bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0534THE EFFECT OF HIGH FAT DIET INTAKE AND FOOD SUPPLY RESTRICTION ON CISPLATIN NEPHROTOXICITY IN MICE
Authors: Kim Ji Su , Kong Min Jung , Park Kwon Moo 
Published: June 2020

Abstract

Background and Aims
Nephrotoxicity is a major side effect of cis-diamminedichloroplatinum (II) (cisplatin), which is widely used for cancer therapy. The nephrotoxicity is associated with the excessive formation of reactive oxygen species (ROS) and oxidation of cell components. Here, we investigate whether cisplatin nephrotoxicity can be controlled by the regulation of food supply which is associated with cellular production of ROS.

Method
Male mice were administered with either cisplatin or saline. Before cisplatin administration, mice were high-fat diet (HFD) feeding for 7 days, no-food supply for 2 days, 2 days no-food supply and refeeding with normal diet (ND), and normal diet. Renal function was analyzed by plasma creatinine (PCr) and blood urea nitrogen (BUN) concentration. Kidney cell damage was evaluated by periodic acid shiff staining and transmission electron microscope analysis.

Results
Cisplatin injection induced the disruption of kidney tubular cells and also increased BUN and PCr concentration. These increases were greatest in the HFD feeding mice, whereas .these increases were lowest in the food restricted mice. Levels of DNA oxidation and lipid peroxidation increased in the kidney after cisplatin injection and these increase were also greatest in the kidney of HFD feeding mice and lowest food restricted mice. Mitochondrial damage was observed in the proximal tubule cells after cisplatin injection and this mitochondria damage was more severe in the HFD feeding mice than ND feeding mice. Cisplatin increased the expression of fission 1 in the kidney, whereas reduced the expression of opa-1 expression. These cisplatin induced changes were greater in the HFD feeding mice than the ND feeding mice.

Conclusion
High fat diet feeding worsens cisplatin-induced nephrotoxicity along with increased oxidative stress and mitochondrial damage, whereas food restriction reduces this cisplatin nephrotoxicity. These data indicate that cisplatin nephrotoxicity is controlled by food supply, suggesting that energy metabolism is associated with cisplatin nephrotoxicity.
P0535ATG5 OVEREXPRESSION IN PACS SIGNIFICANTLY IMPROVES CELL-MEDIATED AKI PROTECTION
Authors: Patschan Daniel , Schwarze Katrin , Ritter Oliver , Patschan Susann , Müller Gerhard Anton 
Published: June 2020

Abstract

Background and Aims
Acute Kidney Injury (AKI) significantly worsens the prognosis of hospitalized patients. Cell-based strategies have been established as reliable option for improving AKI outcomes in experimental AKI. Own studies performed in recent years utilized Pro-angiogenic Cells (PACs). Autophagy (AP) is commonly regarded as process of en-dogenous self-defense. The AP cascade, which may be stimulated by either substrate deprivation or certain exogenous / endogenous stressors, involves the activation of numerous proteins, the so-called Autophagy-related proteins (Atg proteins). Among these, Atg5 has been suggested to play a key role in augmenting AP. The current study evaluated whether selective Atg5 activation in syngeneic murine PACs may result in improved cell-mediated AKI protection.

Method
Cultured murine PACs were selectively transfected for Atg5. Successful transfection was verified by detecting red fluorescing cells. AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI - 40 minutes). Transfected cells were i.v. injected post-ischemia. Mice were analyzed 48 hours and 6 weeks later.

Results
IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels (48 hours and 6 weeks). Cell administration (either native or after transfection) did not improve AKI outcomes at 48 hours. At 6 weeks, injection of native cells resulted in lower serum cystatin C, this effect was even more pronounced if transcfected cells were applied.

Conclusion
Together, our data show that selective Atg5 overexpression in murine PACs sub-stantially augments cell-mediated AKI protection in the long-term. Thus, a new strategy for improving AKI protective effects of PACs has been identified.
P0543NQO1ATTENUATES RENAL INJURY BY RENAL ISCHEMIA REPERFUSION OF MICE
Authors: Lee Kang Wook , Jeong Jin Young , CHOI DAE EUN , Na Ki Ryang , Kim Haeri , Ham Young Rok , Choi Wonjung , Chang Yoon-Kyung , JEON JAE WAN 
Published: June 2020

Abstract

Background and Aims
Ischemia-reperfusion (I-R)-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation. We investigate whether NQO1 modulates the renal I-R injury.

Method
C57BL/6N NQO1-deficient mice (NQO1/) were generated. Mice were sacrificed at 4, 12, 24, and 48 h after the surgical procedure. I-R was performed using vascular clamp for 30min. We analyzed renal function, oxidative stress, and tubular apoptosis after I-R injury.

Results
NQO1/ mice showed increased blood urea nitrogen and creatinine levels, tubular damage, oxidative stress, and apoptosis. In the kidneys of NQO1/ mice, the cellular NADPH/NADPþ ratio was significantly higher and NOX activity was markedly higher than in those of NQO1þ/þ mice. The activation of NQO1 by β-lapachone (βL) significantly improved renal dysfunction and reduced tubular cell damage, oxidative stress, and apoptosis by renal I-R. Moreover, the βL treatment significantly lowered the cellular NADPH/NADPþ ratio and dramatically reduced NOX activity in the kidneys after IRI. From these results, it was concluded that NQO1 has a protective role against renal injury induced by I-R and that this effect appears to be mediated by decreased NOX activity via cellular NADPH/NADPþ modulation.

Conclusion
NQO1 activation might be beneficial for ameliorating renal injury induced by I-R.
P0544INHIBITION OF 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE (15-PGDH) PROTECTS MICE AGAINST CONTRAST-INDUCED ACUTE KIDNEY INJURY
Authors: KIm Byeong Woo , Kim Sun hee , Bae Ki beom 
Published: June 2020

Abstract

Background and Aims
Although the mechanism of contrast-induced acute kidney injury (CI-AKI) is not fully known, the imbalance of vasoconstrictive and vasodilative mediators plays a major role. Prostaglandin E2 (PGE2) is one of the vasodilators involved in this process. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) causes elevation of PGE2 level in tissue by delaying the rapid degradation of PGE2 by the enzyme. We tested the hypothesis that the 15-PGE2 inhibitor would protect against CI-AKI in a mouse model and attempted to elucidate the mechanism involved.

Method
10-week aged male C57/BL6 Mice were injected with 10gI/kg of iodixanol by tail vein. Renal blood flow measurement, right nephrectomy, and blood sampling were taken at 48 hours after iodixanol injection. The 15-PGDH inhibitor was injected before and after iodixanol administration. Plasma creatinine, NGAL, KIM-1 were measured as biomarkers for renal function. Histological evaluation was analyzed by the necrosis scoring system and TUNEL assay. Arteriolar area of outer medulla was analyzed by α-smooth muscle actin stain. Renal blood flow was measured by the non-invasive laser doppler.

Results
Plasma creatinine (1.94±0.75 vs 1.11±0.44 mg/dL, p=0.005), NGAL (299.7±115.87 vs 140.4±76.56 ng/mL, p=0.004), and KIM-1 (2.09±2.34 vs 0.43±0.89 ng/mL, p=0.024) levels were significantly lower when the 15-PGDH inhibitor was injected before and after iodixanol administration than the vehicle group. But no significant renal protective effect was shown when the 15-PGDH inhibitor was injected before or after iodixanol administration. The 15-PGDH inhibitor administration before and after iodixanol injection showed a significantly wider renal arteriolar area (683.63±248.46 vs 1132.97±357.46 μm2, p=0.039) and larger renal blood flow (360.0±49.72 vs 635.1±27.20, p=0.011) than vehicle administration.

Conclusion
The 15-PGDH inhibitor has a renal protective effect against CI-AKI in mice by increasing renal blood flow when injected intravenously before and after iodine contrast media administration.
P0553PROTECTIVE EFFECT OF (-)-ALPHA-BISABOLOL OVER RENAL CYTOTOXICITY INDUCED BY AMPHOTERICIN B
Authors: Paula Magalhães Emanuel , Pinheiro Silva Brenna , Paula Pessoa Bezerra de Menezes Ramon , Lima Sampaio Tiago , Bandeira Lima Danya , Bezerra da Silva Junior Geraldo , De Francesco Daher Elizabeth , Costa Martins Alice Maria 
Published: June 2020

Abstract

Background and Aims
Drug-induced acute kidney injury (AKI) is a health problem that increases morbidity and mortality rates as well as costs to health systems. Amphotericin B (AnB) is a widely used antifungal, which its therapy is closely associated with nephrotoxicity. The mechanisms of nephrotoxicity are not yet fully understood and there is a need to search for substances that prevent and / or reverse the associated renal damage. (-) - α-Bisabolol (BIS) has been demonstrated nephroprotective effect due to its antioxidant action. Thus, the aim of this study was to evaluated the effect of BIS as a protective substance on renal cell injury induced by amphotericin B.

Method
LLC-MK2 tubular renal cells were treated with different concentrations of BIS and AnB and its viability was measured by MTT assay to define the working concentrations of BIS and AnB. Then, cells were pretreated or post treated with BIS (31.25 - 125 μM) and AnB (13.97 μM) for 24 hours to evaluate the protective effect of BIS. Control (CT) was treated with sterile PBS. The experimental groups were further submitted to flow cytometry assays for membrane integrity evaluation using 7-AAD and measurement of cytoplasmic ROS production using DCFH-DA. The experiments were performed in triplicate (n = 3), and the data analyzed by One-Way ANOVA with Bonferroni post-test.

Results
BIS concentrations from 31.25 to 125 μM were selected, as well as the IC50 for AnB (13.97 ± 1.45 μM) for the furthers assays. Pretreatment with BIS increased cell viability by about 10% (31.25 – 63.31 ± 2.04%; 62.5 – 64.75 ± 2.10%; 125 – 63.92 ± 2.72%) compared to the AnB-only group (49.79 ± 1.25%), which had its cell viability reduced by about 50% (CT – 100.70 ± 0.83%). BIS was also able to increase the whole cell population at concentrations of 62.5 (83.10 ± 1.10%) and 125 μM (84.67 ± 0.98%) when compared to the AnB group (76.54 ± 1.18%). In DCF labeling, it was observed that AnB increased the production of ROS in 20% (IFR = 1.21 ± 0.02) when compared to the control (IFR = 1.00 ± 0.01), and BIS (31.25 μM) was able to reduce in 41% (IFR = 0.79 ± 0.01) when compared to the AnB group.

Conclusion
The (-)-α-bisabolol was able to prevent the renal cytotoxicity induced by amphotericin.
P0554IN VITRO ASSESSMENT OF HA330 CARTRIDGE ADSORPTION CAPACITY REALTED TO VANCOMYCIN
Authors: Lorenzin Anna , Godi Llaria , De Cal Massimo , Ronco Claudio 
Published: June 2020

Abstract

Background and Aims
The rationale for blood purification as adjunctive therapy during sepsis involved the capacity in removing endogenous and exogenous toxins, but currently no recommendations exists [1]. A critical point may be the potential interaction with antimicrobial therapy, which remains the mainstay of sepsis treatment. HA330 cartridge (Jafron, Zhuhai City, China), widely used in China and actually available in Europe, is used in hemoperfusion for blood purification in septic patients.The aim of this in vitro study was to investigate the adsorptive capacity of HA330 related to vancomycin (VAN).
Reference: 1. Rhodes A et al. Crit Care Med 45:486-552. 2017

Method
This is an experimental study, simulating an hemoperfusion treatment with HA330. We circulated (250 ml/min) in a closed loop 500 ml of normal saline solution enriched with VAN, stirred and maintained at 37°C. We spiked 100 mg of VAN every 15 minutes to increase the antibiotic load until reaching 1500 mg, the last injection was 500 mg to get a total amount of 2 g. Samples were collected from the inlet line at each VAN adjunct, after system stabilization. Measured VAN concentrations were used to get the adsorption isotherm: for each VAN load, the adsorbed amount of VAN was obtained by multiplying VAN reduction ratio and the quantity of VAN injected.

Results
Figure 1 shows VAN adsorption isotherm obtained with HA330 cartridge. We observed that, at each injection, after 15 minutes VAN was almost entirely adsorbed by the cartridge, with an average reduction ratio of 0.96. Interestingly, this was confirmed even adding 500 mg at once. Even increasing the VAN load to 500 mg at once, the reduction ratio was maintained.

Conclusion
In our study, simulating hemoperfusion using HA330, a rapid and clinically relevant removal of VAN has been shown. A significant amount of VAN (2g) was adsorbed without reaching membrane saturation nor reducing its adsorptive capacity.
In a clinical setting, we recommend a therapeutic drug monitoring to optimize VAN levels during blood purification with HA330 and a VAN loading dose may be considered. Further in vivo studies are warranted to confirm these findings.
P0566INCIDENCE AND IMPACT OF ACUTE KIDNEY INJURY (AKI) IN ANDALUSIA
Authors: Aguilera Morales Wenceslao , Lara Ruiz Alfonso , Díaz Díez Irene , Salgueira Lazo Mercedes 
Published: June 2020

Abstract

Background and Aims
Acute Kidney Injury (AKI) is an insufficiently reported clinical entity with significant impact on overall mortality, hospital stay and associated costs, increasing the risk of progression to Chronic Kidney Disease. It is especially relevant in hospitalized patients, where the incidence has doubled in the last decade, reaching 22-25%. Aims: Know the reported incidence of AKI in the Andalusian Autonomous Community, and its impact on mortality, average stay and associated costs.

Method
Cross-sectional descriptive study that analyzes data from all Andalusian hospitals, extracted from CMBDA corresponding to 2017. Hospitalization episodes, reference units, episodes with AKI at discharge, exitus and average stays were collected. An associated cost estimate analysis was also carried out using as reference the costs/day hospitalization in each SAS Assistance Unit according to BOJA Number 218 (14nov2016). The groups were compared according to the presence of the diagnosis of AKI.

Results
There were 525,757 hospital admissions in Andalusia; 25,727 reported the diagnosis of AKI at discharge, assuming an incidence of 4.89%. Patients with AKI total 316,938 stays, with an average stay of 15.5 + 13.8 days, compared to 6.5 + 6 days in which they have no associated diagnosis (p &lt;0.01). The estimated costs associated with the diagnosis of AKI were 168,922,706 euros, with a cost / episode of 24,693 euros vs 3796 in the rest (p &lt;0.01) (AKI/noAKI cost ratio: 6.5), and a cost / day / patient of 823 + 437 euros for AKI compared to 571 euros in the rest. The overall mortality associated with AKI was 26.8% (median 16.6%) vs. 4.76% (median 0.7%) in the rest (p &lt;0.01). AKI/noAKI mortality ratio: 16.
These data may be underestimated since the completion of the CMBDA is not complete in all hospitals and also the diagnosis of AKI may have been present and not reported upon discharge. Estimated costs did not include dialysis sessions.

Conclusion
The incidence of hospital AKI in our Autonomous Community is lower than that reported in the literature, probably due to inadequate reporting to CMBD. In spite of the limitations, our data show the impact of the diagnosis of AKI in hospitalized patients, multiplying by 2.5 the average stay, by 6.5 the associated costs and by 16 mortality, assuming a big problem Public Health that makes it imperative to develop measures to reduce the impact it entails.
P0572ABSENCE OF RENAL FUNCTION RECOVERY AFTER AN ACUTE KIDNEY INJURY PREDICTS SHORT-TERM MORTALITY
Authors: Quiroga Borja , Sanz Sainz Marta , Santos Sánchez-Rey Begoña , Muñoz Ramos Patricia , Ruano Pablo 
Published: June 2020

Abstract

Background and Aims
The incidence of acute kidney injury (AKI) during a hospitalization is frequent and worsen the prognosis. Recovery of renal function after AKI has been lightly studied and cut-off for establishing full recovery has not been determined. The aim of the present study is to evaluate the association between different degrees of renal function recovery after AKI and short-term mortality post-discharge.

Method
This is a retrospective study that included all the AKI codified in the electronic records of our center in 2013 and 2014. We collect epidemiological data and comorbidities at baseline and laboratory values at admission and discharge. To analyze the impact of recovery of renal function after AKI we performed a univariate logistic regression with different cutoff of creatinine after 7 days of the AKI in comparison to baseline. We used the most sensitive cutoff to define recovery and evaluated associated factors (figure 1). Patients were followed during 30 days to assess associated factors to prognosis after AKI.

Results
We included 1720 patients in this study. After the hospitalization due to AKI, 1194 (69%) entered in the final analysis. Of them 869 (73%) recovered renal function. Factors associated to recovery were age (p=0.01), presence of CKD (p=0.04), basal renal function (p&lt;0.001), history of heart failure (p=0.02), having cognitive impairment (p=0.01), dependence (using Barthel index, p=0.002), renal function at admission (p&lt;0.001), severity of AKI (p&lt;0.001), blood pressure at admission (p=0.02) and hemoglobin at admission (p=0.04). Independent predictors of recovery were basal CKD-EPI (p&lt;0.001), CKD-EPI at admission (p&lt;0.001), severity of AKI (p=0.037), hemoglobin at admission (p=0.016), blood pressure at admission (p&lt;0.001) and history of heart failure (0.001). After discharge, 46 (3%) patients died in the first 30 days. Associated factors to mortality were history of neoplasia (p=0.02), cognitive impairment (p&lt;0.001), Barthel index (p&lt;0.001) and the absence of renal recovery after AKI (defined as reaching a creatinine above 1.2 times of the baseline) (p=0.01). In an adjusted model, renal function recovery independently predicted short term mortality (HR 2.6, 95%CI [1.2-5.4], p=0.01).

Conclusion
The absence of recovery after an AKI is an independent predictor of 30-day mortality.
P0573CLINICAL PRESENTATION AND OUTCOMES OF ACUTE INTERSTITIAL NEPHRITIS: A TEN YEARS' EXPERIENCE FROM A TERTIARY CARE HOSPITAL IN KARACHI, PAKISTAN
Authors: Yaqub Sonia , Aziz Rehman Ayesha , Awan Safia 
Published: June 2020

Abstract

Background and Aims
Acute interstitial nephritis (AIN) is a potentially reversible, but relatively under-diagnosed cause of acute kidney injury. The effectiveness of steroids for treatment of AIN is debated. Data is scarce regarding the clinical presentation, use of steroids and its impacts on outcomes in AIN in our part of the world. The objective of our study was to study the clinical features, causes and outcomes of AIN and to evaluate the role of steroids in the management.

Method
We performed a retrospective study of 48 patients with biopsy proven AIN. Exposure was defined as the use of steroids. The main outcomes were recovery of renal function (Early (≤3 weeks) or Late (&gt;3 weeks)) and hemodialysis dependence at 12 weeks

Results
48 (4.9%) AIN cases were found among 978 renal biopsies performed from 2007-2018. Mean age was 47.6 ± 12.1 years. 56.3% were males. The offending agent was identified in 45.8% cases with NSAIDs (45.4%) being the most common, followed by antibiotics (22.7%), diuretics (9%), and PPI (4.5%). 75% presented with eGFR &lt;15 ml/min/1.73m2 (n=36) out of which 58.3 % (n=21) needed hemodialysis. Mean proteinuria was 2.28 ± 0.99 g/day. 81.3% (n=39) patients received steroids out of which 39.6% were started on steroids after an initial period of observation after stopping the offending agent. Mean dose of prednisone was 0.8 ± 0.2 mg/kg per day. Mean time to steroid commencement was 14 ± 17.39 days.
Early use of steroids (≤11 days after presentation) was significantly associated with earlier recovery (p= 0.009) as compared to late steroids (&gt;11 days). A non-significant trend towards complete recovery (within 25% of baseline Creatinine) was noted in early steroid group (52.9%, n=17) vs “no steroid” (33.3%, n=9) or “late steroids” (10.5%, n=19) groups (p=0.208). 47.4% remained dialysis dependent on follow up with no difference made by steroid use (p=0.971).

Conclusion
Our data showed the benefit of earlier use of steroids in achieving rapid and complete renal recovery. Late steroid use was not associated with any further recovery of renal function at an additional risk of exposing patients to undue adverse effects. This is the first report from Pakistan documenting the tendency of nephrologists towards use of steroids for AIN.
P0576LEFT VENTRICULAR FUNCTION ON TISSUE PERFUSION AND RENAL OUTCOMES IN CRITICALLY ILL PATIENTS WITH SEPSIS
Authors: Shin Jungho , Hwang Jin Ho , Kim Su-Hyun 
Published: June 2020

Abstract

Background and Aims
Left ventricular (LV) dysfunction has been regarded as a predictor of mortality in patients with sepsis. However, it remains uncertain whether LV dysfunction deteriorates multiple organ failure by impairing tissue perfusion or it has an independent impact. In this study, we investigated the association between LV dysfunction and tissue perfusion, and their impacts on renal outcomes in critically ill patients with sepsis.

Method
We retrospectively reviewed a total of 162 adult patients with sepsis who met the Sepsis-3 definition. Subjects included 83 (51.2%) with normal LV function, 39 (24.1%) with diastolic dysfunction defined as the septal E/e’ ratio &gt;15 among patients with ejection fraction ≥50% and 40 (24.7%) with systolic dysfunction defined as an ejection fraction &lt;50%. Tissue perfusion was assessed by the levels of blood lactate.

Results
The initial and 24h levels of lactate, and lactate clearance did not differ regardless of the presence of LV dysfunction (P=0.861, 0.907 and 0.363). The incidence rate of acute kidney injury (AKI) among the patients with initial lactate &lt;2 mmol/L was higher in those with LV dysfunction (P=0.044), conversely, the incidence rate was comparable in the patients with initial lactate ≥2 mmol/L (P=0.797). Risks of AKI and renal replacement therapy implementation increased if subjects had blood lactate levels ≥2 mmol/L (P=0.009 and 0.080), however, the impact of LV dysfunction on these outcomes depended on previous chronic kidney disease and lactate levels (diastolic dysfunction: P=0.449 and 0.663; systolic dysfunction: P=0.062 and 0.161). However, renal replacement therapy-free days were shorter in those with LV dysfunction, independent of previous chronic kidney disease (P=0.003). Renal function at discharge was not related to the lactate levels and LV function in this study (P=0.685 and 0.089)

Conclusion
LV dysfunction might not influence tissue perfusion in patients with sepsis, on the other hand, it could lengthen the duration of renal replacement therapy. Therapeutic options for preserving microcirculation should be warranted in patients with sepsis, in addition to individualized therapies tailored their LV function.