bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0855ASSOCIATIONS BETWEEN A COMPREHENSIVE PANEL OF BIOMARKERS WITH ESA HYPORESPONSIVENESS: ROLE OF IMMUNE DYSFUNCTION IN THE PATHOPHYSIOLOGY OF CKD ANEMIA
Authors: Batalha Guilherme , Eugênia Canziani Maria , Guedes Murilo , Almeida Ana Clara , Moreno-Amaral Andrea N , Barra Ana Beatriz , Cuvello Américo , Poli De Figueiredo Carlos Eduardo , Pecoits-Filho Roberto 
Published: June 2020

Abstract

Background and Aims
An inadequate response to the treatment of anemia with erythropoiesis-stimulating agents (ESAs) in patients with chronic kidney disease is a challenging and common clinical condition previously associated with signs of inflammation and episodic clinical events. The associations between different immune response pathways and ESA hyporesponsiveness remain poorly understood. Here we describe the associations between a comprehensive panel of inflammatory biomarkers and ESA resistance in a group of stable HD patients.

Method
This is post-hoc analysis of the baseline evaluation of patients enrolled in the HDFIT, a randomized controlled trial. A panel comprising a more general (CRP), innate (IL-1β and IL-6), adaptive (IFNγ, IFNα2) biomarkers of immune response, and also a specific vascular inflammation (MCP-1) biomarkers were simultaneously measured with the same serum sample through turbidimetry and Milliplexï£¨ Human Cytokine Magnetic Bead Panel - EMD Milipore Corporation, USA. Multivariable analysis was used to assess the association of their concentrations with the erythropoietin resistance index (ERI), defined as the weekly ESA dose divided by hemoglobin level.

Results
A total of 155 patients were included in this analysis (mean age 52 ± 6; 70% male; 32% with diabetes; mean hemoglobin 11.7 ± 1.5; median ESA dose/week 8000 IU IQR: 4000-12.000). Patients in the highest ERI tercile were mostly female, younger, more diabetic and with slightly higher proportion of iron prescription compared to those in the lowest tercile of ERI. The multivariable models adjusted for age, sex, diabetes and vascular access demonstrated that higher serum levels of IL-1β and IFN-γ were associated with higher ESA resistance, while there were no detectable associations of serum levels of IL-6 or CRP and ERI.

Conclusion
Among the biomarkers included in this comprehensive panel of biomarkers representing the multilevel nature of immune dysfunction in CKD, we observed associations between higher concentrations of innate (IL-1β) and adaptive (IFN) immune response and ESA hyporesponsiveness. Our results support the role of immune dysfunction in the pathophysiology of CKD anemia.
P0856LOW BONE MASS IS SIGNIFICANTLY ASSOCIATED WITH AN INCREASED RISK OF ANEMIA IN PATIENTS WITH CKD
Authors: Lee Seonyeong , Nam Yooju , Kim Hyung Woo , Chang Jae Hyun , Yoo Tae-Hyun 
Published: June 2020

Abstract

Background and Aims
Hypoxia has been considered to be a risk factor for osteoporosis. Several studies have reported on the close associations between the anemia and an increased risk of bone loss. However, the relationship between hemoglobin levels and bone mineral density(BMD) has not been established in chronic kidney disease (CKD) patients. Therefore, the aim of this study is to investigate the relationship between BMD and anemia in a non-dialysis CKD cohort.

Method
Among 2,238 patients with non-dialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD), 2,115 patients who measured hemoglobin(Hb) and BMD were included in the analysis. We defined anemia as hemoglobin(Hb) levels of &lt; 13.0 g/dL and 12.0 g/dL for males and females, respectively. The primary endpoint was the onset of a 15% decline in Hemoglobin 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, 0.658; 95% CI, 0.215-1.101; P 0.004). In the multivariable logistic regression model, the prevalence of anemia was significantly higher in the osteoporosis group than that in the normal BMD group (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.03-2.46, P=0.038). Among 1010 patients without data of following hemoglobin levels, 396 (19.7%) patients developed 15% decline in hemoglobin level during a median follow-up duration of 36 (interquartile range, 10-60) months. In the fully adjusted multivariable Cox models, risk of developing the 15% decline of hemoglobin was significantly higher in the osteoporosis group (HR, 1.45; 95% CI, 1.03-2.05; P= 0.035) as compared to normal BMD group.

Conclusion
This study showed that low bone mass density was independently related with anemia and hemoglobin levels in patients with non-dialysis CKD. Our findings suggest that preserve bone mass be important to maintain the levels of hemoglobin with CKD patients.
P0859ACTIVATE ENDOGENOUS HYDROXYMETHYLATION TO RESTORE ERYTHROPOIETIN PRODUCTION IN FIBROTIC KIDNEYS
Authors: LUO AN JIE , LIN SHUEI-LIONG 
Published: June 2020

Abstract

Background and Aims
Our previous studies have shown that DNA methyltransferases (Dnmt) and Epo hypermethylation are upregulated in myofibroblasts in fibrotic murine kidneys. Demethylation leads to redifferentiation of myofibroblasts into pericytes. Furthermore, nontoxic doses of 5-azacytidine can restore EPO production and ameliorate anemia in mice with kidney fibrosis. Physiologic hydroxymethylation in zygotes is mediated by the 10 − 11 translocation enzymes (Tet1, Tet2, and Tet3).

Method
The mouse model of unilateral ureteral obstruction (UUO)-induced kidney fibrosis has been found to display enhanced Tet1 and Tet3 mRNA expression at day 7 and marked increase with the disease progression.

Results
According to the results, Tet expression significantly increased in fibrotic kidney. To study the effect of myofibroblast-specific Tet3 knockout in murine models of renal fibrosis. Tet3F/F mice were generated by a targeting vector with floxed region contains exons 8-9 of Tet3, which included the coding region for the conserved Fe2+-binding motif of dioxygenase. Gli1CreERT2/+;Tet3F/F mice were used to induce knockout of Tet3 in pericytes and myofibroblasts after tamoxifen administration. Tet3F/F mice were used as the control. Oral gavage of tamoxifen 8 mg/day for 3 days was used to activate Cre recombinase in Gli1+ pericytes and myofibroblasts in adult mice (6-8 week). After two-week washout period, mice were subjected to UUO for 7 or 14 days. The body weight, plasma creatinine and BUN levels showed no significant differences between groups in mice after induction and also UUO surgery. Plasma levels of BUN and creatinine were maintained within the normal range by normally functioning contralateral kidneys after UUO surgery. In UUO kidneys, knockout of Tet3 decreased renal α-SMA and Col1a1 expression. But plasma hematocrit and renal Epo mRNA level were not different between groups. In addition to Gli1CreERT2/+ mice we also used Pdgfrb-rtTATg;LC1Tg mice to breed with Tet3F/F mice for inducible knockout of Tet3. The plasma creatinine, BUN, and hematocrit were no different between groups after UUO surgery again.

Conclusion
Overall, these findings suggested increased Tet3 in myofibroblasts may play an important role in myofibroblast activation and fibrosis. Further studies need to explore the mechanisms.
P0862DAPRODUSTAT INTERACTION WITH PHOSPHATE BINDERS HAS MINIMAL IMPACT ON HEMOGLOBIN VALUES IN HEMODIALYSIS POPULATION
Authors: Cizman Borut , Meadowcroft Amy , Biswas Nandita , Sprys Michael , Cobitz Alexander 
Published: June 2020

Abstract

Background and Aims
Daprodustat is a novel hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) currently in phase 3 development for the treatment of anemia of chronic kidney disease (CKD). Phosphate binders (PB) are widely prescribed for hemodialysis (HD) patients to control for hyperphosphatemia. The coadministration of PB and HIF-PHI may potentially impact hemoglobin values thus requiring time between PB administration and HIF-PHI. The purpose of this analysis was to determine whether daprodustat interaction with PB has an impact on hemoglobin (Hgb) values in the HD population.

Method
GSK PHI113633 study (NCT01977482) included 216 subjects on maintenance HD previously treated with rhEPO. This study included daprodustat dose-ranging for the first 4 weeks, followed by a Hgb correction/maintenance phase for the next 20 weeks; daprodustat was dosed daily without regard to the timing of PB administration. The control group received placebo for 4 weeks, followed by rhEPO for the next 20 weeks as previously reported (Clin Kidney J 2019;12(1):139-148). Target Hgb range was 10.0-11.5 g/dL from Week 4 through Week 24. Baseline PB use was a prespecified study subgroup of interest. The difference in mean Hgb values at Week 24 between treatment groups was summarized overall and by subgroup. Comparisons were performed for the Week 24 Hgb (post hoc), as well as the final dose of daprodustat, for those receiving/not receiving PB.

Results
The majority of HD subjects in this 24-week safety and efficacy study received PB at baseline; 136 of 177 (77%) of subjects on daprodustat and 33 of 39 (85%) of subjects on control were taking PBs, with comparable phosphate control at baseline [mean (±SD) phosphate: daprodustat 1.76 mmol/L (0.56); control 1.67 mmol/L (0.44)].
No meaningful difference in Hgb change from baseline (CFB) at Week 24 was noted between daprodustat and rhEPO groups (Table 1).

Conclusion
These results suggest that daprodustat can be taken without regard to the timing of PB administration. Results of the large, phase 3 dialysis study of daprodustat will be important to definitively confirm these initial observations.
P0867ANEMIA AND IRON DEFICIENCY IN NON-DIALYISIS CHRONIC KIDNEY DISEASE: A LINK WITH ADVERSE OUTOCOMES?
Authors: Fernandes Sara , Falcao Luis , Fernandes Adriana Paixão , Donato Beatriz , Costa Ana Cortesão , Raimundo Mário , Teixeira Catarina , Silva Sónia , Macedo Ana , Almeida Edgar 
Published: June 2020

Abstract

Background and Aims
Anemia is a major complication of Chronic Kidney Disease (CKD). There are few large observational studies analyzing the association between anemia and significant clinical outcomes in non-dialysis dependent CKD (ND-CKD) patients. Our aim was to evaluate the prevalence of anemia and iron deficiency and their association with mortality, cardiovascular events, need for renal replacement therapy and hospitalizations in an outpatient ND-CKD population.

Method
A patient-level, retrospective, cohort analysis of all adult ND-CKD patients evaluated in an outpatient nephrology clinic between January 2012 to December 2017 with at least one year follow up. Anemia (defined according to the WHO definition - Hemoglobin [Hb] &lt; 13.0 g/dL in men and 12.0g/dL in women), absolute iron deficiency (ferritin &lt; 100 ng/mL), other demographic and clinical data (CKD staging and etiology, comorbidities) were assessed at the first visit through individual consultation of electronic medical records.

Results
During the 6-year period, 3008 patients were identified (mean age 70.9±14.1 years; 54.5% male; 91.7% white) with a mean follow-up of 3.3±2.0 years. The most frequent cardiovascular comorbidities were arterial hypertension (81.9%), obesity (58%), diabetes mellitus (57.9%) and dyslipidemia (43.9%). The mean Hb was 11.8 ±1.9 g/dL. Anemia was present in 49.9 % of patients, with similar distribution between genders (50.4% in men vs 49.6% in women) and more frequent in white patients (92% vs 8% p= 0.019). Anemia prevalence increased across CKD stages - 12.9%, 25.9%, 57.2%, 72.7% and 86.4% for stages 1 to 5, respectively (p&lt;0,001 for the trend). Anemia was associated with cardiovascular comorbidities, such as diabetes (52% vs 32%, p&lt;0.001), hypertension (86.7% vs 77.7%, p&lt;0.001), obesity (65.5% vs 60.8 %, p=0.012) and dyslipidemia (46% vs 41.2%, p=0.01). Among patients with ferritin levels available (1638), 41.7% had absolute iron deficiency. Anemia was associated with increased mortality (74% vs 26%, p &lt;0,001) and hospitalization (61,8% vs 38.2%, p &lt;0.001). In multivariate logistic regression analysis, anemia (OR 1,923; 95%IC 1,362-2.716; p&lt;0,001) and absolute iron deficiency (OR 0.531 95% IC 0.348-0.809; p=0.003) emerged as independent predictors of death. Cardiovascular events were more prevalent in the group of patients with Hb levels 10-12 g/dL (4.1 vs2.3% 2p=0.006).

Conclusion
As expected, anemia prevalence increases across CKD stages and, as well as absolute iron deficiency, is independently associated with adverse clinical outcomes in ND-CKD patients, including death. Future studies should be developed to investigate if correction of these factors improves adverse outcomes.
P0889TO WHAT EXTENT CAN WE ACHIEVE MINERAL BONE METABOLISM TREATMENT TARGETS AS SUGGESTED BY UPDATED 2017 KDIGO GUIDELINES IN PATIENTS WITH PREDIALYSIS CHRONIC KIDNEY DISEASE
Authors: Dincer Mevlut Tamer , Özcan Şeyda Gül , Alagoz Selma , Karaca Cebrail , Gulcicek Sibel , Trabulus Sinan , Pekpak Meltem , Seyahi Nurhan 
Published: June 2020

Abstract

Background and Aims
The mineral bone disorder is an essential problem in chronic kidney disease (CKD). It is an independent modifiable risk factor for renal damage progression and CKD related mortality. Therefore, it is important to treat chronic kidney disease mineral bone disorder (CKD-MBD) according to international guidelines. Data on the management of mineral bone disorders in predialysis patients is scarce. We aimed to investigate the proportion of CKD-MBD patients reaching targets suggested by the updated 2017 KDIGO guidelines.

Method
We performed a multicenter cross-sectional study. We recruited consecutive adult (&gt;18 years of age) CKD 3-5 patients who were on regular nephrology outpatient clinic follow up. Patients who have GFR loss over 30% in the last six months, patients with malignancy, and decreased life expectancy due to severe comorbid disease and patients on renal replacement therapy were excluded. Data were collected in two-time points: one during the recruitment (second data point) and one, three to six months prior to the current visit (first data point). Persistent laboratory abnormalities were defined by out of normal range values in both time points. Therapeutic inertia was calculated for hyperphosphatemia. It was defined as a lack of using phosphate binders despite hyperphosphatemia.

Results
We examined a total of 213 patients for 3 different nephrology outpatient clinics. Of these patients, 49.5 % were male, with a mean age of 64,9 ± 12,0 years. 51.7 % of the patients were diabetic, 78 % were hypertensive, and 20.1 % had a history of coronary artery disease. Laboratory values related to MBD are shown in Table 1. KDIGO guideline targets were not reached in 14.8%, 18.4%, 59.0%, 71.0% patients regarding Ca, P, PTH, and vitamin D in the first visit. The targets were not reached in 15.0%, 19,2%, 61,2%, 81% patients regarding Ca, P, PTH, and vitamin D in the second visit. Persistence of out of target values were observed in 5.8%, 9.9%, 49.2% and 65.4% of the patients for Ca,P, PTH and Vitamin D respectively. The prevalence of therapeutic inertia for hyperphosphatemia was 34,4 % in the second visit

Conclusion
Regarding KDIGO guidelines, MBD is not optimally managed in predialysis CKD patients. Clinicians should have an active attitude regarding the correction of MBD even at the earlier stages of CKD.
P0896TRABECULAR BONE SCORE PREDICTS OSTEOPOROTIC FRACTURE IN CHRONIC KIDNEY DISEASE PATIENTS
Authors: Bae Eunjin , Lee Tae Won , Jang Ha Nee , Cho Hyun Seop , Kim Hyun-Jung , Chang Se-Ho , Park Dong Jun 
Published: June 2020

Abstract

Background and Aims
Chronic kidney disease and mineral bone disease (CKD-MBD) is a common complication of CKD and this is associated with higher risk of fracture, morbidity and mortality. Current guidelines recommend measurement of bone mineral density (BMD) in CKD patients. However, the focus is only on bone turnover and bone density, and there is no guideline for trabecular bone score (TBS) for trabecular bone microarchitecture in CKD patients. We aim to evaluate the role of TBS in predicting osteoporotic fracture in CKD patients

Method
We retrospectively enrolled 125 patients with CKD between 2016 and March 2019. Lumbar spine TBS was extracted from dual-energy X-ray absorptiometry, and we categorized the TBS into three groups as lowest (≥ 1.31), moderate (1.31-1.23), and highest risk group (≤ 1.23). The logistic regression analysis was used to assess osteoporotic fracture risk.

Results
Of 125 patients, mean age was 65.9 ± 14.2 years, 49.6% were on dialysis, 11.2% was highest risk group by TBS. Patients with highest risk group by TBS were significantly older, had lower height, weight, serum 25-OH vitamin D, serum sodium level, BMD T-score (lumbar spine, femur neck and total hip) than lower risk group. TBS significantly correlated with BMD T-score (lumbar spine, femur neck and total hip), height, weight and serum creatinine level (P &lt;0.001). Osteoporotic fracture was identified in 20 (16.0%) patients. In univariate analyses, old age, women, lower weight, TBS tertile group, lower potassium level were significantly associated with osteoporotic fracture. In multivariate analyses, only highest risk group by TBS was significantly associated with increased osteoporotic fracture risk after adjustment for demographic, comorbid, medication use, and previous fracture.

Conclusion
Lumbar spine TBS significantly correlated with BMD T-score and predicts osteoporotic fractures in patients with CKD.
P0902DAILY TERIPARATIDE TREATMENT AND PHARMACOKINETICS IN HEMODIALYSIS PATIENTS WITH LOW BONE MASS
Authors: Hiramatsu Rikako 
Published: June 2020

Abstract

Background and Aims
Daily 20µg teriparatide (PTH1-34) is an osteoanabolic agent approved for use treating osteoporosis. However, there are few reports about concerning use of this agent in hemodialysis patients.

Method
We conducted an observational study, single centre study on 5 patients with low bone mineral density (BMD) and low iPTH levels defied as iPTH below 60 pg/mL, who were treated with recombinant human PTH1-34; teriparatide 20 µg 3 times per week between January 2012 and January 2015. All patients were 20 years of age or older, had undergone regular hemodialysis treatment and were without skeletal malignancies and bone metastasis. Low BMD in this study was defined either as BMD T-score -2.5 at the lumbar spine (LS) or /and femoral neck (FN) and distal one –third radius (RS) analyzed by dual-energy X-ray absorptiometry (DXA), or BMD T-score of -2.5 to -1.0 with history of fragility fractures. We analyzed the biochemical data including bone metabolic makers (intact amino-terminal propeptide of type I collagen (iP1NP), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) at baseline, and after 3, 6, and 12 months of teriparatide treatment. BMD at LS and FN were evaluated at 6months of treatment.

Results
Data from five patients (mean age: 69.2±7.4years; mean hemodialysis time: 23.2±6.2years) were reviewed. Laboratory data at baseline were iPTH: 34.2±24.2 pg/mL, BAP: 13.0±4.9 µg/L, iP1NP: 45.3±14.3 ng/mL, TRACP-5b: 350±201 mU/dL, corrected Ca (cCa): 9.7±0.3 mg/dL, and P:4.1±0.7 mg/dL. Baseline BMD T-score at LS and FN were -2.8±1.7 and -3.0±0.6, respectively. During a 12 month- teriparatide treatment, mean cCa levels significantly decreased from 9.7±0.3 to 9.1±0.2 mg/dL at 3 months (P &lt; 0.05) and returned to 9.5±0.4 mg/dL at 12 months. As for bone metabolic markers, BAP and iP1NP significantly increased from baseline by 31.3±12.9 (P &lt; 0.05) and 47.4±14.5% (P &lt; 0.05) at 6 months of teriparatide treatment, while TRACP-5b significantly decreased by 10.5±2.5% at 3 months, which did not reach a statistical significance. BMD changes from baseline at LS and FN were 2.1±2.5% and 1.2±1.5% at 6 months of treatment with a significant change at LS.
Pharmacokinetics of Teriparatide The time-course of changes in plasma teriparatide acetate concentration was evaluated in one patient who had undergone parathyroidectomy 20 years before enrollment in this study and her serum endogenous iPTH level was undetectable at baseline. After teriparatide injection, serum teriparatide acetate levels peaked at 30 minutes at 157.2 pg/mL, and then rapidly decreased to undetectable levels at 240 minutes.

Conclusion
We report that teriparatide improved LS and FN BMD in hemodialysis patients with low iPTH. Pharmacokinetics showed this agent might not accumulate in dialysis patients and can be used safely. Adequate Ca supplementation might be needed to adjust serum Ca levels.
P0910CLINICAL-LABORATORY AND CYTOMORPHOLOGICAL CHARACTERISTICS OF HYPERPARATHYROIDISM IN PATIENTS WITH CRONIC KIDNEY DISEASE
Authors: Ivanova Maria , Vetchinnikova Olga , Zakharova Natalia 
Published: June 2020

Abstract

Background and Aims
Secondary hyperparathyroidism (HPT) is a serious complication of chronic kidney disease (CKD), which decrease the medical and social rehabilitation of patients, increases cardiovascular morbidity and mortality. The aim of the study is analysis the clinical and laboratory manifestations of secondary HPT and cytomorphological signs of parathyroid glands (PG) tissue in patients with CKD.

Method
51 patients (age 24-66 years) with CKD G5D (on hemodialysis – 30 patients and peritoneal dialysis – 21 patients) and HPT were examined. Clinical and laboratory examination included determination of laboratory parameters of mineral and bone metabolism, an ultrasound study of the PG, a fine needle aspiration biopsy of the visualized lesions in the projection of the PG, and light microscopy of the material obtained (х400). The method of logical-semantic analysis (program “Consilium”) is used.

Results
All patients had severe HPT with high turnover bone disease: bone pain and deformity, increase of serum PTH to 2200±817 pg/ml, calcium and phosphorus of blood, respectively 2.4±0.2 and 2.2±0.4 mmol/l, alkaline phosphatase activity 489±205 u/l (norm 30-117), a decrease in bone mineral density according to dual energy X-ray absorptiometry in the distal forearm – 100% patients, proximal femur and lumbar spine – 50% patient. An ultrasound procedure visualized from two to four enlarged PG with a diameter of more than 1 cm and a heterogeneous ultrasound structure. A large number of epithelial elements were determined in the puncture material of the PG tissue, multicellular clusters of major dark parathyrocytes in combination with groups of major light parathyrocytes, the presence of pronounced intercellular contacts and the absence of macrophages and fat cells (fig).

Conclusion
Severe HPT in patients with CKD is characterized by an increase in PG by more than 1 cm with a heterogeneous ultrasound structure and pronounced proliferative activity in the parenchyma of glands tissue.