bluuebunny/crossref_metadata_2025 huggingface dataset:
P0925EFFECTS OF A NUTRITION INTERVENTION IN ADDITION TO AN INTRADIALYTIC EXERCISE PROGRAM IN HEMODIALYSIS PATIENTS
Authors: Valente Ana , Caetano Cristina , Ramos Inês , Sebastião Joana , Pinto Mariana , Oliveira Telma , Martins Pedro , Garagarza Cristina
Published: June 2020

Background and Aims

Physical inactivity and low protein intake are related with protein-energy wasting syndrome. This is a very common condition in hemodialysis (HD) patients and is related with poor survival. Both, intradialytic exercise programmes (IEP) and nutrition interventions, are proposed as strategies to increase lean tissue mass in these population. The aim of this study was to analyze the effect of specific nutritional counseling in nutrition, body composition parameters and in eating habits, in patients undergoing HD with an IEP.

Method

This was a multicenter longitudinal intervention study with 3 months of follow-up. We enrolled 88 patients already performing intradialytic exercise (aerobic and strength training) for more than 3 months. These patients had an appointment with the dietitian and received specific nutritional counseling (NC) and a flyer with focus on nutrition recommendations for exercise. Eating habits were obtained through a questionnaire and body composition with bioimpedance spectroscopy (Body Composition Monitor®). Potassium and phosphorus were collected at baseline and 3 months after. Statistical tests were performed with SPSS, version 26.0. A p < 0.05 was considered significant.

Results

Patient’s mean age was 63.5±1.5 years and median HD time was 34 (Interquartil range (IQR): 20-58) months. 61.4% (n=54) were male and 26.1% (n=23) were diabetics. Results pre and pos intervention for the parameters studied were, respectively: Body Mass Index (BMI) 25.4[IQR: 23.7-28.4] Kg/m2 vs. 25.6[IQR: 23.4-28.9] Kg/m2; Fat Tissue Mass 12.6±5.0 Kg/m2 vs. 12.5±4.8 Kg/m2; Lean Tissue Mass 13.5[IQR: 11.5-15.3] Kg/m2 vs. 13.4[IQR: 12.1-15.3] Kg/m2; Body Cell Mass 20.1[IQR: 15.7-25.1] Kg/m2 vs. 20.4[IQR: 16.4-24.8] Kg/m2; % Interdialytic Weight Gain 2.7±1.1 Kg/m2 vs. 2.8±1.1 Kg/m2; potassium 5.1±0.7 mEq/L vs. 5.2±0.8 mEq/L and phosphorus 4.6±1.3 mg/dl vs. 4.8±1.2 mg/dl. No statistically significant differences were observed between baseline and follow-up. Concerning eating habits, the intake of protein sources from meat and fish before the HD session increased after the 3 months (17% vs. 20.5%; p=0.002). About 23% of the patients reported having made changes in their diet after the NC and 60% felt positive changes in performance and fatigue.

Conclusion

We can conclude that NC contributed to increase the consumption of high biological value protein-rich foods and to improve the patient´s perception of fatigue and performance. Moreover, this intervention did not have a worrying effect on potassium and phosphorus levels. Longer follow up studies are needed to analyze the effect on body composition.
P0927THE IMPACT OF NUTRITIONAL EDUCATION ON PHOSPHORUS CONTROL IN HEMODIALYSIS PATIENTS
Authors: Salem Kariem Mohamed , Nassar Mohammed Kamal , El-Sabakhawi Doaa Hamed , Elshahat Ousama , Amin Malak Nabil , Sayed-Ahmed Nagy , Sheashaa Hussein
Published: June 2020

Background and Aims

Hyperphosphatemia is frequently encountered in hemodialysis patients and is an important risk factor of cardiovascular diseases. It is usually difficult to be managed by phosphate binders and hemodialysis. This study was carried out to assess the effect of nutritional education (NE) on the control of serum phosphorus level in hemodialysis patients.

Method

An open label, single center randomized controlled trial was conducted in the nephrology department, New Mansoura General Hospital, Egypt. One hundred hemodialysis patients were randomized into two groups; intervention Group (IG) (n=50) subjected to NE program for 3 months and Control group (CG) (n=50) received the usual care. Nutritional education was applied for the intervention group, by a trained renal dietitian, in the form of educational sessions, booklets, procures, audio visual teaching aids and patient-tailored counselling. Nutritional evaluation was done for all patients using dietary history, 24 hour diet recall sheet and malnutrition inflammation score (MIS) in addition to assessment of anthropometrics measurements and routine laboratory tests before randomization and at the end of the study.

Results

Three months after randomization, body mass index, waist circumference and midarm muscle circumference (MAMC) were significantly lower among IG versus the CG (p=0.04, 0.04 and 0.004 respectively). MIS score was significantly lower among the IG compared to the CG (p=0.02). Regarding laboratory tests, serum phosphorus level and calcium X phosphorus product were significantly lower among IG compared to the CG at the end of the study (p<0.001 and =0.04 respectively) with a percent change of serum phosphorus of -13.8 ± 21.41 after NE. The percentage of patients with hyperphosphatemia (> 5.5 mg/dl) were significantly lower in the IG at the end of study (p=0.04). Other laboratory tests including serum albumin, hemoglobin level, iron status and urea reduction ratio did not show any significant difference between both groups.

Conclusion

NE applied to dialysis patients added to the control of hyperphosphaemia without exposing the patients to the risk of malnutrition, resulting from injudicious dietary restrictions.
P0931PROTEIN ENERGY WASTING ON MORTALITY IN HEMODIALYSIS PATIENTS IN DIFFERENT SERUM ALBUMIN AND CHOLESTEROL LEVELS: A POPULATION STUDY IN TAIWAN
Authors: LIN YEN-CHUNG , Zheng Cai-Mei
Published: June 2020

Background and Aims

Protein-energy wasting, hypoalbuminemia and hypercholesterolemia play an important role in mortality among hemodialysis (HD) patients. How hypoalbuminemia and hypercholesterolemia influence the nutrition (normalized protein catabolic rate (nPCR)) related mortality among HD patients is still unclear.

Method

Using the nationwide data from the Taiwan Renal Registry Data System (TWRDS) between 2005 and 2012, we divided the HD patients into nPCR<1.2 and nPCR≥1.2 groups. The relation of nPCR with three-year all-cause and cardiovascular mortality were determined. The influence of serum albumin (Alb) and cholesterol (TC) on nPCR related mortality were further analysed.

Results

Of 88,330 HD patients, 58122 (85.6%) patients were among nPCR <1.2 group and 30,208 (14.4%) in nPCR≥1.2 group. Both all-cause and cardiovascular mortality were increased in nPCR <1.2 group. In the nPCR <1.2 subjects, Alb ≥ 3.7 was associated with increased risk of both overall and CV mortality (adjusted hazard ratio [HR]; 95% confidence interval [CI]: 1.16; 1.07–1.25, p=0.0003 and 1.15; 1.02–1.13, p=0.03) compared to the those with Alb < 3.7 (adjusted hazard ratio [HR]; 95% confidence interval [CI]: 1.00; 0.90–1.08, p=0.74 and 1.15; 1.02–1.31, p=0.03). Further analysis revealed that in nPCR < 1.2 and Alb ≥ 3.7 group, TC ≥ 150 had increased risk of both all-cause and CV mortalities (adjusted hazard ratio [HR]; 95% confidence interval [CI]: 1.14; 1.04–1.25, p=0.005 and 1.17; 1.02–1.35, p=0.026). No significant relation was found betweent mortality and nPCR among patients with Alb < 3.7 irrespective of TC levels.

Conclusion

From this nationwide study, we found the close relation between dietary protein intake and mortality among those with Alb ≥ 3.7 and TC ≥ 150 group. Thus, we need to emphasize the importance of cholesterol control and dietary protein intake even among HD patients with normal serum albumin levels.
P0933PROTECTIVE EFFECT OF AN SGLT2 INHIBITOR ON ER STRESS THROUGH REDUCTION OF ECTOPIC LIPID DEPOSITION IN RENAL TUBULES IN OBESE MICE
Authors: Takata Tomoaki , Hosokawa Kohshiro , Sugihara Takaaki , Matono Tomomitsu , Koda Masahiko , Kanda Tsutomu , Ogawa Masaya , Ida Ayami , Mae Yukari , Yamamoto Marie , Iyama Takuji , Fukuda Satoko , Isomoto Hajime
Published: June 2020

Background and Aims

Chronic kidney disease (CKD) is a major health issue closely related to metabolic syndrome. Although a potential link between ectopic lipid-induced ER stress and the progression of CKD has been suggested, the underlying mechanism has not yet been fully elucidated. SGLT2 inhibitors have been reported to be effective in reducing fat accumulation. However the effect on lipid-associated kidney disease remains unclear. The aim of this study was to investigate the role of ectopic lipid and ER stress in the development of CKD, and evaluate the efficacy of an SGLT2 inhibitor.

Method

FLS-ob/ob mice, a model that shows significant ectopic lipid deposition and closely imitate the pathophysiology of non-alcoholic steatohepatitis, were treated with vehicle or an SGLT2 inhibitor, Ipragliflozin (1 mg/kg body weight) for 12 weeks. Metabolic characteristics, histology of the kidney, ER stress and apoptotic signals were evaluated.

Results

Ipragliflozin significantly reduced the serum triglyceride level. Ectopic lipid deposition in renal tubules found in FLS-ob/ob mice was prevented by Ipragliflozin, accompanied by reduced interstitial fibrosis. Both GRP78, a master regulator or ER stress, and CHOP, a downstream mediator of ER stress, were significantly downregulated in mice treated with Ipragliflozin. Apoptotic signal in kidney tissue was also reduced.

Conclusion

Ipragliflozin improved the pathogenesis of CKD by reducing ER stress through preventing ectopic lipid deposition in the kidney. SGLT2 inhibitors may have therapeutic effect on lipid-associated kidney disease.
P0939THE ASSOCIATION BETWEEN MUSCULAR STRENGTH, MUSCLE MASS AND DEPRESSION IN KIDNEY TRANSPLANT RECIPIENTS: A CROSS-SECTIONAL ANALYSIS
Authors: Vučković Marijana , Raos Hrvoje , Kovačević Katja , Orešković Josip , Gelemanović Andrea , Roguljić Marija , Radic Josipa
Published: June 2020

Background and Aims

While kidney transplantation (Ktx) offers several advantages in terms of improved clinical outcomes and quality of life compared to dialysis modalities, depressive symptoms are still present in approximately 25% of patients, rates comparable to that of the hemodialysis population. Correlates of depressive symptoms include marital status, income, and kidney function, history of affective illness, malnutrition, and inflammation. The aim of this study was to evaluate possible correlations between nutritional status evaluated through body mass composition parameters, muscle strength and depression in kidney transplant recipients (KtR).

Method

115 KtR, 61 (53 %) men and 54 (47 %) women, aged 59.3 (range 25 - 83) years were included. For each patient data about duration after Ktx, duration of dialysis before Ktx, age, gender, body weight and height were collected and body mass index (BMI) was calculated. Tanita MC780 Multi Frequency segmental body composition analyser was used to measure content of body fat, muscle mass, and visceral fat each study subject measured in kilograms (kg) and percentage (%.) Peripheral muscle strength of KtR was measured by using a standardized handgrip dynamometry protocol. The Beck Depression Inventory-Second Edition (BDI-II) was used as an indicator of the severity of depression.

Results

Out of all 115 KtR patients, according BDI-II score 25 (21.7 %) were depressed; 15 (13 %) had mild, 6 (5.2 %) moderate and 4 (3.5 %) severe depression. Significantly negative correlations between BDI-II scores (higher score – more depressive symptoms) and muscle mass (kg and %) was found (R=-0.205, P=0.032), (R=-0.278, P=0.003), respectively. Therefore, significantly positive correlations between BDI-II scores (higher score – more depressive symptoms), fat mass (%) and age was found (R=-0.24, P=0.012), (R=-0.231, P=0.013), respectively. Those KtR patients with more depressive symptoms (higher BDI-II score) had statistically lower muscle strength (R=-0.205, P=0.032). Significantly correlation between duration after Ktx and duration of dialysis before Ktx with BDI-II score was not found.

Conclusion

Prevalence rates for depression in this study is similar with previous reports and results have shown that depressive KtR patients were older and had significantly lower muscle mass and muscle strength and significantly higher fat mass content. Possible explanation for this findings might be that depression in KtR is associated with unhealthy behaviours including lower activity levels and worse dietary habits, which may in turn impact body mass composition parameters and upon transplant-related outcomes. Efforts to detect and treat depression should be a priority if one is to improve treatment and dietary adherence, quality of life, and outcomes in KtR.
P0952NEUTROPHIL GELATINASE - ASSOCIATED LIPOCALIN LEVEL AS A MARKER OF MALNUTRITION IN HEMODIALYSIS PATIENTS
Authors: Sabry Alaa , Mahmoud Rasha , Alsaody Shimaa
Published: June 2020

Background and Aims

Among hemodialysis patients, malnutrition is a common health problem, it is a marker of poor prognosis in these patients, associated with increased risk of hospitalization and mortality. NGAL is an iron transporting factor which increases in the serum in acute and chronic kidney disease. The aim of our study is to assess the use of NGAL as a marker of malnutrition in patients with stage 5 CKD maintained on hemodialysis.

Method

This is a cross-sectional study of 80 regular hemodialysis (HD) patients (51 males and 29 females). All cases of this study were subjected to: Anthropometric measurements . Biochemical measurements: Neutrophil Gelatinase-associated Lipocalin Level in blood using commercially available ELIZA kits, Serum albumin, Blood urea, Complete blood count, Serum electrolytes .

Results

According to the result we found in our study 100% of CKD having malnutrition according to SGA, MIS and our data however most of our patients are mild malnutrition.

We found also a significant decrease in some anthropometric parameters including BMI, fat mass, TSF, MAC, MAMC and MAMA with advanced malnutrition in hemodialysis patients. In this study, we use Twenty-four hours dietary recall and we found most of patients were with low protein (96.2%) and calorie (68.8%) contents. Dialysis adequacy (Kt/V) can affect the nutritional status of patients Kt/V was adequate in all malnutrition groups. These findings are consistent with an earlier report in which HD patients with Kt/V>1.4 had a significantly higher rate of malnutrition than patients with Kt/V ≤1.4. in this study NGAL serum levels were significantly (P=0.018) reduced with the severity of malnutrition. In this study, Spearman correlation analysis revealed that NGAL serum levels were significantly correlated with SGA (r =o,247 P =0.027) and albumin serum levels (r =0.402, P <0.001).

NGAL serum levels were significantly (P=0.018) reduced with the severity of malnutrition. Using ROC curve analysis, NGAL serum levels had a good ability (AUC=0.845) to predict severe malnutrition with good sensitivity (83.3%) and specificity (78.4%).

Conclusion

NGAL is well correlated with other standard markers used routinely in assessment of nutritional status of hemodialysis patients. Patients with high NGAL levels were closely related to good nutritional status. Its serum levels had a good diagnostic power for severe-malnourished patients, as it helps us for early prediction to malnutrition.
P0962CHRONIC KIDNEY DESEASE AND URINARY TRACT INFECTION IN PREGNANTS
Authors: Vetchinnikova Olga , Nikol`skaya Irina
Published: June 2020

Background and Aims

Pregnant women with chronic kidney disease (CKD) are at risk of developing/exacerbating urinary tract infection (UTI) due to the presence of additional (“specific”) risk factors. The aim of our study was estimation the features of UTI in women with CKD during pregnancy.

Method

The study included 139 women with CKD G1-G3 who had UTI during pregnancy. Most women (63) had chronic glomerulonephritis, 47 had with chronic pyelonephritis, and the rest had diabetic nephropathy (11), chronic tubulointerstitial nephritis (9), renal transplant (7) and lupus nephritis (2). An analysis of the bacteriological examination of urine, the sensitivity of pathogens to antibiotics, clinical manifestations and perinatal complications was performed.

Results

The following forms UTI are diagnosed: asymptomatic bacteriuria (50.4%), exacerbation of chronic pyelonephritis, including renal transplant (33.1%), acute pyelonephritis (16.5%). The true bacteriuria is determined identically at all stages of CKD, in those with chronic pyelonephritis in 70%, chronic glomerulonephritis in 45% of cases (p = 0.02). Gram-negative microorganisms become apparent in 73.6% of pregnant women with CKD, less often in patients with glomerular pathology than with chronic pyelonephritis (66% versus 81%). Escherichia coli among gram-negative microorganisms was 74.4%, a high frequency of detection of strains with the production of extended-spectrum β-lactamases was established. The course of asymptomatic bacteriuria in pregnant women with non-diabetic glomerulopathy was characterized by a moderate tendency to relapse and moderate release of resistant pathogens. The course of asymptomatic bacteriuria in patients with diabetic nephropathy and after kidney transplantation, on the contrary, had a pronounced tendency to relapse and the frequent release of resistant pathogens. Exacerbation of chronic pyelonephritis proceeded with minimal clinical manifestations, a vivid clinical picture of exacerbation of the disease was determined in one third of pregnant women. It was characterized by a high tendency to relapse and the development of systemic infection, a high frequency of release of resistant pathogens. Pregnant women with CKD who underwent UTI had a high risk of giving birth to premature babies (23% versus 11% p=0.01) who were required to carry out artificial lung ventilation and transfer to stage nursing (34% versus 16%, p=0.01).

Conclusion

The course of UTI in pregnant women with CKD is characterized by a high prevalence, dependence on primary renal disease, the release of resistant pathogens, and a high probability of an atypical clinical picture.
P0970EXOSOMAL MIR-92A-1-5P DERIVED FROM PROXIMAL TUBULAR EPITHELIAL CELLS INDUCES EPITHELIAL-MESENCHYMAL TRANSITION IN MESANGIAL CELLS IN DIABETIC NEPHROPATHY
Authors: Tsai Yi-Chun , Kuo Mei-Chuan , Hsu Ya-Ling
Published: June 2020

Background and Aims

Diabetic nephropathy (DN) has been the leading cause of end-stage renal disease in the world-wide. Exosomes play a key role in signal transduction between cell-cell communication in kidney pathophysiology. The aim of this study is to investigate that HK-2 cells-derived exosomal miR-92a-1-5p causes epithelial-mesenchymal transition (EMT) in mesangial cells (MCs), further leading to DN progression.

Method

The function of HK-2 cells-derived exosomes under normal glucose (NG) and high glucose (HG) was analyzed in mouse MCs model. Total RNAs were extracted from renal proximal tubular epithelial cells (RPTECs) of normal individual and type 2 diabetes for small RNA expression profiling using next-generation sequencing (NGS), then analyzed using systematic bioinformatics analyses. The expression of miR-92a-1-5p was examined in HK-2 cells-derived exosomes and MCs treated with HK-2 cells-derived exosomes under HG. The role of miR-92a-1-5p in EMT was evaluated using MCs model under NG and HG conditions. Urinary exosomal miR-92a-1-5p levels were measured in 50 type 2 diabetic patients and 34 healthy volunteers who were enrolled to determine the relationship between urinary exosomal miR-92a-1-5p and kidney function.

Results

Decreased E-cadherin, and increased N-cadherin and Vimentin expression were found in mouse MCs treated with HK-2 cells-derived exosomes under HG. Transcriptome analysis of RPTECs of normal individual and type 2 diabetic patient indicated that miR-92a-1-5p contributes to HG-induced renal proliferation. HG elevated miR-92a-1-5p expression in HK-2 cells and exosomes derived from-HK-2 cells, at meanwhile exosomal miR-92a-1-5p derived from-HK-2 cells under HG leads to EMT in mouse MCs. miR-92a-1-5p mimic increased EMT in mouse MCs under NG, and miR-92a-1-5p inhibitor reversed EMT in mouse MCs induced by exosomes derived from HK-2 cells under HG. EMT of mouse MCs was enhanced in the presence of exosomes isolated from the urine of type 2 diabetic patients with high levels of exosomal miR-92a-1-5p. Type 2 diabetic patients had higher urinary exosomal miR-92a-1-5p levels than normal individuals. Higher urinary exosomal miR-92a-1-5p levels were significantly correlated with lower renal function and higher albuminuria in human model.

Conclusion

Exosomal miR-92a-1-5p derived from HK-2 cells under HG induces EMT in mesangial cells. Blocking miR-92a-1-5p epigenetic regulatory network might be a potential therapeutic strategy to prevent EMT in DN.
P0977LOW EXPRESSION OF AUTOPHAGY-RELATED PROTEIN 5 (ATG5) LEADS TO SUPPRESSION OF AUTOPHAGY IN PATIENTS WITH DIABETIC NEPROPATHY AND RETINOPATHY
Authors: Nakhoul Nakhoul , Nakhoul Rula , Abass Remah , Farber Evgeny , Tadmor Hagar , Nakhoul Farid
Published: June 2020

Background and Aims

Autophagy is a catabolic mechanism that involves lysosomal-dependent degradation of unnecessary or dysfunctional intracellular components. Autophagy plays role in many biological processes, including diabetic nephropathy (DN) and diabetic retinopathy (DR). Autophagy-related gene 5 (ATG5) is one of the most important participants in the autophagy mechanism. Deficiencies in ATG5 protein levels are associated with several diseases by influencing the level of autophagy pathway. Our study's aim was to investigate if aberrant expression of ATG5 protein or Atg5 gene is associated with DN or DR.

Method

The study included 120 human participants in 4 groups – Healthy, diabetic (DM), DN and DR; and 10 mice in 2 groups – healthy and DN. Western blot analyses of ATG5 and its downstream collaborator LC3B were performed on human white blood cell (WBC) lysates and murine renal lysates. Immunohistochemical analysis was performed on mice renal tissues. Quantitative real-time PCR analysis of ATG5 was performed on total mRNA isolated from human WBC.

Results

Conclusion
P0979BENEFICIAL EFFECT OF CHLOROQUINE AND AMODIAQUINE ON DIABETIC TUBULOPATHY BY ATTENUATING MITOCHONDRIAL NOX4 AND ENDOPLASMIC RETICULUM STRESS
Authors: Lee So-Young , Yang Dong Ho , Lee Yu Ho , Lee Mi Jung , Kim Hyung-Jong , Sung MinJi , An Hyun-Ju , Lee Sang-Ho
Published: June 2020

Background and Aims

Oxidative stress induced by chronic hyperglycemia is recognized as a significant mechanistic contributor to the development of diabetic kidney disease (DKD). Nonphagocytic nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in many cell types and in the kidney tissue of diabetic animals. We designed this study to explore the therapeutic potential of chloroquine and amodiaquine for inhibiting mitochondrial Nox4 and diabetic tubular injury.

Method

Human renal proximal tubular epithelial cells (hRPTCs) were cultured in high-glucose media (30 mM D-glucose), and diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57/BL6J mice. Chloroquine and amodiaquine were administered to the mice via intraperitoneal injection for 14 weeks.

Results

Chloroquine and amodiaquine inhibited mitochondrial Nox4 and increased mitochondrial mass in hRPTCs under high-glucose conditions. Reduced mitochondrial ROS production after treatment with the drugs resulted in decreased endoplasmic reticulum (ER) stress, suppressed inflammatory protein expression and reduced cell apoptosis in hRPTCs under high-glucose conditions. Notably, chloroquine and amodiaquine treatment diminished Nox4 activation and ER stress in the kidneys of STZ-induced diabetic mice. In addition, we observed attenuated inflammatory protein expression and albuminuria in STZ-induced diabetic mice after chloroquine and amodiaquine treatment.

Conclusion

We substantiated the protective actions of chloroquine and amodiaquine in diabetic tubulopathy associated with reduced mitochondrial Nox4 activation and ER stress alleviation. Further studies exploring the roles of mitochondrial Nox4 in the pathogenesis of DKD could suggest new therapeutic targets for patients with DKD.

Figure

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P0989VDR/ATG3 AXIS REGULATES SLIT DIAGRAM TO TIGHT JUNCTION TRANSITION VIA P62-MEDIATED AUTOPHAGY PATHWAY IN DIABETIC NEPHROPATHY
Authors: Qian Jingyi , Wang Bin , Liu Bicheng
Published: June 2020

Background and Aims

Vitamin D receptor (VDR) loss, slit diagram (SD) to tight junction (TJ) transition and impaired autophagic flux contribute to podocyte injury in diabetic nephrology. This study aims to examine the effect and mechanism of VDR on autophagic flux and SD-TJ transition in diabetic nephropathy.

Method

Renal biopsy tissues from DN patients at stage IIa, IIb, III, IV and patients with minimal lesions were used to evaluate the expression of VDR, autophagic flux and SD-TJ transition glomeruli. In vitro, cultured podocytes were treated with serum starvation (SS), autophagic inhibitors (3-methyladenine 3-MA or chloroquine CQ) to determine the degradation pathway of TJ marker ZO-1. Meanwhile, db/db mice and STZ-induced rats were used to explore the therapeutic effect and mechanism of VDR agonist in diabetic nephropathy.

Results

SD-TJ transition between foot processes could be observed under electron microscopy in DN patients at all stages, whereas foot processes were separated by the filtration slit and appeared to be single cross-strands in the normal glomeruli. There was a trend of increasing expression of autophagic marker p62 and ZO-1 and the expression of p62 is positively correlated with the changes of ZO-1 in the glomeruli of DN patients. In vitro, inhibiting autophagy with 3-MA and CQ resulted in the accumulation of ZO-1 in cultured podocytes. In addition, Co-IP experiments further convinced the interaction between p62 and ZO-1, which was enhanced by the activation of autophagy. Podocytes apoptosis and the activity of caspase 3 and caspase 8 were significantly increased in the presence of 3-MA or CQ, while these effects were rescued by silencing p62. According to VDR gene expression data in GEO database, VDR expression was decreased in diabetic nephropathy patients compared with normal people. Knocking down VDR lowered the expression of atg3 and leaded to the blockage of autophagy, which could be reversed by over-expressing Atg3. Podocytes treated with high glucose resulted in the decrease of VDR and Atg3, impaired autophagic flux and aggravated podocytes injury. However, VDR agonist treatment partially reversed all the changes. In vivo, db/db mice and STZ-induced rats (DN animal models) exhibited SD-TJ transition, massive proteinuria, decreased expression of VDR and podocin and the increased accumulation of p62 and ZO-1, all of which could be partially reversed by VDR agonist.

Conclusion

VDR loss contributed to the impairment of autophagic flux and SD-TJ transition via down-regulation Atg3 in diabetic nephropathy. Here, we identified a new mechanism and evidence for VDR agonist to treat diabetic nephropathy.
P0999URINARY EXCRETION OF ADENYLATE AND URIDYLATE NUCLEOTIDES IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
Authors: Sałaga-Zaleska Kornelia , Pikuł Piotr , Kreft Ewelina , Chyła Gabriela , Kuchta Agnieszka , Jankowski Maciej
Published: June 2020

Background and Aims

Extracellular nucleotides (ATP, ADP, UTP, UDP) acting through P2-receptors regulate renal vascular tone and glomerular permeability tor albumin. Both phenomenons are dysregulated in diabetes and are conducive to development of diabetic nephropathy. The aim of study was to investigate the urinary excretion of adenylate and uridynate nucleotides and the effects of suramin, P2-receptors antagonist and non-competitive inhibitor of ectoATPase, on those parameters in streptozotocin-induced diabetic rats.

Method

Diabetes in Wistar rats was induced by streptozotocin injection (65 mg/kg, i.p, day 0) and suramin was injected (10 mg/kg, i.p) on day 7 and 14. Nucleotides concentration in urine collected in metabolic cages on day 21 (3-weeks diabetes) were measured using HPLC method wit UV detector. All values are expressed as mean ± SEM.

Results

The excretion of ATP, UTP, ADP and UDP in diabetes were increased i.e. ATP: 34.99±1.73 vs 18.56±1.59 μmol/24h (p<0.001); UTP: 0,72±0.06 vs 0.47±0,08 vs μmol/24h (p=0.03); ADP: 0,70±0.56 vs 0.28±0,04 vs μmol/24h (p=0.001); UDP: 9.08±1.28 vs 5.06±0,83 vs μmol/24h (p=0.02). UMP excretion was decreased 7.04±0.89 vs 11.36±0,621 μmol/24h (p=0.002) but AMP excretion was not affected by diabetes i.e. 0.86±0.09 vs 0.89±0.12 μmol/24h (p=0.08). Suramin administration did not affect urinary excretion of investigated nucleotides.

Conclusion

diabetes increases the urinary excretion of ATP, ADP, UTP and UDP and this effect is not modified by suramin. The changes in extracellular metabolism of nucleotides may affect the renal function during diabetes. This work was supported by National Science Centre Poland Grant (2016/23/B/NZ5/02632) to MJ.
P1001RENAL DAMAGE ASSOCIATED WITH INTRAVITREAL ADMINISTRATION OF ANTI-VEGF DRUGS
Authors: Fernandez-Vidal Maria , Moliz Candela , Redondo Beatriz , Bada Bosch Teresa , Aubert Lucia , Sandino Justo , Praga Manuel , Garcia Florencio , Morales Enrique
Published: June 2020

Background and Aims

Vascular endothelial growth factor inhibitors (anti-VEGF) have been shown to be effective in the treatment of macular degeneration and diabetic macular edema. It is known that systemic administration of these drugs can produce adverse renal effects, such as decreased glomerular filtration rate (eFGR), proteinuria, hypertension or thrombotic microangiopathy. However, there is little information about it when the administration is intravitreal. The aim of this study was analyzed the effect of anti-VEGF drugs on renal function and proteinuria.

Method

Observational and prospective study on diabetic patients, which were divided into two groups: non-cronic kidney disease (CKD) (group 1) and CKD (group 2). We analyzed clinical and analytical variables during follow-up.

Results

We included 45 diabetic patients (55.6% males) with a median age of 75 (50-91) years. Forty one patients (91.1%) were hypertensive and thirty three (73.3%) were CKD patients. Twenty six (57.8%) received bevazicumab, while the rest (42.2%) received ranibizumab, with a median dose of 6 (1-22). The median follow-up was 25 (9-94) months.

The evolution of eFGR and albuminuria are described in Figure 1, where it stands out the increase in albuminuria in group 2. Regarding the drug type, there were no differences. Within the CKD group, one patient presented two episodes of decompensation of heart failure after the administration of an anti-VEGF drug, and two required the initiation of renal replacement therapy.

Conclusion

Based on the results of our cohort, we believe that it would be advisable to establish a closer monitoring in diabetic patients who are administered an intravitreal anti-VEGF drug, with determination of renal function as well as albuminuria to establish an early diagnosis of possible complications.
P1002EFFECT OF VITAMIN D ON URINARY ANGIOTENSIOGEN LEVEL IN EARLY DIABETIC NEPHROPATHY
Authors: Mahapatra Himansu , Kumar Adarsh , Kulshreshtha Bindu , Chirkara Anubhuti
Published: June 2020

Background and Aims

UrinaryAngiotensinogen (UAGT) is supposed to be a marker of activation of intrarenalreninangiotensin system (RAS) system in early Diabetic Nephropathy (DN). Vitamin D has been studied as a negative regulator of the circulating and tissue RAS activity; so its supplementation may prevent progression of DN. This study was planned to assess the RAS activation and effect of vitamin D supplementation in early diabetic nephropathy progression by estimatingUAGT level.

Method

A total of 730 Diabetic subjects were screened for early DN based on Inclusion criteria(eGFR ≥ 120ml/min/1.73m2 with unrestricted ACR value eGFR of 60- 120 mL/min/1.73m2 and ACR 30-300mg) and Exclusion criteria(on ACE I or ARB, eGFR<60ml/min/1.73m2, Hypercalcemia (>11.5mg%), UTI, Pregnancy, Hypertension, HbA1c (>8.0 %), vitamin D supplementation during the last 6 month).Of them 103 included subjects were underwent randomization to receive either Cholecalciferol(54) or matching Placebo(49) in a double blind method. All were subjected to routine investigations, urinary albumin: creatinine (UACR), UAGT, serum 25(OH)vitamin D, and intact parathyroid hormone (iPTH) at the zero and six months. A total 40 healthy controls without any comorbidity were also includedfor assessment of same investigations at zero month. Comparative results at zero months of all three groups were analyzed.

Results

The change in levels of UACR (mg/g), UAGT (ng/ml), vitamin D (ng/ml) and iPTH(pg/ml)in Cholecalciferol group from zero to six month were [Median (IQR)] : 12.50 (-24.82 to -5.95); p<0.001, -6.60 (-20.91 to -2.63);p<0.001, 5.75 (2.07-9.70); p<0.001, -5.35 (-11.55 to -3.67) ;p<0.001, respectively. After six months, median (IQR) of UAGT and UACR levels were significantly lower in the Cholecalciferol group as compared to Placebo group (p<0.001 and p= 0.04 respectively).Significant reduction of UACR (mg/g) and UAGT (ng/ml) level corroborating with increase in 25(OH) vitamin D(ng/ml) levelfrom zero to six months (all three p<0.001). There was significant correlation of vitamin D3 level with UAGT (r value: -0.255 & p value: 0.009) and UACR level (r value: -0.28& p value: <0.01). The median UAGT level was significantly higher in patients with early DN (Cholecalciferol&Placebo Group) than Control Group at zero month (p =0.001).

Conclusion

Significantly higher UAGT levels in early DN supports role of intrarenal RAS activation. Significant decrease in UAGT level in cholecalciferol group supports beneficial role of vitamin D supplementation in progression of early DN.
P1005LONG NONCODING RNAS MAY INTERVENE IN PODOCYTE INJURY AND PROXIMAL TUBULE DYSFUNCTION THROUGH MODULATING MIRNAS EXPRESSION IN EARLY DIABETIC KIDNEY DISEASE OF TYPE 2 DIABETES MELLITUS PATIENTS
Authors: Petrica Ligia , GADALEAN FLORICA , VLAD ADRIAN , Vlad Mihaela , DUMITRASCU VICTOR , VELCIOV SILVIA , Gluhovschi Cristina Anca , Bob Flaviu , URSONIU SORIN , JIANU CATALIN , MATUSZ PETRU , Pusztai Agneta , CRETU OCTAVIAN , OANA MILAS , GOLEA-SECARA ALINA , SIMULESCU ANCA , MOGOS-STEFAN MARIA , PATRUICA MIHAELA , POPESCU ROXANA , Vlad Daliborca
Published: June 2020

Background and Aims

Interactions among multiple molecules and signalling pathways contribute to the pathogenesis and progression of diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aim of the study was to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients. The molecular mechanisms of lncRNAs intervention were evaluated in relation to a particular miRNA profile.

Method

A total of 136 patients with type 2 DM and 25 healthy subjects were enrolled in a cross-sectional case series study and assessed concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), and urinary miRNA21, 124, 93, 29a (quantified by a real-time PCR System).

Results

Multivariable regression analysis yielded models in which urinary lncRNA MALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93 and 29a (p<0.0001; R2=0.727); urinary lncRNA NEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, and 29a (p<0.0001; R2=0.702); urinary lncRNA MIAT correlated directly with miRNA93 and 29a, and eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, and 124 (p<0.0001; R2=0.654); urinary lncRNA TUG1 correlated directly with eGFR, miRNA93 and 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, and 124 (p<0.0001; R2=0.748). The results provided document upregulated lncRNA MALAT1 and NEAT1, as well as miRNA21 and 124. By contrast, lncRNA MIAT and TUG1, and miRNA93 and 29a were downregulated.

Conclusion

In patients with type 2 DM lncRNAs exert distinct functions in different cell types, either deleterious or protective, at both glomerular and tubular level. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.
P1009RENAL OUTCOMES IN DIABETIC KIDNEY PATIENTS TREATED WITH GLP1 AGONIST RECEPTORS VS SGLT2 INHIBITORS
Authors: Maroto Alba , Marques Vidas Maria , Sanz Ignacio , López Paula , Portoles Jose' M
Published: June 2020

Background and Aims

End stage renal disease of diabetic cause is an increasing issue worldwide. Both GLP1 antagonist receptors (GLP1ar) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown promising results in preventing or ameliorating the progression of renal disease, however there is no data comparing the effect of both drugs on renal outcomes.

Method

Here we present the result of a retrospective study analyzing the main renal outcomes of 98 T2DM patients treated with GLP1ar (25% dulaglutide, 25% liraglutide, 50% semaglutide) or SLGT2 (46.9% dapagliflozin, 21% empagliflozin, 32.1% canagliflozin). All participants were on ACEi/ARB on maximally tolerated dose and patients that have been on both treatments at any time during observation period were excluded. Mean follow-up was 1,9 years, (SD 1,1).

Results

Main descriptive data are shown on the table: in summary, patients on SGLT2i had higher eGFR (64,7 SD 22,7 vs 43,7 SD 13,5) ml/min/1,73m2 (p<0.001), lower BMI (30,2 SD 4,8 vs 35,0 SD 4,0 p<0,001) and were more frequently free from previous cardiovascular events (60% vs 29,4%, p 0,02)Incident kidney disease defined as drop of eGFR below 60 ml/min/1,73m2 and/or new onset albuminuria occurred on 18 (39,1%) and 7 (87,5%) of patients on SGLT2i and GLP1ar respectively (p 0,01), however, nor SGLT2i or GLP1ar treated patients suffered significant decrease on eGFR along the study period (2.5% change in eGFR-SGLT2i and 5% in GLP1ar). We found no significant differences on arterial blood pressure or glycemic control along the study period and BMI decrease was only significative on GLP1ar patients (-7,7%, p<0.001)6,7% and 15,8% of patients treated with GLP1ar and SGLT2i respectively suffered one CV event along the follow-up period (p ns) with 6,7% deaths on both groups (0.03 death/patient-year). Adverse events were similar on both groups though discontinuation rate was higher on SGLT2i (16,7% gastrointestinal intolerance, 58% “others”)

Conclusion

We conclude that both GLP1ar and SGLT2i prevent progression of kidney disease in T2DM patients. Though GLP1ar patients showed higher rates of incident kidney disease, when initiated on already decreased GFR this treatment achieved similar results to SGLT2i in preventing progression of kidney disease even in high cardiovascular risk patients.
P1012NAIL CAPILLARY DENSITY DURING POSTOCCLUSIVE REACTIVE HYPEREMIA AND VENOUS CONGESTION IS MORE IMPAIRED IN DIABETIC COMPARED TO NON-DIABETIC CKD PATIENTS
Authors: Schoina Maria , Loutradis Charalampos , Memmos Evangelos , Triantafillidou Eva , Pagkopoulou Eleni , Dimitroulas Theodoros , Garyfallos Alexandros , Papagianni Aikaterini , Sarafidis Panteleimon
Published: June 2020

Background and Aims

Αlterations in endothelial function and capillary circulation have been associated with increased cardiovascular events and overall mortality. Both diabetes mellitus (DM) and chronic kidney disease (CKD) have been associated with microcirculatory damage. Nailfold video-capillaroscory can provide a thorough assessment of capillary density and microcirculation changes. This is the first study examining in comparison microcirculatory function parameters in diabetic and non-diabetic patients with CKD.

Method

We included 48 diabetic and 48 non-diabetic adult patients (>18 years) with CKD (eGFR: <90 and ≥15mL/min/1.73m2), matched in a 1:1 ratio for age, sex and eGFR within each CKD stage (2, 3a, 3b and 4). All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia) and at the end of a 2-minute venous occlusion (congestion phase).

Results

Baseline demographic, anthropometric and laboratory characteristics were similar between patients with and without diabetes in total and in CKD stages. Overall, no significant differences at baseline capillary density were observed between groups; however diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3±3.8 vs 38.3±4.3 capillaries/mm2, p=0.022) and at venous congestion (37.8±4.0 vs 39.8±4.2 capillaries/mm2, p=0.015). When stratified according to CKD stages, the between-group differences in parameters of interest were not significant in stages 2, 3a and 4. In stage 3b, capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline (31.1±2.8 vs 33.4±3.4 capillaries/mm2, p=0.044), during postocclusive hyperemia (36.8±2.7 vs 40.0±4.3 capillaries/mm2, p=0.037) and venous congestion (38.3±2.8 vs 41.5±3.5 capillaries/mm2, p=0.022).

Conclusion

Capillary density during postocclusive reactive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory functional impairment in CKD. These differences are more prominent in CKD stage 3b, and less prominent in earlier and later stages.
P1020ROLE OF CHRONIC KIDNEY DISEASE AND ASSOCIATED BIOCHEMICAL ALTERATION ON ARTERIAL STIFFNESS IN T2 DIABETIC PATIENTS WITHOUT CARDIOVASCULAR DISEASE
Authors: Rotondi Silverio , Tartaglione Lida , Pasquali Marzia , Muci Maria Luisa , Mazzaferro Sandro , D'onofrio Luca , Carbone Angela , Leto Gaetano , Mignogna Carmen
Published: June 2020

Background and Aims

DMT2 and its complications such as chronic kidney disease (CKD) lead to increase vascular stiffness, measurable with CAVI, and biochemical alterations in substances implicated in vascular damage like Klotho, FGF23, and Sclerostin. The aim of the study was to evaluate the role of CKD stage 1-2 and possible alterations of 25 (OH)Vitamin-D, FGF23, Klotho, and Sclerostin on early vascular damage in DMT2 patients

Method

Patients included: DMT2 from <10 years, age <60 years, no insulin therapy, eGFR≥60 ml/min/1.73m2, absence of vascular complications. We have evaluated CAVI, albumin-excretion-rate (ACR), 25(OH)Vitamin-D, Klotho, FGF23, and Sclerostin. 30 healthy subjects were the control for CAVI, Klotho, FGF23 and Sclerostin.

Results

We enrolled 40 women and 60 men, average age 56 years (IQR: 52-59), 5-year DMT2 (IQR: 2.7-7), HbA1c 6.3% (5.8-6.7), eGFR of 95 ml/min/1.73m2. FGF23 (42±10 vs controls 29.8±11 pmol/l, p<.05) and Sclerostin (36.2±7 vs 26.6±1 pmol/l, p<.05) were increased and Klotho reduced (673±300 vs 845±330 pg/ml, p<.05). CKD (ACR≥30mg/gr; eGFR between 60-90 ml/min /1.73m2) was present in 12.6%. The mean CAVI value was normal. Patients with borderline (≥8, 33%) and pathological (≥9, 13%) CAVI were older (p.001), with longer duration of DMT2 (p.022) and lower 25(OH)Vitamin-D (p.041). CAVI correlated positively with age (p.001), Hb1Ac (p.036), systolic blood pressure (SBP) (p.012) and diastolic blood pressure (DBP) (p.001) and correlated negatively with 25(OH)Vitamin-D (p.046). The multivariate analysis showed positive predictors of CAVI age (p.001), DBP (p.0001), ACR (p.008) and Klotho (p.017).

Conclusion

In our DMT2 population, borderline and pathological CAVI is associated with increased ACR, elevated DBP and reduced 25(OH)Vitamin-D. Furthermore the alterations of FGF23, Sclerostin and Klotho, secondary to CKD, are an early sign of possible vascular damage. ACR, 25(OH)Vitamin-D and DBP can be modifiable risk factors for early vascular damage in DMT2
P1023DEPRESSION IS A MAJOR DETERMINANT OF HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH DIABETIC KIDNEY DISEASE
Authors: Kim Suhyun , Boo Hyo jin , Jeon Jeunseok , Jang Hye Ryoun , Huh Wooseong , Kim Yoon-Goo , Kim Dae Joong , Lee Jung Eun
Published: June 2020

Background and Aims

Poor health-related quality of life (HRQOL) is associated with increased cardiovascular risk and mortality in patients with kidney disease. Therefore, it is critical to identify and modify clinical contributors of poor HRQOL. This study examined modifiable factors associated with poor HRQOL in patients with diabetic kidney disease (DKD) focusing on depression, anxiety, sleep quality, and physical activity.

Method

Between April 2017 and March 2018, 141 adults (aged ≥18 years) with DKD were recruited in single tertiary hospital. HRQOL was assessed at baseline with the Short Form 36 of life Health Survey Question (SF-36) questionnaire. Poor HRQOL was defined as a score below the median value at baseline. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. Sleep quality and physical activity were measured using Korean version of the Pittsburgh Sleep Quality Index and International Physical Activity Questionnaire respectively.

Results

The age was 65 [57-72] years old, and 73% (n=103) of participants were men. Prevalence of anxiety and depression were 8% (n=11) and 17% (n=24) respectively. Forty-eight (34%) subjects corresponded to poor sleepers and 40 (28%) subjects showed low physical activity. SF-36 scores were decreased with advanced CKD stages (stage 3, 79 [71-82]; stage 4, 71 [56-82]; stage 5, 70 [57-82]; p = 0.029 for trend) progressively. Anxiety, depression, and poor sleep quality were negatively correlated with SF-36 scores (p < 0.05). eGFR and physical activity were positively correlated with HRQOL scores (p < 0.05). In multivariable logistic analysis, depression scores were associated poor HRQOL independently of age, sex, comorbidity, eGFR, anemia, sleep quality, anxiety and physical activity (odds ratio per 1-score increment, 1.51; 95% confidence interval, 1.27-1.80, p < 0.001).

Conclusion

In patients with DKD, depression was a major determinant of poor HRQOL among the modifiable clinical factors such as anxiety and sleep. Active surveillance of depression and psychosocial intervention should be considered to improve the well-being of these patients.