bluuebunny/crossref_metadata_2025 huggingface dataset:
P0943FAT MASS/FAT FREE MASS RATIO AS A CARDIOVASCULAR RISK FACTOR. SURVIVAL STUDY
Authors: Barril Guillermina , Nogueira Angel , Garcia Nuria , Sanz Paloma , Alvarez Graciela , Gil Giraldo Leydy Yohana , Muñoz Patricia , Giorgi Martin , Nuñez Almudena , Sanchez Tomero Jose Antonio
Published: June 2020

Background and Aims

Excess fat mass correlates with cardiovascular risk and if the increase in BMI is at the expense of fat mass it can increase mortality.

Aims- To evaluate the Fat Mass/Fat Free Mass ratio (FM/FFM)in 195 CKD patients and establish a correlation with nutrition-inflammation parameters, body composition and hand grip strenght

Method

We have studied 195 patients aged 67.01 ± 14.52 years, 126 (64.6%) men and 69 (35.4%) women. 41% in HD and 59% with advanced CKD. We have determined FM/FFM ratio using BIA monofrequency Bodigram Plus (Akhern) and hand grip stengh ( baseline).We determine biochemical nutrition-inflammation parameters also.

Results

xRatio FM/FFM = 0.499 ± 0.2304, in men = 0.41 ± 0.16 and in women = 0.64 ± 0.26 (both less than published 0.57 men and 0.867 in women). Median 0.4558 and percentils (p) with cut-off points 0.3868 and 0.5574. In HD 31 in P1, 23 in P2 and 26 in P3. In advanced CKD 32 in P1, 41 in P2 and 42 in P3. Anova significant according to percentiles: SMI, age, TBW% BCMI, albumin, waist circunference, and Hand grip strenght.

Correlations

Men

FM / FFM ratio direct sig correlation with weight, AEC% and Trasferrin%, inverse with MIS, SMI, Na / K, BCM%, TBW%, IBW%, BCMI and right dynamometry. Do not continue with BMI, Phase Angle, Hb, lymphocytes, prealbumin, PCR.

Women

FM/FFM ratio direct sig correlation wih: weight, Na / k, BMI, prealbumin, CRP, MIS, inverse with: TBW. No sig: SMI, BCM%, EBW%, IBW%, MAMC, BCMI, Hb, hand grip strenght, lymphocytes or transferrin.

In the 24-month mortality study we found no significant differences in Kaplan Meier overall mortality using the 3 percentiles. They died 7/63 in P1, 1/64 in P2 and 8/68 in P3. If we make the union of 1 and 2 vs percentil3 we find significant differences in mortality between strata, especially in HD with Long Rank 0.05.

Conclusions

1.-The FM /FFM ratio is a useful tool for diagnosis of sarcopenic obesity

2.-It correlates significantly with parameters of CRP (direct) inflammation, muscle strength (inverse) and CV risk (direct waist circumference and tricipital fold)

3.- In a survival study joining P1 + P2 vs P3 we found greater survival in P1 + P2, mainly in HD.
P0950EFFECT OF THYROID HORMONE TREATMENT ON RENAL REABSORPTION OF GLUCOSE IN ALLOXAN-INDUCED DIABETIC RATS
Authors: Dayma Gireesh
Published: June 2020

Background and Aims

The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan-induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney.

Method

Adult male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 ?g/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study.

Results

After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria.

Conclusion

Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats.
P0961PHYSICAL REHABILITATION OF PATIENTS WITH CHRONIC KIDNEY DISEASE OF PRE -DIALYSIS STAGES
Authors: Saipova Durdona
Published: June 2020

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<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

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 < 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, < 0.0001, < 0.002, < 0.008, <0.0001, and < 0.005. Sleep apnoea was also significantly associated with other sleep disorders such as restless leg syndrome, insomnia, habitual snoring, and EDS (P-values, < 0.001, < 0.001, < 0.001, and < 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

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<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

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

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<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<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

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 <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 <0.05), renal inflammatory infiltrates (p <0.05) and tyrosine hydroxylase expression (p <0.01) as compared to the control rats. Treatment with empagliflozin reduced glomerular and tubulo-interstitial fibrosis (p <0.05), inflammatory cell infiltration (p <0.01) and tyrosine hydroxylase expression (p <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

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<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<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

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.
P0998IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES AND SIGNALING PATHWAYS IN DIABETIC NEPHROPATHY BY BIOINFORMATICS ANALYSIS
Authors: Tang Shumei , Xiao Xiangcheng
Published: June 2020

Background and Aims

Diabetes has considerable negative impact on morbidity and mortality and causes huge social and economic burden. As one of the most serious microvascular complication of diabetes, diabetic nephropathy (DN) leads to a large population of end-stage renal disease in many countries. The pathogenesis of DN is always a hot topic and the underlying molecular events are not completely clear. Tubular injury plays an important role and may be the initial event. Although few therapeutic treatments could postpone the onset and development, the morbidity of DN remains high. More available therapeutic treatments are urgently needed as well as early stage diagnostic markers and more credible prognostic molecular markers. As a wide range application of high-throughput omics technology, various public network database platforms have included extensive transcriptomics data for deeper bioinformatics analysis. Integrating these data provides better understandings of molecular functions and biological processes. We performed integrated bioinformatics to recognize differentially expressed genes and discussed potential molecular mechanisms in DN.

Method

The expression profiles of GSE30529, GSE47184, GSE99325 and GSE104954 were downloaded from the Gene Expression Omnibus database. The four microarray datasets were centralized, integrated and performed a difference analysis. Next, differentially expressed genes (DEGs) were deeply analyzed by gene ontology annotation and enrichment analysis. STRING database was used to conducted a PPI network and Molecular Complex Detection (MCODE) software was used to identify central genes.

Results

The four files contain 63 tubular biopsy samples from patients with DN and 41 control tubule samples. We identified 18 target DEGs, C3, PROM1, LUM, CPA3, SERPINA3, ANXA1, CX3CR1, AGR2, CD48, REG1A, RARRES1, CYP24A1, C1R, CFB, CDH6, PVALB, GADD45B and KLK1. GO analysis indicated that biological processes of DEGs concentrate on proteolysis, inflammatory response, complement activation and regulation of complement activation. Main cellular components include extracellular exosome, extracellular region, extracellular space, blood microparticle, protein complex and plasma membrane. Molecular functions include calcium ion binding and serine-type endopeptidase activity. DEGs were found that maybe mainly involved in staphylococcus aureus infection, renin-angiotensin system, and complement and coagulation cascades by KEGG pathway analysis. The PPI network of DEGs were established by STRING database and one significant modules were identified by MCODE software. In addition, 3 hub genes, C3, CX3CR1 and ANXA1, were discerned from the PPI network.

Conclusion

To better clarify the underlying molecular mechanisms and provide more effective targets, this study screened DEGs and pathways in DN using bioinformatics analyses.
P1004REDUCED ERYTHROCYTE LIFE SPAN IN PATIENTS WITH TYPE 2 DIABETES UNDERGOING LONG-TERM HAEMODIALYSIS
Authors: Bomholt Tobias , Oturai Peter , Rix Marianne , Feldt-Rasmussen Bo , Hornum Mads
Published: June 2020

Background and Aims

Anaemia in long-term haemodialysis (HD) is caused by reduced erythropoietin levels but shortened erythrocyte life span is thought to contribute. However, reduced erythrocyte life span has never been documented in patients with type 2 diabetes (T2D) undergoing long-term HD. The aim of the study was to establish if the erythrocyte life span is decreased in in patients with type 2 diabetes (T2D) undergoing long-term HD and to investigate predictors of reduced erythrocyte life span.

Method

Patients with T2D undergoing long-term HD and patients with T2D without nephropathy (control group) (eGFR above 60ml/min) were included. Erythrocyte life span was measured using Chromium-51 (51Cr) labelled erythrocytes. Blood radiotracer activity was measured 6-8 times over 3-5 weeks to calculate the erythrocyte half-life for each patient. Markers for haemolysis, blood pressure and time spend in dialysis were obtained 5 times over 16 weeks and correlated to the erythrocyte half-life.

Results

For patients with T2D undergoing HD (n=13), the median half-life was 34.5 days (30.6 - 40.7) compared with 44.6 days (43.5 - 58.0) in the control group (n=10) corresponding to a 23 % difference (p=0.0003). From the half-life, the median erythrocyte life span was estimated to 49.7 days (44.1-58.6) and 64.2 days (62.6-83.5), respectively. For patients with T2D undergoing HD no correlation was found between the erythrocyte half-life and markers of haemolysis, blood pressure or time spend in dialysis.

Conclusion

The half-life of erythrocytes was reduced by 23 % in patients with T2D undergoing long-term HD compared with a control group. This reflects that erythrocyte life span is reduced in these patients. No specific markers of haemolysis could be correlated to the findings.
P1016EMPAGLIFLOZIN REDUCES URINARY MITOCHONDRIAL DNA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Lee Haekyung , Yang Wonmi , Kim Hyoungnae , Jeon Jin Seok , Noh Hyunjin , Han Dong cheol , Byun Dong Won , Kim Hye Jeong , Suh Kyoil , Park Hyeong Kyu , Kwon Soon hyo
Published: June 2020

Background and Aims

Recent evidences has shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes of type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve clinical outcomes are unclear. Mitochondrial dysfunction plays a principal role in the pathophysiology of T2DM and its complications. We hypothesized empagliflozin, an SGLT2 inhibitor improves mitochondrial dysfunction in T2DM patients.

Method

We prospectively recruited healthy volunteers (n = 22) and SGLT2 naïve T2DM patients (n = 21). Copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) were measured using quantitative polymerase chain reaction in healthy volunteers and T2DM patients at baseline and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4).

Results

Patients with T2DM were older than healthy volunteers and had higher body mass index and systolic blood pressure, but lower estimated glomerular filtration rate. Urinary mtND-1 and mtCOX-3 copy numbers were significantly higher in the T2DM group than in healthy volunteers. Urinary mtDNA copy numbers were correlated with diabetes duration (8.74 ± 7.60 years, r = 0.54, P = 0.01 for mtND-1, r = 0.50, P = 0.02 for mtCOX-3). Urinary copy numbers of mtND-1 and mtCOX-3 decreased after empagliflozin treatment. The amount of reduction of urinary mtDNA copy number did not differ according to empagliflozin dose (P = 0.897 for mtND-1, P = 0.462 for mtCOX-3).

Conclusion

In this study, we found that T2DM is associated with elevated urinary mtND-1 and mtCOX-3 copy numbers. Empagliflozin reduces the elevated urinary mtND-1 and mtCOX-3 copy numbers in patients with T2DM. Our results suggest that empagliflozin could attenuate mitochondrial damage in the kidney cells of T2DM patients.
P1017A RANDOMIZED, PLACEBO-CONTROLLED MULTICENTER STUDY OF THE EFFECTS OF 12 WEEKS OF SODIUM ZIRCONIUM CYCLOSILICATE (SZC) ON ALBUMINURIA (UACR) IN PATIENTS WITH TYPE 2 DIABETES AND HYPERKALEMIA
Authors: Persson Frederik , Heinrich Niels Søndergaard , Borg Rikke , Hellberg Olof , Fernström Anders , Furuland Hans
Published: June 2020

Background and Aims

Hyperkalemia is a frequent challenge in the treatment of type 2 diabetes and chronic kidney disease. It often leads to suboptimal dosing or discontinuation of renin-angiotensin (RAS) blockade, thus increasing the risk of renal disease progression. Furthermore, epidemiological findings indicate that high potassium levels impair the renoprotective effect of RAS blockade. We want to test whether adjunctive treatment with sodium zirconium cyclosilicate (SZC) a new treatment for hyperkalemia, improves the effect of standard RAS blocking treatment as measured by urinary albumin creatinine ratio (UACR) in individuals with type 2 diabetes.

Method

Randomized, double-blind placebo-controlled multicenter study with 2 sites in Denmark and 3 sites in Sweden. Individuals (n=100) with type 2 diabetes (age 18-85), persistent macroalbuminuria (UACR≥ 200 mg/g) on chronic RAS blocking treatment and documented hyperkalemia (plasma potassium ≥ 5.0 mmol/L at least once within 90 days of inclusion) will be enrolled in the study. Participants with plasma potassium >5.0 mmol/L at the last assessment before randomization will be randomized to receive SZC 10 g or placebo three times a day (tid) for 2 days followed by SZC 5g or placebo once a day (qd). Participants with serum potassium ≤ 5.0 mmol/L will be randomized to receive SZC qd or placebo qd.UACR will be measured in three consecutive morning spot urine collections at baseline and the end of study after 12 weeks of treatment with Lokelma or placebo.

Results

The primary outcome is change in geometric mean UACR from baseline to end of studySecondary outcomes include changes in estimated glomerular filtration rate (eGFR, calculated by CKD-EPI formula) and 24-h urinary sodium and potassium excretion.In an exploratory analysis the long-term effect of potassium reduction will be modelled using the PRE-SCORE risk calculator. In addition, changes in plasma aldosterone levels will be assessed, and safety will be monitored according to good clinical practice.

Conclusion

This study will test the concept of SZC as an add-on therapy to improve the renoprotective effect of standard RAS blocking treatment. This could provide future potential for keeping more individuals on optimal dosing of RAS blockade.
P1018LIPID PROFILES AND RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN CKD AND DIABETES: A NATIONWIDE POPULATION-BASED STUDY
Authors: Lee Yeonhee , Park Sehoon , Lee Soojin , Kang Min Woo , Park SangHyun , Han Kyungdo , Joo Kwon Wook , Kim Yon su , Kim Dong Ki , Kim Jung-Hyun
Published: June 2020

Background and Aims

The association of lipid parameters with cardiovascular outcomes and the impact of kidney function on this association have not been thoroughly evaluated in chronic kidney disease (CKD) patients with diabetes.

Method

We reviewed the National Health Insurance Database of Korea, containing the data of 10,505,818 subjects who received routine check-ups in 2009. We analyzed the association of lipid profile parameters with major adverse cardiovascular events (MACEs) risk and all-cause mortality in a nationally representative cohort of 51,757 lipid-lowering medication-naïve patients who had CKD and diabetes.

Results

Advanced CKD patients with eGFR <30 mL/min/1.73 m2 (n=10,775) had lower serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) but higher non-HDL-c levels and triglyceride (TG) to HDL-c ratios. There was a positive linear association between serum LDL-c and MACE risk in both early and advanced CKD patients (P <0.001 for trend). A U-shaped relationship was observed between serum LDL-c and all-cause mortality (the 4th and 8th octile groups; lowest hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.87-1.05 and highest HR 1.14, 95% CI 1.04-1.26, respectively). A similar pattern remained in both early and advanced CKD patients. The TG/HDL-c ratio categories showed a positive linear association for MACE risk in early CKD (P <0.001 for trend), but this correlation disappeared in advanced CKD patients. There was no correlation between the serum TG/HDL-c ratio and all-cause mortality in the study patients.

Conclusion

The LDL-c level predicted the risk for MACEs and all-cause mortality in both early and advanced CKD patients with diabetes, although the patterns of the association differed from each other. However, the TG/HDL-c ratio categories could not predict the risk for either MACEs or all-cause mortality in advanced CKD patients with diabetes, except that the TG/HDL-c ratio predicted MACE risk in early CKD patients with diabetes.
P1024INFLUENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE IN THE EVOLUTION OF RENAL FUNCTION IN DIABETIC PATIENTS
Authors: Aubert Lucia , Sandino Justo , Garcia Florencio , Gutiérrez Elena , Segura Julian , Bada Teresa , Fernandez-Vidal Maria , Praga Manuel , Morales Enrique
Published: June 2020

Background and Aims

Nowadays, there is growing evidence that non-alcoholic fatty liver disease (NAFLD) may be associated with renal impairment and have an impact on the evolution of renal function in patients with type 2 diabetes mellitus (DM). Our aim was to compare the effect on renal function and proteinuria in patients with type 2 DM according to the presence of NAFLD.

Method

Retrospective and observational study, including patients with type 2 DM, < 70 years of age and with estimated glomerular filtration rate (eGFR) > 30 ml/min/1,73 m2. NAFLD was defined with the presence of compatible ultrasonography and/or presence of fibrosis using NAFLD score. Metabolic syndrome (MSd) was defined as: obesity (body mass index (BMI) > 30 kg/m2), hypertension and dyslipidaemia. Patients were classified according to the presence or absence of NAFLD. We analysed different clinical and analytical variables along the follow up.

Results

A total of 71 patients were included (66% males) with mean age of 57.4 ± 7.8 years. The median evolution of type 2 DM was 72.2 months (34.7 - 125.5 months) and 90.1% of the patients were treated with renin-angiotensin blockade. When comparing patients with (group 1, n=38) and without (group 2, n=33) NAFLD at the beginning of this study, we found no significant difference in eGFR (80.2 ± 40.4 ml/min vs 71.4 ± 31.8 ml/min), proteinuria (1.4 ± 2.7 g/24h vs 0.8 ± 1.0 g/24h) and glycated haemoglobin (6.8 ± 1.4% vs 7.2 ± 1.6%). On the other hand, we found significant difference in the presence of higher BMI (33.8 vs 29.3 kg/m2; .001) and presence of MSd (67.7 vs 32.3%; .03) in those patients with NAFLD. After a mean follow-up time of 74 months, we found significant differences in the loss of eFGR (-33.8 vs -13.9 ml/min; .003), but no difference in increase of proteinuria. We found an increase in incidence of chronic kidney disease in group 1 (50%) vs group 2 (10.5%). There were no differences in the need to initiate renal replacement therapy or all-cause mortality.

Conclusion

NAFLD in type 2 DM caused a mayor decline in renal function. We should, therefore, take into consideration the presence of NALFD and the presence of MSd to optimise treatment of associated risk factors.
P1026THE EFFECT OF DAPAGLIFLOZIN ON 24-HOUR BLOOD PRESSURE IN PATIENTS WITH TYPE-2 DIABETES MELLITUS: A DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL
Authors: Papadopoulou Eirini , Loutradis Charalampos , Tzatzagou Glyceria , Kotsa Kalliopi , Zografou Ioanna , Minopoulou Ioanna , Theodorakopoulou Marieta , Tsapas Apostolos , Karagiannis Asterios , Sarafidis Pantelis
Published: June 2020

Background and Aims

Arterial hypertension is present in >90% of patients with type-2 diabetes mellitus (DM). Previous evidence suggests that sodium-glucose transporter 2 (SGLT-2) inhibitors can effectively manage hyperglycemia, but also reduce office blood pressure (BP) levels. The aim of this study is to evaluate the effects of dapagliflozin on ambulatory brachial BP in patients with type-2 DM.

Method

This is a double-blind, randomized, placebo-controlled clinical trial including 85 adult patients with type-2 DM on monotherapy or combination therapy with two of: metformin, sulphonylurea, DDP-4 inhibitor, or insulin. Patients were randomized in a 1:1 ratio to oral dapagliflozin 10 mg per day or placebo for 12 weeks. Study participants underwent 24-h ambulatory BP monitoring with the Mobil-O-Graph NG monitor at baseline and study-end.

Results

Baseline demographic, clinical and laboratory parameters were similar in the two groups (age 61.74±6.73 vs 60.64±9.35; p=0.534). During follow-up, 24-hour brachial SBP decreased in the active (128.97±12.57 vs 123.17±12.35; p<0.001) but was similar in the control group (128.95±12.41 vs 128.86±13.45; p=0.942). Corresponding changes in 24-hour SBP levels was greater in the dapagliflozin group compared with the placebo group (-5.80±9.48 vs -0.10±8.70 mmHg; p=0.005). Similarly, 24-hour DBP decreased in the active (77.33±7.30 vs 75.11±6.37; p=0.008) and was unchanged in the placebo group (78.86±8.66 vs 78.96±7.64; p=0.911). Decrease in brachial pulse pressure (PP) was greater in the active group (-3.57±6.67 vs -0.21±6.31 mmHg; p=0.019), while 24-hour heart rate was stable in both groups. Dapagliflozin and placebo treatments were associated with similar rates of generally mild adverse effects.

Conclusion

Treatment with dapagliflozin can produce statistically significant and clinically meaningful reductions in 24-hour BP levels in type-2 diabetics. These agents can improve BP control in this population.
P1035URINARY HEME OXYGENASE 1 AS A MARKER FOR EARLY DIAGNOSIS OF DIABETIC NEPHROPATHY
Authors: Ahmed Fatma , Abo el leel Hesham , Hebah Hayam Ahmed , Magdy Aya
Published: June 2020

Background and Aims

Heme oxygenase 1 is an essential enzyme in heme catabolism induced by oxidative stress.It induced in avariety of kidney substructres in response to injury, including proximal tubules, glomeruli and renal interstitium.We aimed to assess the possible role of heme Oxygenase-1 as a potential marker in early diagnosis of diabetic nephropathy.

Method

This case control study was conducted in Ain Shams university hospital, Cairo, Egypt. It included 80 type 2 diabetic patients diagnosed according to the American Diabetes Association (ADA) criteria, with and without DN ,and 20 healthy control subjects matched in age and sex .Patients were divided into two groups according to the value of the urinary albumin-to-creatinine ratio (ACR) : Group I: 40 normoalbuminuric patients(16 M and 24 F) with ACR<30 mg/g, and Group II: 40 microalbuminuric patients (18M and 22 F) with ACR 30-300mg/g. We excluded patients with history of diabetic ketoacidosis or hypoglycemic coma in the past 3 months preceding the study. Patients with glomerulonephritis, nephrolithiasis, tumors or any other renal diseases were excluded as well. For all studied groups,full history taking and clinical examination were done. We assessed glycosylated hemoglobin (HbA1C),blood urea, serum creatinine, urine creatinine, urinary albumin-to creatinine ratio (ACR mg/g) ,and urinary hemeoxygenase 1(UHO-1) by ELISA . Glomerular filtration rate (eGFR) was estimated by modification of diet in renal disease formula(MDRD)and uHO-1/cr was calculated.

Results

Group I patients were diabetic for 6.18±0.75 years, while group II patients for 6.05±0.81 years(p = 0.477). Normoalbuminuric patients had significantly higher levels of uHO-1 compared to control (3.01ng/ml vs 0.3 ng/ml,p<0.001).UHO-1 reached highest value among the microalbuminuric group (5.02 ng/ml) with P<0.001.UHO-1/cr ratio was significantly positively correlated with urinary ACR (r = 0.61,p<0.001) and significantly negatively correlated with eGFR(r = -0.71,p <0.001). There was highly significant correlation between uHO-1and eGFR by linear regression. ROC curves showed that AUC of uHO-1is comparable to uHO-1/ Cr ratio (0.957 vs 0.954) respectively with equivocal sensitivity 100 % and specificity 95% and cut off value of uHO-1 >0.46 ng/mland > 0.7 for uHO-1/ Cr ratio.

Conclusion

UHO-1 is increased in normoalbuminuric patients before the presence of any proteinuria and level increased with the progression of proteinuria and falling of eGFR as well as with the uncontrol of diabetes. UHO-1 is more sensitive than albumin for the detection of early diabetic nephropathy.
P1046GENDER DIFFERENCES IN CORRELATIONS BETWEEN THE LEVEL OF NT-PROBNP AND PLATELET PARAMETERS IN PATIENTS WITH EARLY DIABETIC NEPHROPATHY AND CHRONIC HEART FAILURE
Authors: Pchelin Ivan , Shishkin Alexander , Vasilev Petr , Vasilkova Volha , Kulibaba Tatyana , Slepykh Liudmila , Sheveleva Marina
Published: June 2020

Background and Aims

Many studies have shown that platelet parameters represent important markers of cardiovascular risk, but the data on gender differences are limited. In this study, we aimed to assess correlations between the level of NT-proBNP and platelet parameters in men and women with early diabetic nephropathy and chronic heart failure.

Method

We investigated 65 patients with type 2 diabetes who also had chronic kidney disease (stage 1-3) and chronic heart failure (42 women and 23 men). eGFR was calculated using CKD-EPI formula. In addition to routine clinical tests, we assessed mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW) and serum levels of NT-proBNP and erythropoietin. Mann-Whitney U-test and Spearmen’s correlation coefficient (rs) were used for statistical analysis.

Results

Mean levels of NT-proBNP were similar in men and women: 1019±267 and 1192±176 pg/ml (p>0.05), respectively, and there were no significant differences in platelet count, MPV, PCT and PDW between the groups. In women platelet indices were not related to age, body mass index, GFR, erythropoietin and hemoglobin levels, while in men PDW was positively correlated with body mass index (rs=0.600, p=0.009) and hemoglobin level (rs=0.506, p=0.021). Only in the female group serum level of NT-proBNP was interconnected with platelet count (rs= -0.419, p=0.006) and plateletcrit (rs= -0.559, p<0.001). Both in men and in women serum concentration of NT-proBNP was not correlated with the values of MPV and PDW.

Conclusion

The results of the study suggest that platelet count and plateletcrit are negatively correlated with serum level of NT-proBNP in women, but not in men with early diabetic nephropathy and chronic heart failure. Further studies are needed to clarify clinical implications of these findings.