bluuebunny/crossref_metadata_2025_split huggingface dataset:
FC 119: Kidney-Specific Silencing of Neat1 Alleviates Diabetic Kidney Injury
Authors: Xue Rui , Han Yiu Wai , Chi Kam Leung Joseph , Yuk Ying Chan Loretta , Neng Lai Kar , Yao Lan Hui , Tang Sydney 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Long noncoding RNA Nuclear Enriched Abundant Transcript 1 (Neat1) not only serves as a key structural component of nuclear paraspeckle, but is also involved in a variety of pathophysiological processes. Our previous study shows that increased Neat1 expression is closely associated with the pathogenesis of acute kidney injury. Here, we investigate whether Neat1 plays a role in chronic kidney disease and diabetes (DKD).

METHOD
Neat1 expression on kidney biopsies of patients with DKD and other nondiabetic kidney disease was measured by in situ hybridization. Normal portions of kidney tissues removed from nephrectomy specimens for the treatment of renal carcinoma was used as control. In vivo, streptozotocin (STZ)-induced DKD was established in uninephrectomized C57BL/6 mice with low-dose STZ (50 mg/kg) injection for five consecutive days. Mice injected with citrate buffer were used as control. Neat 1 gene was subsequently knocked down in the kidney by shRNA gene silencing via ultrasound-mediated microbubble technique every 2 weeks. All mice were sacrificed at 10 weeks after STZ injection for renal histopathological examination, urine albumin-to-creatinine ratio (UACR) measurement and Neat 1 expression analysis.

RESULTS
Kidney Neat 1 expression was increased significantly in DKD patients compared with control and other kidney diseases (Figure 1). Similarly, Neat1 was induced in STZ-induced diabetic kidneys while its expression was markedly suppressed following shRNA knockdown as confirmed by real-time qPCR (Figure 2A, C and E). Compared with nondiabetic control, diabetic mice presented increased UACR with significant tubular dilatation and atrophy, while knockdown of Neat1 attenuated both proteinuria and kidney injury in the diabetic mice (Figure 2B, D and F).

CONCLUSION
Increased Neat 1 expression contributes to the pathogenesis of DKD and targeting Neat 1 may be a novel and potential therapeutic strategy for diabetic kidney injury.
FC 123: Baseline Characteristics of the Flow Trial Population: Kidney Outcomes Trial With Once-Weekly Semaglutide in People With Type 2 Diabetes and Chronic Kidney Disease
Authors: Perkovic Vlado , Baeres Florian , Bakris George , Bosch-Traberg Heidrun , Idorn Thomas , Mahaffey Kenneth , Mann Johannes , Mersebach Henriette , Rossing Peter , Tuttle Katherine , Pratley Richard 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chronic kidney disease (CKD) in type 2 diabetes (T2D) is the most common cause of kidney failure. Despite treatment advances, there is still a large unmet need to prevent CKD progression, which can increase the risk for cardiovascular (CV) disease and kidney failure. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have beneficial effects on glycaemic control and body weight. Some agents have also shown CV benefit and can be used in people with T2D regardless of CKD status (except in end-stage renal disease). CV outcomes trials have suggested that GLP-1RAs may have kidney-protective effects, reducing albuminuria and preserving estimated glomerular filtration rate (eGFR). FLOW (NCT03819153) is a dedicated kidney outcomes trial designed to evaluate the effect of the once-weekly (OW) GLP-1RA semaglutide on major kidney outcomes in subjects with T2D and CKD; we report the blinded baseline characteristics of the FLOW trial population.

METHOD
FLOW is an ongoing randomized, double-blinded, multinational, phase 3b trial in which 3535 subjects with T2D with an eGFR ≥25–≤75 mL/min/1.73 m², and urine albumin-to-creatinine ratio (UACR) &gt;100 to &lt;5000 mg/g were randomly assigned 1:1 to OW semaglutide 1.0 mg or placebo, as add-on to standard-of-care (including maximum labelled/tolerated renin–angiotensin–aldosterone system inhibitors). The primary endpoint is the time to first occurrence of kidney failure (as measured by persistent eGFR &lt;15 mL/min/1.73 m² or initiation of chronic dialysis or kidney transplantation); ≥50% persistent eGFR reduction compared with baseline; and kidney or CV death.

RESULTS
Baseline characteristics from FLOW are shown in the Table 1. Overall, mean eGFR at baseline was 47.0 mL/min/1.73 m2 with 79.6% of subjects having an eGFR of &lt;60 mL/min/1.73 m2. Median UACR at baseline was 567 mg/g, and 68.5% of subjects had macroalbuminuria (≥300 mg/g). According to Kidney Disease: Improving Global Outcomes categories, 24.8% of subjects were classified as high risk and 68.2% of subjects were classified as very high risk for CKD progression (Figure 1).

CONCLUSION
The FLOW trial will evaluate the efficacy and safety of semaglutide on kidney outcomes in subjects with T2D and high risk of kidney disease progression, a group for which additional therapies are urgently required.
FC 124: Real-World Use of Once-Weekly Semaglutide by Baseline Estimated Glomerular Filtration Rate—A Post-Hoc Analysis of Pooled Data From the Sure Studies (Canada, Denmark/Sweden, Switzerland and UK)
Authors: Rudofsky Gottfried , Catarig Andrei-Mircea , Erhan Umut , Jain Rashmi , Tang Knudsen Søren , Saravanan Ponnusamy , Yale Jean-François 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The SURE programme of observational real-world studies is investigating once-weekly (OW) subcutaneous semaglutide in routine clinical practice across a diverse type 2 diabetes (T2D) patient population, including those with chronic kidney disease. This pooled post-hoc analysis of SURE Canada, Denmark/Sweden, Switzerland and UK evaluated OW semaglutide use and outcomes according to kidney function at semaglutide initiation.

METHOD
The SURE studies (all ∼30 weeks’ duration) enrolled adults (≥18 years) with T2D who received OW semaglutide and other anti-hyperglycaemic drugs prescribed at physician discretion; pooled data were analysed to determine change from baseline to end of study (EOS) in HbA1c and body weight (BW) by estimated glomerular function rate (eGFR) subgroups (&lt;30, 30 to &lt;45, 45 to &lt;60, 60 to &lt;90, and ≥90 mL/min/1.73 m2). Safety outcomes were assessed; only serious adverse drug reactions (SADRs) were systematically recorded.

RESULTS
Data from 913 patients with median (interquartile range) age of 61 (54–68) years and T2D duration of 11.0 (6.2–17.2) years were included. Patients with eGFR &lt;45 mL/min/1.73 m2 were more likely to be older with longer T2D duration than those with eGFR ≥45 mL/min/1.73 m2. Patients with low eGFR were more likely to be receiving insulin at baseline than those in higher eGFR subgroups. At EOS, there were significant reductions in HbA1c and BW in all subgroups with eGFR ≥30 mL/min/1.73 m2 (P &lt;0.0001; Figure 1). The rates of SADRs and adverse events leading to treatment discontinuation were low across all eGFR subgroups (≤0.3% and ≤1.8%, respectively). Overall, 50/72 patients who experienced more than or equal to severe or documented hypoglycaemic episode were receiving insulin at baseline.

CONCLUSION
OW semaglutide provided clinically relevant glycaemic control and BW improvements, and was well tolerated, in patients with varying degrees of kidney impairment at treatment initiation in a real-world setting. These findings support semaglutide use in routine clinical practice regardless of patients’ kidney function.
MO085: 10-Year Clinical Events Avoided in Diabetic and Chronic Kidney Disease Hypertension Patients Treated With Radiofrequency Renal Denervation: Projections Based on 3-Year Data From the Global Symplicity Registry
Authors: Schmieder Roland E , Cao Khoa , Esler Murray , Kandzari David , Lobo Melvin , Sharp Andrew , Mancia Giuseppe , Böhm Michael , Pietzch Jan 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Clinical event rates over 3 years have been published for patients with uncontrolled hypertension treated with radiofrequency renal denervation (RDN) in the Global SYMPLICITY Registry (GSR). We estimated 10-year clinical event reductions following RDN versus a simulated control group without RDN, for the type 2 diabetes (T2DM) and chronic kidney disease (CKD) subgroups and the full GSR cohort.

METHOD
A Markov model based on Framingham and other multivariate risk equations [1] was used to compare projected 10-year clinical events [stroke, myocardial infarction (MI), cardiovascular death (CVD), heart failure (HF), all-cause death (ACD) and a composite of major adverse cardiac events (MACE, calculated as sum of stroke, MI and CVD)] for RDN patients versus a hypothetical control for the T2DM subgroup (n = 1007; 64 ± 10 years), the CKD subgroup (n = 630; 65 ± 12 years), and for all GSR patients (n = 2651; 61 ± 12 years). The simulated control assumed maintenance of baseline office systolic blood pressure (oSBP) over time. The model was calibrated to 3-year stroke and MI events reported in the GSR and used published meta-regression data [2] to calculate risk reduction based on cohort-specific changes in oSBP from baseline. Relative risks (RRs), events avoided, and numbers needed to treat (NNTs) were calculated at 3 and 10 years, along with the ratio of 10- versus 3-year projected events avoided.

RESULTS
Ten-year MACE rates were 35.8% versus 48.5% (-12.7%, RR = 0.74) for RDN versus simulated control for all patients, 40.5% versus 54.0% (-13.5%, RR = 0.75) for the T2DM subgroup and 48.4% versus 61.3% (-12.9%, RR = 0.79) for the CKD subgroup. Across the studied subgroups, avoided stroke events contributed the most to overall event reductions. RRs of events were lowest for HF (0.53–0.61) and highest for all-cause death (0.88–0.90) across the three subgroups (Table 1). Ten-year NNTs for MACE were comparable between the three cohorts, estimated between 7 and 8. The ratio of 10- versus 3-year events avoided ranged from 4.44 to 4.87 for stroke, 3.74 to 3.96 for MI and 4.22 to 5.20 for MACE across studied cohorts.

CONCLUSION
Based on 10-year model projections from the GSR, RDN may lead to meaningful clinical event reductions in diabetic and chronic kidney disease patients. Ten-year events avoided can be expected to be 3 to 5 times higher than those recently reported for a 3-year horizon.
MO086: Sex Differences in Ambulatory Blood Pressure Trajectories and Blood Pressure Variability in Hemodialysis Patients
Authors: Theodorakopoulou Marieta , Karagiannidis Artemios , Eleni Alexandrou Maria , Pella Eva , Karpetas Antonios , Baksiova Afroditi , Tsouchnikas Ioannis , Papagianni Aikaterini , Sarafidis Pantelis 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Ambulatory blood pressure (BP) control is worse in men than in women with chronic kidney disease (CKD), and this may partially explain the faster CKD progression in men. The aim of this study is to investigate possible sex-differences in ambulatory BP levels, BP trajectories and BP variability (BPV) in hemodialysis patients.

METHOD
129 male and 91 female hemodialysis patients that underwent 48-h ABPM with Mobil-O-Graph-NG were included in this analysis. Ambulatory BP levels over the 2-day interdialytic interval (including two daytime and two nighttime periods) were recorded. We calculated the standard deviation (SD), weighted SD (wSD), coefficient of variation (CV) and average real variability (ARV) of BP with validated formulas.

RESULTS
Age, dialysis vintage, antihypertensive treatment and history of major comorbidities did not differ between men and women. Pre-dialysis SBP levels did not differ between men and women (145.1 ± 22.7 versus 145.9 ± 25.7 mmHg, P = 0.808), but DBP was marginally higher in men (87.6 ± 14.0 versus 84.0 ± 13.7 mmHg, P =0.055). About 48-h SBP/DBP (137.2 ± 17.4/81.9 ± 12.1 mmHg versus 132.2 ± 19.2/75.9 ± 11.7 mmHg, P = 0.045/&lt;0.001) as well as DBP during the first and SBP/DBP during the second 24-h period were significantly higher in men than in women. Similarly, daytime SBP/DBP was significantly higher in men (138.3 ± 17.5/83.2 ± 12.3 mmHg versus 131.9 ± 19.4/76.4 ± 11.5 mmHg, P = 0.011/&lt;0.001). No significant between-group differences were detected for nighttime SBP. All SBP variability indices were similar between men and women; DBP-SD, DBP-wSD and DBP-ARV were higher in men (44-h DBP-ARV 9.4 ± 1.8 versus 8.6 ± 1.9, P = 0.002). No significant differences were revealed in the dipping pattern between men and women.

CONCLUSION
Ambulatory BP levels and trajectories, as well as DBP variability indices are higher in men than women hemodialysis patients. This worse ambulatory BP profile in male compared to female patients may impact on the incidence of cardiovascular events.
MO089: Comparison of Ambulatory Central Hemodynamics and Arterial Stiffness in Hemodialysis Patients With And Without Intradialytic Hypertension
Authors: Theodorakopoulou Marieta , Eleni Alexandrou Maria , Iatridi Foteini , Faitatzidou Danai , Karpetas Antonios , Bikos Athanasios , Papagianni Aikaterini , Sarafidis Pantelis 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Increased arterial stiffness is suggested to be involved in the pathogenesis of intradialytic hypertension (IDH). Ambulatory pulse wave velocity (PWV) is an independent predictor for all-cause-mortality in hemodialysis patients and its prognostic power is better than office PWV. This is the first study comparing ambulatory central blood pressure (BP) and arterial stiffness parameters between patients with and without IDH.

METHOD
This study examined 45 patients with IDH (defined as: SBP rise ≥ 10 mmHg from pre- to post-dialysis and post-dialysis SBP ≥ 150 mmHg) in comparison 197 without IDH. All participants underwent 48-h ABPM with the Mobil-O-Graph-NG device; parameters of central hemodynamics [central systolic (cSBP) and diastolic BP (cDBP), pulse pressure (PP)], wave reflection [augmentation index (AIx) and pressure (AP)] and PWV were estimated.

RESULTS
Age, dialysis vintage, interdialytic weight gain and prevalence of major comorbidities did not differ between the two study groups. Patients with IDH had higher 44-h cSBP (131.6 ± 16.7 versus 119.3 ± 15.6, P &lt; 0.001), 44-h cDBP (86.4 ± 12.8 versus 79.3 ± 11.7, P &lt; 0.001) and 44-h cPP (45.7 ± 10.7 versus 40.3 ± 10.3, P = 0.002) levels compared with patients without IDH. Similarly, during day- and nighttime periods, cSBP/cDBP and cPP levels were higher in IDH patients compared with non-IDH. 44-h augmentation pressure and index, but not AIx(75) were higher in patients with IDH than those without IDH. 44-h PWV (10.0 ± 2.0 vs. 9.2 ± 2.1 m/s, P = 0.020) was significantly higher in patients with IDH.

CONCLUSION
Patients with IDH have higher ambulatory central BP and increased arterial stiffness, as indicated by higher ambulatory cPP and PWV. Increased arterial stiffness could be a prominent factor associated with the high burden of cardiovascular disease in this population.
MO362: Braunschweig Body Composition, Butterfly Sonography and Drug Dosing in AKI Study (B3 D2 AKI––Study)
Authors: Jasbutis Kim , Drescher Julia , Hansen-Hagge Christian , Borchina Dan N , Diedrich Ulrike , Kielstein Jan T 
Published: May 2022

Abstract

BACKGROUND AND AIMS
In-hospital AKI is associated with increased morbidity and mortality. AKI Alert systems are frequently used to allow time detection of AKI patients based on changes in creatinine. We aimed to examine the hydration status, medication errors and prior existing CKD in a series of AKI 3 patients in a tertiary care hospital.

METHOD
Prospective single centre cohort study. Study was approved by the local IRB. Hydration status was assessed by Bioimpedance using the body composition monitor (Fresenius Medical Care). Renal size and exclusion of postrenal failure were accomplished using a point of care ultrasound system (Butterfly Network Inc.). Pharmacotherapy was entered into the Federal Medication Plan of Germany (Bundesmedikationsplan).

RESULTS
A total of 101 patients with AKI 3 were identified based on changes in creatinine only. The median (IQR) age was 74.0 (64.7–82.0) years with a BMI of 27.8 (23.5–34.2) kg/m2. The baseline creatinine of the patients was 1.53 (0.92–2.85) mg/dL. At the time of AKI 3 diagnosis the median [IQR] 4.1 (1.9–5.9) L. Systolic blood pressure was 116 (100–140) mmHg (Fig. 1). Median (IQR) kidney length was 10.4 (9.2–11.7) cm.
Polypharmacy (&gt; 5 drugs) was seen in 89.7% of all patients. Almost half of the patients (48.3%) received 10 or more drugs. A total of 38% of patients receiving an antibiotic received an inadequately high dose, followed by 7.8% receiving an inadequate dosing of oral antidiabetic drugs.

CONCLUSION
Patients detected by an AKI alert in a tertiary care hospital did mostly neither exhibit low blood pressure nor volume depletion. Postrenal AKI was undetected in 1 out of 101 patients. Medication dosing errors were frequently seen, especially in the dosing of antibiotics. A joined nephron-pharmacological approach seems to be important in patients with hospital acquired AKI 3.
Transitional care models in adolescent kidney transplant recipients—a systematic review
Authors: Wildes Dermot Michael , Costigan Caoimhe S , Kinlough Mairead , Flynn Joan , Dolan Niamh , Riordan Michael , Sweeney Clodagh , Stack Maria , Waldron Mary , Walsh Orla , Gorman Kathleen M , Awan Atif 
Published: May 2022

ABSTRACTBackgroundAdolescence is a time of significant change for patients, guardians and clinicians. The paediatrician must ensure patients develop the necessary skills and knowledge required to transition and to function as an independent entity, with autonomy over their own care. The transfer from paediatric to adult care carries an increased risk of graft-related complications attributable to a multitude of reasons, particularly non-adherence to immunosuppressive medicines and poor attendance at scheduled appointments. This systematic review was conducted to ascertain the transitional care models available to clinicians caring for kidney transplant recipients and to compare the approach in each respective case.MethodsA systematic review was performed, in a methodology outlined by the PRISMA guidelines. OVID MEDLINE and EMBASE databases were searched for studies that outlined valid, replicable models pertaining to transitional care of paediatric kidney transplant recipients between 1946 and Quarter 3 of 2021. The reference lists of selected articles were also perused for further eligible studies and experts in the field were consulted for further eligible articles. Two investigators assessed all studies for eligibility and independently performed data extraction. Any discrepancies were settled by consensus.ResultsA total of 1121 abstracts were identified, which was reduced to 1029 upon removal of duplicates. A total of 51 articles were deemed appropriate for full-text review and critical appraisal. A total of 12 articles that described models for transition pertaining to kidney transplant patients were included in qualitative synthesis. Every paper utilized a different transition model. All but one model included a physician and nurse at minimum in the transition process. The involvement of adult nephrologists, medical social work, psychology and psychiatry was variable. The mean age for the initiation of transition was 13.4 years (range: 10–17.5 years). The mean age at transfer to adult services was 18.3 years (range: 16–20.5 years).ConclusionsDespite the well-established need for good transitional care for paediatric solid-organ transplant recipients, models tailored specifically for kidney transplant recipients are lacking. Further research and validation studies are required to ascertain the best method of providing effective transitional care to these patients. Transitional care should become a standardized process for adolescents and young adults with kidney transplants.
Abnormalities of structural brain connectivity in pediatric brain tumor survivors
Authors: Oyefiade Adeoye , Moxon-Emre Iska , Beera Kiran , Bouffet Eric , Taylor Michael , Ramaswamy Vijay , Laughlin Suzanne , Skocic Jovanka , Mabbott Donald J 
Published: May 2022

Abstract

Background
Pediatric brain tumor survivors are at an increased risk for white matter (WM) injury. However, damage to whole-brain structural connectivity is unelucidated. The impact of treatment on WM connectivity was investigated.

Methods
Whole-brain WM networks were derived from diffusion tensor imaging data acquired for 28 irradiated patients (radiotherapy, RT) (mean age = 13.74 ± 3.32 years), 13 patients not irradiated (No RT) (mean age = 12.57 ± 2.87), and 41 typically developing children (TDC) (mean age = 13.32 ± 2.92 years). Differences in network properties were analyzed using robust regressions.

Results
Participation coefficient was lower in both patient groups (RT: adj. P = .015; No RT: adj. P = .042). Compared to TDC, RT had greater clustering (adj. P = .015), local efficiency (adj. P = .003), and modularity (adj. P = .000003). WM traced from hubs was damaged in patients: left hemisphere pericallosal sulcus (FA [F = 4.97; q &lt; 0.01]; MD [F = 11.02; q &lt; 0.0001]; AD [F = 10.00; q &lt; 0.0001]; RD [F = 8.53; q &lt; 0.0001]), right hemisphere pericallosal sulcus (FA [F = 8.87; q &lt; 0.0001]; RD [F = 8.27; q &lt; 0.001]), and right hemisphere parietooccipital sulcus (MD [F = 5.78; q &lt; 0.05]; RD [F = 5.12; q &lt; 0.05]).

Conclusions
Findings indicate greater segregation of WM networks after RT. Intermodular connectivity was lower after treatment with and without RT. No significant network differences were observed between patient groups. Our results are discussed in the context of a network approach that emphasizes interactions between brain regions.
Clinical outcomes of dose-escalated re-irradiation in patients with recurrent high-grade glioma
Authors: Helis Corbin A , Prim Shih-Ni , Cramer Christina K , Strowd Roy , Lesser Glenn J , White Jaclyn J , Tatter Stephen B , Laxton Adrian W , Whitlow Christopher , Lo Hui-Wen , Debinski Waldemar , Ververs James D , Black Paul J , Chan Michael D 
Published: May 2022

Abstract

Background
Re-irradiation for recurrent gliomas is a controversial treatment option with no clear standard dose or concurrent systemic therapy.

Methods
This series represents a single-institution retrospective review of patients treated with re-irradiation for recurrent high-grade glioma. After 2012, patients were commonly offered concurrent bevacizumab as a cytoprotective agent against radiation necrosis. Kaplan-Meier method was used to estimate overall survival and progression-free survival. Cox proportional hazards regression was used to identify factors associated with overall survival and progression-free survival.

Results
Between 2001 and 2021, 52 patients underwent re-irradiation for a diagnosis of recurrent high-grade glioma. 36 patients (69.2%) had a histologic diagnosis of glioblastoma at the time of re-irradiation. The median BED10 (biological equivalent dose 10 Gy) of re-irradiation was 53.1 Gy. Twenty-one patients (40.4%) received concurrent bevacizumab with re-irradiation. Median survival for the entire cohort and for glioblastoma at the time of recurrence patients was 6.7 months and 6.0 months, respectively. For patients with glioblastoma at the time of recurrence, completing re-irradiation (HR 0.03, P &lt; .001), use of concurrent bevacizumab (HR 0.3, P = .009), and the BED10 (HR 0.9, P = .005) were predictive of overall survival. Nine patients developed grade 3-5 toxicity; of these, 2 received concurrent bevacizumab and 7 did not (P = .15).

Conclusion
High dose re-irradiation with concurrent bevacizumab is feasible in patients with recurrent gliomas. Concurrent bevacizumab and increasing radiation dose may improve survival in patients with recurrent glioblastoma.