bluuebunny/crossref_metadata_2025 huggingface dataset:
MO537INTERACTION OF PLASMA HOMOCYSTIENE, RENAL FUNCTION AND CARDIO-METABOLIC RISK FACTORS- AN OBSERVATION IN A RURAL POPULATION OF BANGLADESH
Authors: Rahman Md Hafizur , Alam Kazi Shahnoor , Alam Babrul , Banerjee Sajal Krishna , Chaudhury S R , Arslan M I , Hassan M S , Chowdhury MAA , Iqbal Md M
Published: May 2021

Background and Aims

Elevated plasma total homocystiene (tHcy) levels are associated with atherosclerotic diseases in coronary, cerebral and peripheral blood vessels. It is possible that hyperhomocysteinemia may lead to intrarenal arteriosclerotic lesions and decline in GFR or impaired renal function. Aim of this study was to elucidate the association of plasma homocystiene level with renal function and cardiovascular risk factors in rural population.

Method

A well defined rural area was selected. Study subjects were identified by computer generated random numbers after entering household listings and then Kish table was used to choose a participant. Adult subjects (≥18 years) were only included. The approached participant was explained the purpose, if consented, then given an appointment to be present at a research hospital on a separate date for clinical and biochemical evaluation. A face to face interview was conducted. Clinical history, physical examination anthropometrics were recorded on data sheet. Fasting blood sample and morning spot urine was collected. Then serum tHcy was measured by chemiluminescent microparticle immunoassay (CMIA) technology. Study population were investigated with Spot urine ACR, Fasting glucose, serum lipid profile, creatinine, homocysteinine , Folic acid and Vit B12.

Results

Early results of 234 random subjects are presented here. The mean age was 41 ± 13(18-92) years with male 33% and female 67%. Mean eGFR was 99± 26 ml/min, tHcy 11.6 ± 5.9 μmol/l, Vit B12 329 ± 187 pg/ml and Folic Acid 5.57 ± 2.63 ng/ml. A tHcy cut-off value in study subjects ≥15 μmol/l was seen in 17 % and <15 μmol/l in 83%. Serum creatinine, Uric Acid, Cholesterol, LDL was significantly higher and Vit B12, Folic acid lower in tHcy ≥15 μmol/l group. Further grouping showed tHcy level was significantly higher in Vit B12<200 pg/ml and Folic acid <3ng/l group. Correlation studies showed homocystiene positively correlated with age, systolic blood pressure, creatinine, LDL and negatively with Folic acid and Vit B12.

Conclusion

Our findings suggest that elevated plasma homocystiene level might influence and are associated with altered markers of renal, cardiac and metabolic risk factors in rural population. Preventive approaches are required towards this issue as larger population segment belongs to rural areas.
MO487DYSNATRAEMIA AND ASSOCIATED MORTALITY RISK THRESHOLDS ARE MODIFIED BY KIDNEY FUNCTION IN THE IRISH HEALTH SYSTEM: THE NATIONAL KIDNEY DISEASE SURVEILLANCE SYSTEM (NKDSS)
Authors: Walsh Conor , Browne Leonard , Stack Austin
Published: May 2021

Background and Aims

Dysnatraemia is associated with increased mortality risk in the general population, but it is unclear to what extent kidney function influences this relationship. We investigated the impact of dysnatraemia on total and cardiovascular (CV) mortality while exploring the concurrent impact of chronic kidney disease.

Method

We utilised data from the Irish Kidney Disease Surveillance System (NKSS) to explore the association of serum sodium (Na+) (mmol/L) and mortality in a longitudinal cohort study. We identified all adult individuals (age > 18 years) who accessed health care from January 1st, 2007 and December 31st, 2013 in a regional health system with complete data on serum Na+, associated laboratory indicators and vital status up to 31st December 2013 (n = 32, 686). Patients receiving dialysis were excluded. The primary exposure was serum Na+ first recorded during the study period for each patient with a concurrent serum glucose measurement. Chronic kidney disease was defined as eGFR <60ml/min/1.73m² vs greater recorded at index date. The association of serum Na+ with all-cause (ACM) and CV mortality was explored in categories and as a continuous variable using polynomial splines. Multivariable Cox regression with competing risks determined hazard ratios (HR) and 95% confidence intervals with adjustment for baseline health indicators.

Results

There were 5,118 deaths (15.7%) over a median follow up of 5.5 years. In multivariable adjusted models, the association of serum Na+ with all-cause and CV mortality followed a non-linear, u-shaped pattern. For all-cause mortality, the optimal range for greatest survival was between 139-146 mmol/L [HR 1.02 (1.00-1.03) and HR 1.19 (1.02-1.38) respectively, while for CV mortality, the optimal range was much narrower at 134-143mmol/L [HR 1.16 (1.02-1.23) and HR 1.09 (1.01-1.89) respectively] (Figure 1). The impact of serum Na+ on mortality was modified by baseline kidney function (p value < 0.001 for interaction). In stratified analysis, the impact of serum Na+ on all-cause mortality was greatly attenuated among patients with GFR< 60 ml/min/m², than above. This pattern was replicated in analyses of CV mortality.

Conclusion

This study supports the view that hypernatraemia and hyponatraemia are better tolerated with poorer kidney function. The risk thresholds for mortality were much narrower for CV death than all-cause death suggesting that these thresholds be taken into account to inform decision making and therapeutic interventions.

Funding source

Health Research Board (HRB-SDAP-2019-036), Midwest Research and Education Foundation (MKid)
MO430MASS-SPECTROMETRIC IDENTIFICATION OF POST-TRANSLATIONAL GUANIDINYLATED PROTEINS IN THE CONTEXT OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Hermann Juliane , Raffetseder Ute , Lellig Michaela , Jankowski Joachim , Jankowski Vera
Published: May 2021

Background and Aims

With continuous identification of post-translational modified isoforms of proteins, it is becoming increasingly clear that post-translational modifications limit or modify the biological functions of native proteins are majorly involved in development of various chronic disease. This is mostly due to technically advanced molecular identification and quantification methods, mainly based on mass spectrometry. Mass spectrometry has become one of the most powerful tools for the identification of lipids.

Method

In this study, we used sophisticated high-resolution mass-spectrometric methods to analyze the soluble ligand of receptor Notch-3, namely the Y-box protein (YB)-1, in serum from systemic lupus erythematosus (SLE) patients. In addition, kidneys of lupus-prone (MRL.lpr) mice were analyzed by mass-spectrometric imaging techniques to identify the underlying pathomechanisms. Serum YB-1 was isolated by chromatographic methods, afterwards digested by trypsin and analyzed by matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). The kidneys were fixed in paraffin, then kidney sections were deparaffinized, tryptic digested and analyzed by mass-spectrometric imaging techniques. Mass-spectrometry of extracellular YB-1 in SLE patient serum revealed post-translational guanidinylation of two lysine’s within the highly conserved cold shock domain (CSD) of the YB-1 protein (YB-1-2G). Patients with increased disease activity and those with active renal involvement (lupus nephritis, LN) had a higher degree of dual-guanidinylation within the CSD. Of note, at least one of these modifications was present in all analyzed LN patients, whereas single-guanidinylated YB-1 was present in only one and double modification in none of the control individuals. Mass-spectrometric imaging analyses specifically localized YB-1-2G and increases Notch-3 expression in kidney sections from MRL.lpr mice.

Results

The data from this study clearly demonstrate the high potential of high-resolution mass spectrometric methods as well as mass spectrometric imaging techniques to identify pathomechanisms of diseases like SLE/LN.
MO433IDENTIFICATION AND VALIDATION OF PEPTIDIC FEATURES IN CKD PATIENTS AND UNRAVELLING OF A POTENTIAL INFLAMMATION INDUCER
Authors: Bagarolo Giulia Ilaria , Stricker Laura , Hemmers Christian , Vondenhoff Sonja , Jankowski Vera , Bruck Heike , Jankowski Joachim
Published: May 2021

Background and Aims

Chronic Kidney Disease (CKD) is causing serious cardiovascular diseases. Creatinine quantification and eGFR estimation are suboptimal approaches for the diagnosis of CKD, especially at early stages. Therefore, there is a strong need for identification of mediators for CKD diagnosis and prediction of disease progression. In this study we follow a cohort of renal healthy patients (controls) and CKD patients (cases) for two years, defining three time points (baseline, after 12 months and after 24 months), with the aim of identifying and characterizing mediators of disease which could be an indication for the development and progression of CKD and its outcome.

Method

By the employment of liquid chromatography-mass spectrometry (LC-MS) we analyzed the plasma samples from the patients and identified the mediators1 : lysine (K), an angio-associated migratory cell protein (AAMP) peptide and an amiloride-sensitive oxidase (AOC1) peptide, which were consistently and differentially expressed in cases and controls at all time points.

Correlation analyses between the mediators and clinical markers were performed using the software R-Studio (RStudio Team (2020). RStudio: Integrated Development for R. RStudio, PBC, Boston, MA URL http://www.rstudio.com/).

The AAMP peptide was subsequently tested in a fibroblasts cells culture to investigate whether it was an inflammation inducer, its action was investigated at four different concentrations (0.1nM, 1nM, 100nM, 1000nM). Cells were stimulated for 48h and relative expression of two inflammation markers (CCL2 and IL6) was measured through PCR.

Results

Correlation analyses revealed that the AAMP peptide showed from modest to strong relations with clinical markers such as creatinine, hemoglobin, blood urea nitrogen, homocysteine, fibrinogen and parathyroid hormone.

Results showed that the peptide after 48h of stimulation did not cause an increase in the expression of gene CCL2 at any concentration, but caused a strong increase of gene IL6 (interleukin-6), a cytokine promoting inflammation and B cells maturation.

Conclusion

In conclusion, angio-associated migratory cell peptide, might be involved in CKD by inducing inflammation and driving the development of cardiovascular consequences such as atherosclerosis.

Acknowledgments

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 764474.
MO597ESTIMATING INDIVIDUAL-LEVEL SODIUM INTAKE WITH REPEATED SPOT URINE SAMPLING
Authors: Ginos Gina , Vogt Liffert , Frings-Meuthen Petra , Heer Martina , Olde Engberink Rik
Published: May 2021

Background and Aims

In daily clinical practice, individual-level sodium (Na) intake is often estimated by measuring Na excretion in a single 24h urine collection, but long-term Na balance studies indicate that 7 consecutive 24h urine collections are needed. However, this approach is not feasible in clinical settings. In this study, we investigate whether the use of repeated spot urine sampling is an appropriate alternative for repeated 24h urine collections.

Method

We performed a post-hoc analysis of a metabolic ward study in 8 healthy male adults who consumed a 7-day diet with a fixed amount of Na (200 mmol/d). Urine was collected in four daily intervals: 7-13h, 13-19h, 19-23h and 23-7h. After reaching steady state, we estimated Na intake with 1 and 3 consecutive 24h urine collections and 3-day spot urine sampling, using the Kawasaki formula with measured 24h urine creatinine excretion.

Results: On

day 5, mean 24h Na excretion matched intake, indicating that steady state was achieved (Fig A). Mean and standard deviation of absolute differences between estimated and measured Na intake (ΔNa) for each method were: 18.8 ±14.6 mmol (3 x spot urine 7-13h), 32.3 ±18.7 mmol (3 x spot urine 13-19h), 74.6 ±30.0 mmol (3 x spot urine 19-23h), 28.2 ±19.8 mmol (3 x spot urine 23-7h), 29.8 ±23.9 mmol (1 x 24h urine) and 22.9 ±11.3 mmol (3 x 24h urine) (Fig B). With the exception of the 19-23h spot urine collection period, the accuracy of 3-day spot urine sampling did not significantly differ from accuracy of 1 and 3 consecutive 24h urine collections. When combining the pre-night and morning spot urine collections (19-7h), the accuracy of the estimation did not improve (ΔNa 28.7 ±19.6 mmol).

Conclusion

3-day spot urine sampling did not perform significantly different than 1 and 3 24h urine collections for estimation of individual-level Na intake. Adequately powered studies need to confirm whether repeated spot urine sampling is an accurate and low burden alternative to repeated 24h urine collections.
MO600DIFFERENCES IN BODY COMPOSITION, MUSCLE STRENGHT AND BIOCHEMICAL PARAMETERS IN CKD PATIENTS WITH AND WITHOUT PROTEIN ENERGY WASTING (PEW)
Authors: Barril Guillermina , Nogueira Ángel , Alvarez Graciela , Romasco Paula , Gil Yohana , Nuñez Almudena , Sanchez Glez Carmen , Tromborelli Natalia
Published: May 2021

Background and Aims

PEW sometimes produces irreversible alterations in nutritional status, and early diagnosis could mark the sindrome reversibility.

Aim.-To establish the prevalence of PEW in an advanced CKD unit in a sample of 325 patients with CKD and to establish the differences in nutritional parameters, body composition and muscle strength.

Method

The patients treated in Advanced CKD Unit (ACKD) nutritional status monitoring is performed every 3 months, will be assessed through a cross-sectional , with the frequency being able to increase if malnutrition is detected in the screening.

The ISRNM criteria are applied to diagnose PEW, and the patients are classified according to whether or not they have PEW and the differences in nutritional parameters are analyzed: albumin, transferrin, CRP, linphocytes, Hb, body composition with Akhern HD-01 monofrequency BIA and anthropometric measurements and muscular strength with dynamometer (baseline).

Results

We have evaluated 325 patients with CKD xage 70.88 ± 12.55 years, 66.8% 217pac are men with xCKD-EPI of 19.19 ± 9.28ml / min / 1.73m2 PEW prevalence 8.9% (29 patients) aged 74.06 ± 12.79 years, with no significant difference between sexes with and without PEW (18/215 men and 11/108 women). We found significant differences between the groups with PEW vs without PEW in protein intake (nPNA) 0.73 ± 0.21 vs 0.93 ± 0.26, p0.003, albumin 3.74 ± 0.66 vs 4.21 ± 0.41, CRP 1.20 ± 2.09 vs 0.68 ± 1.20, p0.05, Hb 11.33 ± 1.52 vs 11.90 ± 1.50, p0.023, transferrin 199.71 ± 48.38 vs224.95 ± 48.85, p0.013.

Data on anthropometric and body composition measures as showing in the table. The values of biochemical parameters and body composition in patients with PEW are striking, as some are close to the low limit of normality, which suggests the possible reversibility if action is taken on time.

Conclusion

The monitoring of nutritional status in a protocolized way provides low prevalences of PEW and allows its early detection, which favors its reversibility with the appropriate intervention.
MO602HIGH LEVELS OF ADVANCED OXIDATIVE PROTEIN PRODUCTS (AOPP) HELP TO PREDICT THE PROGRESSION OF ATHEROSCLEROSIS IN CHRONIC KIDNEY DISEASE WITH VITAMINE E TREATEMENT MIGHT STABILIZE AOPP LEVELS
Authors: Azouaou toualbi Leila , Adnane Mounir , Ballouti Wafa , Arab Medina , Abderrezak Khelfi , Toualbi Chahine , Chader Henni , Benoui Abdelghani , Seba Atmane
Published: May 2021

Background and Aims

Advanced Oxidation Protein Product (AOPP) are created during oxidative stress and are considered as markers of this phenomenon and of inflammation. Vitamin E (Vit-E) is a powerful antioxidant, whoever no consensus on its effectiveness on the level of AOPP or the process of atherosclerosis have been made. The aim of the present study was to determine AOPP levels in patients with chronic kidney disease (CKD) at different stages and their relationship with the progression of atherosclerosis in patients under Vit-E treatment.

Method

A longitudinal study has been conducted on 205 patients with CKD and 40 controls. the correlations between AOPP and glomerular filtration rate (GFR) and different biological markers were analyzed. Doppler of the supraoptic trunks was conducted to assess the correlation of AOPP with intima-media thickness. The effectiveness of Vit-E treatment on AOPP levels and atherosclerosis progression was also investigated.

Results

AOPP levels were significantly higher in CKD patients compared to the control group (P < 0.05) and increased with the alteration of renal functions. The mean value of AOPP increased concomitantly with intima-media thickness (P < 0.05). Furthermore, AOPP mean value was relatively higher in patients with atherosclerotic plaques (P < 0.05) compared to those without plaques. Vit-E treatment stabilized the levels of AOPP but had no effect of atherosclerotic progression.

Conclusion

AOPPs were proved to be effective markers of oxidative stress and their high levels help to predict the progression of the atherosclerosis process. As a powerful antioxidant, Vit-E stabilized the AOPP levels.
MO605INFLAMMATION-BASED MODIFIED GLASGOW PROGNOSTIC SCORE AND CHRONIC KIDNEY DISEASE PROGRESSION
Authors: Stefan Gabriel , Stancu Simona , Zugravu Adrian Dorin , Capusa Cristina-Stela
Published: May 2021

Background and Aims

The modified Glasgow prognostic score (mGPS), based on combination between albumin (sAlb) and C-reactive protein (CRP), has been derived from oncology and validated in multiple diseases. Since chronic kidney disease (CKD) progression is related to inflammation, we aimed to evaluate the relationship between the mGPS and CKD outcome.

Method

The present retrospective unicentric cohort study included 547 CKD patients (age 60.2 years, 53% male, eGFR 42.0 mL/min, mean change -2 mL/min/year) admitted between January 1, 2007 and December 31, 2012.

The mGPS assessment: zero points if CRP ≤10 mg/L and sAlb ≥3.5 g/dL; one point if CRP >10 mg/L and sAlb ≥3.5 g/dL, two points if CRP >10 mg/L and sAlb <3.5 g/dL.

Patients records were reviewed from the CKD diagnosis to one of the four outcomes: end-stage kidney disease (ESKD), death, loss to follow-up, or until July 31, 2017.

Results

The mGPS score was 0 for 420 (78%), 1 for 110 (19%), and 2 for 17 (3%) patients. Rapid progression defined as a sustained decline in eGFR of more than 5 mL/min/year was found in 17% of the studied patients. More patients with rapid CKD progression were found in the group with the highest mGPS (30% vs 17%, vs 16%, p=0.05).

In the multivariate analysis, mGPS was associated with the eGFR slope (OR 1.42 (95%CI 0.29, 2.55), p 0.01). Moreover, mGPS was negatively correlated with baseline eGFR (OR -3.74 (95%CI 7.8, 0.33), p 0.05) and positively with albuminuria (0.87 (95%CI 0.51, 1.23), p 0.001).

During the study period, 130 patients (24%) died and 109 (20%) reached ESKD. The mean kidney survival time was 8.1 (95%CI 7.9, 8.4) years. Kidney survivals at 12, 24, 36, 48, 60, and 72 months were 96, 95, 89, 86, 83 and 82%, respectively.

In univariate time-dependent analysis, patients with zero mGPS had better kidney survival than those with the score of one and two (99.9 (95%CI 96.9, 102.9) vs 92.1 (95%CI 85.2, 99.0) vs 78.1 (95%CI 60.4, 95.4) months, log rank p=0.02). However, the kidney survival differences were not present after adjusting for CKD progression risk factors (HR 1.12 (95%CI 0.78, 1.62), p 0.5).

Conclusion

The inflammation-based mGPS score was associated with eGFR decline in CKD patients. Therefore, could prove useful in improving risk stratification of CKD patients.
MO606FUNCTIONAL CAPACITY AND NUTRITION-INFLAMMATION BINOMIUM IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE (ACKD)
Authors: Nogueira Ángel , Alvarez Graciela , Barril Guillermina
Published: May 2021

Background and Aims

There are differents factors that will influence the functional capacity of ACKD patients, among them the nutritional condition.

Aim

to assess the functional capacity of ACKD patients with the Short Physical Performance test Battery (SPPB), and its relationship with the malnutrition-inflammation binomium.

Method

We have evaluated 216 ACKD patients, 66.2% (143) male. xage 70.85 ?12.01 years, being female older than male (72.58 ?13.19 vs 69.96 ?11.32, p = 0.129). We have determine plasma proteins indicators of nutritional status such as albumin, prealbumin and CRP as a marker of the status of inflammation. And we have applied malnutrition inflamation score (MIS).

Results

In the univariate analysis, we found an association between the functionality determined with the test and the age (RR95% 0.866 p = 0.000), sex (RR95% 0.387 p = 0.005). albumin (RR95% 2,222 p = 0.035), prealbumin (RR95% 1.065 p = 0.018), CRP (RR95% 0.733 p = 0.022) and the state nutritional value determined with the MIS scale (RR95% 0.791 p = 0.000). We donot any found any association with DM, transferrin and total lymphocytes. Albumin values were established as 3.8g / dl, and CRP at 1g / dl, obtaining 4 groups: (G1: alb> 3,7-PCR <1, G2: alb> 3,7-PCR> 1, G3: alb <3,7-PCR <1 and G4: alb <3,7-PCR> 1 ).

The table shows the results of the relationship between groups and the limitations determined with SPBB. Group 1 was the most numerous, also being the one with the best nutrition-inflammation profile, observing that in this group 68 patients (78.2%) presented minimal / no limitations.

Conclusions

1. The nutritional-inflammation status will influence the functional capacity of the patient with ERCA.

2. The SPPB test, in addition to being a good choice to evaluate the functional capacity of patients with ACKD, can provide guidance on the nutritional status of patients.

3. Maintaining a good nutritional status will also have a positive influence on the functional capacity of ACKD patients.
MO608INTUITIVE EATING CHANGES AFTER A BEHAVIORAL MULTI-SESSION GROUP INTERVENTION FOR DIETARY MANAGEMENT OF WOMEN WITH CKD
Authors: Antunes Pereira Raíssa , Alvarenga Marle , S. Andrade Laila , R. Teixeira Renata , C. Teixeira Paula , R. da Silva Wanderson , Cuppari Lilian
Published: May 2021

Background and Aims

Approaches promoting eating guided by internal cues, such as intuitive eating (IE), have emerged as an alternative to decrease the impact of external cues on eating behavior while simultaneously avoiding the risk for dysfunctional eating. IE helps to connect with internal cues (i.e. hunger and satiety) and feelings rather than relying on external strategies to regulate what, how much and when to eat. In obese women, IE-based approaches have shown to enhance motivation and adherence to lifestyle changes, hence improving metabolic and psychological parameters, quality of life and diet quality. However, studies evaluating IE in chronic kidney disease (CKD) patients are scarce. Thus, we aimed to evaluate the impact of a behavioral multi-session group intervention on IE scores of overweight non-dialysis-dependent (NDD) CKD women.

Method

This is a prospective non-controlled clinical trial of a behavioral multi-session group intervention for dietary management. It was conducted with overweight women with chronic kidney disease (CKD). Each group comprised 5-8 participants in fifteen weekly or biweekly sessions lasting about 90 minutes. Most of IE principles were discussed throughout the meetings. IE scale 2 (IES2) translated and adapted to Brazilian population and composed of 23 questions with 5-point Likert response scale ranging from 1=“strongly disagree” to 5=“strongly agree” and four-factor model (Unconditional Permission to Eat, Eating for Physical Rather than Emotional Reasons, Reliance on Hunger and Satiety Cues, and Body-Food Choice Congruence) was applied before and after the intervention. The higher the score, the higher the intuitive eating attitudes.

Results

Of the 33 patients that initiated the study, 23 patients [age=62.0 (58.0-68.0) years; schooling= 9.0 (7.0-12.0) years of study; BMI=32.6 (30.2-39.3); eGFR=28.0 (22.0-31.0) ml/min/1.73m²] completed the intervention. Figure 1 shows the results regarding IES2.

Conclusion

The intervention approaching IE principles was effective to improve IE attitudes in the studied patients. With exception for “body-food choice congruence”, all IE subscales improved after intervention. These results are promising and may contribute to a paradigm change in the strategies aiming to enhance motivation and adherence to dietary recommendations in CKD population.
MO592INTERLEUKIN-1A (IL-1A) IS A CENTRAL REGULATOR OF INFLAMMATION IN CARDIOVASCULAR AND KIDNEY DISEASES
Authors: Schunk Stefan , Sarah Triem , Kramann Rafael , Boor Peter , Ampofo Emmanuel , Fliser Danilo , Speer Thimoteus
Published: May 2021

Background and Aims

Cardiovascular diseases (CVD) and chronic kidney disease (CKD) are highly prevalent, aggravate each other, and account for substantial mortality. Both conditions are characterized by activation of the innate immune system. The alarmin IL-1α is expressed in a variety of cell types promoting (sterile) systemic inflammation. The aim of the present study is to examine the role of IL-1α in mediating inflammation in the setting of cardiorenal diseases.

Method

We assessed the expression of IL-1α on the surface of monocytes from patients with acute myocardial infarction (AMI) and patients with CKD and determined its association with atherosclerotic CVD events during follow-up in an explorative clinical study. Furthermore, we assessed the inflammatory effects of IL-1α in several organ injury models in Il1a -/- and Il1b -/- mice and investigated the underlying mechanisms in vitro in monocytes and endothelial cells.

Results

IL-1α is strongly expressed on the surface of monocytes from patients with AMI and CKD compared to healthy controls. Higher IL-1α surface expression on monocytes from patients with AMI was associated with a higher risk for atherosclerotic CVD events, which underlines the clinical relevance of IL-1α. In mice, IL-1α, but not IL-1β, mediates leukocyte-endothelial adhesion as determined by intravital microscopy. IL-1α promotes accumulation of macrophages and neutrophils in inflamed tissue in-vivo . Furthermore, IL-1α on monocytes stimulates their homing at sites of vascular injury. A variety of stimuli such as free fatty acids or oxalate crystals induce IL-1α surface expression and release by monocytes, which then mediates their adhesion to the endothelium via IL-1 receptor-1. Besides, IL-1α promotes expression of the vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells thereby fostering the adhesion of circulating leukocytes. IL-1α induces inflammatory injury after experimental AMI and abrogation of IL-1α prevents the development of CKD in oxalate or adenine-fed mice.

Conclusion

IL-1α represents a key mediator of leukocyte-endothelial adhesion and inflammation in cardiorenal diseases. Inhibition of IL-1α may serve as a novel anti-inflammatory treatment strategy.
MO596HYPERPHOSPHATEMIA INDUCES ENDOTHELIN-1 SYNTHESIS AND INFLAMMATION IN LUNG FIBROBLASTS
Authors: Asenjo-Bueno Ana , Alcalde-Estevez Elena , Olmos Gemma , Rodríguez-Puyol Diego , Ruiz-Torres Maria Piedad , López-Ongil Susana
Published: May 2021

Background and Aims

Hyperphosphatemia is an aging-related condition associated to chronic diseases such as chronic kidney disease (CKD). In both cases, aging and CKD, it has been described a decline lung function, however, relationship between high serum levels of phosphate and lung damage has not been described yet. The aim of this work was to evaluate if phosphate could induce inflammation in lung, studying the mechanisms implied.

Method

In vitro studies were performed on a cell line from human lung fibroblasts (Wi-38) which were treated with a phosphate donor termed β-glycerophosphate (BGP, 10 mM) and also with endothelin 1 (ET-1, 10 nM) at different times. To assess inflammation, the expression of several cytokines such as TNF-α,IL-1β, IL-6 and MCP-1 were measured by real time PCR. mRNA expressions of prepro-ET-1 and endothelin-converting enzyme-1 (ECE-1) were also analyzed by real time PCR. Reactive oxygen species (ROS) production was evaluated by confocal microscopy in live cells using the fluorogenic probe CellROX as oxidative stress reagent.

Results

Treatment with BGP induced a significant rise of the pro-inflammatory cytokines expression, TNF-α, IL-1β, IL-6 and MCP-1, on lung fibroblasts. Moreover, BGP was able to regulate ET-1 system, as we found a significant increase of mRNA expressions not only of prepro-ET-1 but also of ECE-1, reaching a peak around 2 and 6 hours, respectively. Later, it was checked whether ET-1 could induce inflammation itself in lung fibroblasts. Cells incubated with ET-1 show similar results as BGP, increasing expressions of all cytokines, TNF-α, IL-1β, IL-6 and MCP-1.ET-1 response was earlier than BGP, around at 2 hours with ET-1 instead of at 8 hours with BGP. In order to elucidate a possible mechanism, ROS production was assessed after BGP treatment. BGP induced ROS production at 15 min in lung fibroblasts.

Conclusion

BGP induces the synthesis of pro-inflammatory cytokines as well as the system of synthesis of ET-1, besides to rise ROS production.ET-1 itself also increases pro-inflammatory cytokines expression. ET-1 could contribute to the inflammation observed in lung fibroblast after BGP treatment. We propose oxidative stress as a potential mechanism implied, as it is well known that ROS can mediate in inflammation and in the ET system. However, more studies are necessary to confirm this role. All in all, these results relate hyperphosphatemia with a higher inflammation in lung fibroblasts which could decline lung function in chronic diseases associated to aging as CKD.
MO439NATURAL IMMUNISATION AGAINST ATHEROSCLEROSIS IN BEARS DURING HIBERNATION*
Authors: Stenvinkel Peter , Shamal Shailesh , Fröbert Ole , Frostegård Johan
Published: May 2021

Background and Aims

Brown bears (Ursus arctos) hibernate for 5-6 months during winter, but in spite of kidney insufficiency, dyslipidemia, insulin resistance and inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD). Antibodies against phosphorylcholine (anti-PC) are associated with protection in atherosclerosis, CVD and uremia. Potential underlying protective mechanisms include anti-inflammatory effects, inhibition of cell death, promotion of T regulatory cells, clearance of dead cells and inhibition of oxidized Low density lipoprotein (OxLDL)-uptake in macrophages in atherosclerotic plaques. PC is an important antigen on nematodes, parasites, some bacteria, dead and dying cells and OxLDL.

Method

Paired serum from 12 brown bears sampled during winter and summer were analyzed for metabolic parameters and for IgM, IgG, IgG1/2 and IgA anti-PC by enzyme linked immunosorbent assay (ELISA). Differences in antibody levels between winter and summer were determined by paired Student´s t test or Wilcoxon´s signed rank test (when not normally distributed).

Results

As expected, marked differences in metabolic parameters were found comparing median summer vs winter values; Cholesterol 5.9 vs 11.3 mmol/L; p<0.001, triglycerides 1.9 vs 3.7 mmol/L; p<0.001, glucose 5.4 vs 7.7 mmol/L; p<0.05, S-creatinine 76 vs 203 µmol/L; p<0.001, urea 12.1 vs 2.9 mmol/L; p<0.002. When determined as arbitrary units (AU; median set at 100 at summer), marked and significant differences were observed between summer and winter.

Conclusion

Anti-PC (strikingly so for IgA and IgG1) are significantly raised during hibernation as compared to levels during summer. We hypothesize that these changes contribute to the protection of arteries, but also kidneys and other organs, during the metabolic vulnerable hibernation period. Our observation may represent a natural immunization with microorganisms, preventing atherosclerosis during a period of severe kidney insufficiency and could have therapeutic implications for patients with chronic kidney disease.
MO452CHRONIC KIDNEY DISEASE TEN YEARS AFTER PEDIATRIC ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Bresters Dorine , Jol-van der Zijde Els , Dorresteijn Eiske , Louwerens Marloes , Jordans Carlijn , Lankester Arjan , Lugthart Gertjan , De Pagter Anne , Van Rooij-Kouwenhoven Roos , Sukhai Ram
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) is an important sequela of hematopoietic stem cell transplantation (HSCT), but data regarding CKD after pediatric HSCT are limited.

Method

In this single center cohort study, we evaluated eGFR dynamics, proteinuria and hypertension in the first decade after HSCT and assessed risk factors for chronic kidney disease in 216 pediatric long term HSCT survivors, transplanted between 2002 and 2012.

Results

The eGFR decreased from median 148 to 116 ml/min/1.73m2 between pre-HSCT and ten years after HSCT. CKD, defined as an eGFR <90 ml/min/1.73m2 and/or proteinuria (KDIGO stage ≥G2 or ≥A2) occurred in 21% of patients. In multivariate analysis, hematological malignancy as HSCT indication (HR 5.5, 95% CI 1.2-25) and cytomegalovirus reactivation (HR 2.4, 95% CI 1.1-5.4) were independent risk factors for CKD. One third of patients with CKD had both an eGFR <90 ml/min/1.73m2 as well as proteinuria, one third had isolated eGFR reduction and one third only had proteinuria. Hypertension was observed in 27% of patients with CKD compared to 4.4% of patients without CKD. Tubular proteinuria was present in 7% of the subgroup of patients (n=71) in which β2-microglobulinuria was measured.

Conclusion

In conclusion, a significant proportion of pediatric HSCT recipients developed chronic kidney disease within ten years after HSCT. Our data stress the importance of structural long term monitoring of eGFR, urine and blood pressure after HSCT to identify patients with beginning CKD who could benefit most from nephroprotective interventions.
MO456DOES PHOSPHORUS EXCRETION PER NEPHRON AFFECT THE PROGNOSIS OF CHRONIC KIDNEY DISEASE?
Authors: Fujii Takayuki , Koshizaka Junya , Yamauchi Nobuaki , Matsunaga Takahiro , Morimoto Mayu , Terasaki Noriko , Tanaka Hiroaki , Suzuki Satoshi
Published: May 2021

Background and Aims

Serum phosphorus is an important factor associated with mortality and cardiovascular disease in dialysis patients as well as in non-dialysis patients with chronic kidney disease (CKD) and healthy individuals. One observational study reported that elevated phosphorus is a risk factor for end-stage renal disease and is linked to reduced renal function, even within the normal range. Although the mechanism is unknown, an excessive load of phosphorus to the kidney is presumed to cause renal damage via phosphorus-containing nanoparticles. In this study, we examined the association between phosphorus excretion per nephron and the prognosis of CKD.

Method

A single-center, retrospective cohort study was conducted in 276 patients with CKD category G3 to G5 who were admitted to our hospital and received an inpatient educational program on CKD between June 2016 and November 2019 and who could be followed up for at least 1 year or started on dialysis within 1 year after hospitalization. Phosphorus excretion per nephron was defined as daily phosphorus excretion divided by creatinine clearance (Ccr), and its association with the annual rate of decline in estimated glomerular filtration rate (eGFR) was investigated for each CKD category. For statistical analysis, multiple regression analysis was performed using the following covariates: age, sex, presence/absence of diabetes mellitus, mean arterial blood pressure, amount of daily urine protein, serum phosphorus level, and use of a renin-angiotensin system inhibitor.

Results

There were 108 patients with CKD G3, 106 patients with CKD G4, and 62 patients with CKD G5. Daily phosphorus excretion was 442 mg in G3, 350 mg in G4, and 350 mg in G5 patients. Phosphorus excretion per nephron was 8.4 mg/Ccr in G3, 14.0 mg/Ccr in G4, and 24.2 mg/Ccr in G5 patients. It increased with the progression of renal damage. In G4 patients, phosphorus excretion per nephron was significantly negatively correlated with the rate of decline in eGFR (p = 0.004); however, no correlation was found between the two in G3 and G5 patients (p = 0.09 and p = 0.16, respectively). Multiple regression analysis showed that phosphorus excretion per nephron was not a significant worsening factor for renal function in G3, G4, and G5 patients (p = 0.09, p = 0.36, and p = 0.41, respectively). On the other hand, serum phosphorus level was a significant worsening factor for renal function in G3 and G5 patients (p = 0.03 and p = 0.01, respectively).

Conclusion

No association was found between phosphorus excretion per nephron and the rate of the subsequent decline in renal function.
MO457PREVALENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A CASE-CONTROL STUDY
Authors: Adrian Therese , Hornum Mads , Soerensen Ida Maria Hjelm , Freese Ballegaard Ellen Linnea , Bro Susanne , Kühl Joergen Tobias , Sigvardsen Per Ejlstrup , Fuchs Andreas , Kofoed Klaus F , Knop Filip K , Feldt-Rasmussen Bo
Published: May 2021

Background and Aims

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and is characterised by hepatic accumulation of lipids. NAFLD represents a wide spectrum ranging from mild steatosis over non-alcoholic steatohepatitis with and without fibrosis to overt cirrhosis. Patients with NAFLD have a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So far, there is scarce evidence of the prevalence of NAFLD among patients with CKD. The aim of this study was to investigate the prevalence of moderate to severe steatosis in a cohort with patients with different stages of CKD not on dialysis.

Method

A total of 291 patients from the Copenhagen Chronic Kidney Disease Study were included. For comparison, 866 participants with normal kidney function from the Copenhagen General Population Study were identified as controls. Blood samples, clinical demographics, information about smoking and alcohol were collected. Hepatic liver fat fraction was evaluated in all participants by computed tomography (CT). Liver attenuation density <48 Hounsfield Units was used as cut-off value for moderate to severe steatosis corresponding to 10% liver fat after transformation of the CT attenuation.

Results

The prevalence of moderate to severe steatosis was 7.9% and 10.7% among patients with CKD and controls, respectively. Data of the continuous Hounsfield Units showed lower values among patients with CKD compared with the control group. No significant association between liver fat fraction and CKD stage was found. Pooled data from both cohorts showed that adjusted odds ratios (OR) for steatosis were strongly significant among persons with diabetes (OR 3.1, 95% confidence interval (CI) 1.6-5.9), overweight (OR 14.8, 95% CI 4.6-47.9) and obesity (OR 42.0, 95% CI 12.9-136.6), respectively.

Conclusion

In the present cohort of 291 patients with CKD, kidney function was not associated with the prevalence of hepatic steatosis as assessed by CT scan.
MO458URINARY GROWTH DIFFERENTIATION FACTOR-15 (GDF15) LEVELS AS BIOMARKER OF ADVERSE OUTCOMES AND BIOPSY FINDINGS IN CHRONIC KIDNEY DISEASE
Authors: Perez Gomez Maria Vanessa , Gomá-Garcés Elena , Pizarro Sanchez Maria Soledad , Gracia-Iguacel Carolina , Cano Santiago , Cannata-Ortiz Pablo , Sánchez-Rodríguez Jinny , Sanz Ana , Sanchez-Nino Maria Dolores , Ortiz Alberto
Published: May 2021

Background and Aims

Growth differentiation factor-15 (GDF15) is a member of the TGF-β superfamily. Increased serum GDF15 has been associated with increased risk of CKD progression. However, no prior study had addressed the significance of urinary GDF15 in adult CKD.

Method

We have now assessed serum and urinary GDF15 in a prospective cohort of 84 patients who underwent kidney biopsy and then were followed for 29±17 months.

Results

There was a statistically significant correlation between serum and urine GDF15 values. However, while serum GDF15 values increased with decreasing glomerular filtration rate, urinary GDF15 did not. Immunohistochemistry located kidney GDF15 expression mainly to tubular cells and kidney GDF15 staining correlated with urinary GDF15 values. Urine GDF15 was significantly higher in patients with a histological diagnosis of diabetic nephropathy than in diabetic patients without diabetic nephropathy. This was not the case for serum GDF15. Both serum and urine GDF15 were associated with patient survival in multivariate models. However, when both urine and serum GDF15 were present in the model, lower urine GDF15 predicted patient survival [B coefficient (SEM) -0.395 (0.182) p 0.03], and higher urine GDF15 predicted a composite of mortality or renal replacement therapy [0.191 (0.06) p 0.002] while serum GDF15 was not predictive. Decision tree analysis yielded similar results. The AUC of the ROC for urine GDF15 as a predictor of mortality was 0.95 (95% CI 0.89-1.00, p <0.001).

Conclusion

In conclusion, urine GDF15 is associated with kidney histology patterns, mortality and need for renal replacement therapy in biopsied CKD patients.
MO459RENAL FUNCTION AMONG PATIENTS WITH NEW DIAGNOSIS OF ATRIAL FIBRILLATION - RESULTS FROM THE NATIONWIDE FINACAF- STUDY
Authors: Jyrkilä Heini , Kaartinen Kati , Martola Leena , Halminen Olli , Haukka Jari , Linna Miika , Mustonen Pirjo , Putaala Jukka , Itäinen-Strömberg Saga , Kinnunen Janne , Kouki Elis , Luojus Alex , Tiili Paula , Hartikainen Juha , Airaksinen K E Juhani , Lehto Mika
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) is a global public health problem with increasing number of patients due to obesity, hypertension, diabetes, and aging. CKD is an independent risk factor for atrial fibrillation (AF) and the incidence of AF in patients with CKD is two- to threefold higher compared to the general population. Relationship between CKD and AF is bidirectional, and the incidence of impaired renal function is higher in patients with AF. Both AF and CKD are associated with increased risk of stroke and systemic thromboembolism, and also bleeding. The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study among AF patients conducted as a retrospective register-based linkage study combining data from several Finnish health care registers. We aimed to characterize demographics and comorbities of AF patients included in FinACAF according to stages of renal function.

Method

FinACAF- study collects data from 411 000 patients covering all Finnish AF patients from 1 January 2004 to 31 December 2018. Using national unique personal identification number, individual patients’ data from ten nationwide population registries and six regional laboratory databases (∼282 000, 77% of the patients) are linked together. Inclusion criteria of this substudy were all patients who had new ICD-10 AF diagnosis (code I48) between January 2010 and December 2018 and measured estimated glomerular filtration rate (eGFR) within the proximity of AF the diagnosis.

Results

Of the whole study cohort, 128 538 were included in this substudy. The mean age at the time of AF diagnosis was 73 years (range 18 to 107 years) and 48.9 % of the patients were female. The age of AF patients increased (Figure 1) and eGFR decreased (Figure 2) in various stages of glomerular filtration at the cohort entry during 2010-2018 are shown in Figures 1 and 2. Prevalence of various comorbidities and the mean age at the baseline are shown in the Table. Most of the comorbidities were more common in patients with lower eGFR levels.

Conclusion

During 2010-2018 the mean age of new AF patients increased in Finland, and simultaneously the renal function decreased. Also, patients with impaired glomerular filtration rate had more often comorbidities increasing the risk of thromboembolism and bleeding. The findings emphasize appropriate control of these risks in AF patients, especially with reduced renal function.
MO461FGF19 IMPROVES GLUCOSE METABOLISM IN CKD MICE
Authors: Bres Emilie , Benoit Bérengère , Pinteur Claudie , Fouque Denis , Vidal Hubert , Koppe Laetitia
Published: May 2021

Background and Aims

Chronic kidney disease (CKD) is associated with high cardiovascular mortality rate, especially because of altered glucose metabolism and insulin resistance. Fibroblast growth factor 19 (FGF19), an intestinal postprandial hormone, has been shown to improve metabolic disturbances and insulin resistance. In CKD, postprandial secretion of FGF19 seems blunted in hemodialyzed patients but the role and regulation of FGF19 in this population is unknown. The aim of our study is to ascertain if FGF19 can improve glucose homeostasis in a mouse model of CKD induced by 5/6 subtotal nephrectomy.

Method

Four weeks post-surgery, CKD mice or sham mice were treated during 18 days with subcutaneous injections of placebo or human recombinant FGF19 (0.01mg/kg of body weight). The effect on metabolic disturbances was estimated in vivo by glucose tolerance test (GTT, 1g/kg/body weight).

Results

Fasted hyperglycemia was observed in CKD groups compared to sham mice (151.3 +/- 10.6mg/l and 170.7 +/- 10.9mg/L, p < 0.001 in sham and CKD mice, respectively) and FGF19 tended to improve fasting glycemia in CKD mice (158.9 +/- 18mg/L, p<0.09). The GTT area under the curve (AUC) was significantly decreased in CKD-FGF19 group compared to CKD placebo (P < 0.0001) and control groups (P = 0.0063). Urea blood level was significantly higher in CKD groups (9.6 +/- 1.4 mmol/L and 25.5 +/- 5.6 mmol/L in sham and CKD, respectively) and was not affected by FGF19 treatment (24.8 +/- 5.8 mmol/L, p = 0.91).

Conclusion

Our results show that FGF19 could contribute to improve glucose intolerance observed in CKD and suggest that this hormone could be a novel therapeutic target for reducing mortality associated with CKD. The comprehension of the molecular and cellular events through which FGF19 exerted its benefits needs however further studies.
MO469POSSIBLE MECHANISMS OF THE SARS-COV-2-INDUCED AKI PROGRESSION TO CKD: A FORWARD-LOOKING PERSPECTIVE
Authors: Masjedi Fatemeh , Roozbeh Jamshid , Karimi Zeinab
Published: May 2021

Background and Aims

Coronavirus disease 2019 (COVID 19) was identified in December 2020 and is still growing in most parts of the world. The wide range of affected organs is likely based on the shared expression of the main severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry-receptor angiotensin-converting enzyme 2 (ACE2). Therefore, broad distribution of ACE2 receptors in various tissues play a key role in the multi-organ dysfunction and death due to COVID-19.

Method

International databases including PubMed, Embase, Web of Science, Scopus, and Cochrane Library Databases were used for search of articles by 30 December 2020. Keywords were nephropathy, COVID-19, coronavirus, renal injury, acute kidney injury, chronic kidney injury, and SARS-CoV-2 or a combination of them in the titles/abstracts.

After the collection of related studies, Mendeley software was used to categorize and eliminate the duplicate titles. Then, studies with inappropriate purposes were removed. The selected studies were done on humans and published in English.

Results

Due to high prevalence of acute kidney injury (AKI) in patients with COVID-19, we summarize the molecular insights into viral infection mechanisms and implications for AKI. Moreover, mechanisms of the AKI to chronic kidney disease (CKD) transition such as relative contribution of immune cell response, fibroblasts activation, endothelial dysfunction and subsequent hypoxia may contribute to association of AKI with worse outcomes during this virus pandemic.

Conclusion

We highlight the state of the knowledge on SARS-CoV-2-dependent mechanisms for AKI and list the potential management options for prevention of AKI worsening and the imminent possibility of CKD. Finally, we aim to provide a better understanding of why Coronavirus induce AKI and, subsequently, progression to CKD in the coming years and further discuss the acute as well as long-term renal consequences.

MO469   Figure: Potential interrelationship between endothelial dysfunction, tubular epithelial injury, interstitial inflammation, and fibrosis are likely to create a vicious cycle that can lead to the progression of acute kidney injury to chronic kidney disease (AKI to CKD) during COVID-19.