bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0948ASSOCIATION OF PHASE ANGLE WITH NUTRITION, MORTALITY, MAJOR ADVERSE CARDIOVASCULAR EVENTS AND SARCOPENIA IN MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Bae Eunjin , Lee Tae Won , Jang Ha Nee , Cho Hyun Seop , Kim Hyun-Jung , Chang Se-Ho , Park Dong Jun 
Published: June 2020

Abstract

Background and Aims
Nutrition has been consistently important in end stage renal disease patients. However, it is difficult to obtain adequate nutritional status while avoiding fluid overload, hyperphosphatemia and hyperkalemia in hemodialysis patients. In addition, there is no golden standard for diagnosing protein energy wasting (PEW) in maintenance hemodialysis patients. We studied the clinical significance of phase angle using bioelectrical impedance analysis (BIA), one of the PEW diagnostic tools, to predict various clinical outcomes in maintenance hemodialysis patients.

Method
We retrospectively enrolled patients who received hemodialysis for more than 3 months from 2016 to March 2019, excluding patients had active cancer, or died within 30 days, had no BIA data. We evaluated the factors related phase angle and the role of phase angle as predictors of all-cause mortality and major adverse cardiovascular events (MACE), sarcopenia.

Results
Of 191 patients, 63.4% were men, mean age was 64.2 ± 12.4 years, mean body mass index (BMI) was 23.8 ± 6.9 kg/m2, and the most common underlying disease were hypertension and diabetes mellitus. Lower phase angle group (phase angle ≤4°) patients had older age, higher portion of women, malnourished, and history of coronary artery disease (CAD) than higher phase angle group (phase angle &gt;4°) patients. Phase was significantly related with nutritional parameters. During a median follow up of 16.7 months, 14.1% (n=27) patients experienced a MACE, 11.0% (n=21) patients died. In multivariate Cox analyses, lower phase angle, higher CRP level and history of CAD were significantly related with all-cause mortality even after adjustment for covariates. However, phase angle was not significantly associated with MACE and sarcopenia.

Conclusion
In maintenance hemodialysis patients, phase angle was significantly related to mortality as well as nutritional status, but MACE and sarcopenia were not. Clinicians should be careful to find and treat correctable factors with low phase angle and high CRP level in maintenance hemodialysis patients.
P0960HOME BASED RESISTANCE EXERCISE PROGRAM AND SARCOPENIA IN HEMODIALYSIS PATIENTS: IT IS A USEFUL INTERVENTION?
Authors: Esteve Simó Vicent , Junqué Jiménez Anna , Duarte Gallego Verónica , Tapia González Irati , Moreno Guzmán Fátima , Fulquet Nicolás Miquel , Pou Potau Mónica , Saurina Solé Anna , Ramírez de Arellano Serna Manel 
Published: June 2020

Abstract

Background and Aims
Sarcopenia is a skeletal muscle disorder associated with adverse outcomes including falls, physical disability and mortality particularly in hemodialysis (HD) patients. Currently, progressive resistance training exercise has been shown a proven method to treat and prevent sarcopenia. Nevertheless, these findings are poorly investigated in HD patients since exercise programs are not widespread.
The aim of our study was to assess the effect of a home-based resistance exercise program (HBREP) on muscular strength, functional capacity and body composition in our hemodialysis patients with sarcopenia according to the European Working Group on Sarcopenia in Older People criteria (EWGSOP2).

Method
A 12 weeks single-center prospective study. HD patients from our institution with EWGSOP2 sarcopenia diagnosis were enrolled in a HBREP. Demographical an anthropometrical data, main biochemical and nutritional parameters, hand grip (HG) muscular strength, functional capacity tests: Sit to stand to seat 5 (STS5); Short Physical Performance Battery (SPPB), gait speed (GS), as well as body composition determined by electrical bioimpedance (BIA) and sarcopenia severity were analized.

Results
18 HD patients with sarcopenia (71.4% severe) were included (4 drop out).78.6% men. Mean age 74.7 years and 53.3 months on HD. The main etiologies of ESRD were the HBP (21.4%) and DM (14.3%). Globally, a significant improvement was observed at the end of the study in relation to muscular strength (HG 19.9±6.1 vs 22.2±7.1 kg, p 0.001) and functional capacity tests (STS5 21.9±10.3 vs 17.2±9.9 sec, p 0.001; SPPB (6.9±2.3 vs 9.1±2.5 score, p 0.001 and GS 0.8±0.1 vs 0.9±0.2 m/s, p 0.015). Likewise, higher total skeletal muscle mass (SMM, 14.3±2.8 vs 14.5±2.9 kg) and SMM index (SMM/height2, 5.5±0.7 vs 5.7±0.9 Kg/m2 ) were found at the end of the study, although these differences were not significant. Finally, 2 patients (14.8%) reverse the EWGSOP2 sarcopenia criteria and 3 (21.4%) enhanced their severe sarcopenia. No relevant changes regarding anthropometrical data, main biochemical and nutritional parameters or dialysis adequacy were observed at the end of the study.

Conclusion
A home-based resistance exercise program improves muscular strength, functional capacity and body composition in our sarcopenic hemodialysis patients. With our results, home-based resistance exercise programs should be considered a key point in the prevention and treatment of skeletal muscle mass reduction due to sarcopenia in these patients. Further studies are mandatory to confirm our encouraging results.
P0983INHIBITION OF ATF3 BY RAF INHIBITOR GW5074 ON DIABETIC NEPHROPATHY
Authors: Han Jee Young , Cha Jin Joo , Kang Young Sun , Ghee Jung Yeon , Yoo Ji Ae , Cha Dae 
Published: June 2020

Abstract

Background and Aims
Activating Transcription Factor 3 (ATF3) is a stress-adaptive transcription factor, which has been suggested to be involved in maintaining glucose homeostasis. ATF3 respond rapidly to various stimuli like high glucose, fatty acids and oxidative stress, and is observed to either protective or detrimental effects in diabetic condition. Therefore to elucidate the exact role in diabetic nephropathy of ATF3, we investigated the role of ATF3 by inhibition with Raf-inhibitor GW5047 on diabetic mice model.

Method
ATF3 level was examined in the mouse podocytes and NRK cells with either overexpression or downregulation with ATF3. 8 week db/m and db/db mice as the model of diabetic mice were examined for the expression of ATF3 and were treated with GW5074, a Raf1 kinase inhibitor targeting the ATF3 intraperitoneally with a dose of 0.5mg/kg for 12 weeks.

Results
In cultured mouse podocytes and NRK cells, high glucose and angiotensin II markedly increased ATF3 expression. Gene Expressions of NOX4, MCP-1 and NF-kB were augmented by ATF3, and were attenuated by ATF3 siRNA. In db/db mice, plasma ATF3 level was not different from control db/m, however the urinary ATF3 excretion was significantly higher. Treatment of GW5074 decreased urinary ATF3 excretion. After 12 week treatment, serum creatinine level was significantly lower in the treatment db/db group, with less systemic oxidative stress. There were no significant differences in body weight, whereas the food intake was decreased in GW5047 group. Overall lipid profile or HOMA-IR, HbA1c level was not different from each group. Serum adiponectin were otherwise increased in GW5074 group. Urinary excretion of albumin at 2 month of treatment decreased with urinary nephrin excretion. Trend of increased gene expression of JNK, p-38, smad2, ERK which was downregulated by GW5074 was noted.

Conclusion
These findings suggest that in diabetic condition, the activation of ATF3 is associated pathogenesis of diabetic nephropathy and targeting ATF3 may have a protective role in the disease progression.
P0986NO/CGMP PATHWAY MODULATES GLUCOSE UPTAKE VIA REGULATION OF SIRT1 DEACETYLASE EXPRESSION AND ACTIVITY IN PODOCYTES EXPOSED TO HIGH GLUCOSE CONCENTRATIONS
Authors: Rogacka Dorota , Audzeyenka Irena , Piwkowska Agnieszka 
Published: June 2020

Abstract

Background and Aims
Glomerular podocytes have become the aim of the extensive research in diabetes because of their importance in the development of diabetic nephropathy. High glucose concentration affects podocyte metabolism and function leading to the development of insulin resistance. Moreover, it decreases deacetylase SIRT1 protein amount and activity, leading to abolition of insulin effect on glucose uptake into the cells. The aim of our study was to examine the involvement of NO/cGMP pathway in the regulation of sirtuin 1 (SIRT1) protein expression and activity in podocytes, in the context of high-glucose induced insulin resistance. This work was supported by grant from the National Science Centre (2016/23/B/NZ4/03448).

Method
Experiments were performed in primary rat podocytes cultured with normal (NG, 11.1 mM) or high (HG, 30 mM) glucose concentrations for 5 days. RT-PCR and immunodetection methods were used to detect mRNA and protein expressions. Glucose uptake was measured by the addition of 1 µCi/well of 2-deoxy-(1,2-3H)-D-glucose uptake diluted in non-radioactive dglucose (50 µM final concentration) with or without 300 nM insulin. SIRT1 activity was determined with a SIRT1 Fluorometric Kit according to the manufacturer’s instructions. SIRT1 expression was modified by transfection with SIRT1 siRNA. To examine the effect of NO/cGMP pathway activity on SIRT1, cells were incubated in the presence of SNAP, a mimetic of nitric oxide synthase activity (NOS), and 8-Br-cGMP, protein kinase G (PKG) activator. We also used L-NAME – NOS inhibitor, and Rp-8-Br-cGMPs, PKG inhibitor.

Results
SIRT1 protein expression and activity were decreased in podocytes exposed to high glucose concentrations. We showed that in the presence of SNAP and 8-Br-cGMP, SIRT1 protein amount and activity were increased, leading also to enhancement of basal and insulin-dependent glucose uptake. In podocytes, transfected with SIRT1 siRNA, treatment with NO/cGMP pathway activators SNAP or 8-Br-cGMP increased glucose uptake. NO/cGMP pathway inhibitors exerted opposite effects on SIRT1 protein level and activity as well as on glucose uptake. Insulin action on glucose uptake into podocytes cultivated in the presence of normal glucose concentrations was abolished after NO/cGMP pathway inhibition.

Conclusion
We found that impairment of insulin effect on glucose uptake in HG-exposed podocytes, which was associated with SIRT1 downregulation, may be prevented by NO-dependent signaling modulation.
P0987MIR-181A IMPROVED RENAL INFLAMMATION VIA TARGETING TNF-Α IN DIABETIC NEPHROPATHY
Authors: Liu Dan , Liu Bicheng 
Published: June 2020

Abstract

Background and Aims
Recent studies have revealed that miR-181a is involved in various inflammation associated diseases, however, its participation in pathogenesis of diabetic nephropathy (DN) remains unclear. Hence, we investigated the involvement of miR-181a in the pathogenesis of DN patients and in animal model.

Method
miR-181a level was measured in the kidney of DN patients and DN mice model (db/db mice) by RT-PCR. To investigate the interaction of miR-181 a with the 3’-UTR of potential target transcripts, Luciferase reporter assays were performed. miR-181a-GFP-AAV and miR-181a inhibitor was generated to over-express or downregulate miR-181a in the kidney of db/db mice respectively. The expression of target gene and inflammatory proteins were measured in the kidney of our animal model.

Results
In DN patients and DN mice, a significant decrease in miR-181a levels in kidney were revealed by Expression analyses performed. Overexpression of miR-181a reduced proinflammatory genes (TNF-ɑ, IL-1β, and IL-18 ) expression, whereas suppression of miR-181a worsened these changes. Furthermore, there was a negative linear correlation between miR-181a and TNF-ɑ, IL-1β, and IL-18 expression levels in the kidney from DN patients. Luciferase assays revealed TNF-ɑ as a direct target of miR-181a.

Conclusion
Our data emphasized on the anti-inflammatory actions of miR-181a via targeting TNF-ɑ in the context of renal inflammation in DN. Hence, miR-181a could be served as a potential therapeutic options for controlling renal inflammation in DN.
P0993GYMNEMA SYLVESTRE EXTRACT ATTENUATE THE PATHOLOGICAL PROGESSION OF DIABETIC NEPHROPATHY IN RATS
Authors: Rajput Sumit 
Published: June 2020

Abstract

Background and Aims
Diabetic nephropathy is not only a common and severe microvascular complication of diabetes mellitus but also the leading cause of renal failure. Aqueous extract of leaves of Gymnema sylvestre (ALGS) has been reported to cause reversible increases in intracellular calcium, hypolipidemic activity and insulin secretion in mouse and human β cells with type 2 diabetes.
The present study aimed to investigate the antidiabetic and renoprotective effects of ALGS in a rat model of type 2 diabetic mellitus.

Method
Male Sprague-Dawley rats with type 2 diabetes induced by a high-fat diet (HFD)/streptozotocin (STZ) were treated with ALGS at dosages of 0.5% and 1% (w/w) daily for 4 weeks. At the end of the experimental period, body weight, serum glucose levels, insulin levels, and kidney function were assessed. Furthermore, antioxidant enzyme and lipid peroxide levels were determined in the kidney with histopathological examination Molecular mechanism underlying the functioning of ALGS, mouse glomerular mesangial cells (MES-13) treated with high glucose (HG, 25 mM glucose) were chosen as a model for an examination of the signal transduction pathway of ALGS.

Results
The results revealed that ALGS improved diabetic kidney injury by reducing blood glucose, serum creatinine, and blood urea nitrogen levels and enhanced antioxidant enzyme activities in kidney tissue. Treatment with ALGS significantly reduced the malondialdehyde and 8-hydroxy-2-deoxyguanosine levels and increased serum insulin levels; expression of renal superoxide dismutase, catalase, and glutathione peroxidase activities; and glutathione content. Histological studies have also demonstrated that ALGS treatment inhibited the dilation of Bowman's capsule, which confirmed its renoprotective action in diabetes. In addition, treatment with ALGS attenuated 25 mM HG-induced suppressed nuclear factor erythroid 2-related factor 2 and antioxidant enzyme expression in MES-13 cells.

Conclusion
The results of present study reveal that ALGS extract could be useful intervention in the treatment of diabetes mellitus and, through antioxidative pathways.
P0994PROTECTIVE EFFECTS OF CATECHIN ON GENE EXPRESSION OF GLUCOSE METABOLISM IN STREPTOZOTOCIN-INDUCED DAIBETIC NEPHROPATHY IN RATS
Authors: SHIN BYUNG CHUL , CHUNG JONG HOON , Kim Hyun Lee 
Published: June 2020

Abstract

Background and Aims
Diabetes patients continue to increase worldwide, and persistent hyperglycemia could induce diverse complications, such as diabetic nephropathy. The purpose of this study was to investigate the transcriptoms of liver, muscle and adipose tissue to observe the effects of catechin on glucose metabolism in diabetic nephropathy rats.

Method
The experimental group was divided into control group, diabetic nephropathy (DN) group and DN + catechin group. The control and diabetic groups received tap water as drinking water and the DN + catechin group received tap water containing 0.1% catechin as drinking water for 12 weeks. After 12 weeks, blood glucose, BUN and creatinine levels were measured in the blood and transcriptomes were examined in liver, soleus muscle and visceral fat. The gene expression levels of glucose metabolism-related enzymes, lipid metabolism-related enzymes and insulin signaling pathway-related proteins were compared between each experimental group.

Results
Fasting blood glucose in the diabetic + catechin group was decreased by 8%, 13%, 15% and 18% at 2, 4, 8 and 12 weeks, respectively, compared to the diabetic group. After 12 weeks, serum BUN levels in the DN + catechin group decreased by 35% and serum creatinine levels by 33%, respectively, compared to the DN group. Glucose metabolism-related genes in the DN group were decreased in liver Gck, Pdp2 and Phkb mRNA levels, and Aldob mRNA levels in soleus muscle were decreased. In DN group, expression of Pfkm, Eno3 and Pgam2 in visceral fat were increased and Aldob and Pklr expression was decreased. Hepatic Gck, Pdk4 and Phkb mRNA levels were increased in the DN + catechin group compared to the DN group.

Conclusion
Catechin has the effect of improving diabetic nephropathy, which is thought to be the result of increased expression of liver glucose metabolism related enzymes and proteins related to insulin signal transduction pathways. Further study is needed to elucidate the mechanism of action on catechin gene expression and its usefulness as a functional substance.
P0995EVALUATION OF ANTIDIABETIC, ANTIOXIDANT AND NEPHROPROTECTIVE ACTIVITY OF FLAVONOID RICH FRACTION OF HYBANTHUS ENNEASPERMUS IN DIABETIC RATS: IN-SILICO MOLECULAR DOCKING STUDIES FOR SOD, CATALASE, GPX, XANTHINE OXIDASE AND NF-KB
Authors: Patel Dinesh Kumar 
Published: June 2020

Abstract

Background and Aims
Diabetes mellitus is a chronic metabolic disease affected a wide range of population all over the world and leads to development of secondary complications. Enzymes play key role in the development of secondary complication.

Method
The flavonoid rich fraction was prepared using ethyl acetate. Oral glucose tolerance test normoglycemic effect of flavonoid rich fraction of Hybanthus enneaspermus (EHE) was evaluated at a dose of 45 and 90 mg/kg, p.o. Further effect of EHE on blood glucose, body weight, enzymes such as super oxide dismutase (SOD), catalase and thiobarbituric acid reactive substances (TBARS) and lipid parameters were estimated out at 45 and 90 mg/kg p.o. per day for 21 days in streptozotocin-induced type-2 diabetic rats. Molecular docking technique was also performed against Super Oxide Dismutase (SOD), Catalase, Glutathione Peroxidase (Gpx), xanthine oxidase and nuclear factor kappa B (NF-κB) for selected phytoconstituents.

Results
EHE contain significant amount of phenolic, tannin, flavonoid and saponin. EHE significantly decreased blood glucose level in diabetic rats. All the tested lipid parameters and enzyme level of SOD, Catalase and Gpx were significantly restored to the normal level in the EHE treated rats. Moreover, there was a significant increase in the body weight in the EHE treated rats. Docking study showed the best binding affinity and interaction of phytoconstituents with xanthine oxidase and NF-κB signified their role in kidney disorders.

Conclusion
EHE has very impressive profile as an antidiabetic, antioxidant and nephroprotective activity via enzymes modulation and it may prove to be effective treatment for kidney disorders in hyperglycemia.
P1003STUDY DESIGN OF THE ROTATION FOR OPTIMAL TARGETING OF ALBUMINURIA AND TREATMENT EVALUATION (ROTATE-3): A ROTATION STUDY OF DIFFERENT ALBUMINURIA LOWERING DRUGS CLASSES TO STUDY INDIVIDUAL DRUG RESPONSE IN DIABETIC AND NON-DIABETIC CKD
Authors: Provenzano Michele , Puchades Montesa Maria Jesãºs , De Nicola Luca , D'Marco Luis , Garofalo Carlo , Sasso Ferdinando Carlo , Acierno Carlo , Panizo Gonzalez Nayara , Romero-Parra Maria , Sen Taha , Gagliardi Ida , Hoyo-Garcia Rafael , Andreucci Michele , Lambers Heerspink Hiddo , Gorriz Jose Luis 
Published: June 2020

Abstract

Background and Aims
Patients with diabetic kidney disease show a wide variability in their response to established and new treatments. SGLT2 inhibitors have also shown to slow the progression of kidney disease. Some studies have also shown kidney benefits for Mineralocorticoid Receptor Antagonists (MRA). A large outcome trial with the MRA finerenone is currently ongoing to assess effects of this MRA on major kidney outcomes. The individual trials will solve the issue whether a patient may have benefit from an SGLT2 inhibitor or MRA, but they do not address the key question which of the two or their combination is better to reduce albuminuria for each individual patient. Therefore, we designed the ROTATE-3 trial is designed to investigate the individual albuminuria response to MRA (eplerenone), SGLT2 inhibitor (dapagliflozin) or the combination.

Method
ROTATE-3 is a randomized, prospective, open label, multicentre, crossover trial with a total duration of 28 (to 42) weeks [EudraCT number: 2017-004641-25]. Patients with or without type 2 diabetes, ≥18 years and elevated albuminuria (100-3500 mg/24 hour) already receiving a stable (same dose at least 4 weeks) maximum tolerated dose of an ACE-inhibitor or Angiotensin Receptor Blocker will be enrolled.Patients receive in random order 4 weeks of treatment with the eplerenone 50 mg/day, dapagliflozin 10 mg/day or combination of both drugs with a 4-weeks wash-out period in between. After the last treatment period patients will proceed to a 4-weeks wash-out period. The primary study outcome is the correlation in albuminuria response to eplerenone and dapagliflozin for which 46 patients provides 80% power to detect a Pearson correlation coefficient of 0.4 between the log transformed albuminuria response to eplerenone and dapagliflozin. Blood is collected for clinical chemistry every two weeks during each treatment period. Patients are requested to collect one 24-hour urine sample at start and at end of each treatment period. Home blood pressure is monitored every 2 days.

Results
As of January 1st 2020 the study has enrolled 13 patients. It is anticipated that recruitment will be completed by December 2020 with study completion in August 2021.

Conclusion
The results of the ROTATE-3 study will provide more insight in the individual albuminuria lowering response to potentially two new treatment options for patients with CKD and may help to implement personalized medicine in diabetic kidney disease.Study sponsored by University Medical Center Groningen. The Netherlands.