bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO434: Bemcentinib Targets Macrophage and Mesangial Cells in Renal Fibrosis
Authors: Magnus Grøndal Sturla , Hodneland Nilsson Linn , Blø Magnus , Boniecka Anna , Milde Eline , Jackson Akil , Gausdal Gro , Lorens James B 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Renal fibrosis, a progressive process of extracellular matrix accumulation leading to renal failure, lacks effective treatment. Expression of the AXL receptor tyrosine kinase has been implicated in kidney injury and mesangial proliferation [1]. Inhibition of AXL signalling with the selective AXL kinase inhibitor bemcentinib reduces fibrosis and inflammation in murine models of unilateral ureteral obstruction (UUO) and in glomerulonephritis [2, 3].

METHOD
Male C57Bl/6 mice were subjected to UUO for 3 or 15 days and treated twice daily with vehicle or bemcentinib (50 mg/kg) by oral gavage. Kidneys were divided into pieces that were either dissociated into single cells for mass cytometry analysis or subjected to Sirius Red staining to evaluate collagen deposition. Samples for mass cytometry were stained with a 45-plex antibody panel, acquired on Helios, then cleaned and analysed using UMAP [4] for dimensionality reduction and PARC [5] for clustering. The effect of ligation was modelled with the least absolute shrinkage and selection operator (LASSO) using centered log-ratio transformed cluster compositions to predict the number of days of ligation. LASSO is a regression method that prevents overfitting by penalizing variables and is commonly used for variable selection.

RESULTS
Sirius Red staining confirmed, as previously published, reduced fibrosis development in kidneys from bemcentinib treated animals compared to the vehicle following 15 days of UUO. No significant effect of bemcentinib was observed after 3 days of obstruction.
Mass cytometry analysis yielded 31 clusters representing immune, endothelial, pericyte, mesangial and epithelial cells from proximal tubules, loop of Henle, distal tubules and collecting duct. AXL was expressed by pericytes, endothelial cells, mesangial cells and macrophages. Modelling with LASSO suggested that the most important feature of ligation was the expansion of mesangial cells. Bemcentinib treatment did not result in any significant changes in non-ligated kidneys and kidneys ligated for 3 days. At 15 days, post-bemcentinib treatment, the number of mesangial cells and macrophages decreased, while the number of epithelial cells comprising the proximal tubules and loop of Henle increased. The LASSO model estimation corresponded to an apparent reduction in disease progression of 30% (corresponding to day 10 or 11 post-ligation).

CONCLUSION
AXL targeting macrophages and mesangial cells delays the progression of kidney fibrosis in the UUO model and represents a valid approach to treat kidney disease.
MO462: Change in KDIGO Kidney Risk Category With Semaglutide Treatment—A Post Hoc Analysis of the Sustain 6 Trial
Authors: Tuttle Katherine , Bain Stephen C , Cherney David , Lawson Jack , Rasmussen Søren , Vrhnjak Blaz , Khunti Kamlesh 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Glucagon-like peptide-1 receptor agonists, such as semaglutide, have been associated with reductions in albuminuria, and may preserve estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (T2D). However, it has not been explored whether treatment with semaglutide affects a person's chronic kidney disease (CKD) risk category. The Kidney Disease: Improving Global Outcomes (KDIGO) risk category classification is a validated approach for defining the likelihood of CKD and cardiovascular (CV) disease progression, based on eGFR and urinary albumin-to-creatinine ratio (UACR). The aim of this analysis was to determine whether treatment with once-weekly (OW) semaglutide resulted in improvements in KDIGO risk category compared with placebo.

METHOD
The proportion of subjects with T2D moving to a lower KDIGO risk category, remaining in the same category or moving to a higher risk category between baseline and 2 years on treatment with OW subcutaneous semaglutide versus placebo was assessed post hoc using SUSTAIN 6 (NCT01720446) CV outcomes trial data. The endpoints were assessed for the overall population and by baseline KDIGO risk category (low, moderate, high and very high). Sensitivity analyses were conducted to investigate the contributions of UACR and eGFR to change in risk category.

RESULTS
Data from 2804 of the 3297 subjects randomized in SUSTAIN 6 were available for this post hoc analysis. At 2 years, in the overall population, subjects receiving OW semaglutide were more likely to move to a lower risk category (n = 183; 13.0%) than subjects receiving placebo (n = 114; 8.2%); odds ratio (OR; semaglutide versus placebo) 1.69 [95% confidence interval (CI) 1.32; 2.16, P &lt; 0.0001) (Figure). Conversely, subjects receiving OW semaglutide were less likely to move to a higher risk category (n = 254; 18.1%) than those receiving placebo (n = 330; 23.6%); OR 0.71 (95% CI 0.59;0.86, P = 0.0003) (Figure). When the data were stratified by baseline KDIGO risk categories, across all categories, greater proportions of subjects receiving semaglutide than placebo moved to a lower risk category and lower proportions of subjects receiving semaglutide than placebo moved to a higher risk category (Figure). The effects of semaglutide on UACR and eGFR both contributed to the favourable change-in-risk-category profile compared with placebo (Table).

CONCLUSION
Subjects receiving semaglutide versus placebo were more likely to move to a lower KDIGO risk category and less likely to move to a higher risk category, both in the overall population and across KDIGO risk category subgroups. The potential kidney protective effects of semaglutide and the mechanisms underlying these are being investigated in subjects with T2D and CKD in the FLOW and REMODEL trials.
MO472: Comparison of the Quality of Life and Survival in Children Undergoing Hemodialysis Versus Peritoneal Dialysis: A Comparative Cross-Sectional Study
Authors: Mazighi Sara , Nabil Hamouche , Chettati Mariam , Fadili Wafaa , Laouad Inass 
Published: May 2022

Abstract

BACKGROUND AND AIMS
A child with end-stage renal disease (ESRD) hopes for a kidney transplant to avoid dialysis. Despite the recent priority rules for assigning transplants to children. Most of them, due to their young age, the time required to prepare for the transplant, and especially the limited availability of grafts, will go on dialysis. The objective of this study is to compare the quality of life and survival of children with ESRD treated by hemodialysis (HD) and those treated by peritoneal dialysis (PD).

METHOD
All children with end-stage renal disease under the age of 16 who started dialysis treatment between 2018 and 2021 were included, for a total of 72 children. Data were collected from an HRQOL questionnaire (Health Related Quality of Life ESRD Module questionnaire).

RESULTS
A total of 72 children on ESRD started dialysis between 2018 and 2021. A total of 62 children on hemodialysis (87.5%) versus 10 children on peritoneal dialysis. The mean age in our study was 10 years ± 8 years, with a 58% female predominance. Causal nephropathy was dominated by malformative uropathy in 36% of cases, indeterminate nephropathy in 24% and lupus in 12.5% ​​of cases. Growth retardation was observed in 49 children in our population (79%) (48 in HD versus 1 in PD P &lt; .001). Residual renal function was preserved in 48.6% of our children with a state of normal extracellular hydration (HD 40%, DP 8%). The mean HD and DP hemoglobin level was 8 mg/dL. The initial GFR was 5 with an average urea level at the start of dialysis of 3 g (3 g for HD and 2 g for children on PD). The evolution was marked by the occurrence of complications in PD (6 peritonitis and 2 infections of emergence of KTT) and HD (arteriovenous fistulae hematoma in 10 children, secondary hyperparathyroidism in 65% of children), 10 children are deceased (1 in PD and 9 in HD). Children on PD have a lower co-morbidity and dialysis initiation is more planned.

CONCLUSION
PD remains the technique of choice in our context to ensure a better quality of life for children.
MO477: Predicting 1-Year Mortality After Haemodialysis Start: The Role of the Cha₂Ds₂-VASC Score
Authors: Marques Da Silva Bernardo , Mafalda Abrantes Ana , Branco Carolina , Costa Claudia , Peres Nadiesda , Cardoso Ana , Sant'ana Mariana , Agapito Fonseca José , Outerelo Cristina , Resina Cristina , António Lopes José , Gameiro Joana 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease (CKD) is a significant cause of morbidity, cardiovascular and all-cause mortality. CHA2DS2VASc is a score system used in patients with atrial fibrillation to predict thromboembolic risk. However, it also appears to be useful to predict mortality risk. The aim of the study was to evaluate the CHA2D2SVASc score as a tool to predict 1-year mortality after starting haemodialysis and identify factors associated with higher mortality.

METHOD
Retrospective analysis of patients who started haemodialysis between January of 2014 and December of 2019 at Centro Hospitalar Universitário Lisboa Norte. We evaluated mortality within 1 year of starting haemodialysis. The CHA2D2SVASc score was calculated at the start of haemodialysis. Variables were submitted to univariate and multivariate analysis to determine factors predictive of 1-year mortality after HD start. We assessed the logistic regression method of the CHA2DS2VASc to predict 1-year mortality and the discriminatory ability was determined using the receiver operating characteristic curve.

RESULTS
Of 856 patients analyzed, the mean age was 68.3 ± 15.5 years, the majority were male (61.1%) and Caucasian (84.5%). Mortality within 1 year after haemodialysis started was 17.8% (n = 152). The CHA2D2SVASc score was significantly higher (4.4 ± 1.7 versus 3.5 ± 1.8; P &lt; .001) in patients who died and accurately predicted the 1-year risk of mortality {AUC: 0.646, [95% confidence interval (95% CI) 0.6–0.7]; P &lt; .001}, with a sensitivity 71.7% and specificity of 49.1%, a positive predictive value of 23.9% and a negative predictive value of 89.2%. In the multivariate analysis, CHA2D2SVASc ≥3.5 (adjusted OR: 2.24, 95% CI 1.48–3.37; P &lt; .001] and central venous catheter at dialysis start (adjusted HR: 3.06, 95% CI 1.93–4.85) were significant predictors of 1-year mortality.

CONCLUSION
CHA2D2SVASc score ≥ 3.5 and central venous catheter at haemodialysis start were predictors of 1-year mortality, allowing for risk stratification in haemodialysis patients.
MO482: End-Stage Renal Disease in the Elderly: Dialysis or Conservative Management?
Authors: Denden Ghada , Ben Mahmoud Nouha , Ben Salem Meriem , Ben Salah Manel , Letaief Ahmed , Hammouda Mouna , Sabra Aloui , Skhiri Habib 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Nowadays, end-stage renal disease (ESRD) is overrepresented in elderly patients. The presence of medical comorbidities, limited life expectancy, frailty and poor functional status in these patients poses substantial challenges in clinical decision-making and provision of optimal care. The decision to start dialysis or not should always be based on shared decision-making. The objective of our study was to compare clinical outcomes for patients who had chosen either maximum conservative management (MCM) or renal replacement therapy (RRT).

METHOD
This is an observational study of a single-center cohort in Tunisia that includes 152 elderly patients (&gt;80 years), with chronic kidney disease (CKD) who consulted our center during the period from 1 January 2015 to 31 December 2016. Demographic and comorbidity data were collected on all patients. Then, we evaluated the management of patients who had reached the end stage of CKD during the study period (dialysis or conservative treatment), and we compared the survival of the two groups.

RESULTS
Of 152 patients, 54.6% were women. The mean age was 82 ± 2.6 years. High blood pressure, diabetes and dyslipidemia were the most common comorbidities. During follow-up, 65 patients have reached stage 5 of CKD. A total of 46.1% started dialysis and the rest received conservative treatment. Patients choosing dialysis were younger compared with those opting for conservative management and were less functionally impaired. Survival was better in those receiving conservative treatment: The mean survival was 24 months for RRT patients and 30 months for maximum conservative management (MCM) patients (P &lt; .01). A total of 1- and 2-year survival rates were 76.3% and 22% in the dialysis group (n = 30) and 75.3% and 45% in the conservative group (n = 35), respectively.

CONCLUSION
When caring for older adults with advanced CKD who are contemplating dialysis therapy vs. conservative management, efforts must focus on promoting patient values and preferences, shared decision-making, and symptom burden alleviation.
MO489: Weight Change and Risk of Depression in Patients With Diabetic Kidney Disease: A Nationwide Population-Based Study
Authors: Sang Choi Hong , Ryon Oh Tae , Heon Suh Sang , Seong Kim Chang , Hui Bae Eun , Kwon MA Seong , Wan Kim Soo 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Several studies have reported that depression has a high prevalence in patients with diabetes or chronic kidney disease. However, the relationship between weight changes and the risk of depression has not been elucidated in patients with diabetic kidney disease (DKD).

METHOD
From the Korean National Health Insurance Service database, we selected 67 866 patients with DKD with body weight data from two consecutive health examinations with a 2-year interval between 2009 and 2012. The weight change &gt;2 years was categorized into five groups: ≥10% weight loss, 5%–10% weight loss, &lt;5% weight change, 5%–10% weight gain and ≥10% weight gain. The occurrence of depression was monitored through the end of 2018 by the ICD-10 codes.

RESULTS
During the 5.24-year follow-up, 17 023 patients with DKD developed depression. The weight change and the risk of depression showed a U-shaped relationship: patients with ≥10% weight loss [hazard ratio (HR): 1.116] and those with ≥10% weight gain (HR: 1.114) showed higher HRs than those with ≤5% weight change, even after adjusting for several confounding factors. In subgroup analyses, the risk of depression tended to increase as weight gain or weight loss increased in all subgroups.

CONCLUSION
Both weight loss and weight gain increased the risk of depression in patients with DKD
MO499: Incidence of Cause-Specific Cardiovascular Events in Men and Women With CKD
Authors: Faucon Anne-Laure , Lambert Oriane , Alencar de Pinho Natalia , Ayav Carole , Combe Christian , Fouque Denis , Frimat Luc , Jacquelinet Christian , Laville Maurice , Liabeuf Sophie , Massy Ziad , Nicolas Mansencal , Stengel Benedicte 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Men are at higher risk of cardiovascular disease (CVD) than women in the general population, and chronic kidney disease (CKD) is a well-established cardiovascular (CV) risk factor [1–4]. However, the incidence of cause-specific CV events in men and women with CKD is poorly documented.

METHOD
All hospitalization and death reports for CV events of the 3033 patients (1983 men and 1050 women) with non-dialysis CKD (stage 3–5) included in the French CKD-REIN Cohort were reviewed and classified by cause using criteria from the Cardiovascular and Stroke Endpoint Definitions for Clinical Trials [5]. Cause-specific Cox proportional hazard models were used to estimate hazard ratios for death and each fatal or nonfatal CV event according to gender.

RESULTS
At baseline, in men (mean age: 68 years; mean eGFR 33 mL/min/1.73 m²), the prevalence of atheromatous CVD was 30% for coronary artery disease, 14% for cerebrovascular disease and 17% for lower limb artery disease, and that of non-atheromatous CVD was 14% for heart failure and 13% for atrial fibrillation. In women (65 years old, 32 mL/min/1.73 m²), these prevalences were 15%, 7%, 9%, 11% and 9%, respectively.
During a median follow-up of 5 (IQR: 3–5) years, 98 men and 43 women died from CVD {i.e. 1.3 [95% confidence interval (95% CI): 1.0–1.5] versus 1.0 (0.7–1.3)/100 person-years}, including 53% versus 46% from heart failure, 31% versus 19% from sudden death, and 16% versus 35% from other cardiovascular causes, respectively.
Crude incidence rates of death or hospitalization for coronary artery disease and lower limb artery disease were higher in men than in women, slightly higher for CV death, cerebrovascular disease and atrial fibrillation, but similar for both genders for heart failure (Fig. 1). History of CVD was strongly associated with subsequent CV events of any type.
In multivariable analyses, gender was no longer associated with any cause-specific CV event, whereas a lower eGFR was significantly associated with an increased risk of coronary artery disease and heart failure, but not with other CV events (Table 1).

CONCLUSION
In patients with moderate or advanced CKD, the burden of atheromatous CVD is higher in men than in women and explained by their higher prevalence of cardiovascular risk factors, but that for heart failure and atrial fibrillation appears to be similar for both genders.
MO508: Estimated Glomerular Filtration Rate and the Risk of Inflammatory Bowel Disease in Adults: A Swedish Population-Based Study
Authors: Yang Yuanhang , Ludvigsson Jonas , Olén Ola , Sjolander Arvid , Jesus Carrero Juan 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease (CKD) and inflammatory bowel disease (IBD) share many risk factors. While kidney complications are seen in 4%–23% of patients with longstanding IBD, it is unknown whether low kidney function may predispose to developing IBD.

METHOD
We analyzed the association between estimated glomerular filtration rate (eGFR) and the risk of being diagnosed with IBD among 1 612 160 adults without prior IBD history who accessed healthcare in Stockholm during 2006–18. We categorized eGFR into five groups: &lt;30, 30–59, 60–89, 90–104, 105 + mL/min/1.73m2 with 90–104 being the reference group. Flexible parametric survival models with stepwise adjustments and piecewise linear splines were used to investigate the association between eGFR, IBD and IBD-subtypes (Crohn's disease, ulcerative colitis and IBD unclassified). IBD cases were identified by two or more records with an IBD diagnosis. Subgroup analyses explored the consistency of the associations between age strata, sex, background education and the presence of selected comorbidities. To explore the possibility of detection bias and reverse causation, we estimated IBD risks from the first year after baseline eGFR.

RESULTS
We detected 9663 new cases of IBD (Crohn's disease: n = 3299 and ulcerative colitis: n = 5072), over a median follow-up of 9 years. Linear splines suggested the association between eGFR and IBD to be J-shaped, with higher IBD risk at both eGFR extremes. After multivariable adjustment and compared with eGFR 90–104 mL/min/1.73 m2 lower eGFR strata were associated with higher IBD risk {adjusted hazard ratio (HR), 1.14; [95% confidence interval (95% CI) 0.99–1.32] for eGFR = 30–59 mL/min and 1.63; 1.14–2.33 for eGFR &lt;30 mL/min}. This association was stronger in magnitude for Crohn's disease, with an HR of 1.32 (1.03–1.71) for eGFR = 30–59 mL/min and 2.22 (1.24–3.97) for eGFR &lt;30 mL/min. Subgroup analyses showed consistency across age, education categories, presence of diabetes and of CVD, but suggested that the association between low eGFR and IBD was stronger in women and in the absence of hypertension (P for interaction &lt;.05). Associations were slightly attenuated after excluding IBD cases during the first year of follow-up, indicating the presence of detection bias and/or reverse causation.

CONCLUSION
We observed an association between decreased eGFR and the risk of developing IBD, which was stronger in magnitude for Crohn's disease, but that could be partly explained by bias.
MO519: Ferric Citrate Hydrate Improves Levels of Transferrin Saturation in Hemodialysis Patients With Lower Levels of Transferrin Saturation
Authors: Yokoyama Keitaro , Inoue Ryo , Ito Kyoko , Mitobe Yuko , Matsumoto Yu , Yamada Ryoichi , Susai Hiroyuki , Nishino Noriaki 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Iron deficiency identified by transferrin saturation (TSAT) is reported as a risk factor for all-cause mortality and cardiovascular events in non-dialysis dependent (NDD) chronic kidney disease (CKD) [1, 2] and for all-cause mortality in hemodialysis patients [3]. Ferric citrate hydrate (FC, Riona®), an oral iron-based phosphate binder in CKD patients, is also approved as an iron preparation for iron-deficiency anemia (IDA) in Japan in 2021. In the USA, ferric citrate (Auryxia®) is approved as a phosphate binder for dialysis-dependent CKD and an iron replacement product for the treatment of IDA in patients with NDD-CKD. FC or ferric citrate increased TSAT in patients with NDD-CKD and IDA [4]. However, a few data show that whether FC or ferric citrate has the similar effect in hemodialysis patients whose TSAT is &lt;20%. Considering the additional indication of IDA in Japan, we investigated the FC's effect on TSAT by using the data obtained from the ASTRIO study [5], which was conducted in Japanese hemodialysis (HD) patients.

METHOD
We conducted a retrospective study using the data of ASTRIO study [5], which is a randomized, prospective, open-label, multicenter 24-week study to investigate the FC's effect on anemia management compared with non-iron-based phosphate binders (PBs) in Japanese HD patients with hyperphosphatemia. Ninety-three patients taking non-iron-based PBs were randomized 1:1 to continue PBs (control) or switch to FC. During 24-week study, serum phosphate and hemoglobin were controlled, 3.5–6.0 mg/dL and 10–12 g/dL, respectively. From 93 patients (FC, n = 48; control, n = 45), we extracted 41 patients (FC, n = 21; control, n = 20) whose TSAT at baseline was &lt;20% and compared the levels of TSAT and other iron related parameters between FC group and control group.

RESULTS
In the ASTRIO study, the mean (SD) levels of TSAT (%) was 14.3 (4.0) at baseline and rapidly increased to 25.0 (11.1) at 4 weeks in the FC group. After that, the levels of TSAT were almost unchanged in the FC group, whereas, in the control group, the mean (SD) levels of TSAT were almost unchanged during the 24-week study. The mean (SD) levels of serum ferritin gradually increased until week 12 and subsequently showed to be stabilized in the FC group, whereas, in the control group, these were almost unchanged during the 24-week study (Table 1).

CONCLUSION
In Japanese HD patients whose TSAT was &lt;20%, FC rapidly increased TSAT compared with control. We will also investigate the FC's effect on TSAT in HD patients from the post-marketing surveillance study, the prospective, multicenter and observational, up to maximum 2 years treatment.