bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0961PHYSICAL REHABILITATION OF PATIENTS WITH CHRONIC KIDNEY DISEASE OF PRE -DIALYSIS STAGES
Authors: Saipova Durdona 
Published: June 2020

Abstract

Background and Aims
Chronic kidney disease is a global public health problem. Poor physical condition and skeletal muscle depletion are associated with the combined effects of uremic acidosis, protein-energy deficiency and inflammatory depletion, which leads to further exacerbation of a sedentary lifestyle. The aim of the determination of physical performance and the effectiveness of physical training during the 12-week program in patients with CKD of pre-dialysis stages.

Method
We examined 130 patients with CKD 2-4 stages. Clinical parameters (BP, BMI, mid-thigh circumference, mid-shoulder circumference, mid-calf circumference), laboratory data (serum creatinine, serum cholesterol, serum albumin, serum phosphorus, serum calcium) were evaluated in all patients according to the formula CKD-EPI 2011. Physical performance was determined by the results of cardiopulmonary stress test. In accordance with the initial data of the patients, a 12-week physical rehabilitation program was individually selected, which included morning exercises, physiotherapy exercises and dosed walking . The data obtained were subjected to statistical processing.

Results
The average age of patients was 54.8 years. Of these, 52 women (40%) and 78 (60%) men. The estimated glomerular filtration rate varied from 30 to 60 ml / min / 1.73 m2, which corresponded to the indicators of the pre-dialysis stages of CKD. After a 12-week rehabilitation program, the maximal oxygen consumption (V O2peak) increased in 70% of regularly engaged patients by 1.2 times (22.31 ml / min / kg and 27.05 ml / min / kg, respectively), and in 30% of those who did not pass the course Exercise therapy, the indicator of maximum oxygen consumption after 12 weeks was 21.7 ml / min / kg (with an initial 23.7 ml / min / kg) The average blood pressure decreased slightly (from 111 ± 5 initially to 106 ± 5 mm Hg after 12 weeks, p&lt;0.05) When measuring anthropometric parameters, it was found that the circle the mid-thigh increased from 46.5 ± 6.0 cm to 0.6 cm, the circumference of the middle of the shoulder increased from 31.1 ± 4.0 cm to 0.4 cm. The circumference of the middle part of the lower leg was initially 356.7 ± 3.8 cm, and after 12 weeks of training it increased 0.3 cm. In 9 patients, these parameters did not change after a 12-week program.

Conclusion
Regular physical training led to an increase in the maximum oxygen consumption by 1.2 times. It was noted that regular training contributes to a slight increase in muscle mass in patients with CKD. The importance of regularity of physical therapy classes was also revealed.
P0963MANAGEMENT OF SLEEP DISORDERS IN END-STAGE RENAL DISEASE, IS IT REALLY IMPORTANT?
Authors: Tuta Liliana-Ana , Doina-Ecaterina Tofolean , Alexandra Tudor , Bogdan Campineanu 
Published: June 2020

Abstract

Background and Aims
Sleep apnoea (SA), either obstructive and central (OSA and CSA, respectively) associated with and excessive daytime sleepiness (EDS) are common sleep disorders among patients with end-stage renal disease (ESRD). Fluid overload characterizes end-stage kidney disease and plays an important role in the pathogenesis of OSA, CSA and EDS. In our study we assessed the prevalence of sleep apnoea and excessive daytime sleepiness in patients from a nephrology and dialysis unit from south-eastern Romania.

Method
86 patients with ESRD pre-dialysis (eGFR &lt; 15 ml/min/1,73 m) or on maintenance haemodialysis were monitored for an interval of 2 years. We used questionnaires to assess the prevalence of SA and EDS. All subjects underwent overnight polysomnography (PSG). Extracellular fluid volume of the total body, neck, thorax and right leg were measured using bioelectrical impedance. We also examined the association between sleep apnoea, EDS, the underlying causes of ESRD, co-morbidities, medication used, and other demographic data.

Results
The mean patients age was 57.5 years ± 14.9 years; 65.1% were male, and 34.9% were female. The prevalence of SA as defined by the Berlin questionnaire (BQ) was 49.5% in males and 34.8% in females, which was not a statistically significant difference (P = 0.029). Sleep apnoea was significantly associated with age, obesity, diabetes, hypertension, fluid overload and 2nd or 3rd haemodialysis shift (P-values, 0.001, &lt; 0.0001, &lt; 0.002, &lt; 0.008, &lt;0.0001, and &lt; 0.005. Sleep apnoea was also significantly associated with other sleep disorders such as restless leg syndrome, insomnia, habitual snoring, and EDS (P-values, &lt; 0.001, &lt; 0.001, &lt; 0.001, and &lt; 0.001, respectively). The prevalence of EDS was 35,5%, and EDS was significantly associated with age (over 60 years old), diabetes mellitus, hypertension and obesity. 18 patients (20.9%) had refractory hypertension, that improved after CPAP administration, and 10 of these patients (over 50% with refractory HT), that refused the application of appropriate therapy of sleep disorders, suffered a major cardiovascular event during our study.

Conclusion
Sleep apnoea, excessive daytime sleepiness and other sleep disorders are relatively common in pre-dialysis and haemodialysis patients and are significantly associated with refractory hypertension and severe cardio-vascular events. That is why a greater attention should be given to the diagnosis and management of sleep disorders, as one of the important steps in nursing and our patients’ rehabilitation.
P0973ALLOSTERIC C-C CHEMOKINE RECEPTOR TYPE 2 (CCR2) INHIBITION IMPROVES RENAL FUNCTION IN A MURINE MODEL OF DIABETIC NEPHROPATHY
Authors: Miao Zhenhua , Ertl Linda S , Zhao Bin , Wang Yu , Newland Dale , Zeng Yibin , McMahon Jeffrey , Liu Xiaoli , Dang Ton , Miao Shichang , Zhang Penglie , Li Chris , Campbell James , Singh Rajinder , Charo Israel F , Schall Thomas J 
Published: June 2020

Abstract

Background and Aims
Diabetic nephropathy (DN) is a syndrome characterized by pathological levels of proteinuria, glomerular lesions and reduction in the glomerular filtration rate (GFR) in diabetic patients. Several lines of evidence support a role of CCR2 in the pathogenesis of DN. Recent studies have demonstrated that existing small molecule CCR2 antagonists can be placed in two classes, distinguished by their interaction with one of two distinct binding sites on CCR2: an extracellular site for which antagonists compete directly with native ligands (the orthosteric site), or an intracellular allosteric binding site. To better understand the functional differences between these antagonists we compared an example of each class in a murine model of DN. Our results revealed that the allosteric, but not the orthosteric CCR2 inhibitors ameliorated the proteinuria and improved glomerular histopathology in this model of DN.

Method
We used db/db mice to model DN. Several structurally distinct CCR2 inhibitors with that bind to either the allosteric (CCR2-RA-[R] and CCX872) or orthosteric (MK-0812 and CCX598) sites were compared. Pharmacokinetic (PK) properties and renal functional parameters were assessed, including trough drug levels and proteinuria (urinary albumin excretion rate UAER; urine albumin creatinine ratio UACR). Histopathology and electron microscopy (EM) were performed to assess any potential tissue-protective effects of the antagonists.

Results
Both the allosteric inhibitors (CCR2-RA-[R] and CCX872) and the orthosteric inhibitors (MK-0812 and CCX598) were potent CCR2 antagonists with desirable PK in mouse in so far as both classes effectively blocked CCR2-mediated monocyte migration into the peritoneal cavity in the thioglycollate-induced peritonitis model. At comparable drug coverage levels, CCR2-RA-[R] and CCX872 rapidly and significantly reduced UAER/UACR (CCX872: 70 % at day 7 vs vehicle, p&lt;0.0001; and 60 % at day 14 vs vehicle, p=0.001; CCR2-RA-[R]: 60 % at day 7 vs vehicle, p=0.0001; and 58 % at day 14 vs vehicle, p=0.005), but MK-0812 and CCX598 did not exhibit proteinuria lowering effect. Histological parameters including glomerular injury and glomerular basement membrane (GBM) thickness were also improved after CCX872 treatment in db/db mice.

Conclusion
Allosteric antagonists of CCR2 provide significant and rapid renal protection in the db/db murine model of DN, as evidenced by improvements in renal function and histological parameters, while potent orthosteric CCR2 antagonists were not effective in the model. Our data suggest that targeting the effectiveness of CCR2 antagonists in DN are directly dependent on binding to the allosteric site of CCR2.
P0974ADIPORON AMELIORATES DIABETIC CARDIOMYOPATHY IN DBDB MICE THROUGH IMPROVING CERAMIDE-DEPENDENT LIPOTOXICITY
Authors: Kim Yaeni , Lim Ji Hee , Kim Eun Nim , JIN YONGJIE , Kim Hyung Duk , Ban Tae Hyun , Choi Bum Soon , Park Cheol Whee 
Published: June 2020

Abstract

Background and Aims
The accumulation of lipid and its metabolites in tissues, including the heart, causes lipotoxicity. Sphingolipids such as ceramides are particularly deleterious. Lowering the accumulation of ceramide can improve metabolic damage of various tissues. Recent reports showed that adiponectin receptors (AdipoRs) have sequence homology with ceramidase enzymes, and an increase of ceramidase activity with overexpression of adiponectin in mice improves ceramide-dependent lipotoxicity. Therefore, we investigated the possible roles of Adiporon, which mimics the effects of adiponectin, in the view of prevention and development of diabetic cardiomyopathy in diabetic mouse model.

Method
Male db/db mice and db/m controls were fed either a regular diet chow or a diet containing adiporon (30 mg/kg/day p.o. for 4 weeks from 17 to 20 weeks of age) and biochemical and morphological parameters were examined at 20 weeks of age.

Results
In db/db mice, left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow rate (CFR) were decreased compared to db/m control mice, indicating cardiovascular dysfunction in diabetic heart. The treatment with AdipoRon remarkably improved the diabetes-induced contractile impairment, without any influence on HR. Adioporon also decreased fibrosis, inflammation cell infiltration and accumulations of free fatty acid, triglycerides and ceramide in the heart. In the molecular level, increased expressions of AdipoR1 and AdipoR2 and acid ceramidase activity in the heart were observed in db/db mice with Adiporon administration. Consistent up-regulations of phosphorylated AMPK and PPAR-α level were associated within the same group. Subsequent improvement of enhanced lipid metabolism and decrement of cellular apoptosis with adiporon treatment were also noted.

Conclusion
Adiporon may control oxidative stress in heart through AMPK and PPAR-α activated pathway and further contribute to prevent deterioration of cardiac function. The protective role of adiporon against the development of diabetic cardiomyopathy seems to occur through a direct action on the heart independently of systemic effects of adiponectin. Our results suggest adiporon as a promising therapeutic agent of diabetic cardiomyopathy through ameliorating ceramide-dependent lipotoxicity.
P0976ALTERED EXPRESSION OF LONG NON-CODING AND MESSENGER RNAS IN DIABETIC NEPHROPATHY FOLLOWING TREATMENT WITH ROSIGLITAZONE
Authors: Zhang Liwen , Zhou Ying , Zhou Fangfang , Yu Xialian , Liu Jian , Liu Yunzi , Wang Weiming 
Published: June 2020

Abstract

Background and Aims
The value of rosiglitazone (RSG) in the protection of kidneys from diabetic injury was recognized, however, the adverse systemic side effects limit its clinical application. Long noncoding RNAs (lncRNAs) are primarily described as signal molecules since they interact with cellular components, and have been shown to exhibit strong tissue and cell specificity. The aim of this study is to elucidate the novel renoprotective molecular mechanism of RSG and to propose lncRNA targets for diabetic nephropathy treatment, which may provide a new approach to avoid systemic side effects of RSG.

Method
Db/db mice were treated with RSG as dbR group or vehicle as dbdb group, and db/m mice as control group. Plasma, urine and kidney cortex were collected, and unbiased RNA sequencing of three renal cortical samples from each group was performed.

Results
Db/db mice developed hyperglycemia, impaired intra-peritoneal glucose tolerance, proteinuria, decreased mitochondrial SOD activity, podocyte impairment, epithelial-mesenchymal transition, glomerulosclerosis and tubulointerstitial fibrosis, however, RSG treatment improved these changes. RNA-seq profiling revealed that the development of DN caused an up-regulation in the expression of 1176 mRNAs and a down-regulation in the expression of 1010 mRNAs (p&lt;0.05) compared to controls, with the expression of 251 mRNAs being returned to normal following treatment with RSG. Further, 88 up-regulated and 68 down-regulated lncRNAs (p&lt;0.05) were identified in db/db mice compared to controls, 10 of which had their normal expression restored following treatment with RSG. Bioinformatic analysis revealed that the primary pathways involved in the pathogenesis of DN, and subsequently in the therapeutic effects of PPARγ, are related to inflammatory and metabolic processes. Six lncRNAs that exhibited opposite expression patterns in dbdb vs. control and dbR vs. dbdb analyses were randomly chosen and qualified by qRT-PCR, including a novel lncRNA and lncRNA-AI838599. From GSEA analysis, three co-expressed mRNAs of lncRNA-AI838599 (Gadd45b, Per1 and Sphk1) were cores enriched in the Hallmark TNFα signaling via NFκb Gene Set (MSigDB).

Conclusion
RSG treatment can attenuate DN in experimental models through regulation of metabolism and inflammation, and lncRNA-AI838599 emerges as a key rosiglitazone-regulated gene in DN treatment through TNFα-NFκb pathway.
P0984SGLT2 INHIBITION PREVENTS RENAL FIBROSIS IN CYCLOSPORINE NEPHROPATHY
Authors: Castoldi Giovanna , Carletti Raffaella , Ippolito Silvia , Colzani Massimiliano , Barzaghi Francesca , Stella Andrea , Zerbini Gianpaolo , Perseghin Gianluca , Zatti Giovanni , Di Gioia Cira 
Published: June 2020

Abstract

Background and Aims
Sodium glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic drugs, showed nephroprotection in type 2 diabetic patients. The mechanisms underlying nephroprotection are not completely known and it is unclear whether the nephroprotective effects are present also in non-diabetic nephropathy. The aim of this study was to evaluate the effects of empagliflozin, a SGLT-2 inhibitor, in cyclosporine nephropathy in the absence of diabetes.

Method
Ten days before the beginning and then during the entire experimental periods, low-salt diet (Teklad 7034) was administered to Sprague Dawley rats. Cyclosporine-A (CsA, 15 mg/kg/day, intraperitoneal injection; n=6) and CsA plus empagliflozin (Empa, 10 mg/kg /day, per os; n=6) were administered for 4 weeks. Control group was treated with placebo (n=6). Blood pressure was measured by plethysmographic method at the beginning and at the end of the experimental period. At the end of the protocol, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and tyrosine hydroxylase expression, used as marker of symphatetic nerve activity.

Results
The rats treated with CsA showed a significant increase (p &lt;0.01) in blood pressure, which was slightly reduced by administration of empagliflozin. CsA administration caused an increase in glomerular and tubulo-interstitial fibrosis (p &lt;0.05), renal inflammatory infiltrates (p &lt;0.05) and tyrosine hydroxylase expression (p &lt;0.01) as compared to the control rats. Treatment with empagliflozin reduced glomerular and tubulo-interstitial fibrosis (p &lt;0.05), inflammatory cell infiltration (p &lt;0.01) and tyrosine hydroxylase expression (p &lt;0.01), as compared to CsA-treated rats.

Conclusion
Empagliflozin administration showed protective effects on cyclosporine nephropathy, decreasing renal fibrosis, macrophage infiltration and tyrosine hydroxylase expression. These data suggest that the nephroprotective role of empagliflozin could not be restricted only to diabetic nephropathy.
P0988THE PROTECTIVE EFFECT OF RED ORANGE AND LEMON EXTRACT (RLE) IN DIABETIC OBESE ZUCKER RATS IS RELATED TO ITS ACTION ON THE NADPH OXIDASE SUBUNIT
Authors: Damiano Sara , Longobardi Consiglia , Lauritano Chiara , Andretta Emanuela , Capasso Giovambattista , Florio Salvatore , Ciarcia Roberto 
Published: June 2020

Abstract

Background and Aims
Type 2 diabetes mellitus is a pathological and chronical condition that induce a rearrangement in carbohydrate metabolism (Kaneto H et al. Antioxid Redox Signal. 2007). Even if the pathological mechanism of DN is not yet clear, NADPH oxidase (NOX) has been demonstrated to be involved in kidney ROS (Reactive Oxygen Species) generation during diabetic state (Palicz A. et al. J Biol Chem. 2001). Therefore, NOX-4, whose p22-phox subunit have shown a pivotal role in diabetes development, has been considered a potential pharmacological target in DN (Gill PS and Wilcox CS. Antioxid Redox Signal. 2006). In previous experiments performed on diabetic rat animal model with DN, we have found a beneficial effect of an extract rich in anthocyanins (ANT), members of flavonoids group (Shih PH. J Agric Food Chem. 2007). The aim of the present work was to investigate the molecular mechanisms involved in the DN and the protective effects of the new extract particularly abundant in ANT, the Red orange and Lemon Extract (RLE).

Method
Zucker diabetic fatty rats were divided into three groups and treated by gavage daily until 30 weeks of age, as follows: control group (ZF rats) received 1 mL of normal saline; ZDF Group (ZDF rats) received 1mL of normal saline; ZDF + RLE group (ZDF rats) treated with 90 mg/ kg of RLE dissolved in 1mL of normal saline. We examined the gene and protein expression of NOX4 catalytic subunit and its regulatory subunit p22-phox through Real Time PCR and western blot analysis.

Results
The expression gene levels of NOX4 significantly increased in diabetic rats ZDF, compared to control ZF (***p&lt;0.001). Exposure of ZDF rats with RLE induces a decreased expression of NOX4 (Figure 1) compared to ZDF. On the contrary, there were not significant expression levels variations for regulatory subunit p22-phox. Western blot results are in agreement with Real Time PCR data, in fact an increase in NOX4 protein levels (*p&lt;0.05) is evident, but no significant increase in p22-phox subunit was observed.

Conclusion
In conclusion, we hypothesize that the protective effect of RLE on the development of DN is related to its ability to inhibit NADPH oxidase activity and opens new perspectives for the treatment of DN.
P0996THE INVOLVEMENT OF PRO-INFLAMMATORY IL-1 CYTOKINES IN TUBULAR INJURY IN DIABETIC KIDNEY DISEASE
Authors: Slobodsky Vladislav , Litmanovich Adi , Hassan Kamal , Khazim Khaled 
Published: June 2020

Abstract

Background and Aims
Pro-inflammatory cytokines are one of several factors which contribute to the progression of diabetic kidney disease (DKD), a condition characterized by chronic kidney inflammation which results in the tubulointerstitial fibrosis which contributes to the progression of DKD. Interleukin 1 (IL-1) two main agonists IL-1α and IL-1β activate a pro-inflammatory cascade in response to different inflammatory stimuli, including hyperglycemia. It was previously shown that a deficiency of NLRP3 which is required for the conversion of IL-1 to its active state, protects mice from the development and progression of DKD. We hypothesize that the chronic hyperglycemia in diabetic patients triggers the activation and release of IL1α and/or IL-1β from renal tubular cells and that this activation leads to the tissue fibrosis. We aim to assess Il-1 and fibronectin expression in an immortalized proximal tubule epithelial cell line from normal adult human kidney (HK-2). In addition, we evaluate the influence of Anakinra™, a pharmaceutical inhibitor of the Il-1 receptor, currently indicated mainly for rheumatoid diseases, on the levels of fibronectin expression in this model.

Methods
HK-2 cells were cultured and treated with either physiological glucose concentration (5.5mM), high glucose (30mM) or 30mM mannitol as osmotic control for 24 hours to evaluate their effects on Il-1 expression and fibronectin expression. mRNA levels of IL-1α, IL-1β and fibronectin were assessed in q-PCR, and protein expression levels were quantified by western blotting. Immunofluorescence was used to visually demonstrate the presence of IL-1α and IL-1β upon stimulation. Finally, Anakinra™ was added to the tissue cultures in a range of physiologic prescribed concentrations and its effect on cell fibrosis was assessed by the measurement of fibronectin expression 24 hours later by western blotting.

Results
mRNA and protein expression of IL-1α but mostly IL-1β was elevated in HK-2 cells under hyperglycemic conditions but not in physiological glucose environment or under high osmotic conditions. Fibronectin levels were elevated in the high glucose treated cells compared with control. Finally, Anakinra™ was found to attenuate fibronectin expression under high glucose conditions, compared with the untreated cells.

Conclusion
Proinflammatory IL-1α and IL-1β cytokines are expressed by HK-2 cells upon stimulation with glucose and result in the fibrosis on the cells measured by the production of fibronectin. The addition of Anakinra™, an IL-1 receptor blocker, to the cell culture attenuate the expression of fibronectin by the tubular cells. Our research is the first to describe a causation between hyperglycemia, IL-1 elevated levels and fibrosis in HK-2 cells, as demonstrated by the beneficial effect of Anakinra™ on lowering fibronectin expression.