin , Lu Kuo-Cheng 
Published: June 2020

Abstract

Background and Aims
In chronic kidney disease (CKD), dysregulation in mineral and bone metabolism cause abnormal bone turnover disease. Over the past years, we focus the dysregulation of osteoblast and osteoclast in CKD. Numerous evidences have shown beauvericin (BEA), a cyclic hexadepsipeptide from Codyceps cicadae, possesses anti-convulsion, anti-arrhythmia, sedation, and anti-tumor activities. The mechanism of the BEA cytotoxicity on osteoblast remains fully unclear. During bone formation and fracture healing, osteoblasts and chondrocytes undergo an orderly developmental progression that ultimately ends in apoptosis. It is still unclear what signal transduction pathways are used of beauvericin in programmed cell death in osteoblasts and its effect on bone turnover.

Method
7F2 cell line is cultured in Dulbecco’s modified eagle medium (DMEM). To induce osteoblast differentiation, a total of 1 × 105 7F2 cells were plated in a 6-cm dish containing 100 μg/mL ascorbic acid, and 10 mM β-glycerol phosphate in the absence or presence of a 0-3μM dose of Beauvericin overnight. The cytotoxic effect of BEA was first determined using the MTT method. Cell lysates were prepared by extracting proteins with lysis buffer, and western blots were developed with a peroxidase-conjugated secondary antibody, and then proteins were visualized by enhanced chemiluminescence (ECL) procedures.

Results
To clarify the rational of inhibitory effect of beauvericin on osteoblast, preosteoblast 7F2 cells were treated with 0-3μM beauvericin overnight. The extent of cell viability after 5-day culture period and observed through microscopy and MTT assay. Figure 1 showed Beauvericin can significantly decrease the number of differentiated osteoblasts in a dose dependent manner. Figure 2 in MTT assay showed the 7F2 osteoblast cells survival rate was significant reduced under beauvericin treatment, especially in high dose of beauvercin. Western blot analysis in Figure 3 showed that under 2 μM Beauvericin dose treatment, the expression of Bax protein was increased and conversely the expression of BCl-2 was decreased.

Conclusion
Taken together, we thought Beauvercin induce 7F2 osteoblast cells death and might be in a relation to apoptosis. However, the further detail mechanism is need further investigated.
P0903EFFECTS OF OSTEOPOROSIS MEDICATIONS ON BONE FRACTURE IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Kao Chih-Chin , Wu Pei-Chen , Chuang Ming-Tsang , Wu Mai-Szu , Chang Tzu-Hao 
Published: June 2020

Abstract

Background and Aims
To evaluate the association of osteoporosis medications and outcomes of patients at risk of CKD.

Method
We included patients with stage 3-5 CKD from three Taipei Medical University-affiliated hospitals between January 1, 2011 and August 31, 2016. Patients were divided into two groups based on whether they received osteoporosis medications (bisphosphonates, raloxifene, teriparatide, or denosumab) and then matched at a 1:1 ratio by using propensity scores. The outcomes of interest were bone fractures, cardiovascular (CV) events, and all-cause mortality. Cox proportional hazard regression models were applied to identify the risk factors.

Results
A total of 39128 patients with CKD were included. After propensity score matching, 763 patients were in the study and control groups, respectively. The mean age of patients was 71.9 ± 12.5 years, and 34.4% of patients were men. After a median follow-up of 2.9 years, the incidence rates of bone fracture, CV events, and all-cause mortality were 10.4%, 7.5%, and 7.5%, respectively. Multivariate analysis results indicated that osteoporosis treatment was note associated with reduced risks of bone fracture (HR 0.85; 95% CI 0.43–1.68; P = 0.65), CV events (HR 0.82; 95% CI 0.56–1.20; P = 0.30), and all-cause mortality (HR 0.74; 95% CI 0.51–1.08; P = 0.12). Subgroup analysis demonstrated only patients with CKD stage 3 who received osteoporosis medications associated with better survival.

Conclusion
Osteoporosis medications did not reduce bone fractures, CV events or mortality in patients with CKD. Improved overall survival was observed in patients with CKD stage 3.
P0909HYPOCALCAEMIA MANAGEMENT POST PARATHYROIDECTOMY IN RENAL PATIENTS - A REVIEW OF PRACTICE
Authors: Tay Tricia , Chinnadurai Rajkumar , Chrysochou Tina , Doran Helen , Sinha Smeeta 
Published: June 2020

Abstract

Background and aims
Hypocalcaemia is a common post-parathyroidectomy complication in renal patients with secondary hyperparathyroidism. This is due to reduced parathormone (PTH) mediated calcium absorption in the kidneys and increased influx of calcium to bones. Our initial study in January 2015 showed preloading patients with one alfacalcidol 2 microgram once a day for 5 days preoperatively was ineffective in reducing hypocalcaemia related complications. We re-investigated the outcomes in patients following a change in practice to use one alfacalcidol 5 microgram once a day for 5 days preoperatively.

Method
All patients with pre-existing chronic kidney disease (CKD) who underwent parathyroidectomy by a single surgeon in our centre between March 2016 and October 2017 were included (12 patients). The outcomes (length of hospital stay and hypocalcaemia requiring IV calcium replacements) were compared with a previous study on patients operated on by the same surgeon between April 2008 and September 2014 (24 patients). Statistical analysis was conducted using Microsoft excel and SPSS version-22.

Results
Twelve patients were included in this study; 5 were females. Mean age at surgery was 54 (range 45-61) years. Eight patients were on long-term haemodialysis, 3 had a functioning renal transplant and 1 had CKD stage 5. Eight patients had been receiving cinacalcet for more than one month preoperatively.
Mean length of stay (LoS) was 5.3 days (range 3-10), half (n=6) were discharged four days post-op. Ten had a total parathyroidectomy, of which half (n=5) were discharged after post-op day 4. Four patients were not preloaded with 5mcg as per protocol; reasons for non-adherence to the protocol included regular prescription of alfacalcidol and physician discretion to utilise a lower dose. Patients with lower pre-op corrected calcium levels (2.4-2.6 mg/dL) stayed for a mean of 6.74 days after surgery. This was a longer LoS compared to other calcium ranges. No hypercalcemia related complications were recorded. The need for post-operative intravenous calcium use decreased from 10/24 to 2/12. Despite more patients having total parathyroidectomy and being on dialysis, a smaller proportion required IV calcium in the post-operative phase, although this was not statistically significant due to the small sample size (p=0.26).

Conclusion
Our study highlights that the current practice of preloading one alphacalcidol 5 mcg once a day for 5 days preoperatively in renal patients undergoing parathyroidectomy appears to be a safe and effective approach. Ongoing monitoring and further studies on a larger cohort of patients is needed to strengthen these observations.