bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0849LOWER TRANSFERRIN SATURATION INDEX (TSAT) IS ASSOCIATED WITH WORSE HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN NON-DIALYSIS DEPENDENT CHRONIC KIDNEY DISEASE (NDD-CKD) PATIENTS AT BOTH HIGHER AND LOWER HEMOGLOBIN LEVELS
Authors: Guedes Murilo , Muenz Daniel , Zee Jarcy , Lopes Marcelo , Waechter Sandra , Stengel Benedicte , Massy Ziad , Speyer Elodie , Finkelstein Fredric , Sesso Ricardo , Pisoni Ronald , Robinson Bruce , Pecoits-Filho Roberto 
Published: June 2020

Abstract

Background and Aims
Iron Deficiency (ID) is a common condition in NDD-CKD patients that is associated with poorer clinical outcomes. In different populations, such as congestive heart failure patients, treatment of ID leads to better clinical outcomes and HRQOL. However, the impact of ID on HRQOL is previously unknown among NDD-CKD individuals. We analyzed real world data from a multinational cohort of NDD-CKD stage 3 to 5 patients under nephrology care to evaluate the association between TSAT and HRQOL measures from the KDQOL-36.

Method
Patients from Brazil (N=205), France (N=2015), and the US (N=293) enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps, 2013 to 2019) with available TSAT, ferritin, and HRQOL data were included in the analysis. We grouped patients according to their TSAT levels as ≤15%, &gt;15-20%, &gt;20-30% (reference group), &gt;30-50%, and &gt;50%. We considered the TSAT value that preceded the HRQOL measurement closest in time as the predictor. Linear mixed regression was used to estimate the mean differences (95% CI) in physical composite summary (PCS), mental composite summary (MCS), and KDQOL-36 subdomains across TSAT categories. Models were adjusted for potential confounders.

Results
2513 patients (62% male, 44% with diabetes, mean (SD) age 67 (13) years; 48%, 44% and 8% having stage 3, 4 and 5 NDD-CKD, respectively) were included in the analysis. Mean TSAT was 25 % (10). Distribution across TSAT categories was 14%, 19%, 42%, 23, and 2%, respectively. The median [IQR] number of days between TSAT measurement and PRO collection was 24 [13, 49] days. Mean PCS was 41 (10) and MCS was 45 (11). In the multivariate analysis, TSAT ≤15% was associated with lower HRQOL scores, in particular PCS, and with less favorable effects and symptoms of kidney disease (Figure). Similarly, less favorable HRQOL scores captured in the SF-12 subdomains indicative of physical HRQOL were observed in patients with lower TSAT. The adjustment for Hb only slightly attenuated the effects, and the results were not different for subgroup of patients with hemoglobin &lt;11.5 vs ≥ 11.5 g/dL.

Conclusion
Lower TSAT levels, indicative of iron deficiency, are associated with poorer HRQOL in NDD-CKD patients, particularly for physical domains and effects of kidney disease, even after adjustment for potential confounders and stratification for normal and low hemoglobin levels. Randomized controlled trials of iron replacement therapy aiming to evaluate its impact on HRQOL among NDD-CKD individuals are needed to confirm and integrate these findings into clinical practice.
P0851THE DIFFERENTIAL IMPACT OF INTRAVENOUS IRON IN A MODEL OF EXPERIMENTAL URAEMIA ON TISSUE MARKERS OF OXIDATIVE STRESS
Authors: Bhandari Sunil , Nuhu Faisal , Seymour Anne Marie 
Published: June 2020

Abstract

Background and Aims
Uraemia leads to changes in cardiac structure, metabolic remodelling and anaemia, key factors in the development of heart failure in patients with chronic kidney disease (CKD). Previous studies have identified abnormalities in mitochondrial function in experimental uraemia, potentially impairing energy provision and enhancing oxidative stress. The aim of this study was to characterise oxidant status and changes in mitochondrial function in uraemia and the impact of iron therapy.

Method
Experimental uraemia was induced in male Sprague-Dawley rats via a subtotal nephrectomy and parenteral iron administration at 6 weeks post-surgery (10mg/Kg body weight). Pro-oxidant activities and antioxidant capacities (oxidised glutathione (GSSG) relative to reduced (GSH)) in both sham and uraemic animals and lipid peroxidation (thiobarbituric acid-reactive substances (TBARS) was measured. Mitochondrial function was assessed using the SEAHORSE analyser.

Results
Oxidative stress was increased in cardiac tissue (69% increase in GSSG/GSH ratio, 38% rise in TBARS and significantly (79%) upregulated NADPH oxidase activity. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities were significantly increased by 30%. Iron reduced GSSG/GSH ratio and TBARS by 62% and 51% respectively. Iron therapy was also associated with significantly increased aconitase activity. Parenteral iron improved respiratory reserve in cardiac mitochondria and skeletal mitochondria suggests IV iron restores mitochondrial function.

Conclusion
Uraemia leads or oxidative stress and mitochondrial dysfunction in cardiac tissue. Iron therapy reduces oxidative stress and improves cardiac mitochondrial function. This might lead to reduced adverse cardiovascular outcomes in CKD.
P0879EARLY STEROID WITHDRAWAL HAS A POSITIVE EFFECT ON BONE KIDNEY TRANSPLANT RECIPIENTS: A PROPENSITY SCORE STUDY WITH INVERSE PROBABILITY-OF-TREATMENT WEIGHTING
Authors: Batteux Benjamin , Gras-Champel Valérie , Lando Mathilde , Brazier François , Desailly-Henry Isabelle , Rey Amayelle , Benis Youssef , Masmoudi Kamel , Choukroun Gabriel , Liabeuf Sophie 
Published: June 2020

Abstract

Background and Aims
Long-term corticosteroid use after kidney transplantation is associated with a decrease in bone mineral density and a high fracture risk. We hypothesized that patients with early steroid withdrawal (ESW) would display a gain in bone mineral density in the year following kidney transplantation, when compared with patients on long-term corticosteroid therapy (LTCT).

Method
In a cohort of kidney transplant recipients, 317 patients were included between 2012 and 2018. Dual-energy X-ray absorptiometry was performed 1 and 12 months after transplantation. The data were analyzed using linear regression with inverse probability-of-treatment weighting based on a propensity score.

Results
One year after transplantation, the gain in bone mineral density was significantly greater in recipients with ESW than in recipients on LTCT for the lumbar spine (+0.027 g/cm, P &lt; 0.001) and the femoral neck (+0.021 g/cm, P = 0.035). Among patients with ESW, (i) none had osteoporosis, (ii) the percentage with normal bone mineral density increased from 35.0% at month 1 to 56.4% at month 12, and (ii) the percentage with osteopenia fell from 52.5% to 43.6%. In patients undergoing LTCT, the fracture incidence was 14.5 per 1000 person-years. None of the patients in the ESW group experienced a fracture. Cardiovascular risk factors were more prominent in the LTCT group relative to the ESW group: patients in LTCT group (i) were more likely to have high blood pressure (p&lt;0.001), (ii) gained more weight gain (p=0.032) and (iii) displayed a greater increase in serum triglyceride levels (p=0.004).The acute rejection rate was similar in the two groups.

Conclusion
Early steroid withdrawal is associated with a spontaneous increase in bone mineral density at 12 months post-transplantation (relative to patients on long-term steroid therapy), with a reduction in several cardiovascular risk factors and does not appear to harm the graft.
P0886EFFICACY AND SAFETY OF EVOCALCET IN PERITONEAL DIALYSIS PATIENTS: A SINGLE CENTER LONGITUDINAL STUDY IN JAPAN
Authors: Uchida Hiroki , Kurahashi Motoyasu , Harada Kenji , Kanai Hidetoshi 
Published: June 2020

Abstract

Background and Aims
Calcimimetic agent is used for secondaryhyperparathyroidism (SHPT), but it might cause gastrointestinal side-effects. These side effects are severe problem for PD patients with gastrointestinal symptoms due to dialysis fluid storage. Evocalcet is a new calcimimetic agent for SHPT, and expected to reduce gastrointestinal related symptoms. There have been some reports about switching from cinacalcet to evocalcet or administered for HD patients. However, there have been few reports on PD patients. Here, we reported the efficiency and safety of evocalcet in PD patients.

Method
PD patients who had newly started to treat for SHPT with evocalcet, between August 2018 to August 2019 were selected. Patients who died or transferred to HD within 6 months after administered evocalcet were excluded. We compared the changes in whole PTH level, serum phosphorus level and serum corrected calcium level with baseline and after administration. Moreover, we investigated adverse events of gastrointestinal related symptoms.

Results
Overall, 34 PD patients were included, (mean age: 67.5 years old, male/female: 23/11, average PD vintage: 39.6 months, serum phosphorus level: 5.1 ± 1.0 mg/dl). There was a significant reduction in whole PTH at week 16 from baseline (346 ± 187 pg/ml vs 258 ± 196 pg/ml, p &lt;0.001), and this relation was continued at week 32. There was no significant change in serum phosphorus level during this study. Serum corrected calcium level was the lowest at week 12 from baseline (9.4±0.7 mg/dl vs 9.0±0.1 mg/dl: p=0.004), thereafter, serum calcium level was not decline with adjustment of vitamin D receptor activators and calcium preparation. Adverse events were observed in 6 patients (18.2 %), nausea occurred in 3 patients, decreased appetite occurred in 2 patients, and diarrhea occurred in 2 patients. Although some adverse events had occurred, all patients continued study.

Conclusion
These results suggested that evocalcet might be efficient and safety in PD patients with SHPT.
P0887MAJOR OSTEOPOROTIC FRACTURES AFTER KIDNEY TRANSPLANTATION: INCIDENCE, PREDICTORS AND ASSOCIATION WITH MORTALITY
Authors: Iseri Ken , Carrero Juan Jesus , Evans Marie , Felländer-Tsai Li , Berg Hans , Runesson Björn , Stenvinkel Peter , Lindholm Bengt , Qureshi Abdul Rashid Tony 
Published: June 2020

Abstract

Background and Aims
Major osteoporotic fractures (MOF) are associated with increased morbidity and mortality in ESRD patients. We investigated incidence, predictors and clinical outcomes associated with first MOF (MOFfirst) following kidney transplantation (KT).

Method
In Swedish Renal Registry of 3992 first KT recipients (2005 -2016) (age 53 years, 65% men), we identified all MOFfirst in hip, spine, humerus and forearm following KT. We estimated incidence rates and predictors of MOFfirst using flexible parametric hazard models and Fine-Gray analysis accounting for competing risk of death, and risk of all-cause mortality following MOFfirst using Cox proportional hazards models with fracture as time-varying exposure.

Results
During median follow-up of 4.8 years (IQR 2.2-7.9 years), there were 279 fractures of which 139 were forearm fractures. The crude incidence rate of MOFfirst (n=279) was 14/1000 patient-years and that of hip fractures (n=69) 3/1000 patient-years. The multivariate-adjusted fracture incidence rates were highest during the first 6 months following KT, and two-fold increased among women. High age, female sex, previous history of MOF, diabetes nephropathy, pretransplant dialysis therapy and acute rejection were associated with increased risk for MOFfirst, whereas pre-emptive KT was associated with lower risk of MOFfirst. Spline curves showed that impact of age in women on MOFfirst was markedly higher than in men. MOFfirst (including all cases) independently predicted increased all-cause mortality (hazard ratio, HR, 1.78(95%CI 1.35-2.36)). Among MOFfirst, hip fracture (HR, 4.68(95%CI 1.56-14.06)) and spine fracture (HR, 4.02(95%CI 1.19-13.54)) were significantly associated with increased all-cause mortality.

Conclusion
The initial six months following kidney transplantation is a high-risk period for major osteoporotic fractures, especially forearm fractures. MOFs, especially hip and spine fracture, are associated with increased mortality.
P0894AEFFECTS OF DENOSUMAB ON BONE MINERAL DENSITY AND LOW ENERGY FRACTURES IN KIDNEY TRANSPLANT PATIENTS: SAFE AND EFFECTIVE
Authors: Rolla Davide , Ardini Michela , Trezzi Matteo , Bizzoni Paola , Lauria Francesca , Casabella Andrea 
Published: June 2020

Abstract

Background and Aims
Fractures are a disabling clinical outcome after kidney transplantation (KTx), with incidence 5 to 34 times higher expected in males and females, respectively. Denosumab, a fully human monoclonal antibody that binds to RANKL with high affinity and specificity, blocking the interaction of RANKL with RANK, mimicking the endogenous effects of osteoprotegerina, increase bone mineral density; however, its effects to reduce the risk of vertebral fractures and ameliorate BMD remain undefinite in the KTx.

Method
Thirteen kidney recipients (aged from 50 to 79 yy, 6.2 + 5.5 (SD) yy after KTx), 6 M and 7 F (all postmenopausal) with nearly normal renal function (creat. 1.1+-0.31 mg/dl), affected by low energy vertebral fractures (21 dorsal and 1 lumbar vertebrae), evaluated by morphometric X-ray absorptiometry (Hologic DQR-4500A), were treated with denosumab (four 60-mg doses of denosumab Q6M) over 24 months. Data for vertebral heights and height ratios (P-A), covering 9 vertebral bodies were obtained, besides the data of vertebral, femural and radius BMD.The immunosuppressive regimen consisted of CNI (TAC or CsA), MMF and 8 out of 13 patients were still taking prednisone. Bone mineral metabolism parameters (whole-PTH, 25OHD3 and alcaline phosphatase) were also evaluated.

Results
No sides effects were observed, and all Patients concluded the study.After two years of denosumab treatment, we observed a significative reduction of vertebral T-score (from -2.12 +- 0.35 (SE) to -1.67+-0.35; p&lt; .02), while T score of femural and radius did not show significative variation (-1.86+-0.21 versus -1.84+- 0.23 and -3.04+-0.42 versus -3.19+-0.45, respectively). The number of low energy vertebral fractures, basal versus two years control, had increased for only two dorsal vertebral fractures. However, to one of two subjects, with new dorsal vertebral fractures, was administered high dose of methylprednison for a severe kidney reject. No variations were observed in whole-PTH (89.31+-19.9 versus 68.38+-9.8 pg/ml), 25OHD3 (24.02+-2.75 versus 26.67+-2.29 ug/dl) and alcaline phosphatase (78.46+-12.73 versus 56.77+-7.14 UI).

Conclusion
Treatment with denosumab improve BMD at vertebral site in KTx, despite continuous steroid therapy and reduce the risk of new low energy vertebral fractures
P0907STRIKING NOVEL MULTI-MISMUTATIONS ON GNAS1,FGF23,FGFR3 GENES IN CKD WITH SECONDARY HYPERPARATHYROIDISM.(SH).SAGLIKER SYNDROME(SS).SS IS A COMBINATION-COMPULSION OF BONE DYSPLASIAS-HEREDITARY OSTEODYSTROPHİES AND SH AND CKD
Authors: Sagliker Yahya , Demirhan Osman , Sagliker Hasan Sabit , Sagliker Ozkaynak Piril , Paylar Nuray , Sagliker Cemal , Emir Idris , Ozkaynak Isıl 
Published: June 2020

Abstract

Background and Aims
Sagliker Syndrome seems to be related to CKD and the consequent SH.SS starts and develops particularly before puberty while CKD reaches stage III level with overt SH. Since it occurs in some patients, it is plausible to think SS is genetically predisposed.GNAS1, FGF23 and FGFR3 genes' mismutations on the genesis of SS is unclear, and no data are available.

Method
We conducted clinical, radiological, laboratory studies and screening for mutations in GNAS1 gene in 23 patients, FGF23 and FGFR3 genes in 17 patients.DNA isolations were performed from blood samples and mutations regions were amplified by Polymerase Chain Reaction (PCR).

Results
In 73.9% (17/23) patients, 17 different genetic abnormalities in GNAS1 were detected.Seven (58.3% ) of the 12 nucleotide alterations comprised novel missense mutations in different manners. There were also 6 heterozygous tranversion polymorphism in exons.Six of them were introngenic mismutations found in exons (introns; 65626, 70387 and 70817).We found 10 different mismutations in FGF23 gene. 8 were novel mismutations and are defined first in our study. 3 of them were in intronic region near exon 2.In FGFR3 gene we also found 22 different mutations. 16 were novel mismutations defined first in our study.8 of them were in intronic region near exon 11,last 2 were in non-coding exonic region of exon 18. Twelve mismutations were found in exons, 8 were found in introns and 2 were found in non-coding exonic regions. One was in the exon-exon junction region between exon 11 and 12 Therefore this mutation might be preventing splicing of this intron.

Conclusion
There are plenty of mutations on those three genes in Sagliker Syndrome and are consistent with an insufficiency of those three genes playing a role in the clinical phenotype of loss of function mutations and with functional alleles having predominant roles in preventing the hormonal resistance.Since the incidence of
CKD late stage III is around 8% in the world but the incidence of Sagliker Syndrome is around 0.5% in CKD patients, these gene mismutations might be responsible for bone Displasias-- Hereditary Osteodystrophies such as Mc Cune- Albright syndrome, achondroplasias etc.., although our patients were not resembling any of them but they could be in between and Sagliker Syndrome might be a combination-compulsion of Bone displasias-Hereditary Osteodystrophies and SH and CKD.
P0908FGF-23, MBD AND INFLAMMATION IN CKD
Authors: Chaikovska Mariana , Martynyuk Liliya , Sergii Butvyn 
Published: June 2020

Abstract

Background and Aims
Systemic inflammation, as well as Mineral and Bone Disease, are seen to be inherent complications of CKD, tightly related to cardio-vascular disease, protein-energy wasting and general mortality. It remains an actual problem to study relation between systemic inflammation and CKD-MBD. The aim of the study was to evaluate serum concentrations of c-terminal FGF-23 as an early marker of CKD MBD, Il-1 β, Il-6, Il-8 as inflammatory markers, and to establish relationships between FGF-23 and IL-1 β, Il-6, Il-8.

Method
The study involved 106 patients with CKD stages from 1 to 4, 47 women (44%) and 59 men (56%) aged from 35 to 72, mean (49.6± 13.9) years. The C-terminal FGF-23 fragment was determined using a set of reagents for the enzyme immunoassay «Biomedica». Concentration of IL-1β, IL-6 and IL-8 was determined using an assay «Vector BEST». The glomerular filtration rate (GFR) was calculated using the CKD EPI formula (KDIGO 2012).

Results
A progressive growth in FGF-23 levels was observed simultaneously with GFR decrease in patients with CKD. IL-1 concentration increased from CKD stage 1 ((12.64±4.30) pg/ml) to 4 ((32.06±7.86) pg/ml) (p &lt;0.05) accordingly GFR fall, as well as the level of IL-6 ((7.25±2.14) pg/ml to (46.27±10,06)pg/ml) and Il-8 ((9.39±1.62) pg/ml to (33.00±9.17)pg/ml). The existence of a strong direct association (r = 0.84, p &lt;0.05) between the level of Il-6 and FGF-23 in CKD stages 1-4 was established. IL-1 and Il-8 were found to have a medium strength assotiation (r=0.45, p &lt;0.05 and r=0.57, p &lt;0.05, accordingly) with FGF-23 concentration in patients with CKD stages 2-4.

Conclusion
The increase in the concentration of inflammatory factors along with progression of chronic renal failure was revealed. The existence of a strong link between the level of IL-6 and the C-terminal fragment of FGF-23 in CKD was established. Finding out the issue of the primary stimulation factor of FGF-23 production in CKD requires further research.
P0913HYPERPHOSPHATEMIA INCREASE INFLAMMATION PROMOTING SENESCENCE AND MUSCLE DYSFUNCTION
Authors: Sosa Patricia , Alcalde-Estévez Elena , Asenjo-Bueno Ana , Plaza Patricia , Olmos Gemma , Caballero María Angeles , Rodríguez-Puyol Manuel , López-Ongil Susana , Ruiz Maria Piedad 
Published: June 2020

Abstract

Background and Aims
Hyperphosphatemia has been associated with aging and chronic kidney disease (CKD). Sarcopenia, which is a related condition of these pathologies, is defined by loss of force and muscular mass. During aging, chronic systemic inflammation appears, termed inflammaging, due to changes in immune system function. Inflammaging has been associated with many age-related diseases including Sarcopenia and CKD. The work aimed to evaluate the effect of hyperphosphatemia on proinflammatory profile of cultured myoblast cells and to analyze, in old mice, the effect of a dietary restriction in the phosphate intake on the aging-related sarcopenia.

Methods
Culture murine myoblast C2C12 cells were used for in vitro experiments. Cells were treated with 10 mM beta-glycerophosphate (BGP) as phosphate donor for 24, 48 or 72h. Inflammation was assessed through IL6, TNFα and MCP-1 expression by RT-qPCR. Twenty-four months old, C57BL6 mice were used for in vivo studies. Mice were fed with a normal diet containing 0.6% of phosphate until 21 months, after that, one group of mice continued with a normal diet and the other group was fed with a hypophosphatemic diet, containing a 0.2% of phosphate, for the following 3 months. Old mice were compared with 5 months old mice. Muscle force was measured by a grip strength test. Serum phosphate concentration was evaluated with a commercial kit and inflammation was assessed through IL-1β expression levels by RT-qPCR.

Results
Results showed that BGP treatment augmented pro-inflammatory cytokines levels, in myoblast, at 72h. On the other hand, old mice had a 40% increase in serum phosphate concentration regarding young mice, and, in parallel, they showed a reduction in forelimb strength. Old animals feeding with a hypophosphatemic diet showed a decreased level of phosphate serum linked to a better muscle function. Pro-inflammatory cytokines expression was higher in old mice compared to young mice; those values were reduced in 24-month-mice fed with a low phosphate diet. Furthermore, there was a positive correlation between IL-1β expression levels and serum phosphate levels, suggesting that high levels of serum phosphate were increasing inflammation in vivo and a negative correlation between IL-1β and grip strength test, which shows that high levels of inflammation decrease muscular function

Conclusion
In this work, we propose that high levels of phosphate are related to inflammation in vitro and in vivo. This increase of proinflammatory cytokines decreases muscle function whereas dietary restriction of phosphate decreases inflammation and improves muscle function. These results could point to a direct link between elevated serum phosphate levels and inflammaging presented in sarcopenic people such as CKD patients and aged people.