bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO585EFFECTS OF LANTHANUM CARBONATE AND CALCIUM CARBONATE ON CARDIOVASCULAR CALCIFICATION IN HEMODIALYSIS PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Yang Junlan , Zhang Xiao liang , Wang Lina 
Published: May 2021

Abstract

Background and Aims
Commonly used phosphorus-lowering drugs include calcium-containing phosphate-binding agents and non-calcium-containing phosphate-binding agents, the latter mainly including lanthanum carbonate (LC). In recent years, some studies have explored the effect of lanthanum carbonate compared with calcium carbonate on serum calcium. However, the results are different. Therefore, we conducted this review to systematically review and meta-analyze evidence on the efficacy of lanthanum carbonate and calcium carbonate (CC) and the risk of cardiovascular calcification in hemodialysis (HD) patients, and to provide reference for phosphorus-lowering drugs in HD patients.

Method
The Cochrane library, PubMed, Web of Science, Chinese journal full-text database (CNKI), WANGFANG DATA and Sino Med were searched between January 1946 and December 2020. The literatures with respect to the randomized controlled clinical trial comparing lanthanum carbonate and calcium carbonate in HD patients were selected. The two evaluators independently collected the data according to the retrieval strategy, screened the literatures according to the inclusion criteria and exclusion criteria, and summarized the literatures that met the criteria. The risk ratio (RR) and 95% confidence interval (CI) were used to represent the counting data. The standard deviation from mean (SMD) and 95%CI were used to represent the continuous variables. Forest plots, sensitivity analysis, Egger regression test and TSA were used to summarized the test performance characteristics.

Results
Of 388 original titles screened, data was extracted from 9 studies included 625 participants (Table 1). There was moderate-certainty evidence from 9 trials (625 participants) that LC can significantly reduce the progression of coronary artery calcification than CC (SMD= -0.59, 95%CI -0.94 to -0.25, P&lt; 0.01) (Figure 2). The serum phosphorus level in the LC group was significantly lower than that in the CC group (SMD= -1.35, 95%CI: -2.33 to -0.36, P&lt; 0.01), and the serum calcium level was significantly reduced (SMD= -1.03, 95% CI: -1.83 to -0.23, P= 0.012). The fibroblast growth factor 23 (FGF-23) level in the LC group was significantly lower than that in the CC group (SMD= -4.80, 95%CI: -7.96 to -1.64, P= 0.003). The Egger regression test of coronary artery calcification score (CACS) showed no potential publication bias (P= 0.72).

Conclusion
In this systematic review, compared with calcium carbonate, lanthanum carbonate can significantly delay the process of coronary artery calcification, and at the same time reduce the patient's serum phosphate, serum calcium and FGF-23. Therefore, we recommend LC as phosphorus-lowering drugs for HD patients.
MO586RISK OF OSTEOPOROSIS IN OBESE PATIENTS WITH TYPE 2 DIABETES: A SYSTEMIC REVIEW AND META-ANALYSIS
Authors: Lin Yen-Chung 
Published: May 2021

Abstract

Background and Aims
The aim of this study is to evaluate the alterations in bone marrow density and other surrogate markers for osteoporosis in obese patients with type 2 diabetes mellitus (T2DM) who received Roux-en-Y gastric bypass (RYGB) versus medical treatment as control.

Method
We searched four electronic databases and reference lists of relevant studies for eligible research published before December, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including lumbar spine bone mineral density (L-spine BMD) change, total hip BMD change, osteocalcin level, C-terminal telopeptide (CTX) level and parathyroid hormone (PTH) level.

Results
Three randomized clinical trials and two observational studies concerning 307 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. Patients underwent RYGB surgery were associated with both higher L-spine BMD loss (mean difference: -2.90, 95% CI: -2.99∼-2.81, p&lt;0.00001 )and total hip BMD loss (mean difference: -5.81, 95% CI: -9.22∼-2.40, p=0.0008). As to biochemical markers of bone metabolism, we found signifcantly higher osteocalcin level in medical treatment (control) group compared with RYGB group (mean difference: 11.16, 95% CI: 8.57∼13.75, p&lt;0.00001). However, higher CTX level and PTH level were noted in medical treatment group (control) compared with RYGB group (mean difference: 0.29, 95% CI: 0.11∼0.48, p=0.002; mean difference: 1.56, 95% CI: 0.84∼2.27, p&lt;0.0001).

Conclusion
RYGB surgery is associated with negative impact on bone metabolism and increase the risk of osteoporosis in obese patients with T2DM. We suggest that clinicians acknowledge the adverse effects of surgery and keep monitoring bone mineral components in post-RYGB populations. Further studies regarding the optimal amount of peri-operative and post-surgical supplementation should be evaluated.
MO566THE BONE EXPRESSION OF WNT INHIBITORS IN THE EXPERIMENTAL MODEL OF EARLY CHRONIC KIDNEY DISEASE
Authors: Bogdanova Evdokia , Semenova Natalia , Galkina Olga , Zubina Irina , Beresneva Olga , Ivanova Galina , Parastaeva Marina , Dobronravov Vladimir 
Published: May 2021

Abstract

Background and Aims
Molecular mechanisms implicated in the initial stages of inorganic phosphate (Pi) imbalance in chronic kidney disease (CKD) remain poorly understood.The aim of the study was to evaluate whether canonical Wnt pathway inhibitors (iWnt) involved in early response to Pi retention in CKD.

Methods
Mild CKD was induced by 3/4 nephrectomy (NE) in spontaneously hypertensive rats (SHR) fed rat chow diet containing 0.6 % phosphate. Controls were sham operated SHR (SO). Duration of experimental exposure (NE or SO) was 2 and 6 months. Serum levels of creatinine (Cr), inorganic phosphate (Pi), fractional Pi excretion (FEPi), intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), alfa-Klotho (KL), sclerostin (SOST) and Dickkopf-1 (DKK1) were measured. The following morphological characteristics by light microscopy of bone metaphysis and kidney tissues: the area of renal interstitial fibrosis (RF) (Masson's trichrome), bone matrix volume (MV), the active osteoblasts to trabecular cells number ratio (aOB/cells), eroded surface to bone surface ratio (ES/BS) (hematoxylin & eosin), and bone SOST and DKK1 proteins expression (by IHC) were analyzed and calculated quantitatively. Statistical comparisons among groups were performed using Mann–Whitney U-test and Kruskal-Wallis H-test.

Results
Serum Cr, RF and indices of Pi exchange in the experimental model corresponded to early CKD (Table). Pi elevated in NE6 suggestive for its renal retention. KL level decreased (Table) in all experimental groups vs control. No differences were observed in serum levels FGF23 (p=0.62) and PTH (p=0.63). Serum SOST and DKK1 levels were significantly higher in NE6 group compared to SO6 (Table). The bone SOST and DKK1 expression increased in NE6 compared to SO6 (Figure). aOB/cells were lower in NE2, SO6 and NE6 vs SO2 (all p-values&lt;=0.041). ES/BS increased in NE2 (vs SO2) while being lowest in NE6 and SO6 animals (Table). SOST and DKK1 metaphyseal expression increased in NE6 compared to SO2, SO6, NE2 (Figure). Osteocyte SOST expression increased in SO6 compared to SO2 and NE2 without differences in later groups. Osteoblast SOST expression was also higher in SO6 vs SO2 (Figure).

Conclusion
Increased serum levels of sclerostin and Dickkopf-1 and their bone expression are apparent in early stages of experimental CKD associating with hyperphosphatemia. Alterations of bone resorption and osteoblast depopulation occurred before the increase of serum Pi likely reflecting incipient stages of renal Pi retention. These molecular and cellular events seem to be independent of systemic FGF23 and PTH response.
MO568STATIC PARAMETERS OF HISTOMORPHOMETRY FOR THE EVALUATION OF BONE TURNOVER IN RENAL OSTEODYSTROPHY
Authors: Jørgensen Hanne Skou , Behets Geert , D'Haese Patrick , Evenepoel Pieter 
Published: May 2021

Abstract

Background and Aims
A full histomorphometric analysis of a transiliac bone biopsy with prior tetracycline labeling remains the gold standard to diagnose renal osteodystrophy. Bone turnover is primarly evaluated by the dynamic parameter bone formation rate, calculated from the incorporation of tetracycline in bone. In cases of failed tetracycline labels, however, an evaluation of bone turnover based on static parameters is warranted. This study investigates the diagnostic accuracy of static histomorphometric parameters for the diagnosis of high and low bone turnover.

Method
Bone biopsies with prior tetracycline labeling of sufficient quality for a full histomorpometric analysis were included (n = 205). Mean age of participants was 56±13 years, 67% were men, and 22% had diabetes mellitus. Diagnostic accuracy of static histomorphometric parameters for bone turnover was evaluated by area under the receiver operator characteristics curve (AUC) statistics, against the full set of static and dynamic histomorphometric parameters. The cohort was randomly split to allow calculation of optimal diagnostic cutoffs in an exploration cohort (n=105), with subsequent validation in a separate subset of patients (n=100).

Results
All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover (p &lt; 0.01), and all were significant predictors of both high and low bone turnover (Figure 1). Calculated optimal cutoffs and their sensitivities and specificities in the validation cohort are shown in Table 1.
Diagnostic accuracy was very good for high turnover, as the combination of presence of fibrosis with ObPm&gt;5.4%, OcPm&gt;1.5%, and OAr&gt;2.4% provided a correct diagnosis in 94% of patients, with positive (PPV) and negative (NPV) predictive values of 80% and 96%, respectively. Using the same predefined combination, an accuracy of 80% was achieved for low turnover (no fibrosis, ObPm≤1.9% OcPm≤0.9% and OAr≤1.6%), with a PPV of 71% and a NPV of 82%.

Conclusion
Static histomorphometric parameters provide an acceptable alternative for the diagnosis of high and low bone turnover. In the absence of successful tetracycline labeling, the proposed cutoffs may provide a suitable alternative for the evaluation of bone turnover in renal osteodystrophy.
MO569MACROPHAGE PROMOTE VASCULAR CALCIFICATION VIA THE MIGRASOMES/ INTEGRIN Α5Β1 PATHWAY IN CKD
Authors: Zhu Xiaodong , Liu Yuqiu , Yang Xin , Fang Yaping , Zhang Xiao liang 
Published: May 2021

Abstract

Background and Aims
Patients with chronic kidney disease (CKD) have a predisposition to develop vascular calcification due to dysregulated homeostatic mechanisms. Macrophages can promote vascular calcification by releasing diverse extracellular vehicles including the newly found migrasomes (M-mig). Our previous research had found that M-mig provide nucleating foci for calcific mineral formation and initiating bone mineralization process. However, the specific mechanism by which M-mig influence the formation of vascular calcification remains incompletely understood.

Method
To study calcifying M-mig, we exposed M-mig to high Ca/P (Ca/P=3 mmol/L calcium/2 mmol/L phosphate) and/or with LPS for 1, 3, 5,7 days. The expression of M-mig surface integrin α5β1 was determined by fluorescence staining. To block the M-mig-integrin α5β1 mediated calcification, we modulated the expression of integrin α5 using siRNAs to produce M-migintegrin α5- or using 20 nM ATN-161 (small peptide antagonist of integrin α5β1) or integrin α5 antibody under high Ca/P stimulation. The stray mice artery co-cultivate with M-mig integrin α5- under high level Ca/P. Then the calcifying M-mig were assessed by TEM, Fluo-3 staining and calcium content assay.

Results
We discovered that Ca/P-stimulated macrophages released M-mig capable of mineralization. Amorphous calcium phosphate mineral deposit the surface or internal of M-mig. The M-mig exhibited increased Ca/P mineral content, implying aggregate larger calcifying M-mig that develop over time. Significantly, following a 7 days incubation with high level Ca/P, fiber tube and vesicle structure of M-mig showed rupture or fragmentation and the expression of M-mig surface integrin α5β1 increased. Pre-treatment with integrin α5β1 antagonist or block by integrin α5 antibody significantly reduced the calcifying M-mig formation. Further investigation showed that M-mig induced stray mice artery microcalcification while M-migintegrin α5- exhibited a reduce microcalcification.

Conclusion
Our finding revealed an association between microcalcification and integrin α5β1 signalling in the fiber tube and vesicle structure of M-mig and provide a new insight into vascular calcification in CKD.
MO493PATTERNS OF HYPERKALEMIA AND ASSOCIATED ADVERSE HEALTH OUTCOMES IN PERSONS WITH CHRONIC KIDNEY DISEASE
Authors: Trevisan Marco , Clase Catherine M , Evans Marie , Ludvigsson Jonas , Sjolander Arvid , Carrero Juan Jesus 
Published: May 2021

Abstract

Background and Aims
Patients with CKD are often described as having chronic hyperkalemia, but earlier studies have relied on a single potassium measurement. Whether the hyperkalemia in CKD is chronic or transient, and whether temporal patterns have different outcome implications, is unknown.

Method
Observational study from the Stockholm Creatinine Measurements (SCREAM) project of patients with confirmed CKD G3-5. We extracted all data on potassium measured during routine outpatient care and estimated its longitudinal trajectories. At each month, we created a rolling assessment of the proportion of time in which potassium was abnormal during the previous year, defining patterns of normokalemia (100% of time with potassium 3.5-5.0 mmol/L), transient (&lt;50% of time with potassium &gt;5.0 mmol/L) and chronic hyperkalemia (≥50% of time with potassium &gt;5.0 mmol/L). We described the presence of chronic and transient hyperkalemia throughout the spectrum of CKD G3-5 and identified clinical predictors by logistic regression. Through time-dependent Cox models we examined whether previous hyperkalemia patterns offer prognostic gain beyond that of the current potassium value.

Results
We included 36,511 participants (56% women) with confirmed CKD G3-5, median age 81 years, and eGFR 46 ml/min/1.73 m2. During 3-year-median follow-up, patterns of transient and chronic hyperkalemia were observed in 15% and 4% of patients with CKD G3a, increasing to 50% and 17% of patients with CKD G5. Factors associated with chronic hyperkalemia were younger age, male sex, more severe CKD category, presence of diabetes or heart failure, use of renin-angiotensin system inhibitors, and use of potassium binders. Major cardiovascular events (MACE) occurred in 13,104 (36%) patients and 13,570 (37%) died. In time-dependent models, independent of identified confounders and of time-updated potassium values, compared with the normokalemic pattern, patients with transient (HR 1.37, 95% CI 1.29-1.46) or chronic (HR 1.17, 95% CI 1.04-1.32) hyperkalemia patterns were at higher risk of MACE. Transient hyperkalemia pattern (HR 1.43, 95% CI 1.35-1.52) and time-updated elevated potassium, but not a state of chronic hyperkalemia (HR 1.07, 95% CI 0.95-1.20), predicted the risk of death.

Conclusion
Chronic hyperkalemia occurs in 4-17% of patients with CKD G3-5. We did not observe a clear dose-response for the association between hyperkalemia pattern (normal, transient, chronic) with either MACE or death. There was modest incremental information in the previous potassium pattern, beyond potassium measured at a single time point.
MO482URINE METABOLITE LEVELS OF CKD PATIENTS ARE ASSOCIATED WITH ADVERSE KIDNEY OUTCOMES AND MORTALITY*
Authors: Steinbrenner Inga , Schultheiß Ulla T , Kotsis Fruzsina Kinga , Schlosser Pascal , Stockmann Helena , Mohney Robert P , Schmid Matthias , Oefner Peter , Eckardt Kai-Uwe , Köttgen Anna , Sekula Peggy 
Published: May 2021

Abstract

Background and Aims
Chronic kidney disease (CKD) affects &gt;10% of the adult population worldwide and is associated with increased risk of kidney failure (KF) and mortality. Mechanisms underlying the variable course of disease progression are incompletely understood. This study aimed at identifying novel metabolite biomarkers of adverse kidney outcomes and overall mortality, which may offer insights into pathophysiological mechanisms.

Method
Using measurements of 1,487 metabolites in urine of 5,087 CKD patients enrolled in the German Chronic Kidney Disease study, we evaluated the association of urine metabolite levels with adverse events. Main endpoints include KF, a combined endpoint of KF and acute kidney injury (KF+AKI), and overall mortality. Statistical analysis was based on a discovery-replication design (ratio 2:1) and multivariable adjusted Cox regression models. We performed cause-specific hazard regression as well as subdistribution hazard analyses with death of other causes as a competing event for the endpoints KF and KF+AKI. Statistical significance was defined using a Bonferroni correction for the number of tested metabolites per stage. An association was considered replicated if effect estimates from both stages were significant and direction-consistent.

Results
Median follow-up time was 4 years. At time of analysis, 362 patients died, 241 experienced KF, and 382 KF+AKI. Overall, we identified 55 urine metabolites whose levels were significantly and reproducibly associated with adverse kidney outcomes and/or mortality. Cause-specific and subdistribution hazard analyses showed almost identical results. Higher levels of the amino acid C-glycosyltryptophan in urine were associated with higher risk for all three endpoints (KF: hazard ratio 1.43, 95% confidence interval [1.27;1.61], KF+AKI: 1.40 [1.27;1.55], mortality: 1.47 [1.33;1.63]). The cumulative incidence function of KF was higher for each quartile of urine C-glycosyltryptophan levels and the effect were most pronounced in the highest quartile (see Figure). The replicated metabolites belong to different biochemical classes, and those belonging to the phosphatidylcholines pathway showed enrichment. Members of this pathway contributed to the improvement of the prediction performance for KF observed when multiple metabolites were added to the well-established kidney failure risk equation by Tangri.

Conclusion
This comprehensive screen of the association between urine metabolite levels and adverse kidney outcomes and mortality identified and replicated 55 urine metabolites associated with adverse kidney events, potentially providing new insights into the mechanisms of kidney disease progression. The study represents a valuable resource for future experimental studies of biomarkers of CKD progression.
MO502EGFR TRAJECTORY AND RISKS OF CARDIOVASCULAR EVENTS AND ENDSTAGING KIDNEY DISEASE IN CKD PATIENTS
Authors: Kokubu Maiko , Uemura Takayuki , Matsui Masaru 
Published: May 2021

Abstract

Background and Aims
Growing evidence has shown the eGFR level is an established predictor of cardiovascular events, but the association of eGFR trajectory with cardiovascular and renal events remained limited.

Method
We conducted a retrospective cohort study on 276 CKD patients in whom at least two measurements of eGFR levels to calculate eGFR slope were confirmed. Patients were divided into two groups according to the below and above cut-off values of eGFR slopes for outcomes using ROC curve. Outcomes are cardiovascular events defined as heart failure requiring hospitalization, revascularization for IHD and PAD, stroke or sudden death, and renal events defined as ESRD or baseline eGFR decline of &gt; 30%.

Results
In total, the median (IQR) age of participants was 68 (56∼77) years and 176 (64%) were male. The median (IQR) levels of baseline eGFR were 33 (20∼48) mL/min/1.73m2 with the median eGFR slope of -5.2(-0.85∼-9.5) mL/min/1.73m2/yr. During the study period, 92 cardiovascular events and 89 renal events occurred. Crude Kaplan-Meier analysis showed participants with lower eGFR slopes had higher probabilities of cardiovascular and renal events with statistical significances (p&lt;0.001 and p&lt;0.001, respectively). In the fully adjusted model, having lower eGFR slopes were associated with HRs (95%CIs) for cardiovascular and renal events of 1.71 [1.08-2.70] and 1.79 [1.09-2.93], respectively.

Conclusion
These data suggest not only current eGFR but also eGFR trajectory is an independent risk factor for cardiovascular and renal events in CKD patients.
MO508HEMATOCRIT, UREA AND GENDER (HUGE) EQUATION AND CARDIOVASCULAR EVENTS: A PROSPECTIVE STUDY IN SPANISH POPULATION
Authors: Cancho Castellano Bárbara , Robles Perez-Monteoliva Nicolas-Roberto , Felix Redondo Francisco Javier , Lozano Luis , Fernandez-Berges Daniel 
Published: May 2021

Abstract

Background and Aims
To evaluate the relationship between chronic kidney disease (CKD) diagnosed by the hematocrit, urea and gender (HUGE) equation and the incidence of major adverse cardiovascular events and cardiovascular mortality in a sample of Spanish general population.

Method
The sample consisted of 2,668 subjects (mean age, 50.6±14.5 years; 54.6% were female). Of them, 55 patients have a HUGE score &gt; 0. The median follow-up was 81 (75-89) months. Serum creatinine, urea and haematocrit were analyzed after overnight fast. The HUGE formula score was calculated for all subjects.

Results
Event-free survival was 98.4 % at three years and 97.1% at five years of follow-up for patients with a HUGE score &lt; 0. For patients with a estimated HUGE score higher than 0 survival was 88.9% at three years and 87.0 at five years of follow-up. (p&lt;0.0001). Cardiovascular death survival was 94.4 % at three and 88.0 at five years of follow-up for patients with a HUGE score higher than 0. For patients with a estimated HUGE. score lower than 0 survival was 99.3% at three years, and 99.0% at five years of follow-up. (p&lt;0.001).

Conclusion
A significantly increased cardiovascular risk was associated to the diagnosis of CKD through HUGE formula. This effect on survival could be detected despite of a very small sample of CKD patients. This relationship was close to those obtained using MDRD estimated GFR in a bigger sample of patients. HUGE formula may be a useful tool for diagnosing CKD and to evaluate the cardiovascular risk of these patients.