bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO410: Early Endothelial Glycocalyx Injury Damage Associated With Further Kidney Dysfunction in Hiv Patients: Five Years Follow-Up
Authors: Gadelha Cavalcante Malena , Cavalcante Meneses Gdayllon , Bezerra Geraldo , Maria Costa Martins Alice , Gondim Lima Oliveira Manuela , Gabriel Monteiro Santos Sérgio , Alaíde Andrade Do Vale Vanessa , De Francesco Daher Elizabeth 
Published: May 2022

Abstract

BACKGROUND AND AIMS
HIV patients have an increased risk of chronic kidney disease (CKD) development. Endothelial dysfunction was previously associated with kidney dysfunction markers. This study aims to investigate the association between renal markers and renal dysfunction biomarkers among outpatient HIV patients.

METHOD
Cohort study carried out with HIV patients in chronic use of Antiretroviral therapy followed up at a public outpatient service located in northeastern Brazil. Clinical and laboratory parameters of HIV patients were evaluated annually between 5 years: 2015 and 2019. Kidney dysfunction markers were blood creatinine and estimated glomerular filtration rate (GFR). Urinary kidney biomarkers NGAL, MCP-1, KIM-1 and serum endothelial biomarkers Syndecan-1 (glycocalyx), ICAM-1 and E-selectin were quantified in first-year using ELISA assays.

RESULTS
In total 66 patients completed the follow-up. Most patients were male (77.3%), of mixed race/color (57.6%), aged 39.33 ± 9.04 years. No patient had CKD development. However, Syndecan-1 showed a significant correlation with maximum creatinine (P &lt; 0.001) and minimum GFR (P 0.003) over the years. Moreover, both creatinine and GFR in the last year had a significant association with syndecan-1 levels quantified 4 years ago. Multivariate linear regression with confounders showed a significant and independent association of syndecan-1 levels, current age and CD4 + count with minimum GFR.

CONCLUSION
HIV patients in chronic use of Antiretroviral therapy and glycocalyx injury may have an increased risk for long-term impacts on renal tissue. These data reinforce that endothelial impacts evaluation using biomarkers is a way to optimize the diagnosis and prognosis of kidney diseases, promoting the prevention of complications.
MO414: Sucroferric Oxyhydroxide (Velphoro®) Treatment Mitigates the Signs of Ageing-Related Sarcopaenia in Old Mice
Authors: Alcalde-Estévez Elena , Asenjo-Bueno Ana , Sosa Patricia , Plaza Patricia , Rodríguez-Puyol Diego , Olmos Gemma , López-Ongil Susana , Piedad Ruiz-Torres Maria 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Sarcopaenia, defined as the loss of muscle mass and function, is an ageing-related pathology associated with some important diseases such as chronic kidney disease (CKD). Hyperphosphatemia has been associated with both, ageing and CKD. Old mice show an increase in serum phosphate concentration and a reduction in muscle mass, forelimb strength, gait speed and transition time in the static bar, with respect to young mice. Previous results of our group showed the beneficial effects of a low phosphate diet on ageing-related sarcopaenia. Given that the implementation of dietary phosphate restriction entails difficulties in the elderly, the aim of this work was to analyse the beneficial effects of a diet supplemented with a phosphate binder on the signs of sarcopaenia.

METHOD
C57BL6 male mice were used for in vivo studies: 5-month-old (young) and 24-month-old (old), which were fed with a powder standard diet (containing 0.6% of phosphate). Some old mice were fed with a hypophosphatemic diet (containing 0.2% of phosphate) or with a diet supplemented with 5% sucroferric oxyhydroxide (Velphoro®) for the last 3 months before sacrifice. Serum phosphate levels were analysed with a commercial kit. Muscle mass was estimated by measuring the gastrocnemius muscle mass divided by total body mass, muscle force was measured by a grip test and physical performance was evaluated by a gait test and the static bar test.

RESULTS
Velphoro® treated old mice showed a significant and more effective reduction in phosphate serum levels than old mice fed with the hypophosphatemic diet. No differences were observed in the relative gastrocnemius muscle mass between the three old mice experimental groups. By contrast, old mice fed with the standard diet supplemented with Velphoro® displayed an increased muscular strength and physical performance, improving the gait speed and reducing the transition time in the static bar, compared with old mice fed with the standard diet. Results obtained with Velphoro® treatment were similar to those observed in old mice fed with the hyphophosphatemic diet, but Velphoro® treatment achieve better results in motor coordination in the static bar test.

CONCLUSION
Dietary restriction of phosphate is a useful approach to mitigate the signs of ageing-related sarcopaenia (muscle strength and physical performance) in old mice. The use of Velphoro®, as a phosphate binder, exhibits similar or even better results than the hypophosphatemic diet. Therefore, the administration of Velphoro® could attenuate the signs of sarcopaenia in the elderly or in ageing-related diseases in which sarcopaenia is common, like CKD.
MO415: Kidney Expression of Canonical WNT Inhibitors and Β-Catenin in Experimental Models of Arterial Hypertension and Nephrectomy Induced CKD
Authors: Bogdanova Evdokia , Beresneva Olga 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The canonical Wnt (cWnt) is known to be involved in tubular recovery after kidney injury and fibrosis, while arterial hypertension (AH) promotes cWnt activity. The aim of the study was to investigate the kidney expression of β-catenin and cWnt inhibitors in AH and chronic kidney disease (CKD) models.

METHOD
AH-CKD was performed by 3/4 nephrectomy (NE) in spontaneously hypertensive rats (SHR) with 2 or 6 months of experimental exposure (Table). Sham-operated (SO) SHRs and Wistar Kyoto rats (WKY) served as controls, and 6 mo exposure SO-SHRs were used as AH-induced CKD. Serum creatinine (Cr), renal sclerostin (Sost) and dickkopf-1 (Dkk1) gene expression were measured. The following parameters of kidney morphology were analyzed and calculated quantitatively: the areas of tubular dystrophy (TD) (PAS), renal fibrosis (RF) (Masson's trichrome), β-catenin (BC), sclerostin (SOST) and dickkopf-1 (DKK1) IHC-staining.

RESULTS
The experimental models were corresponded to early (SO6, NE2) and mild (NE6) CKD (Table). In all groups, BC membrane IHC staining in epithelial cells and nuclear expression in podocytes were determined, SOST and DKK1 cytoplasmic IHC staining in tubular epithelium were detected (Figure). The tubular and interstitial lesions in NE (Table) were accompanied by cytoplasmic BC localization in epithelial and interstitial cells (Figure) with a decrease in dickkopf-1 gene (Table) and protein (Figure) expression, increase in Sost gene expression and SOST IHC staining of tubular intracellular vesicles (Figure). Long-term exposure to hypertension (SO6) resulted in the renal function decline and RF comparable to NE2 (Table), while TD and levels of Wnt inhibitors and BC IHC staining area did not differ significantly vs SO2, WKY (Table). In the pooled analysis, the RF directly correlated with the BC renal expression (r = 0.76, P = 0.005) and negatively with Dkk1 expression (r = −0.45, P = 0.028); the TD negatively correlated with Sost expression (r = −0.80, P = 0.002).

CONCLUSION
Tubular and interstitial damage in NE and AH-induced CKD is associated with BC up-regulation. The decrease in dickkopf1 and BC cytoplasmic accumulation may be required for renal fibrosis. The sclerostin expression is likely to be essential for the pathogenesis of TD.
MO421: Chronic Kidney Disease is Associated With Cardiac Downregulation of Vascular Endothelial Growth Factor a (VEGFA) and Development of Diastolic Dysfunction: Epigenetics and Micrornas
Authors: Chade Alejandro , Eirin Alfonso 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Patients with chronic kidney disease (CKD) have a higher risk to develop heart failure with preserved ejection fraction (HFpEF). We showed in a swine model of CKD with diastolic dysfunction and cardiac remodelling that these cardiac features are associated with blunted cardiac mRNA and protein expression of vascular endothelial growth factor (VEGF), a pro-angiogenic cytokine that plays important roles in cardiac vascular development, morphogenesis and contractility. Hence, we aim to identify potential underlying mechanisms of cardiac VEGF downregulation in CKD.

METHOD
CKD and normal pigs (n = 3 each) were studied for 14 weeks. Cardiac morphology and function (echocardiography) were quantified in vivo and microvascular density (3D micro-CT) ex vivo. Then, cardiac micro-RNA (miRNA) and 5-hydroxymethylcytosine (5-hmC) profiles of VEGFA gene were examined by hydroxymethylated DNA immunoprecipitation and miRNA sequencing (hMeDIP-seq and miRNA-seq, respectively) and validated by qPCR and Western blotting.

RESULTS
Blunted renal function in CKD pigs associated with left ventricular (LV) hypertrophy, and abnormal LV strain and diastolic dysfunction with pEF (Figure 1A) and reduced subendocardial microvascular density (Figure 1B) compared to normal. miRNA-seq showed that mir-183 was the only miRNA capable of targeting VEGFA and upregulated in CKD hearts (Figure 1C), accompanied by downregulation of VEGFA gene and VEGF protein (Figure 1D), whereas hMeDIP-seq revealed reduced VEGFA 5hmC levels in the hearts of CKD versus normal pigs (Figure 1E).

CONCLUSION
Our study suggests that miRNA-modulation and cardiac epigenetic changes in VEGF might contribute to cardiac damage and the development of HF in CKD. These observations may assist in developing novel therapies, like miRNA antagonists or epigenetic modulators, to preserve VEGF signalling and protect the heart in patients with CKD.
MO427: Protein Arginine Methyltransferase 1 Increases The Expression of P63 and Promotes Renal Interstitial Fibrosis
Authors: Ye Chaoyang , Lin Junyan , Wu Ming , Chen Dongping 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Mammalian Protein Arginine Methyltransferase 1 (PRMT1) catalyzes the monomethylation and dimethylation of the Arginine residues of proteins. It has been shown that PRMT1 inhibitor attenuates renal fibrosis, however, the role of PRMT1 in renal interstitial fibrosis is not fully understood. Using kidney-specific PRMT1 knockout mice, we aimed to study the role of PRMT1 in renal fibrosis and explored its underlining mechanisms.

METHOD
Sham or unilateral ureteral obstruction (UUO) operation was performed in PRMT1 Ksp-cre knockout mice, which were sacrificed on day 14. The effect of PRMT 1 on renal interstitial fibrosis was further studied using PRMT1 specific inhibitor AMI-1 in WT UUO mice. RNA-seq analysis was performed to analyze differential expressed genes in WT versus PRMT 1 knockout UUO kidneys. Moreover, TGF-β stimulated HK2 renal epithelial cells were treated with various concentrations of AMI-1(2μM to 10μM). Protein samples from in vivo and in vitro experiments were collected to assess renal fibrosis.

RESULTS
Strong interstitial fibrosis was observed in Ksp-Cre- (WT) UUO mice as shown by Masson staining, and kidney-specific deletion of PRMT 1 gene attenuated interstitial fibrosis in mouse kidneys. The expression of collagen-I in mouse kidneys was analyzed by Western blotting. UUO operation increased the expression of collagen-I in WT mouse kidneys, which were reduced by kidney-specific deletion of PRMT 1 gene. Inhibition of AMI-1 on renal interstitial fibrosis in UUO kidneys was confirmed by Masson staining and Western blotting analysis of pro-fibrotic markers. Mechanistically, using RNA-seq analysis, we found P63 was down-regulated in PRMT 1 knockout UUO kidneys. We further confirmed the down-regulation of P63 by qPCR and Western blotting analysis in PRMT1 knockout UUO kidneys and AMI-1 treated UUO kidneys. Moreover, we showed that AMI-1 dose-dependently inhibited the expression of P63 in TGF-β stimulated HK2 renal epithelial cells, which was correlated with down-regulation of pro-fibrotic markers.

CONCLUSION
PRMT1 promotes renal interstitial fibrosis probably through increasing the expression of P63.
MO435: The Prognostic Implication of 24-h Urine Urea Excretion With Renal Progression: Analysis of KNOW-CKD Study
Authors: Cheol Jeong Jong , Oh Kook-Hwan , Chae Dong-Wan 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Urea excretion is the basic function of the nephron. However, its prognostic implication has been not extensively studied in a specific subpopulation of chronic kidney diseases (CKD).

METHOD
Total of 2232 patients in KNOW-CKD cohort were analyzed. Baseline characteristics were used as a prognosticator in the Cox regression model. For categorical comparison, tertiles of 24-h urea excretion were used as high, low and moderate excretion of urea. Linear modelling and nonlinear modelling based on restricted cubic splines were used to study the impact of 24-h urea excretion on renal survival.

RESULTS
Mean daily urea excretion was 8.2 ± 3.6 g/day. Mean daily urea excretion was 12.1 ± 3.1 g/day versus 4.8 ± 1.3 g/day in the high urea excretion group (HUG) and low urea excretion group (LUG) (P &lt; 0.001). Mean eGFR of LUG was 47.0 ± 30.9 mL/min/1.73m2 and mean eGFR of HUG was 60.6 ± 29.9 mL/min/1.73m2 (P &lt; 0.001). Serum albumin level was higher in HUG with 4.3 ± 0.4 g/dL versus 4.1 ± 0.5 g/dL of LUG (P &lt; 0.001). Compared with HUG, LUG showed a hazard ratio of end-stage renal disease (ESRD) with 1.407 [95% confidence interval (CI) 1.115–1.774, P = 0.004] in the linear multiple regression model, which was adjusted by eGFR, age, gender, body mass index, type of CKD, proteinuria amount, systolic blood pressure, hemoglobin, blood urea nitrogen, serum albumin, serum cholesterol, serum uric acid, hsCRP, statin usage, renin-angiotensin-aldosterone system blocker usage. In the non-linear modeling, daily urea excretion showed a two-step change in log hazard ratio to ESRD. Threshold points of log hazard ratio among the whole study population were observed at 5 g/day and 15 g/day, respectively. The reduction of log hazard ratio in the HUG was more clear in the eGFR 30–60 mL/min/1.73m2 subpopulation (Figure 1C). Similarly, a reduction in log hazard ratio in the HUG was observed in glomerulonephritis, polycystic kidney disease subpopulations, but not in the diabetes mellitus nephropathy subpopulation (Figure 1D–F).

CONCLUSION
Daily urea urine excretion showed prognostic implications in the CKD stage 3 subgroups, glomerulonephritis subgroups and polycystic kidney disease subgroups. In the following researches, studies focusing on interventional targets in the context of daily urea excretion in those subgroups should be warranted.
MO440: Intramyocardial Artery Fibrosis and Media Hypertrophy are Associated With Beta-Catenin and Calcineurin Expression in the Model of Arterial Hypertension and CKD
Authors: Bogdanova Evdokia , Beresneva Olga , Ivanova Galina , Dobronravov Vladimir 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Intramyocardial arteries (IA) are one of the components of pathological cardiac remodeling. We have previously shown that cardiomyocytes hypertrophy and interstitial fibrosis are accompanied by calcineurin (CaN) and β-catenin (βCat) up-regulation in the model of arterial hypertension (AH) and chronic kidney disease (AH-CKD). In this pilot study, we investigated whether IA remodeling is associated with CaN and βCat expressions in medial (MC) and adventitial (AC) cells in AH-CKD.

METHOD
AH-CKD was induced by 5/6 nephrectomy (5/6NE) in spontaneously hypertensive rats (SHR-NE, n = 8). Sham-operated (SO) SHR (SHR-SO, n = 8) and Wistar Kyoto rats (WKY-SO, n = 8) were controls. Systolic blood pressure (SBP), myocardial mass index (MMI), serum creatinine (Cr), FGF23, renal Klotho (rKl), IA wall thickness (WT), perivascular fibrosis (PF), number of AC, βCat-positive AC (βCat + AC) to all AC ratio, CaN and βCat expression in MC were analyzed for 2 months after 5/6NE or SO.

RESULTS
The cardiac remodeling indexes—SBP, MMI, WT, AC, PF, as well as FGF23, were higher and rKl was lower in SHRs vs WKY-SO and in SHR-NE versus SHR-SO (Table). The increase in WT was accompanied by MC hypertrophy (Figure 1) with cytoplasmic CaN expression (data not shown) and PF with the increase in the number of AC in SHR-SO vs WKY-SO (Table). PF, medial hypertrophy and fibrosis of IA were accompanied by the apparent expression of CaN and βCat in the MC (Figure 1), an increase in the total number of AC and the βCat + AC accumulation in AH-CKD (Table, Figure 2).

CONCLUSION
IA remodeling in the setting of AH and CKD seems to be associated with СаN and βCat up-regulation in medial and adventitial cells subpopulations. Further study is needed to identify the origin of CaN/βCat expressing cells and the mechanisms of their involvement in the pathology of vascular wall alterations.
MO450: A New Hematuria Score, Semi-Quantitative Analysis of Hematuria Normalized for Urine Concentration Predicts the Progression of Chronic Kidney Disease: From the KNOW-CKD Study
Authors: Koh Jaehee , Min Jo Sang , Kim Sangeun , Hoon Jung Sung , Lee Kyu-Beck , Kim Hyang , Oh Kook-Hwan , Youl Hyun Young 
Published: May 2022

Abstract

BACKGROUND AND AIMS
It is unclear whether hematuria is a risk factor for chronic kidney disease (CKD) progression. In addition, quantitative evaluation considering urine concentration as in proteinuria has not been established in hematuria. The aim of this study is to verify the relationship between semi-quantitative analysis of hematuria normalized for urine concentration and the progression in CKD.

METHOD
We analyzed 1909 patients with pre-dialysis CKD from KNOW-CKD cohort who assessed baseline urine microscopy. Patients were scored according to the number of red blood cells (RBC) in high power field (1 point for &lt; 1, 2 points for 1–4, 3 points for 5̵119 and 4 points for ≥ 20). To obtain the hematuria score, these points were divided by the random urine creatinine level and multiplied by 100. The study endpoint was CKD progression, defined as a composite of a ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from baseline values or end-stage kidney disease.

RESULTS
The hematuria score ranged from 1.86 to 20.3 (2.2 ± 1.86). During a median follow-up of 4.6 years (9657 person-years), 729 patients reached study endpoint. There was a graded association between hematuria score and the risk of progression of CKD. The hazard ratios (95% confidence intervals) for second, third and fourth quartile of hematuria score were 1.32 (1.04–1.67), 1.43 (1.12–1.82) and 1.50 (1.17–1.91), respectively, compared to the first quartile. For each 1 point increase in hematuria score, the risk of progression increased by 5%.

CONCLUSION
This study showed that there was a graded relationship between a new hematuria score and the risk of the progression of CKD. Microscopic hematuria is a risk factor for CKD progression and might be used as a quantitative risk assessment tool.
MO453: Post-Translational Guanidinylation of Apolipoprotein C3 (APOC3) is Associated With Kidney and Vascular Injury
Authors: Schunk Stefan , Jankowski Joachim , Fliser Danilo , Speer Thimoteus , Jankowski Vera 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Cardiovascular diseases (CVD) and chronic kidney diseases (CKD) are highly prevalent in Western populations and account for a substantial proportion of mortality. We recently found that apolipoprotein C-3 (ApoC3), a constituent of triglyceride-rich lipoproteins, induces alternative NLRP3 inflammasome activation leading to sterile inflammation. In the present study, we aimed to assess post-translational modifications (PTMs) of ApoC3 in patients with CKD, to determine the effects of post-translationally modified ApoC3 in vitro and in vivo, and to test the relevance in a prospective clinical trial.

METHOD
Using mass-spectrometry, we screened ApoC3 for PTMs We determined the effects of modified ApoC3 on monocyte inflammatory response in vitro and assessed its effects in humanized mice subjected to a vascular injury model and unilateral ureter ligation. Finally, we assessed the association of post-translationally modified ApoC3 and cardiovascular and renal events in a prospective clinical trial of 543 CKD patients.

RESULTS
We identified post-translational guanidinylation of ApoC3 (gApoC3) in patients with CKD, which augments the proinflammatory effects of ApoC3. Mechanistically, guanidine and urea induced guanidinylation of ApoC3. gApoC3 accumulates in kidneys and plasma of mice subjected to a CKD model as determined by 2D-proteomic analyses. In humanized mice, gApoC3 promotes kidney fibrosis and impedes vascular regeneration. In the clinical trial, higher gApoC3 blood levels as determined by mass spectrometry were associated with increased mortality as well as cardiovascular and renal events.

CONCLUSION
Guanidinylation of ApoC3 represents a novel pathogenic mechanism in CKD and CKD-associated vascular injury, rendering gApoC3 a potential therapeutic target.
MO456: Renal and Major Clinical Outcomes After Nephrectomy in Patients With Pre-Existing Chronic Kidney Disease (ON-CKD Study)
Authors: Schleef Maxime , Roy Pascal , Paparel Philippe , Colombel Marc , Badet Lionel , Guebre-Egziabher Fitsum 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Partial nephrectomy (PN) has progressively replaced radical nephrectomy (RN) whenever feasible for renal tumors. However, its effects on renal outcomes are less known in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We aimed to assess renal and major clinical outcomes after PN or RN in patients with moderate to severe CKD or SK.

METHOD
We included all surgical procedures conducted between 2013 and 2018 in the Hospices Civils de Lyon, in patients with last pre-operative estimated glomerular filtration rate (eGFR) &lt;60mL/min/1.73m², or with SK. Exclusion criteria were eGFR &lt; 15mL/min/1.73m² or dialysis, RN on SK, ablative therapy. Demographic, tumors and surgeries characteristics were collected, as well as eGFR 1 month and 1 year after surgery. Main outcome was a composite criterion including CKD progression or major cardio-vascular events or death, assessed 1 year after surgery. Predictors of the main outcome were determined using multivariate analyses.

RESULTS
We included 173 procedures (67 RN and 79 PN on CKD patients, 27 PN on SK patients). Patients undergoing RN were older, had bigger tumors and higher T stages on TNM classification. Preoperative estimated glomerular filtration rate (eGFR) and CKD stages were not different between the groups. One year after surgery, PN was associated with less occurrence of the main composite outcome compared to RN (42.9% versus 70.7%, P &lt; 0.01). On multivariate analysis, independent risk factors for the main outcome were postoperative AKI (no AKI as reference; AKI stage 1 odds ratio (OR) = 8.68, 95% confidence interval (CI) 3.23–23.33; AKI stage 2 OR = 23.50, 95% CI 2.33–236.51; AKI stage 3 OR = 28.87, 95% CI 4.77–167.61) and bigger tumor size (OR = 1.21/cm, 95% CI 1.02–1.45), while preoperative eGFR was not (Table 1). Compared to pre-operative values, eGFR significantly decreased both after RN or PN 1 month after surgery (eGFR loss -12mL/min 1.73m² after RN P &lt; 0.001, −3mL/min/1.73m² after PN, P &lt; 0.05) and this decrease remained stable 1 year after surgery (eGFR loss -11mL/min/1.73m² after RN, P &lt; 0.001, −3mL/min/1.73m² after PN, P &lt; 0.05), but renal function was better preserved after PN than after RN at 1 month (P &lt; 0.05) or 1 year (P &lt; 0.01) (Figure 1).

CONCLUSION
In moderate to severe CKD patients, PN was associated with less risk of CKD progression or major cardio-vascular event or death 1 year after surgery, compared to RN. Postoperative AKI was the major determinant of clinical and renal outcomes.