bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO216PRELIMINARY STUDY OF THE GLYMPHATIC SYSTEM IN CKD
Authors: Buonincontri Veronica , Viggiano Davide , Capasso Giovambattista 
Published: May 2021

Abstract

Background and Aims
The glymphatic system is a network of extracellular spaces between neurons, glial cells, and capillaries that promotes the elimination of soluble molecules from the brain. Its dysfunction is probably relevant for neurodegenerative diseases such as Alzheimer's disease (AD). It is widely accepted that cognitive impairment accompanies chronic kidney disease (CKD). CKD is also a risk factor for dementia. However, the role of the glymphatic system in this process is unknown. A recent method to study the glymphatic system in human subjects has been proposed based on Diffusion Tensor Imaging (DTI) data and water diffusion calculation along with perivascular spaces. This approach is based on calculating a diffusion index named ALPS and showed that the glymphatic flow is reduced in MCI.

Method
To analyze the role of glymphatic system in CKD patients, we took advantage of the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI is a longitudinal multicenter study helping researchers to monitor Alzheimer's disease and Mild Cognitive Impairment (MCI) progression. This database has a cohort of control patients and MCI patients, among which several patients with CKD stage II-III were identifiable from the creatinine values. Patients with Alzheimer's disease were excluded for this study. Among the control and MCI patients, we identified 12 CKD patients and pair-matched 12 non-CKD patients comparable for age, gender, and MoCA score. Magnetic resonance data with DTI sequences were retrieved for all patients, and the glymphatic system was characterized by the ALPS index. Tensor values were calculated using the FSL software; the diffusion values were calculated on tensor images using the ImageJ software. Differences in ALPS between CKD and non-CKD patients with and without MCI were tested.

Results
Analysis of DTI data confirmed that control patients without CKD had lower ALPS values when MCI was present compared to the non-MCI patients, suggesting a reduction of water diffusion in the glymphatic system. However, the presence of CKD had a different effect: in the absence of MCI, CKD did not modify ALPS values compared to non-CKD patients. At variance, in patients with MCI, CKD resulted in a significant increase of water diffusion in the glymphatic system compared to the controls.

Conclusion
In this preliminary study, MCI and CKD exerted opposite effects on the diffusion of water within the glymphatic system: MCI was accompanied by a reduction of water diffusion whereas CKD by an increased diffusion in the glymphatic spaces.
It is possible that small modification of water balance in CKD may be responsible for the increased diffusion of water in glymphatics in CKD. Further studies are needed to verify whether this unexpected phenomenon may modify cognitive function with a mechanism rather different from Alzheimer's disease.
MO218ALTERNATING EPISODES OF TRUE HYPERKALEMIA AND PSEUDOHYPERKALEMIA IN ADULT SICKLE CELL DISEASE - A NEPHROLOGIST'S DILEMA
Authors: Onuigbo Macaulay , Sherman Sarah , Tan Heng 
Published: May 2021

Abstract

Background and Aims
To illustrate the phenomenon of alternating true hyperkalemia and pseudohyperkalemia in adult sickle cell disease.

Method
Case Report

Results
Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients. The presence of sickled erythrocytes in the renal medullary vessels is the hallmark of the disease and renal manifestations include renal ischemia, microinfarcts, renal papillary necrosis and renal tubular abnormalities with variable clinical presentations. Furthermore, acute hemolytic crisis can be complicated by sepsis. Hemolysis, specifically, intravascular hemolysis, can produce hyperkalemia. Additionally, reduced glomerular filtration rate from SCN predisposes to hyperkalemia. Pseudo-hyperkalemia was first reported by Hartmann and Mellinkoff in 1955 as a marked elevation of serum potassium levels in the absence of clinical evidence of electrolyte imbalance. In pseudohyperkalmia, simultaneously estimated serum potassium exceeds plasma potassium by &gt;0.4 mmol/L. This is often associated with moderate to severe thrombocytosis or leukocytosis. Clearly, hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate treatment of pseudo-hyperkalemia leading to hypokalemia is also equally potentially lethal. We describe a 40-yo African American male patient with sickle cell anemia who exhibited alternating episodes of hyperkalemia and pseudo-hyperkalemia, during consecutive hospital admissions. Pseudohyperkalemia was associated with severe thrombocytosis complicating sepsis. EKG was normal despite measured serum potassium of 6.7 mmol/L (Figure).

Conclusion
We believe that this is the first report of adult SCD demonstrating alternating cycles of true hyperkalemia and pseudo-hyperkalemia at different times. We must draw attention to the new availability of the new potassium binders, Patiromer and sodium zirconium cyclosilicate. We would advocate for caution in the use of these potent potassium binders and to always give consideration to the presence of pseudo-hyperkalemia under appropriate clinical scenarios. We posit that providers managing adult patients with sickle cell disease must be aware of such a phenomenon to avoid the dangers of overtreatment of episodes of pseudo-hyperkalemia in such patients.
MO629XANTHINE OXIDASE INHIBITOR ATTENUATES RENAL OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION THROUGH THE INHIBITION OF VEGF-NADPH OXIDASES IN DIABETIC NEPHROPATHY
Authors: Hong Yu Ah , Yang Keum-Jin , Choi Wonjung , Chang Yoon-Kyung , Park Cheol Whee , Kim Suk Young 
Published: May 2021

Abstract

Background and Aims
Xanthine oxidase (XO) is one of major source of reactive oxygen species, and a XO inhibitor, febuxostat has been reported to the protection of kidney diseases. We investigated whether febuxostat exerts renoprotective effects against diabetic nephropathy (DN).

Method
Eight-week Male C57BL/6 mice were divided into four groups: Control group (Cont), Febuxostat control group (FEB), streptozotocin treated group (STZ) and a febuxostat and STZ-treated diabetes group (STZ+FEB). STZ was used to induce diabetes (50 mg/kg/day, 5 days), and 5 mg/kg of febuxostat was treated to experimental mice for 8 weeks.

Results
STZ-treated diabetic mice were significantly decreased in serum and kidney XO levels, serum cystatin C and albuminuria by febuxostat treatment. Febuxostat treatment decreased renal hypertrophy and mesangial matrix expansion in STZ-treated diabetic mice. Febuxostat treatment suppressed the expression of vascular endothelial growth factor (VEGF)1 and 3, NADPH oxidase (NOX)1, 2, and 4, and the levels of their catalytic subunit mRNA in in STZ-treated diabetic mice. Febuxostat treatment was accompanied by the downregulation of Akt phosphorylation, followed by the suppression of transcription factor forkhead box O3a phosphorylation and the enhancement of endothelial nitric oxide synthase. Finally, febuxostat improved oxidative stress and resulted in decreased 8-hydroxy-2'-deoxyguanosine and kidney malondialdehyde levels, and increased superoxide dismutase activity in STZ-treated diabetic mice.

Conclusions
Febuxostat attenuated DN by modulating oxidative stress and endothelial function through VEGF–NADPH oxidase signaling pathway.
MO630SNOGO-B IS AN IMPORTANT CONTRIBUTOR TO GLOMERULAR ENDOTHELIAL CELL STABILITY AND VASCULAR REMODELLING INTERVENING ON VEGFA/VEGFR2 SIGNALLING
Authors: Ricciardi Carlo Alberto , Long David , Gnudi Luigi 
Published: May 2021

Abstract

Background and Aims
Nogo-B is an endoplasmic reticulum protein present as a full length and circulating soluble isoform (sNogo-B) corresponding to the first ∼200aa of the N-terminus. Nogo-B is expressed in glomerular endothelial cells (GECs) and is downregulated in the diabetic glomeruli; its repletion, ameliorates diabetic glomerulopathy. However, the precise biological role of Nogo-B and its soluble form in GEC is not well understood.
We hypothesise that sNogo-B could modulate VEGFA/VEGFR2 signalling, and vascular remodelling resulting in improved GECs health and vascular remodelling (vessel repair/new vessel formation). We predict that this effect may be mediated by changes in VEGFA/VEGFR2 signalling; a critical signalling pathway which regulates blood vessel function in physiology and disease.

Method
For this experiment we used human conditionally immortalised GECs. Cells were used after differentiation at 37°. GECs were infected with adenovirus vector expressing sNogo-B or identical vector lacking sNogo-B cDNA (control vector). Cells were serum starved (4 hours, FBS 2%) and exposed to VEGFA (50 ng/ml) for 5’ 10’ 15’ min and VEGFR2 phosphorylation assessed with western immunoblotting.

Results
VEGFA-Mediated VEGFR2 phosphorylation was upregulated in wild-type GECs after 15 min VEGFA incubation (P&lt;0.05) n=4. sNogo-B overexpression upregulated the sNogo-B protein level in the supernatant by 10 fold and prevented VEGFA/VEGFR2 phosphorylation in human immortalized glomerular endothelial cells(P&lt;0.05).

Conclusion
sNogo-B prevents the VEGFA mediated VEGFR2 phosphorylation in GECs. Upregulation of VEGFA/VEGFR2 signalling has been implicated in diabetic glomerulopathy. sNogo-B inhibition of VEGFA/VEGFR2 signalling opens new investigations looking at the potential role of sNogo-B as therapeutic target in diabetic nephropathy.
MO631XANTHINE OXIDASE INHIBITOR AMELIORATES HIGH GLUCOSE-INDUCED OXIDATIVE STRESS BY ACTIVATING AMPK VIA THE ACTIVATION OF PURINE SALVAGE PATHWAY IN GLOMERULAR ENDOTHELIAL CELLS
Authors: Hong Yu Ah , Yang Keum-Jin , Choi Won Jung , Chang Yoon-Kyung , Park Cheol Whee , Kim Suk Young 
Published: May 2021

Abstract

Background and Aim
Oxidative stress plays a crucial role in the pathogenesis of diabetic nephropathy (DN). Xanthine oxidase (XO) contribute to reactive oxygen species (ROS) production, and XO inhibitor, febuxostat has been reported to the protection of kidney diseases. However, the mechanism of renoprotective effects for febuxostat remained unclear. We investigated the renoprotective mechanism associated with purine salvage pathway of febuxostat against DN.

Method
Glomerular endothelial cells (GEnCs) exposed to high glucose (HG) were treated with or without febuxostat for 72 hours, and then the changes of purine salvage pathway and the phosphorylation of 5' AMP-activated protein kinase (AMPK) and its related signaling pathway were evaluated.

Results
Cell survival was significantly decreased in HG-treated GEnCs, and febuxostat treatment enhanced cell survival in a dose-dependent manner. The expressions of xanthine/hypoxanthine, and the levels of xanthine oxidoreductase were significantly increased in HG-treated GEnCs, and these findings were attenuated by febuxostat. The AMP/ATP ratio was inhibited in in HG-treated GEnCs and enhanced by febuxostat treatment. Febuxostat treatment enhanced phosphorylation of AMPK, peroxisome proliferator-activated receptor (PPAR)-α, PPAR-gamma coactivator (PGC)-1α, and dephosphorylation of the Forkhead box O (FoxO)3a in HG-treated GEnCs. Febuxostat treatment also suppressed NADPH oxidase expressions and their catalytic subunits and oxidative stress in HG-treated GEnCs. AMPK inhibition using small interfering RNA blunted the antioxidative effects of febuxostat in HG-treated GEnCs.

Conclusions
Febuxostat attenuated HG-induced oxidative stress through the activation of purine salvage pathway and AMPK–PGC-1α–NADPH oxidase signaling.
MO623EFFECT OF PLANTAR ELECTRICAL NERVE STIMULATION DURING ROUTINE HEMODIALYSIS PROCESS ON THE DAILY PHYSICAL ACTIVITY IN ADULTS WITH DIABETES AND END-STAGE RENAL DISEASE - A RANDOMIZED DOUBLE-BLINDED CONTROLLED TRIAL
Authors: Mishra Ram kinker , Al-Ali Fadwa , Hamad Abdullah , Ibrahim Rania , Mathew Mincy , Najafi Bijan 
Published: May 2021

Abstract

Background
Physical inactivity among patients undergoing hemodialysis (HD) is a long-standing clinical problem. While exercise could be beneficial, post-dialysis fatigue, limited time availability, and severe frailty to travel often lead to poor adherence to conventional exercise programs. To address this gap, we proposed testing an alternative therapy using intradialytic plantar electrical nerve stimulation (IPENS) provided during the routine hemodialysis process.

Methods
Participants were randomized into either an intervention group (IG: n=16, age=57.6±3.6 years, BMI=29.7±1.5 kg/m2, female=31%) or a control group (CG: n=15, age=63.5±1.6 years, BMI=29.9±1.6 kg/m2, female=41%). The IG received 1-hour IPENS during routine hemodialysis process (3 sessions/week) for 12 weeks. The CG was provided with an identical but non-functional device for the same period. Participants and therapy-providers were blinded to the group allocation. Daily life physical activity (e.g., cumulative postures including sitting, standing, lying, and walking; walking characteristics including step count, number of unbroken walking bout, and postural transitions including sit to stand and stand to sit) was monitored remotely at baseline and 12-week for a period of 48h using a validated pendant sensor. To determine the effect of intervention, we estimated Cohen’s effect size d. In addition, time effect, group effect, and time×group effect were estimated using general linear model.

Results
All participants in the IG tolerated the IPENS and completed all therapy sessions, indicating the feasibility. In the IG, we observed significant increase in time spent in standing (Cohen's d=0.8, p=0.039) and walking (Cohen's d=0.82, p=0.034), number of walking episodes (d=0.88, p=0.024), and number of postural transitions (d=0.93, p=0.018) with a decrease in the average duration for sit to stand transition (d=0.87, p=0.032) compared to the CG.

Conclusions
This is an ongoing study and our target sample is 100 eligible participants. This study provides earlier results on IPENS therapy's feasibility and effectiveness as an alternative to exercise programs to improve daily life physical activity among people undergoing routine hemodialysis process. If the results were held at a larger sample, we could recommend routine
MO625INHIBITION OF SGLT-2 CANNOT RESCUE NEPHRIN EXPRESSION IN DIABETIC NEPHROPATHY
Authors: Kotb Ahmed , Klanke Bernd , Kroll Jens , Schiffer Mario 
Published: May 2021

Abstract

Background and Aims
Early glomerular damage in diabetes is induced by high blood glucose level (hyperglycemia) which affects the glomerular filtration barrier and leads to proteinuria. Podocyte-specific proteins like the transmembrane protein nephrin form the slit diaphragm that is important for proper function of the glomerular filtration barrier. Sodium-glucose co-transporter 2 (SGLT2) specific proteins are involved in glucose reabsorption in the kidney and maintain the normal glucose level in the blood. Recent studies showed remarkable success of SGLT2-inhibition in patients with diabetic nephropathy. Therefore we wanted to study if hyperglycemia induced reduction of nephrin expression is affected bySGLT-2 inhibition. Therefore we induced hyperglycemia in zebrafish larvae by knockdown of Pancreatic duodenal homeobox 1 (Pdx1) transcription factor and treated zebrafish larvae with Empagliflozin. In parallel we treated Bl/6 mice with streptozotozin and treated them with Empagliflozin. We then analyzed nephrin expression in both model systems.

Method
Zebrafish is an ideal model to study glomerular diseases, because the zebrafish larvae develops a pronephros with high homology to the human glomerulus. In order to inhibit SLGT-2 after Pdx1-knockdown, we treated both control and diabetic zebrafish larvae with 10µM Empagliflozin from 1dpf to 5dpf. We used a zebrafish line that expresses a fluorescent Vitamin D binding plasma protein Tg(l-fabp:DBP:eGFP) to measure proteinuria by measuring the GFP signal in both retinal and glomerular vessels of 120 hpf larvae. Immunohistochemistry against nephrin was performed using a specific zebrafish antibody.

Results

Conclusion
Despite the promising effects of SLGT-2 inhibitor treatment in patients with diabetic nephropathy the early effects on nephrin expression are not addressed and remain an unchanged problem by this novel treatment option.
MO628IMPACT OF INDUCTION OF AUTOPHAGY BY RAPAMYCIN AND METFORMIN ON NATURAL HISTORY OF DIABETIC NEPHROPATHY IN RATS
Authors: Ahmed Samar , Samaan Emad , Abdallah Ibrahim Dina , Sayed-Ahmed Nagy , Sheashaa Hussein 
Published: May 2021

Abstract

Background and Aims
Impaired autophagy in the kidney resulted in podocyte loss and massive proteinuria in diabetic nephropathy. Improvement of autophagy by activation of mTORC1 and reduction of AMPK and Sirt1 may be a novel therapeutic option for the suppression of diabetic nephropathy.

Method
This experimental work was carried out on 48 adult male Sprague dawely rats. The total duration of the study was 10 weeks. All investigation and intervention were carried out at 3 time points, 3 weeks, 6 weeks, 10 weeks. The rats were randomly divided into healthy control group (n = 12) and 3 induced diabetic groups (n = 12 each), the three groups were the non-treated, treated with rapamycin and treated with rapamycin and metformin. To study autophagy, we use electron microscopy and immunohistochemical staining of kidney tissue with LC3 antibody

Results
Diabetic rats treated with rapamycin alone or rapamycin and metformin showed lower level of proteinuria and almost normal serum creatinine through all intervals of the study. Also, their Kidney tissue showed increased autophagosomes and high expression of LC3 compared to diabetic rats. There are no significant differences between both treated groups in terms of induction of autophagy during the experiment period.

Conclusion
we concluded that using a small dose of rapamycin for short duration in early diabetic rats is beneficial in halting the course of diabetic nephropathy, adding metformin to rapamycin aiming to potentiate its effect on autophagy seems to be less beneficial.
MO633GLYCAEMIC MARKERS IN PATIENTS WITH TYPE 2 DIABETES UNDERGOING HAEMODIALYSIS EVALUATED BY LONG-TERM CONTINUOUS GLUCOSE MONITORING*
Authors: Bomholt Tobias , Rix Marianne , Almdal Thomas Peter , Knop Filip K , Rosthøj Susanne , Heinrich Niels Søndergaard , Jørgensen Morten , Larsson Anders , Hilsted Linda , Feldt-Rasmussen Bo , Hornum Mads 
Published: May 2021

Abstract

Background and Aims
The reliability of haemoglobin A1c (HbA1c) as a glycaemic marker in patients receiving haemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose levels measured by continuous glucose monitoring (CGM) in patients with type 2 diabetes receiving HD.

Method
The HD group (maintenance HD and type 2 diabetes) comprised 30 patients who completed the study period of 17 weeks; the control group (type 2 diabetes and an estimated glomerular filtration rate &gt;60 mL/min/1.73 m2) comprised 36 individuals. CGM (Ipro2®, Medtronic) for periods up to seven days was performed five times (with four weeks intervals) during a 16-week period. HbA1c and fructosamine were measured at week 17. The mean sensor glucose from CGM was compared with the measured HbA1c, its estimated mean blood glucose (eMBGA1c) and fructosamine levels.

Results
In the HD group, the mean sensor glucose from CGM was 1.4 (95% confidence interval [CI]: 1.0–1.8) mmol/L higher than the eMBGA1c, whereas the difference was 0.1 mmol/L (95% CI: -0.1–[0.4]; P&lt;0.001) in the control group. Adjusted for the mean sensor glucose, HbA1c was -7.3 (95% CI: -10.0–[-4.7]) mmol/mol lower in the HD group than in controls (P&lt;0.001), whereas no difference was detected for fructosamine (P=0.64).

Conclusion
HbA1c evaluated by CGM underestimates mean blood glucose levels in patients receiving maintenance HD; fructosamine appears to be more accurate. CGM-assessed blood glucose could complement or replace HbA1c in patients where HbA1c underestimates blood glucose levels.
MO642DAPAGLIFLOZIN HAS NO IMPACT ON SHORT-TERM BLOOD PRESSURE VARIABILITY IN PATIENTS WITH TYPE-2 DIABETES MELLITUS
Authors: Papadopoulou Eirini , Theodorakopoulou Marieta , Loutradis Charalampos , Tzanis Georgios , Tzatzagou Glyceria , Kotsa Kalliopi , Zografou Ioanna , Tsapas Apostolos , Karagiannis Asterios , Sarafidis Pantelis 
Published: May 2021

Abstract

Background and Aims
Increased blood-pressure-variability (BPV) is associated with increased cardiovascular and all-cause mortality in patients with type 2 diabetes mellitus (T2DM). Sodium-glucose co-transporter-2 (SGLT-2) inhibitors decrease the incidence of cardiovascular events, renal events, and death in this population. This study aimed to evaluate the effect of dapagliflozin on short-term BPV in patients with T2DM.

Method
This is a secondary analysis of a double-blind, randomized, placebo-controlled trial in 85 patients with T2DM (NCT02887677). Subjects were randomized to oral dapagliflozin 10mg once daily or placebo for 12 weeks. All participants underwent 24-h ambulatory blood pressure (BP) monitoring with the Mobil-O-Graph NG device at baseline and study-end. Standard deviation (SD), weighted SD (wSD), coefficient of variation (CV), average real variability (ARV) and variation independent of mean (VIM) were calculated with validated formulae for the 24-h and the daytime and nighttime periods.

Results
Dapagliflozin reduced 24-h brachial BP compared to placebo. From baseline to study-end 24-h brachial BPV indexes did not change with dapagliflozin (SBP-ARV: 11.51±3.45 vs 11.05±3.35; p=0.326, SBP-wSD: 13.59±3.60 vs 13.48±3.33; p=0.811) or placebo (SBP-ARV: 11.47±3.63 vs 11.05±3.00; p=0.388, SBP-wSD: 13.85±4.38 vs 13.97±3.87; p=0.308). Similarly, no significant changes in BPV indexes for daytime and nighttime were observed in any group. At study-end, no differences between the groups were observed for any BPV index. Deltas (Δ) of all indexes during follow-up were minimal and not different between-groups (SBP-wSD: dapagliflozin: -0.11±3.05 vs placebo: 0.12±4.20; p=0.227).

Conclusion
This study is the first to evaluate the effects of an SGLT-2 inhibitor on short-term BPV in patients with T2DM, showing no effect on dapagliflozin on all BPV indexes studied.