bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO282: Sigma-1 Receptor Agonists are Protective in Renal Ischemia/Reperfusion Injury
Authors: Roland Toth Akos , Lakat Tamas , Hodrea Judit , Balogh Dora B , Vannay Adam , Wagner Laszlo , Szabo Attila , Fekete Andrea , Hosszu Adam 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Renal ischemia/reperfusion injury (IRI)-induced acute kidney injury is associated with high mortality and morbidity and effective therapies are lacking. We previously showed that Sigma-1 receptor (S1R) agonist fluvoxamine treatment is protective against renal IRI (Hosszu et al, 2017). Here in a rat model, we studied the renoprotective effect of specific, high affinity S1R agonists focusing on the S1R-Akt-eNOS signaling pathway and renal vasoregulation.

METHOD
8-week old male Wistar rats (n = 8/group) were subjected to 50 min unilateral ischemia with contralateral nephrectomy, kidney tissue was harvested 24 h after reperfusion. 30 min prior to the ischemic insult rats were treated i.p. as follows: (i) isotonic saline as vehicle; (ii) highly specific, high affinity S1R agonist SA-4503; or (iii) SA-4503 + S1R antagonist NE100. Sham-operated rats were used as controls. Renal functional parameters (BUN, serum creatinine, serum aspartate aminotransferase, kidney injury molecule 1 (Kim1), neutrophil gelatinase-associated lipocalin (Ngal) were evaluated. Structural damage was assessed on PAS-stained kidney sections. Renal S1R, phospho-Akt and phospho-eNOS, Hif-1α protein levels and serum nitric oxide (NO) concentration were measured. In vitro experiments were performed on HK2 human proximal tubular epithelial cells treated with a 10 µM dose of S1R agonist SA-4503 or PRE-084.

RESULTS
Impaired kidney function and structural damage after I/R were ameliorated by SA-4503. Expressions of early and sensitive tubular injury markers Kim1 and Ngal were markedly less elevated in SA-4503-treated rats. This recovery was blocked with the addition of the S1R antagonist NE100. S1R, phospho-Akt and phospho-eNOS protein levels were significantly elevated in the kidneys of SA-4503 treated rats. Vasodilator nitric oxide concentration was reduced in the kidney after IRI, but returned to control levels in SA-4503-treated rats. Treatment with S1R agonists SA-4503 and PRE-084 increased the NO production of HK-2 cells.

CONCLUSION
The specific and high affinity S1R agonist SA-4503 acts directly on proximal tubular cells by activating the S1R-NOS system. Thereby SA-4503 is renoprotective by increasing vasodilative NO production and thus improving post-ischemic renal perfusion. Based on our data activation of S1R and downstream signaling pathways could provide a novel therapeutic option in renal IRI.

Founding
OTKA PD-131 637; FK-124 491; 2020–4.1.1.-TKP2020-6 183 069 269; 2020–4.1.1.-TKP2020-6 183 169 273; KDP-2020/1 019 145
MO303: Impact of Dexamethasone and Inhaled Nitric Oxide on Severe Acute Kidney Injury in Critically ill Patients With COVID-19
Authors: Bobot Mickaël , Tonon David , Peres Noémie , Guervilly Christophe , Lefèvre Flora , Carvelli Julien , Papazian Laurent , Max Howard , Leone Marc , Lopez Alexandre , Bommel Youri , Volff Maxime , Velly Lionel , Bruder Nicolas , Hraiech Sami , Simeone Pierre , Bourenne Jérémy , Forel Jean-Marie 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Kidney failure is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe acute kidney injury (AKI) in critically ill COVID patients.

METHOD
Data from a prospectively collected database of consecutive patients hospitalized in six ICUs for COVID-19 was retrospectively analysed. The incidence and severity of AKI were monitored during the entire ICU stay. Patients older than 18 years hospitalized in for COVID-19-related ARDS requiring mechanical ventilation were included.

RESULTS
A total of 164 patients were included in the final analysis, 97 (59.1%) displayed AKI, of which 39 had severe stage 3 AKI and 21 (12.8%) requiring renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with ACEI exposure (P = .016), high blood pressure (P = .029), APACHE-II score (P = .004) and mortality at D28 (P = .008), D60 (P &lt; .001) and D90 (P &lt; .001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to CEI [OR: 4.238 (1.307–13.736); P = .016], APACHE II score (without age) [OR: 1.138 (1.044–1.241); P = .003] and iNO [OR: 5.694 (1.953–16.606); P = .001], protective factors were prone positioning [OR: 0.234 (0.057–0.967); P = .045] and dexamethasone [OR: 0.194 (0.053–0.713); P = .014].

CONCLUSION
Dexamethasone seems to prevent the risk of severe AKI and RRT, and iNO seems associated with severe AKI and RRT in critically ill patients with COVID-19. iNO must be used with caution in COVID-19 related ARDS.
MO310: Clinical Characteristics and Outcomes of Acute Kidney Injury in Hospitalized Patients With COVID-19: Experience at a Major Tertiary Care Center in Pakistan
Authors: Yaqub Sonia , Hamid Amna , Saeed Marwah , Awan Safia 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Limited data exists on acute kidney injury (AKI) in patients hospitalized with COVID-19, its risk factors and associated outcomes from low-middle income countries. We aimed to determine the epidemiology of AKI and its impact on outcomes at a tertiary-care center in Karachi, Pakistan.

METHOD
A retrospective observational study was conducted at Aga Khan University Hospital from October to December 2020. Data on demographics, presenting clinical symptoms, laboratory results and patient outcomes were collected from medical records. AKI was defined according to KDIGO criteria.

RESULTS
Of 301 patients admitted with COVID-19, AKI developed in 188 (62.5%). The peak stages of AKI were stage 1 in 57%, stage 2 in 14.9% and stage 3 in 27.7%. Of these, 15 (8%) required KRT. Patients requiring ICU admission (63.8% versus 34.5%), vasopressors (31.9% versus 5.3%) or mechanical ventilation (25% versus 2.7%) had a higher risk of AKI. Independent predictors of AKI were elevated blood urea nitrogen and creatinine at the time of presentation, need for mechanical ventilation and use of anticoagulants. AKI, presence of proteinuria, elevated SCr at presentation, use of vasopressors and need for KRT were all significantly associated with in-hospital death, and the likelihood of mortality increased with the advancing stage of AKI.

CONCLUSION
Compared with other countries, AKI occurred more frequently among hospitalized patients with COVID-19 in a Pakistani cohort and was associated with a 7.7-fold increase in odds of in-hospital death. Patients with severe AKI had a greater likelihood of fatal outcomes compared with earlier stages or non-AKI patient groups.
MO315: Risk Factors for CSA-AKI and Performance of Leicester Score in a Spanish Cohort
Authors: Molina Andujar Alicia , Joaquin Escudero Victor , Blasco Miquel , Piñeiro Gaston , Poch Esteban 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The incidence of acute kidney injury following cardiac surgery (CSA-AKI) is up to 30% and it places patients at an increased risk of death. Leicester score (LS) is a new score designed by Birnie et al. [1] and validated in 2014 in a British Cohort. It predicts CSA-AKI at any stage with better discrimination compared with the Clevaland Clinic Score (CCS) and Euroscore II. The aim of this study was to identify risk factors for CSA-AKI and to assess the performance of LS in a Spanish cohort.

METHOD
A unicentric retrospective study of patients that required cardiac surgery with cardio-pulmonary bypass (CPB) during 2015 in the Hospital Clinic de Barcelona. The inclusion criteria were patients &gt;18 years old who were operated on for cardiac surgery [valve substitution (VS), coronary artery bypass graft (CABG) or a combination of both procedures] with the need of CPB. CSA-AKI was defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

RESULTS
A total of 444 patients were included, of which 171 (38.5%) developed CSA-AKI. The most frequent form of AKI was mild AKI (AKI stage 1), which was present in 105 patients (61.4%). AKI stage 3 was developed in 26 patients, 15 of which required RRT. A total of 66.7% of AKI cases met criteria in the first 24 h and the median duration until total recovery was 3 days. In the multivariate analysis, hypertension (OR 1.883), EGFR &lt; 60 mL/min (OR 2.365) and peripheral vascular disease (OR 4.66) were associated with CSA-AKI. Either discrimination or calibration were better with LS compared with CCS and Euroscore II, with an AUC of 0.721 versus 0.595 and 0.662, respectively (Fig. 1).

CONCLUSION
Preoperative hypertension in patients with CKD with or without peripheral vasculopathy can identify patients at risk of CSA-AKI. LS has proved to be a valid score that could be used to identify patients at risk who could benefit in intervention studies.
MO320: Risk Factors and Outcomes Related to Acute Kidney Injury Among Enhanced Recovery After Surgery (ERAS) Colorectal Surgery
Authors: Fernandes Adriana , Ribeiro Daniel , Carvalho Sofia , Raimundo Mário , Almeida Edgar 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Enhanced recovery after surgery (ERAS) protocol is an evidence-based programme that englobe more restrictive fluid therapy to maintain euvolemia and the use of multimodal analgesia, which includes non-steroidal anti-inflammatory drugs (NSAIDs). Consequently, it's pertinent to assess the risk and potential consequences of acute kidney injury (AKI) in the short and medium term.

METHOD
A descriptive and single-center retrospective study, which included 428 patients that were submitted to colon-rectal surgery according to ERAS protocol between November 2016 and May 2020. AKI was defined according to KDIGO criteria.

RESULTS
Data were collected from 428 patients. AKI occurred in 25.2% of patients (108), mostly KDIGO 1 (63.9%) and 6.5% required haemodialysis. The median time of follow-up was 25.6 months (IQ 15.6–38.8). Patient-related variables that positively influenced AKI were ASA Class III/IV [F (1, 426) = 23.2; P &lt; .001], diabetes [F (1, 426) = 9.96; P = .002], severe heart disease [F (1, 426) = 7.12; P = .008], CKD [F (1, 425) = 11.58; P &lt; .001], obesity [F (1, 423) = 14.21; P &lt; .001] and use of ACE inhibitors/ARBs [F (1, 425) = 17.4; P &lt; .001]. Preoperative and surgery-related variables that influenced AKI were preoperative haemoglobin [F (85, 338) = 1.36; P = .030], open approach [F (1, 424) = 21.5; P &lt; .001], NSAIDs [F (1–426) = 5.77; P = .017], iodinated intravenous contrast exposure [F (1, 424) = 26.8; P &lt; .001), postoperative support aminergic [F (1, 424) = 18.9; P &lt; .001], surgery complications [F (1, 426) = 36.5; P &lt; .001] and blood transfusion [F (1, 426) = 10.15; P = 0.002].
AKI group had a superior length of stay (9 versus 6 days; P &lt; .001), ICU admission (31.5% versus 8.8%; P &lt;.001), readmission at 30 days (12% versus 5.6%; P = .027) and mortality (23.1% versus 6.6%; P &lt; .001). Kaplan–Meier analysis showed that the AKI group was associated with lower survival (log-rank test = 26.601; P &lt; .001). We also found that the AKI group was associated with a greater reduction in GFR after 2 years (3.3 mL/min/1.73 m2 versus 1.8 mL/min/1.73 m2; P = .009).

CONCLUSION
AKI was frequent among ERAS patients and was associated with worst outcomes—higher costs (since it was associated to longer hospitalization, higher readmission at 30 days and ICU admission), higher risk of reduction in GFR in the first 2 years and higher mortality.
MO321: The Critical Role of Cytokine Dysregulation in Acute Kidney Injury Development in Patients With COVID-19
Authors: Moreno-Amaral Andrea N , Soares Tozoni Sara , de Castro Deus Marina , Carolina Gadotti Ana , Clara Flórido Ana , Bohnen Gabriela , Bacarin Monte Alegre Julia , Sousa Dias Erika , Proença de Moraes Thyago 
Published: May 2022

Abstract

BACKGROUND AND AIMS
One of the complications described in critically ill patients in intensive care units with severe COVID-19 was acute kidney injury (AKI). The pathophysiology of AKI in patients with COVID-19 is multifactorial. In addition to the direct virulence of SARS-CoV-2 in renal cells, the tissue inflammation and local immune cell infiltration, cytokine storm, secondary infections and nephrotoxicity associated drugs may contribute to AKI [1]. Mounting evidence throughout the pandemic suggests that patients with severe COVID-19 may have a cytokine storm syndrome, one of the possible causes of AKI in these patients [2]. The present prospective cohort study analysed the correlation between circulating cytokine profile and estimated glomerular filtration rate (eGFR) in patients with COVID-19.

METHOD
After signing the informed consent, patients positive for SARS-CoV-2 infection (n = 74) had blood samples (n = 139) collected at hospital admission until the day of the outcome. ELISA measured the cytokines IL-10, IL-4, L-6, TNF-α and IFN-γ, and the eGFR was calculated by the CKD-EPI Cystatin C equation. Statistics description: Continuous variables were checked for normality and presented as mean ± standard deviation or median and interquartile range. The association between continuous variables is shown in scatterplots, and a predicted response with 95% confidence interval (95% CI) is plotted using fractional polynomials. For linear correlations, we obtained P-values using Pearson's correlation coefficient.

RESULTS
There is a more significant distribution of eGFR below 90 mL/min in the population studied, associated with older patients. Glomerular filtration rates were negatively correlated with age as expected (–0.60; P &lt; 0.0001). Lower eGFR was correlated with levels of proinflammatory cytokines such as IL-6 (–0.33; P &lt; .0007) and TNF- α (–0.21; P &lt; .03); but without positive correlation with IL-10 (0.04; P &lt; 0.68) or IFN-γ (–0.14; P &lt; .16), even though higher IFN-γ levels have been linked to a worse prognosis in patients with severe COVID-19 [3]. Curiously, a positive correlation was observed between lower eGFR and IL-4 levels.

CONCLUSION
These results demonstrate that a shift in the immune response profile, cytokines with a Th2 profile such as IL-4, and cytokines with systemic functions such as IL-6 and TNF-α can be related to renal failure. The elucidation of the potential pathophysiological mechanisms of AKI associated with COVID-19 as well as monitoring of cytokine levels can (a) help to identify patients with severe COVID-19 at risk of loss of renal function, (b) provide information on specific therapeutic strategies.
MO330: AKI and Renal Parenchyma Attenuation in Hospitalized Patients With COVID-19
Authors: Russo Elisa , Tagliafico Alberto , Signori Alessio , Brigati Francesca , Cappadona Francesca , Derchi Lorenzo , Martinoli Carlo , Viazzi Francesca 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a worldwide spread since early 2020 and a lot of studies concerning the diagnostic and prognostic role of chest computed tomography (CT) on coronavirus disease (COVID-19) has been published. Renal involvement might be present in up to 75% of cases, significantly impacting on the prognosis.
The aim of this study is to clarify the role of opportunistic kidney assessment on non-enhanced chest CT and to evaluate if radiological findings could be associated with relevant clinical information regarding kidney function and patient's prognosis in hospitalized patients with COVID-19.

METHOD
We collected data on patient demographics, comorbidities, chronic medications, vital signs, baseline laboratory test results and in-hospital treatment in patients with COVID-19 consecutively admitted to our Institution who underwent chest CT. The standard chest CT-scan acquired in full inspiration include large part of both kidneys as per protocol. Three regions of interest (ROI) of 0.5–0.7 cm2 were positioned in every kidney, right and left to include both the cortex and the medulla. The mean values of attenuation of kidney regions were analysed. The primary and secondary outcomes were the occurrence of acute kidney injury (AKI), in-hospital and 9 months of death for all causes.

RESULTS
A total of 86 patients with COVID-19 and unenhanced chest CT were analyzed splitting the cohort into CT renal parenchyma attenuation (RPA) quartiles. Patients with a CT RPA below 24 Hounsfield unit (HU) were more likely to develop AKI when compared with other patients (×2 = 2.77, P = .014). An AKI-specific cut-off point of RPA was identified by performing a survival receiver operating characteristic (ROC) curve. At multivariate logistic regression analysis, being in the first quartile of CT RPA was associated with a four-times higher risk of AKI (Table 1) after adjustment for age, gender, hypertension, kidney function at admission and other comorbidities. During a mean 22 ± 15 days of admission, 32 patients died (37.2%). Patients with lower values of RPA at CT (first quartile, &lt;24 HU) were not at a higher risk of death compared with patients with RPA ≥ 24 HU, as shown by Kaplan Maier curve (Fig. 1) and by multivariate Cox regression analysis [HR 1.84 (95% CI 0.82–4.13); P = .14].

CONCLUSION
The association between AKI and RPA &lt; 24 HU was independent of age, gender, creatinine and comorbidities. RPA values seemed to be predictive of AKI development in COVID-19 patients who underwent chest CT, suggesting RPA values could significantly improve patients’ care. The opportunistic measure of RPA could help physicians identifying patients with a higher risk of AKI, and this increased awareness could guide choices for diagnostic and therapeutic procedures.
MO333: Prevalence of COVID-Associated Renal Injury in ICU and Prognosis of Proximal Tubular Dysfunction in Acute Respiratory Distress Syndrome
Authors: Bobot Mickaël , Heim Xavier , Max Howard , Simeone Pierre , Velly Lionel , Bruder Nicolas , Forel Jean-Marie , Carvelli Julien , Stein Claire , Hraiech Sami , Boucraut José , Gainnier Marc , Mege Jean-Louis , Guervilly Christophe , Jourde-Chiche Noemie , Papazian Laurent , Burtey Stephane 
Published: May 2022

Abstract

BACKGROUND AND AIMS
During COVID-19, the renal impairment is the most frequent after lung impairment and is associated of poor prognosis particularly in the intensive care unit (ICU). In this work, we aim to assess the incidence of acute kidney injury (AKI) in COVID-19-related acute respiratory distress syndrome (ARDS) patients, the existence of an early renal dysfunction and its prognosis, and its specificity compared with patients with non-COVID ARDS.

METHOD
This a prospective and multicentric study led in four ICUs. Patients of 18 years and older in ICU with invasive mechanical ventilation for ARDS were enrolled. Precise evaluation of renal dysfunction markers, including urinary protein electrophoresis, was performed within 24 h after the onset of mechanical ventilation.

RESULTS
From March 2020 to September 2021, 131 patients in ICU for ARDS were enrolled, 98 COVID-19 ARDS and 33 ARDS from other causes. There was more tubular profile in COVID-19 patients (68% versus 24%; P = .001) and a more mixed, tubular and glomerular profile in non-COVID-19 patients (29% versus 14%; P = .001). COVID-19 patients displayed an important tubular proteinuria, tended to display more AKI (49% versus 31%; P = .07), and had a longer duration of mechanical ventilation (18 versus 10 days; P = .002) and longer ICU length of stay (23 versus 15 days; P = .013). In COVID-19 patients, tubular proteinuria was associated with poor renal prognosis with a significant association with the onset of KDIGO ≥ 2 AKI.

CONCLUSION
COVID-19 ARDS patients had a specific renal impairment with tubular dysfunction, which appeared to be of poor prognosis on kidney and disease evolution.
MO335: Reaching SCR 4.0 mg/dL, the Magical Number for KDIGO-2012 AKI Stage 3. Is it Adequate for Stratifying Severity of Acute on Chronic Kidney Disease?
Authors: Acosta-Ochoa Isabel , Lorenzo Arturo , Coca Armando , Martínez Manrique María , Ardura Paula , Lucía Valencia Ana , Mendiluce Alicia 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Reaching a SCr ≥ 4 is one criterion of classification for stage 3 in the KDIGO-2012 AKI guidelines. No previous study has challenged this arbitrary cut point by comparing its performance on how patients with pure AKI (pAKI) versus acute on chronic kidney disease (AoCKD) reach that ‘magical number’, and how it affects the prognosis.

METHOD
Retrospective study of patients with AKI, classified according to the KDIGO-2012 guidelines. We analysed a sub-group of patients that reached a maximum SCr ≥ 4 and divided them in pAKI (basal eGFR ≥ 60) and AoCKD (≥15–≤59). We evaluated epidemiological and clinical variables, and compared the clinical outcomes needed for HD, in-hospital mortality and HD dependence at discharge. As 21 (6%) of AoCKD individuals already had a basal SCr ≥ 4.0, they were excluded in the analysis.

RESULTS
A total of 492 individuals met the inclusion criteria: 341 (69%) in the AoCKD group. Individuals in this group were older and had a higher Charlson's index. Table 1A summarizes the comparison of clinical characteristics, all patients in the pAKI group reached a four SCr with a rate of SCr increments ≥ 3×. We found no statistically significant difference in in-hospital mortality and the need for HD. The AoCKD group was more dependent on HD at discharge (Table 1B). Figure 1 shows the rate of SCr increments by which individuals reached &gt; 4.0 mg/dL.

CONCLUSION
We found that individuals in the AoCKD group differ in their basal characteristics from the pAKI group and need lesser increments in SCr to reach the magical number of 4.0 mg/dL to be classified in stage 3. May be, one size does not fit all, and individuals with prior CKD may benefit from a lower rate of SCr increase to stratify AKI severity. We consider that a pitfall in this staging criterion consists in the small portion of patients in the AoCKD group that have a basal SCr ≥ 4.0, with a skew to AKI-KDIGO stage 3.