bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO416PREDICTORS OF CONTRAST-INDUCED NEPHROPATHY AND THE APPLICABILITY OF THE MEHRAN RISK SCORE IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY
Authors: Chaabouni Emna , Jbali Hela , Mariem Najjar , Khadija Mzoughi , Mohamed karim Zouaghi 
Published: May 2021

Abstract

Background and Aims
Contrast-induced nephropathy (CIN) after coronary angiography (CAG) is associated with poor outcomes. The purpose of our study was to identify predictors of CIN in patients undergoing CAG and to evaluate the applicability of the Mehran Risk Score (MRS) in the prediction of CIN in our population.

Method
We prospectively enrolled 158 patients who underwent coronary angiography with or without percutaneous coronary intervention from December 2017 to February 2018 at a cardiology department .
CIN was defined as an increase in serum creatinine level &gt;25% or 0.5 mg/dL after 48 hours postcardiac catheterization.
The patients who developed CIN were then analysed for the presence of specific risk factors. The patients were categorized into the 4 risk groups based on the MRS.

Results
The incidence of CIN was 9,5%. On multivariate analysis, the presence of anemia (p = 0.043), toxic contrast dose (as defined by ratio volume of contrast media to estimated glomerular filtration rate (V/eGFR) &gt; 2) (p = 0.02) and chronic renal failure (p = 0.026) were independently found to confer a significant risk of CIN. In patients belonging to the high Mehran risk group (MRS10- 15) the risk of CIN was 3,7 fold (OR: 3.7, 95% CI: 0,88–15,6, p = 0.036) higher when compared to intermediate and low risk patients (MRS &lt;10).

Conclusion
Mehran risk score is as a good score for predicting CIN in patients who underwent coronary angiography. According to this, we support its use in order to identify the ones at risk, and to optimize CIN prophylactic therapy prior to and after catheterization.
MO417NEPHROLOGIST INTERVENTION TO AVOID KIDNEY REPLACEMENT THERAPY IN ACUTE KIDNEY INJURY
Authors: Chávez Jonathan , Maggiani-Aguilera Pablo , De la Torre-Quiroga Andres , Martínez-Gallardo Gonzalez Alejandro , Medina-González Ramón , Luna-Ramos Andrea , Alcantar-Vallin Luz , García-García Guillermo 
Published: May 2021

Abstract

Background and Aims
Based on the pathophysiology of acute kidney injury (AKI) it is plausible that certain early interventions by the nephrologist could influence its trajectory. In this study, we investigated the impact of 5 early nephrology interventions on starting kidney replacement therapy (KRT), AKI progression and death.

Method
In a prospective cohort at Hospital Civil of Guadalajara, we followed-up for 10 days AKI patients in whom a nephrology consultation was requested. We analyzed 5 early interventions of the nephrology team (fluid adjustment, nephrotoxic withdrawal, antibiotic dose adjustment, nutritional adjustment and removal of hyperchloremic solutions) after propensity score and multivariate analysis for the risk of starting KRT (primary objective), AKI progression to stage 3 and death (secondary objectives).

Results
From 2017 to 2020 we analyzed 288 AKI patients. The mean age was 55.3 years, 60.7% were male, AKI KDIGO stage 3 was present in 50.5% of them, sepsis was the main etiology 50.3%, and 72 (25%) patients started KRT. The overall survival was 84.4%. Fluid adjustment was the only intervention associated with a decreased risk for starting KRT (OR 0.58, 95% CI 0.48-0.70, p = &lt;0.001) and AKI progression to stage 3 (OR 0.59, 95% CI 0.49-0.71, p = &lt;0.001). Receiving vasopressors and KRT were associated with mortality, but neither of these interventions reduced these risks.

Conclusion
In this prospective cohort study of AKI patients, we found for the first time that early nephrologist intervention and fluid prescription adjustment was associated with a reduction in the risk of starting KRT and progression to AKI stage 3.
MO337UNILATERAL NEPHRECTOMY OVERCOMES PROGRESSION TO CHRONIC KIDNEY DISEASE AFTER ACUTE INJURY IN MICE BY STIMULATING PROLIFERATION OF RENAL PROGENITOR CELLS
Authors: Moonen Lies , Lazzeri Elena , Peired Anna Julie , Conte Carolina , D'Haese Patrick , Romagnani Paola , Vervaet Benjamin 
Published: May 2021

Abstract

Background and Aims
Acute kidney injury (AKI) is a global health concern with an incidence of 13.3 million patients per year, and increasing. AKI is recognized as an important risk factor for the development of chronic kidney disease (CKD). A crucial aspect for successful renal recovery after AKI is an efficient proliferative response of surviving tubular epithelial cells (TECs). Recently, we established a murine model in which the functional and histological recovery of a single kidney, injured by ischemia, is enhanced by removal of the unharmed contralateral kidney; a phenomenon termed nephrectomy-induced recovery. The renal epithelial reparative response in this unique physiological model has not been investigated, yet can provide new insights in unlocking the inherent regenerative potential of the renal epithelium.

Method
AKI was induced in R26RtdTomato and PAX2/Confetti mice by left unilateral ischemia/reperfusion (UIRI) for 21 min at 34°C, after which either right nephrectomy (Nx) or no Nx was performed 3 days later. Mice were euthanized 6 weeks and 28 days after UIRI, respectively. At week 6, kidneys were weighted and renal function was assessed by serum creatinine. At 28 days, renal tissue of Pax2/Confetti mice was collected to perform renal progenitor cell lineage tracing experiments by immunofluorescence and confocal microscopy.

Results
When nephrectomy was performed after UIRI, left kidney-to-body weight ratio did not change significantly over time, whereas, when no nephrectomy was performed, left kidney-to-body weight ratio gradually declined from 7,84 ± 0,48 mg/dl at day 3 till 3,26 ± 0,51 mg/dl at week 6, indicating severe atrophy in the injured left kidney. This loss of renal mass was associated with a significant increase in serum creatinine (1,76 ± 0,13 mg/dl) as compared to control (0,21 ± 0,12 mg/dl), whereas with nephrectomy, renal function fully restored. Clonal analysis in PAX2/Confetti mice revealed that nephrectomy after UIRI led to a significant increase in proliferating (i.e. clonogenic) Pax2+ progenitor cells, resulting in more multicellular clones as compared to un-nephrectomized controls.

Conclusion
Nephrectomy after UIRI overcomes chronic loss of renal mass and function within the investigated 6-week time frame. This study is the first to demonstrate that nephrectomy stimulates clonal expansion of renal progenitor cells in an injured kidney, beyond that observed for spontaneous repair after UIRI. Insight in the signaling mechanisms may reveal new therapeutic approaches to incite the inherent renal regeneration potential.
MO339KIDNEY DERIVED APOM AND ITS ROLE IN ACUTE KIDNEY INJURY
Authors: Bisgaard Line Stattau , Christensen Pernille M , Füchtbauer Ernst-Martin , Nielsen Lars Bo , Christoffersen Christina 
Published: May 2021

Abstract

Background and Aims
Acute kidney injury is a severe disease with detrimental outcomes. The underlying ethiology is still elusive and besides dialysis, treatment options are poor.
Apolipoprotein M (apoM) is mainly expressed in liver and in proximal tubular epithelial cells in the kidney. In plasma, apoM associates with HDL particles via a retained signal peptide. ApoM is a carrier of sphingosine-1-phosphate (S1P), a small bioactive lipid involved in e.g. angiogenesis, lymphocyte trafficking, and vascular barrier function. Recently, it was shown that apoM/S1P protects against development of liver and lung fibrosis. In urine, apoM is normally undetectable in both wild type mice and healthy humans. However, lack of megalin receptors in proximal tubuli induces loss of apoM into the urine. The biological function of kidney-derived apoM is unknown, but it has been hypothesized that apoM might be secreted to the pre-urine to sequester molecules, such as S1P, from secretion.
The aim of this study was to unravel the role of apoM in kidney biology and in acute kidney injury.

Method
A novel kidney specific human apoM transgenic mouse (RPTEC-hapoMTG), was generated by expressing human apoM under the control of the proximal tubular epithelial cell specific Sglt2 promoter. The effect of kidney specific apoM overexpression on acute kidney injury was accessed by inducing either cisplatin or ischemia/reperfusion injury. Further, a stable cell line of HK-2 cells overexpressing hapoM (HK-2hapoM-TG) was generated and the cells were cultured on transwells to assess the secretion of apoM to respectively the apical and basolateral site.

Results
hapoM was present in plasma from RPTEC-hapoMTG mice (mean 0.18 μM), indicating that kidney-derived apoM can be secreted to plasma. When assessing the secretion of hapoM from proximal tubular epithelial cells in vitro, studies support that apoM can be secreted to both the apical (urine) and basolateral (blood) compartment. No differences in kidney injury markers (plasma urea and creatinine) between RPTEC-hapoMTG and wild type (WT) mice subjected to cisplatin injections, or in kidney injury score determined by histological evaluation was found. Similar, we could not detect any histological difference between RPTEC-hapoMTG and WT mice after ischemia/reperfusion injury, and overexpression of hapoM did not affect kidney gene expression of inflammatory markers (i.e. IL6, MCP-1) compared to WT mice.

Conclusion
Our study suggests that apoM can be secreted to both the apical and basolateral compartment, supporting a role for apoM in sequestering molecules from secretion in urine.
Transgenic overexpression of apoM in proximal tubular epithelial cells of mice did not protect against acute kidney injury.
MO340THE EFFECT OF NA+/PI COTRANSPORTER IN TENOFOVIR INDUCED NEPHROTOXITY BY REGULATING INTRACELLULAR PHOSPHORUS BALANCE AND MITOCHONDRIAL FUNCTION
Authors: Ma Tiantian , Shi Xiaoxiao , Zhao Bingbin , Li Jiaying , Ji Peili , Chen Limeng 
Published: May 2021

Abstract

Background and Aims
Tenofovir disoproxil fumarate (TDF), a reverse transcriptase inhibitor used to treat virus infections, could cause proximal tubular (PT) dysfunctions and eGFR decline with mitochondria damages. PDZ domain containing 1 (PDZK1), PDZK1-interacting protein 1 (PDZK1IP1), and Na+/H+ exchanger regulatory factor 1 (NHERF1) are scaffold proteins or membrane-associated proteins that influence the localization and function of membrane proteins. We tried to investigate the changes of both proximal tubular transporters and membrane-associated proteins in TDF induced nephrotoxic model.

Method
C57/BL6 mice (n = 8) were gavaged daily with 10mg/kg/d, 50mg/kg/d of TDF for 8 weeks. The human renal tubular epithelial cells (HK-2) were grown and received 24 to 72 h exposure to 0–128 µM TDF or vehicle.

Results
Chronic TDF administration to mice and HK-2 cells resulted in PT damages including swollen and exfoliated tubular epithelial cells, brush border cilia lodging and dissolving, and serum creatinine elevation (P&lt;0.05, mean 10.23±2.683 vs. 27.18±18.41) compared to the control group. The Na+/Pi cotransporter (Npt) and sodium-glucose cotransporter type 2 (SGLT-2) were decreased in the kidneys of TDF treated mice and HK-2 cells. The intracellular phosphorus concentrations decreased with the increase of TDF concentration and the extension of TDF treatment time, which were in line with down-regulated Npt expressions. Mitochondrial morphological changes were seen in TDF treated mice and HK-2 cells by electron microscope, including unclear boundaries, damaged membrane structures, disappeared mitochondrial cristae, and fragmented mitochondria or abnormal giant mitochondria in PT cells. The expression of cytochrome b was reduced by 52.0% (P&lt;0.0001), indicating the damages of mitochondrial respiratory chain. ATP levels which reflected mitochondrial functions were also decreased after TDF treatment in HK-2 cells with a time- and dose-dependent relationship.

Conclusion
TDF may down-regulate Npt expression, leading to decreased intracellular phosphorus concentrations, mitochondrial dysfunctions, and finally kidney injury.
MO345LIFESAVING BIOMARKERS IN CONTRAST-INDUCED ACUTE KIDNEY INJURY IN ADULT CRITICAL ICU PATIENTS
Authors: Mishra Ravi , SINGH HARSHIT , Chaturvedi Saurabh , Mishra Durga P , Agarwal Vikas , Gurjar Mohan 
Published: May 2021

Abstract

Background : -
Intravenous administration of radiocontrast media is referred to as contrast-induced kidney injury (CI-AKI).CI-AKI is described as the third most common cause of new AKI in hospitalized patients. The occurrence of CI-AKI is reported up to 55% in these high-risk patients.: NGAL (Neutrophil gelatinase-associated Lipocalin)and Cystatin C have been found an early and sensitive marker of acute kidney injury (AKI).

Aims
To evaluate biomarkers in plasma (P) and urine (U) after intravenous contrast in adult ICU patients.

Method
Total of 36 patients recruited as per inclusion criteria. ICU patients who were &gt;18 years with radiographic contrast for diagnostic or interventional computed tomography (CT scan), were included. After ethical approval, samples of 5 ml blood and 5 ml urine were collected before contrast exposure and at 4 h, 24 h, and 48 h after contrast exposure. NGAL and Cystatin C assay was done by ELISA, and urinary levels were normalized as per urine creatinine (UCr) values for each sample. In the present study, CI-AKI is defined as a rise in SCr of ≥0.3 mg/dl within 48 hrs. Data presented in a mean or median analysis performed.

Results
In this study, 30 CT scan episodes requiring intravenous contrast in 25 ICU patients were included. Median age was 36 yrs and 13 (43%) were male. On day of inclusion, median SOFA score was 3; 16% In patients having CI-AKI, mean values changes from pre-contrast to at 4 h, 24 h and 48 h after contrast are presented..Kinetics of plasma (P) and urine (U) NGAL and Cystatin C levels (Mean±SD) with p value among patients having CI-AKI P NGAL (ng/ml), Before Contrast(BC)( 708.5±201.76) , 04hrC(851.5±332.05, p=0.07), 24hrC(1093.25±225.03, p=0.02), 48hrC(788±323.4, p=0.21), UNGAL (ng/mg of U Cr)BC(67.63±48.09) , 04hrC(39.69±19.79, p=0.07) , 24hrC(101.97±90, p=0.12) , 48hrC(59.87±56.85, p=0.73) , P Cystatin C (ng/ml) BC(4698.85±574.71), 04hrC(4704.57±1144.87) , p=0.02) , 24hrC(4428.85±1135.73, p=0.03), 48hrC(4288.85±435.8, p=0.17), U Cystatin C (ng/mg of UCr) BC(3 46.06±224.7), 04hrC(219.66±72.18, p=0.91), 24hrC (470.21±536.28, p=0.99), 48hrC(633.61±811.77, p=0.23).

Conclusion
ROC curve analysis during pre-contrast exposure: NGAL, and Cystatin C), both plasma and urine level AUC was significantly higher in patients who develop CI-AKI and Post-contrast exposure Plasma levels AUC significantly higher than Urine levels.
MO329THE GENETIC DELETION OF THE DUAL SPECIFICITY PHOSPHATASE 3 (DUSP3) ATTENUATES KIDNEY DAMAGE FOLLOWING ISCHEMIA/REPERFUSION INJURY IN MOUSE
Authors: Khbouz Badr , Rowart Pascal , Poma Laurence , Bottner Martina , Bolen Géraldine , Rahmouni Souad , Theilig Franziska , Jouret François 
Published: May 2021

Abstract

Background and Aims
Dual Specificity Phosphatase 3 (DUSP3) is a positive regulator of the innate immune response in case of sepsis, but its role in the ischemic damage is unknown. Here, we study (i) whether and where DUSP3 is expressed in the renal parenchyma, and (ii) whether its genetic deletion in Dusp3 systemic knock-out (Dusp3-/-) mice attenuates the I/R-associated inflammation and injury.

Method
Experiment 1: Ten C57BL/6 male WT and Dusp3-/- mice underwent right nephrectomy and left renal ischemia for 30 minutes followed by a reperfusion of 48 hours. Blood and kidneys were collected. Renal function was assessed upon I/R biomarkers, i.e. blood urea nitrogen (BUN) and creatinine (SCr). Expressions of inflammatory and immune markers were comparatively quantified at both mRNA (real-time qPCR) and protein (immuno-blotting and –staining) levels in ischemic vs. non-ischemic kidneys in Dusp3 WT vs. KO mice.
Experiment 2: Ten C57BL/6 male WT and Dusp3-/- mice were anesthetized. Renal Doppler ultrasound was performed to assess the renal resistivity index (RRI). The expression of CD31 and VEGF vascular markers was quantified by the means of real-time qPCR and and immuno-staining (FiJi software).

Results
Experiment 1: An immuno-reactive signal for DUSP3 was detected in the glomeruli (in co-localization with nephrin) and in Meca-32-positive endothelial cells of both outer and inner medulla of mouse non-ischemic WT kidneys. No significant immunoreactivity for DUSP3 was detected in Dusp3-/- kidneys. Following renal I/R, the mRNA level of Dusp3 was increased 1.8-fold compared to baseline (p&lt;0.001). Immunoblot quantifications showed a 77-fold increased expression of DUSP3 post renal I/R. Serum levels of I/R biomarkers were significantly lower in Dusp3-/- compared to WT mice following renal I/R (BUN: 78.4±33.7 vs. 258.9±162.9mg/dL; SCr: 0.1±0.07 vs. 0.8±0.9 mg/dL; p&lt;0.01). At mRNA levels, Dusp3-/- ischemic kidneys showed a significantly decreased expression level of CD11b, TNF-α, KIM-1, IL-6, IL-1β and caspase-3 compared to controls. The numbers of PCNA-, F4-80- and CD11b-positive cells were significantly reduced in Dusp3-/- vs WT renal parenchyma post I/R.
Experiment 2: The RRI non-invasively measured by ultrasound was lower in Dusp3-/- group compared to controls (0.56± 0.03 vs. 0.66±0.02; p&lt;0.001). The Dusp3-/- non-ischemic kidneys were characterized by a 1.8-fold increased surface of CD31-positive cells compared to WT kidneys (p&lt;0.001). At mRNA levels, the Dusp3-/- kidneys showed significantly increased basal levels of CD31 and VEGF compared to controls.

Conclusion
The genetic deletion of DUSP3 is associated with (i) increased renal vascular density, (ii) decreased RRI and (iii) nephroprotection against renal I/R injury.
MO330ACTIVATION OF Β2 ADRENERGIC RECEPTOR SIGNALING IN MACROPHAGES BLOCKS SYSTEMIC INFLAMMATION AND PROTECTS AGAINST RENAL ISCHEMIA/REPERFUSION INJURY
Authors: Hasegawa Sho , Inoue Tsuyoshi , Nangaku Masaomi , Inagi Reiko 
Published: May 2021

Abstract

Background and Aims
The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of sympathetic signaling in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. Here, we focused on sympathetic signaling in macrophages and sought to determine its detailed roles in lipopolysaccharide (LPS)-induced systemic inflammation and renal ischemia/reperfusion injury (IRI).

Method
In vitro, RAW 264.7 cells and murine peritoneal macrophages were used to determine the effects of β2 adrenergic receptor (Adrb2) signaling on LPS-induced proinflammatory cytokine (tumor necrosis factor-α; TNF-α) production. We also identified the critical gene that mediates the anti-inflammatory effect of Adrb2 signaling by RNA-sequencing.
In vivo, we examined the effects of salbutamol (a selective Adrb2 agonist) in LPS-induced systemic inflammation and renal IRI. The involvement of macrophage Adrb2 signaling was confirmed by macrophage-specific Adrb2 conditional knockout (cKO) mice and adoptive transfer of salbutamol-treated macrophages. We also performed single-cell RNA sequencing of renal tissue to analyze the renoprotective role of salbutamol-treated macrophages in detail.

Results
In vitro, norepinephrine, a sympathetic neurotransmitter, suppressed LPS-induced TNF-α production in macrophages. This anti-inflammatory effect was also induced by salbutamol and reversed by butoxamine (a selective Adrb2 antagonist) in a dose-dependent manner, indicating the importance of Adrb2 in this process.
RNA sequencing of these macrophages revealed that T-cell immunoglobulin and mucin-3 (Tim3) expressions were upregulated by the activation of Adrb2 signaling, which partially mediated the anti-inflammatory phenotypic alteration in macrophages.
In vivo, salbutamol administration mitigated LPS-induced systemic inflammation and protected against renal IRI; this protection was mitigated in macrophage-specific Adrb2 cKO mice. Adoptive transfer of salbutamol-treated macrophages also protected against renal IRI (Figure 1). Single-cell RNA sequencing revealed that this protection was associated with the accumulation of Tim3-expressing macrophages in the renal tissue.

Conclusion
The activation of β2 adrenergic receptor signaling in macrophages induces anti-inflammatory phenotypic alterations partially via the induction of Tim3 expressions, which blocks LPS-induced systemic inflammation and protects against renal IRI.
MO334ERYTHROPOIETIN-STIMULATED HUMAN ENDOTHELIAL PROGENITOR CELLS AMELIORATE INFLAMMATION AND FIBROSIS VIA INFLAMMASOME IN ISCHEMIA/REPERFUSION-INDUCED ACUTE KIDNEY INJURY
Authors: Jang Ha Nee , Kim Jin Hyun , Lee Seunghye , Jung Sehyun , Chang Se-Ho , Kim Hyun-Jung 
Published: May 2021

Abstract

Background and Aims
Ischemia/reperfusion-induced AKI (IR-AKI) is a major cause of AKI and progress to chronic kidney disease. But an effective therapeutic intervention for IR-AKI is not established yet. Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells and is significantly upregulated during hypoxia. Endothelial progenitor cells (EPCs) are derived from the bone marrow or tissue-resident cells and play major roles in the maintenance of vascular integrity and the repair of endothelial damage. So, we investigated if EPO-stimulated human EPCs could have the renoprotective effects in an IR-AKI mouse model.

Method
EPCs originated from human peripheral blood were cultured with EPO (10 IU/mL). Mice were assigned to sham, IR only groups, IR with EPC, and IR with EPO-treated EPC. EPCs (5x105 cells, tail vein) were administered twice at 30 min prior to bilateral renal artery occlusion, and 5 min before reperfusion, with all mice sacrificed 24 h after IR-AKI.

Results
Both EPCs and EPO-treated EPCs significantly attenuated the renal dysfunction associated with IR-AKI, as well as tissue injury. Apoptotic cell death and oxidative stress were significantly reduced in EPC and EPO-treated EPC mice. Expression of PCNA, ICAM-1, MCP-1 and α-SMA were also significantly reduced in EPC and EPO-treated EPC mice. Furthermore, the expression of NLRP3 and caspase-1 via the activation of NF-κB signaling pathways were significantly reduced in EPC and EPO-treated EPC mice. These results show more effective in EPO-treated EPC than EPC alone and suggest EPO might be involved in the development of EPC.

Conclusion
This study provides that inflammasome-mediated inflammation and fibrosis might be a potential target of EPC as a treatment for IR-AKI.