bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0998IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES AND SIGNALING PATHWAYS IN DIABETIC NEPHROPATHY BY BIOINFORMATICS ANALYSIS
Authors: Tang Shumei , Xiao Xiangcheng 
Published: June 2020

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &gt;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

Abstract

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 &lt;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 &lt;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 &lt;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

Abstract

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, &lt; 70 years of age and with estimated glomerular filtration rate (eGFR) &gt; 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) &gt; 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

Abstract

Background and Aims
Arterial hypertension is present in &gt;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&lt;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

Abstract

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&lt;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&lt;0.001).UHO-1 reached highest value among the microalbuminuric group (5.02 ng/ml) with P&lt;0.001.UHO-1/cr ratio was significantly positively correlated with urinary ACR (r = 0.61,p&lt;0.001) and significantly negatively correlated with eGFR(r = -0.71,p &lt;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 &gt;0.46 ng/mland &gt; 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

Abstract

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&gt;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&lt;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.