bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0912THE SERUM CREATININE TO CYSTATIN C RATIO AND CLINICAL OUTCOMES IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE: THE KNOW-CKD COHORT
Authors: Lee Kyu-Beck , Hyun Young Youl , Oh Kook-Hwan , Ahn Curie 
Published: June 2020

Abstract

Background and Aims
Muscle wasting leads to poor outcomes in patient with chronic kidney disease (CKD). The serum creatinine to cystatin C (Cr/CysC) ratio has been reported as marker for muscle mass and may predict outcomes in chronic diseases. We hypothesized that the Cr/CysC ratio would be a predictor of outcomes in CKD.

Method
We investigated a total of 2142 patients (male 61%, aged 54±12 year) with CKD followed for a median of 3.74 years. We assessed the factors associated with Cr/CysC ratio and the relationship between Cr/CysC ratio and outcomes of end-stage renal disease (ESRD), cardiovascular event (CVE), and mortality.

Results
The Cr/CysC ratio significantly correlated with age (r=-0.18), estimated glomerular filtration rate (eGFR) (r=-0.21), serum albumin (r=0.11), 24-hour urine creatinine (r=0.38), and moderate to vigorous physical activity time (r=0.07). After adjusting for age, sex, eGFR, and log urine albumin creatinine ratio (model 1), the hazard ratios for ESRD, CVE, and mortality were 0.96 (95% CI, 0.86-1.07), 0.78 (95% CI, 0.61-0.99), and 0.72 (95% CI, 0.53-0.97) per 1 standard deviation Cr/CysC increase (0.21), respectively. After full adjustment for model 1 variables plus lifestyle factors, laboratory factors, and comorbidities (model 2), the hazard ratios for ESRD, CVE, and mortality were 0.99 (95% CI, 0.88-1.10), 0.84 (95% CI, 0.65-1.07), and 0.75 (95% CI, 0.55-0.99) per 1 standard deviation Cr/CysC increase (0.24), respectively. In subgroup of the elderly (age&gt;65 year) and early stage CKD (eGFR&gt;60 ml/min/1.73m2), the hazard ratios for CVE were significantly lower in patients with high Cr/CysC ratio.

Conclusion
Cr/CysC ratio correlates with muscle biomarkers and physical activity. A higher Cr/CysC ratio is associated with low CVE and mortality, but not ESRD in CKD.
P0912AKIDNEY AGING CONSTITUTES INFLAMMATORY PROCESS THAT CONTRIBUTES TO EXACERBATION OF KIDNEY INJURY
Authors: Jung Su Woong , Moon Ju-Young , Kim Yang-Gyun , Jeong Kyung Hwan , Lee Sang-Ho 
Published: June 2020

Abstract

Background and Aims
Aging is a natural process accompanied by decline of regenerative potential. Some argue that aging process is just an irreversible physiologic process, whereas some advocate that it should be viewed as disease.

Method
To determine the nature of kidney aging and kidney disease at transcriptional level, whole kidney RNA sequencing was performed on young (2-month-old), middle-aged (12-month-old), and old (24-month-old) mice and young mice with adenine-induced nephropathy. In addition, young and old mice were fed with either standard or adenine-enriched diet for 4 weeks, and then the degree of renal injury was compared.

Results
The transcript profile of the old kidneys was mostly involved in inflammation and activation of innate and adaptive immune system and almost same to the transcript alterations of adenine-induced nephropathy. The genes implicated in fibrosis were downregulated until middle-age period, and then upregulated with the advance of age. The old kidneys showed augmented inflammatory response in a model of adenine-induced nephropathy compared with young kidneys, leading to more widespread fibrosis.

Conclusion
These findings showed that the pathophysiologic process of kidney aging and adenine-induced kidney injury shows similar natures in the context of inflammation and immune response. When kidney injury is superimposed on the aged kidneys, age-related inflammation potentiates inflammatory response and results in increased renal damage.
P0914NEUTROPHIL EXTRACELLULAR TRAPS FORMATION IN HEMODIALYSIS PATIENTS
Authors: Litmanovich Adi , Khazim Khaled , Hassan Kamal , Kristal Batya 
Published: June 2020

Abstract

Background and Aims
Hemodialysis (HD) patients suffer from devastatingly high rates of morbidity and mortality due to infections. Neutrophils isolated from HD patients were shown in the past to exhibit impaired phagocytosis in a mechanism yet to be completely elucidated. In 2004, Brinkmann et al. were the first to describe a new form of cell death which they termed Neutrophil Extracellular Trap Formation, or NETosis, in which neutrophils expulse batches of DNA and proteins in response to bacterial or chemical stimuli in order to trap and remove the stimulus. NETosis is further divided into two pathways, NADPH oxidase (NOX)-dependent and NOX-independent, induced in vitro by phorbol 12-myristate 13-acetate (PMA) and Calcium Ionophore (CI), respectively. In this research, we aim to assess the capacities of HD neutrophils to engage in NETosis, hypothesizing they might be diminished similarly to their phagocytic capacities, and to elucidate the underlying mechanism behind this impairment.

Method
Neutrophils were isolated from whole venous blood of normal controls and from the arterial line of HD patients before the onset of a dialysis session using EasySepTM direct human neutrophils isolation kit. Then, NETosis was induced with either PMA, Calcium Ionophore A23187 or Phosphate-buffered saline (PBS) as negative control. cfDNA released from the cells was quantified by measuring SYTOXTM-green nucleic acid stain fluorescence levels in the supernatant after stimulation using Elisa plate reader and morphological analysis was done under fluorescence microscope. Reactive oxygen species levels were quantified using flow cytometry and superoxide dismutase (SOD) activity was measured using the SOD Assay Kit (Sigma-Aldrich). Protein arginine deiminase 4 (PAD4) expression was assessed by western blotting. Hydrogen peroxide (H2O2) was added exogenously in order to restore NETosis.

Results
HD isolated neutrophils exhibit decreased NETosis compared with normal controls in response to both PMA in the NOX-dependent pathway and CI in the NOX-independent pathway, as measured by immunofluorescence and cfDNA quantification. In the NOX-dependent pathway SOD activity was found to be 14% decreased in HD patients, resulting in the accumulation of superoxide radicals and decreased production of H2O2. In the NOX-independent pathway, PAD4 expression was found to be significantly decreased as well. NET formation was restored in vitro in HD neutrophils by the addition of exogenous H2O2.

Conclusion
To date, impaired NETosis was described only in congenital conditions such as chronic granulomatous disease and myeloperoxidase deficiency. To our knowledge, our research is the first to describe an acquired defect in NETosis in end stage renal disease patients undergoing chronic hemodialysis. An intervention aimed to improve neutrophil function in these patients may reduce the morbidity and mortality due to infection-related disease.
P0921ROLE OF UREMIC TOXIN, INDOXYL SULFATE IN SARCOPENIA OF NONDIALYSIS DEPENDENT-CHRONIC KIDNEY DISEASE PATIENTS
Authors: Kim Jun Chul , Kang Seok Hui , Han Miyeun , Kim Su-Hyun , Cha Ran-Hui , An Won Suk , Do Jun Young 
Published: June 2020

Abstract

Background and Aims
Sarcopenia in patients with chronic kidney disease (CKD) is highly prevalent and leads to high rate of morbidity and mortality. The role of indoxyl sulfate (IS) to develop muscle wasting has been researched and proved in several animal model studies. However, there is no human data showing this relationship in CKD population. The aim of the present study was to evaluate the association between serum IS levels and each component of sarcopenia in nondialysis dependent-CKD (NDD-CKD) patients.

Method
We enrolled 150 NDD-CKD adult patients from 6 medical centers and collected data of demographics, blood chemistry such as indoxyl sulfate, interleukin (IL)-6, and estimated glomerular filtration rate using MDRD equation (eGFR), and body mass index (BMI, kg/m2). We also measured hand-grip strength (HGS, kg), walking speed (WS, m/s), skeletal muscle mass (SMM, kg) by bioelectrical impedance analysis (BIA).

Results
The numbers of male sex was 97 (64.7%). Mean age was 63.7±10.8 years old. The numbers of patients with diabetes mellitus was 77 (52.0%). Charlson comorbidity index (CCI) score was 3.9 ± 1.9. The stage of CKD ranged from 3 to 5 (eGFR=33.7±12.0 ml/min/1.73m2, mean±SD). Correlation coefficients with indoxyl sulfate levels were 0.211 for serum IL-6 level (P = 0.010), -0.212 for HGS (P = 0.009), -0.188 for WS (P = 0.021), -0.237 for SMM (P = 0.004), and -0.168 for BMI (P = 0.041), respectively. Correlation analysis showed that indoxyl sulfate levels had inverse association significantly with HGS, WS, SMM, and BMI and were positively associated with serum IL-6 levels.

Conclusion
Our study shows that higher serum indoxyl sulfate level was significantly associated with lower levels of muscle mass, strength, and physical performance function and higher inflammation status in non-dialysis dependent CKD patients. We suggest that the role of AST120 in prevention or treatment of sarcopenia be studied in this CKD population.
P0922A LOW AROMATIC AMINO-ACID DIET IMPROVES RENAL FUNCTION AND PREVENTS KIDNEY FIBROSIS IN MICE WITH CHRONIC KIDNEY DISEASE
Authors: Barba Christophe , Soulage Christophe , Glorieux Griet , PICARD Cecile , Fouque Denis , Koppe Laetitia 
Published: June 2020

Abstract

Background and Aims
Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), the mechanisms through which it delays the progression to end-stage renal disease (ESRD) remain controversial. A reduced production of uremic toxins could contribute to the benefits of the LPD. Aromatic amino-acids are precursors of major uremic toxins such as p-cresyl sulfate (PCS), indoxyl sulfate (IS), indole-3-acetic acid or phenol. We investigated the hypothesis that a low aromatic amino acid diet (LAA, namely low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the specific diminution of uremic toxins production.

Method
Renal failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Thereafter, they received 3 different diets for 6 weeks: normoproteic diet (NPD: 14.7% proteins, aromatics 0.019%), LPD (5% proteins, aromatics 0.007%) and LAA (14% proteins, aromatics 0.007%).

Results
LAA and LPD had no significant effect on body weight. Plasma creatinine was significantly lower in LPD and LAA groups compared to NPD group (72 ± 4 and 73 ± 4 µmol/L vs 127 ± 6 µmol/L, p&lt;0.0001), as well as proteinuria (1.3 ± 0.3 and 1.2 ± 0.1 mg/24h vs 3.8 ± 0.9 mg/24h, p&lt;0.05). Kidney fibrosis was more severe in NPD group vs LPD and LAA groups (17 ± 1% vs 10 ± 1 % and 13 ± 2 %, p&lt;0.0001 and p=0.01). Kidney inflammation was also reduced with LPD and LAA. Free PCS and IS were lower in LPD and LAA groups compared to NPD group.

Conclusion
These results suggest that LAA confers similar benefits as compared with those of LPD to delay the progression of CKD through reduction of uremic toxins production, with lower risk of malnutrition.
Renal function and urinary protein excretion in control and CKD mice Serum creatinine (A), blood urea nitrogen (B) and urinary proteins (C) in control and CKD mice fed with normoproteic diet (NPD), low protein diet (LPD) or low aromatic amino-acid diet (LAA). Data are expressed as mean ± SEM for n = 5-11 animals in each group.
*p &lt; 0.05, **p &lt; 0.01, ***p &lt; 0.001 vs CKD-NPD; (two-way ANOVA and Dunnett post hoc test).
P0924IMMUNE DISTURBANCES INDUCED BY HYPERVOLEMIA DO NOT ACTIVATE THE NLRP3 INFLAMMASOME IN HAEMODIALYSIS PATIENTS
Authors: Ulrich Christof , Wilke Annegret , Schleicher Nadja , Girndt Matthias , Fiedler Roman 
Published: June 2020

Abstract

Background and Aims
Hypervolemia is frequent in haemodialysis (HD) patients and is linked to inflammation, which may be further enhanced by endotoxemia. The impact of hypervolemia on immune cells i.e. a main monocytic defence mechanism - the NLRP3 inflammasome, has not been studied in detail. Therefore, we hypothesized that endotoxinemia putatively present in hyper- but normovolemic patients can trigger the activation of caspase-1 and thus increasing IL-1ß secretion.

Method
45 HD patients were included in the observational study, measuring immune parameters (cell counts, caspase-1, oxidative stress, cytokine gene expression and serum analysis (IL-1ß) at two time points (directly after dialysis BS1) and three days later after the long dialysis free interval (BS2). Fluid status was evaluated by electrical bioimpedance vector analysis, defining hypervolemia (H) as &gt;75 vector percentile. Data collected after the long dialysis interval is presented in this paper.

Results
Seventeen patients were classified as hyper-(H-HD), 19 as normovolemic (N-HD), 9 failed to meet the inclusion criteria. Monocytes were elevated and lymphocytes decreased by hypervolemia. Oxidative stress was slightly elevated in H-HD. However, neither caspase-1 frequency (H: 77.9±4.2% vs. 79.2±6.9%, p=0.916) nor caspase-1 expression (MFI, H: 42.8±13.3 vs. 43.6±17.1, p=0.880) were different. In vitro stimulation of PBMC’s by specific NLRP3 inflammasome stimulation significantly increased caspase activity in both cohorts to the same extent (89.9±22.6 vs. 88.0±23.3, p=0.900). As a result of it both IL-1ß mRNA expression (1.7±1.9 vs N: 1.1±0.8, 0.306) and serum IL-1ß (pg/ml) did not differ between the groups (H: 1.99±0.2 vs. N: 1.98±0.6, p&lt;0.135).

Conclusion
The NLRP3 inflammasome is not activated thus refuting the hypothesis that endotoxemia is a main driver for inflammation in H-HD.
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

Abstract

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 &lt; 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

Abstract

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&lt;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 (&gt; 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

Abstract

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&lt;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 &lt;1.2 group and 30,208 (14.4%) in nPCR≥1.2 group. Both all-cause and cardiovascular mortality were increased in nPCR &lt;1.2 group. In the nPCR &lt;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 &lt; 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 &lt; 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 &lt; 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

Abstract

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.