bluuebunny/crossref_metadata_2025 huggingface dataset:
MO393ACUTE RENAL REPLACEMENT THERAPY IN CRITICAL ILL OCTOGENARIAN OR OLDER PATIENTS: PROGNOSTIC FACTORS AND RENAL OUTCOMES
Authors: Del Risco Jimena , Casals Joaquim , Hermida-Lama Evelyn , Quintana Luis F , Blasco Miquel , Piñeiro Gaston , Poch Esteban , Molina Andujar Ali­cia
Published: May 2021

Background and Aims

a growing number of octogenarians or older patients are being admitted to the intensive care unit (ICU). The aim of this study was to assess factors associated with acute renal replacement therapy (ARRT) requirement in these patients and the impact of ARRT on the 90-day ICU mortality. Also we aimed to identify prognostic factors associated with mortality risk in the group of patients that required ARRT.

Method

retrospective study of octogenarian or older patients admitted to the ICUs of Hospital Clínic de Barcelona from June 2007 to April 2019. Patients on chronic dialysis treatment or kidney transplant, and patients with limitation of therapeutic support or admitted for less than 48 hours were excluded.

Results

217 patients were included in the study, of which 36.4% required ARRT. Use of vasoactive drugs and Sequential Organ Failure Assessment (SOFA) score on admission were higher in ARRT patients (p=0.009 and <0.001). Basal estimated glomerular filtration rate (eGFR) was lower in the ARRT cohort (p<0.001). Hospital and ICU length of stay were longer in the ARRT cohort (p<0.001). Ninety-day mortality was 58.2% in the ARRT cohort and 55.8% in the control cohort, without statistical differences. In the survival analysis, only female sex and non-renal SOFA ≥6.5 were significantly associated with mortality (p= 0.005 and 0.002 respectively) in the ARRT cohort.

Conclusion

mortality was not significatively increased in the octogenarian population that required and got ARRT respect to those who did not require it. Scores like SOFA can help in the process of decision making about initiation of ARRT.
MO394TWO POINT ESTIMATE OF KINETIC GFR IN ACUTE KIDNEY DISEASE
Authors: Keller Frieder
Published: May 2021

Background and Aims

When anuria suddenly occurs, the rise in creatinine and consequently the decrease in the estimated glomerular filtration rate (eGFR) will always be delayed. Thus, the drug dose could be selected too high in the progressive phase whereas it could be adjusted too low in the restitution phase of acute kidney disease (AKD). Sheldon Chen proposed a solution for changing kidney function with the kinetic GFR (KeGFR). A simplified but also more general solution (kinetGFR) might even facilitate the automatic implementation into lab systems.

Method

Deterioration of kidney function is diagnosed when the creatinine increases within a definite time interval (Δ t) and the estimated eGFR declines (Δ eGFR). The new 2-point estimate of the kinetGFR can be derived when the prospective eGFRt+24 predicted for the next day (t+24) will be set equal to the present true GFR at critical day (t2). kinetGFR=eGFR2−eGFR1−eGFR2t2−t1⋅t+24 h

The 24 h delay follows from anuria, the most extreme and most relevant case (GFR = 0). A zero GFR will be associated with a linear rise in creatinine according to the constant production rate by roughly 100 µmol/l every day. This rise leads to the corresponding bisection of the estimated eGFR nearly every day (100 => 50 => 25 => 13 => … ml/min). The curvilinear eGFR decline will never become zero even after > 2 weeks. The new kinetGFR can identify a complete anuria already after one day (24 h). kinetGFR=50−100−5024−0⋅24=0.0 ml/min

This is already at the critical day (t2).

Results

The retrospective look at the anonymized data from 20 patients with AKD allowed for comparing the former KeGFR with the new two-point kinetGFR estimate. For worsening kidney function, the average eGFR2 was 18 ml/min (+ 12) and the KeGFR estimate was not different with 19 ml/min (+ 17). The new 2-point kinetGFR, however, was 13 ml/min (+ 11) and 28 % less than eGFR2 at the critical day (t2). For improving kidney function, the eGFR2 was 15 ml/min (+ 4) and the KeGFR was already much higher at 27 ml/min (+ 3). The new 2-point estimate of the kinetGFR was in between at 21 ml/min (+ 7).

Conclusion

In AKD, the difference between eGFR and presumably true GFR was the higher the more rapidly kidney function declined. The new kinetGFR estimate appears clinically more plausible than the former KeGFR estimates.
MO397THE IMPACT OF NEW-ONSET ATRIAL FIBRILLATION ON ADVERSE OUTCOMES IN PATIENTS WITH SEPSIS-INDUCED ACUTE KIDNEY INJURY
Authors: Dimitrijevic Zorica , Mitic Branka , Salinger Sonja , Paunovic Goran , Glogovac Stevan , Tasic Danijela
Published: May 2021

Background and Aims

The mortality of septic patients with acute kidney injury (s-AKI) prevails high. Atrial fibrillation is commonly observed in the setting of systemic inflammation or infection. The study aimed to assess the incidence and predictors of new-onset atrial fibrillation (NOAF) in this population and its impact on intrahospital mortality.

Method

We conducted a retrospective cohort study of 462 patients admitted to our unit for s-AKI between January 2016 and December 2020. NOAF was defined as AF discovered during hospitalization in patients with sinus rhythm on admission. Subjects were classified into NOAF (n=68) and non-NOAF groups (n=364). There were no major differences in sepsis severity between groups, and all patients underwent intermittent hemodialysis as a renal replacement treatment modality.

Results

The NOAF incidence in the whole s-AKI population was 14.7%. In a univariate analysis, age (72.4 in patients with NOAF vs. 62.1 years in patients without NOAF, respectively; p=0.018), male gender (33.5 vs. 14.6%; p= 0.004), history of coronary disease (23.5 vs. 6.1%; p=0.07) and vasopressor medication use (19.0 vs. 8.2%; p = 0.002) were associated with NOAF. 116 (25.1%) patients died during the hospitalization, while 346 patients (74.9%) were discharged from the hospital. NOAF occurring in s-AKI was independently associated with an increased hazard of intrahospital death (HR: 1.36; 95% CI: 1.09–1.51), compared to the non-NOAF group.

Conclusion

A clinically significant number of patients hospitalized for s-AKI have NOAF, and it is associated with poor hospital outcomes.
MO398DETERIORATION OF RENAL OUTCOMES AND INCREASED MORTALITY RISK DUE TO ACUTE KIDNEY INJURY AFTER ORTHOTOPIC LIVER TRANSPLANTATION: SYSTEMATIC REVIEW AND META-ANALYSIS OF COHORT STUDIES
Authors: Putra Boby Pratama , Putra Felix Nugraha
Published: May 2021

Background and Aims

Orthotopic liver transplantation (OLT) procedure is increased as incremental end-stage liver disease patients’ prevalence. Acute kidney injury (AKI) is one of most common post-OLT complications that is associated with poor renal outcomes and increased mortality risk although the results are still inconclusive. This study aims to measure the risk of deterioration of renal outcomes and mortality risk due to AKI incidence in post-OLT patients.

Method

We did comprehensive searching using predefined terms in online databases of Pubmed, EMBASE, ScienceDirect, and The Cochrane Library, to include all relevant studies from 2000-2020. We included all cohort studies that reported AKI incidence in post-OLT patients and accessed the risk of 3-month renal replacement therapy (RRT) need, 1-year chronic kidney disease (CKD) progression, and 1-year mortality rate. We used The Newcastle-Ottawa Scale for cohort study for accessing bias risk. We conducted analysis to pooled risk ratio (RR) with 95% confidence interval (CI) using random-effect heterogeneity test.

Results

We included 10 cohort studies met our inclusion criteria. The AKI incidence significantly both increases the need of RRT in post-OLT patients (pooled RR = 8.41. 95% CI = 2.82 to 25.09, p = 0.0001, I2 = 0%) then leads the CKD progression in one year (pooled RR = 6.76. 95% CI = 2.03 to 22.51, p = 0.002, I2 = 84%). The post-OLT patients who suffered from AKI has significant incremental 1-year mortality risk (pooled RR = 7.27. 95% CI = 4.34 to 12.18, p<0.00001, I2 = 5%).

Conclusion

The incidence of AKI in post-OLT patients significantly increase the deterioration of renal outcomes and mortality risks. However, further trials are needed to establish the causalities.
MO399PROFILE OF ACUTE KIDNEY INJURY IN CRITICAL CARE PATIENTS
Authors: J Jayannan , Keeppallil Kevin T John , Abraham Georgi
Published: May 2021

Background and Aims

Acute kidney injury is a global health problem. This study aims to determine the risk factors for poor outcome and to describe the clinical profile, etiology & outcomes of patients with Acute Kidney Injury (AKI) admitted to the Critical Care Unit from a tertiary care centre in South India.

Method

It was a prospective cohort study conducted in a tertiary care hospital in South India from December 2016 to Novemeber 2019. All patients in the ICU were screened for enrolment in AKI using RIFLE criteria with creatinine, GFR and urine output daily for a period of seven days.

Results

A total of 152 patients were taken for final analysis after exclusions. The mean age of the subjects was 44.15 years. Majority of the study subjects (55.9%) belonged to 26 – 50 years of age. Majority of the study subjects were females (51.3%) and the rest were males. Sepsis was found to be present in 52% (79) of the study subjects followed by Gastrointestinal loss 36.2% (55), crush injury 9.03% (15), snake bite 3.3% (5), poisoning 4.6% (7) and acute liver failure 1.3% (2). It was found that 62.5% (95) of the study subject’s AKI had resolved after appropriate management. Among the rest of the study subjects,27.6% required haemodialysis for recovery, 3.3% had persistence of AKI, 3.9% progressed to CKD and 2.6% died. The latter three categories were considered as poor outcomes of AKI. In our study, 29.8%people who had systemic hypertension and 28.2%people who had diabetes mellitus had poor outcome. It was found that in our study, sepsis and GI loss both contributes to poor outcome of AKI in univariate regression analysis whereas Gastrointestinal loss alone contributes to poor outcome of AKI with multivariate regression analysis.

Conclusion

In conclusion, even though sepsis is the commonest cause of AKI, Gastrointestinal loss independently contributes to poor outcome of AKI. Majority of the people recovered from AKI spontaneously with conservative management. Few people required dialysis for recovery of AKI & very few people progressed to CKD.
MO400HISTOPATHOLOGICAL SPECTRUM OF SNAKE- BITE INDUCED KIDNEY INJURY IN INDIA: A SYSTEMATIC REVIEW
Authors: Meena Priti , Bhargava Vinant , Bhaumik Soumyadeep
Published: May 2021

Background and Aims

Snakebite is a public health problem leading to about 55,000 deaths every year in India.  Kidney injury subsequent to snakebite envenomation is common ( reported prevalence up to 32%). It is estimated that 3% of total acute kidney injury (AKI) is attributable to snakebites.  The current study aims to elucidate the spectrum of renal histopathology in AKI cases followed by snake bite.

Method

We searched seven electronic database studies to identify studies describing the histopathological findings in the kidney associated with snakebite envenomation from India. Two reviewers independently conducted titles and abstract screening as well as full-text evaluation for final inclusion decision. Data were extracted as per a standardized form and conducted narrative synthesis.

Results

We retrieved 1364 studies and finally included 21 studies involving 961 patients who met the eligibility criteria. Provisional results are presented. Patient ages ranged from 2.5 years to 80 years. Viper bite was the commonest cause related to AKI. 92 % of the  AKI  were oliguric and required dialysis. kidney biopsy was usually done after 3 weeks of AKI onset. Acute tubular necrosis (ATN) was the most common finding followed by acute interstitial nephritis, acute cortical necrosis, and thrombotic microangiopathy (TMA).Vasculitic changes in vessels were rarely reported.

Conclusion

Oligo-anuric presentation and prolonged kidney dysfunction were frequent in post snake bite AKI. ATN was the common histological finding
MO403ACUTE KIDNEY INJURY IN ELDERLY: EPIDEMIOLOGICAL, CLINICAL AND ETIOLOGICAL FEATURES
Authors: Malki abidi Mouna , Aoudia Rajaa , Chargui Soumaya , Gorsane Imen , Jerbi Mouna , Gaied Hanen , Ben abdallah Taieb , Goucha Rym , Ben hamida Fethi
Published: May 2021

Background and Aims

Acute kidney injury (AKI) is common in the elderly due to physiologic renal aging and underlying pathologies. Few studies focused on AKI in Tunisian elderly. The aim of our study was to highlight the epidemiological, clinical, etiological, therapeutic, and progressive characteristics of AKI in elderly.

Method

We conducted a descriptive retrospective study of AKI in patients admitted to our department over a period of 04 years from 01/01/2014 to 31/12/2017.

Results

We collected 40 patients including 25 women and 15 men with a sex ratio of 1.66. The mean age was 74 [65-87] years. We noted the presence of pre-existing chronic kidney disease in 58% of cases, diabetes in 50% of cases and hypertension in 73% of cases. Polypharmacy was found in 40% of cases. AKI was symptomatic in 80% of cases and found on a routine check-up in 20% of cases. Mean creatinine was 612+/-334 µmol/l.

AKI was pre-renal in 37% and parenchymal in 63% of cases. Iatrogenic origin was found in 33% of cases. Renal biopsy was performed for diagnostic purposes in 6 cases. Haemodialysis was necessary in 50% of cases. Etiopathogenic treatment was initiated in 73% of cases. Intra-hospital mortality was 10%, recovery of renal function (RF) was partial in 40 % of cases and total in 20 % of cases. Follow-up time was 16 +/- 23.2 months. And at the last news, recovery of renal function (RF) was partial in 7 cases and total in 10 cases, 6 patients kept a chronic renal failure (CRF), among them 3 cases had and end-stage of CRF.

Conclusion

AKI is a frequent pathology in the elderly and its severity is linked to mortality and the transition to chronicity. Iatrogenic causes are frequent and preventable in this population, hence the major interest of prevention.
MO404ACUTE KIDNEY INJURY DUE TO IMMUNE CHECKPOINT INHIBITORS (CPIS) NEPHROTOXICITY
Authors: Catapano Fausta , Persici Elisa , Ubaldi Giulia , Romani Francesca , Mancini Elena
Published: May 2021

Background and Aims

The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding; however the immune-related toxicities associated with CPIs can limit its efficacy.

Case Report.

A 52 year-old female diagnosed with left ocular melanoma and treated for 14 months with nivolumab developed non-oliguric, stage 3 (KDIGO), Acute Kidney Injury (AKI) and mixed proteinuria (0.6 g/day), then was transferred in our Unit. As known causes of AKI were excluded, kidney biopsy was performed. By Optical Microscopy, there were 33 normal glomeruli; arteries and arterioles were normal. The main damage was interstitial and characterized by tubulitis, tubular necrosis, non-isometric citoplasmatic vacuolization and diffuse, acute and chronic, CD4+,

inflammatory infiltrate (Figure 1, 2). By Immunofluorescence, 27 glomeruli were negative for all eight tested antibodies (IgA, IgM, IgG, F, C3, C1q, kappa and lambda light chains). On the basis of these histological findings, Nivolumab-induced Acute Tubulo-Interstitial Nephritis was diagnosed. Nivolumab was discontinuated. Patient was treated by steroids and she achieved almost complete renal function recovery (Figure 3).

Conclusions.

CPIs can induce a long-term Acute Kidney Injury. Histological features are characterized by Acute Tubulo-Interstitial Nephritis. Steroids can improve renal outcome. In patients treated with CPIs a multidisciplinary management between oncologists and nephrologists is desirable for monitoring renal function at basal, after drug administration and in the long-term follow-up.
MO352RENAL DYSFUNCTION AS A MAJOR PREDICTOR OF CLINICAL OUTCOMES IN ANTERIOR STEMI PATIENTS
Authors: Sens Florence , Amaz Camille , Juillard Laurent , Ovize Michel , Guebre-Egziabher Fitsum
Published: May 2021

Background and Aims

Among ST-segment elevation myocardial infarction (STEMI) patients, the respective impact of the baseline renal function, of the development of acute kidney injury (AKI), and of their combination, on the long-term cardiovascular outcomes, remain unclear.

Method

The present study was based on a post hoc analysis of the CIRCUS trial database, a multicentre randomized study which gathered 969 patients with anterior STEMI treated by primary percutaneous intervention (PPCI) within 12 hours of symptoms onset. Uni and multivariate regressions were performed to identify if the estimated glomerular filtration rate (eGFR) at admission and the development of AKI were associated with (1) cardiovascular death and heart failure (HF) at one year and (2) sub-optimal treatment prescription at discharge.

Results

A total of 822 patients were included. The mean baseline eGFR was 86 ± 19 mL/min/1.73m2. AKI occurred in 97 patients (11.8%). Baseline eGFR <60mL/min/1.73m2 was associated with HF (40.0 vs 16.8%, p<0.001) and with a sub-optimal treatment at discharge (35.9 vs 18.9%, p=0.001). AKI was associated with cardiovascular death (12.4 vs 2.8%, p<0.001), HF (50.5 vs 14.9%, p<0.001), and sub-optimal treatment (35.8 vs 18.5%, p<0.001). The multivariate analysis showed that AKI (OR=4.88, CI=2.89-8.27) and a lower baseline eGFR (OR=1.29 per 10mL/min/1.73m2 decrease, CI=1.11-1.50) are independent predictors of cardiovascular death or HF after anterior STEMI.

Conclusion

In anterior STEMI patients undergoing PPCI, the development of AKI was the strongest independent predictor of poor clinical outcome at one year. The study suggests the need for a tailored monitoring of STEMI patients with AKI or baseline kidney dysfunction.
MO355ACUTE KIDNEY INJURY INCREASES THE RISK FOR SUBSEQUENT HEART FAILURE HOSPITALIZATIONS
Authors: Diebold Matthias , Zimmermann Tobias , Strebel Ivo , Wussler Desiree , Bassetti Stefano , Mueller Christian , Breidthardt Tobias
Published: May 2021

Background and Aims

Acute kidney injury (AKI) is common and associated with increased mortality and morbidity. The impact of AKI on subsequent heart failure remains largely unknown.

Method

The Basics in Acute Shortness of Breath Evaluation Study (BaselV) prospectively enrolled patients presenting the emergency department with acute dyspnea. Two independent specialists adjudicated the final cause of dyspnea. Serum creatinine concentrations were prospectively assessed throughout the hospitalization. AKI was defined according to the serum creatinine criteria of the 2012 KDIGO clinical practice guideline. AKI adjudication occurred blinded to the cause of dyspnea. Mortality and rehospitalizations were prospectively assessed during follow-up (median:768 days [IQR:290-950]. Renal recovery was defined as a discharge creatinine<1.25x baseline creatinine.

Results

AKI occurred in 809 (40%) of 2021 patients and was associated with increased all-cause (adjusted Hazard Ratio [aHR] 1.33, 95%CI 1.13-1.55; p<0.01) and cardiovascular mortality (aHR 1.43, 95%CI 1.16-1.75; p<0.01). However, the impact of AKI on mortality was time-dependent with the highest impact on early 30-day mortality (aHR 2.47, 95%CI 1.62-3.76; p<0.01) (Figure 1A). AKI was not associated with all-cause or cardiovascular mortality in patients achieving renal recovery (p=0.10 and p=0.30). In contrast, AKI displayed a time-independent association with subsequent hospitalisations for heart failure (hHF) (aHR 1.49, 95%CI 1.15-1.94; p<0.01) (Figure 1B). The association with hHF was stronger for higher degrees of AKI (stage 2/3 aHR: 1.89; 95%CI 1.33-2.83; p<0.01). This association with hHF persisted in patients with non-cardiac dyspnea (aHR 2.43, 95%CI 1.05-5.59; p=0.04), even after renal recovery (aHR 2.56, 95%CI 1.00-6.54; p=0.05). Again, in patients with non-cardiac dyspnea the association of advanced AKI (stage 2/3) with hHF was even stronger (aHR 4.25, 95%CI 1.59-11.36; p<0.01).

Conclusion

AKI independently increases the risk of hHF by almost 50%. This association persists in patients with non-cardiac dyspnea, even after renal recovery by discharge. This suggests AKI to be a novel risk-factor for the development of clinically significant HF.
MO420ROLE OF IL-6 ON ACUTE KIDNEY INJURY (AKI) DEVELOPMENT AFTER LIVER TRANSPLANTATION
Authors: Tinti Francesca , Colicchio Martina , Ginanni Corradini Stefano , Mennini Gianluca , Rossi Massimo , Mazzaferro Sandro , Noce Annalisa , Mitterhofer Anna Paola
Published: May 2021

Background and Aims

Acute kidney injury (AKI) post-liver transplantation is a frequent complication with an incidence up to 70%, requiring renal replacement therapy in about 25% of transplant patients. AKI in patients with normal renal function is a recognized risk factor (FR) of chronic renal failure (CKD) de novo, associated with a 4.5 times greater mortality at 5 years post-transplant.

Pathogenesis of AKI is multifactorial. Beyond the classical pre-transplant risk factors, the hypoxia of the graft and the ischemia-reperfusion injury (IRI) have recently been recognized to exert a pathogenetic role with specific mechanisms.

It has been recently demonstrated in experimental setting that ischemic tissues put in place protective mechanisms in response to hypoxia aimed at increasing the release of oxygen with the activation of angiogenesis mediated by the expression of factors induced by hypoxia (HIF)-1-alpha.

HIF1-alfa has been shown to promote cell survival under hypoxic conditions by switching metabolism from oxidative to glycolytic, by affecting the production of ATP to prevent excessive mitochondrial generation of reactive oxygen species, by promoting secondary release of vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-ß1), with following activation of inflammatory cytokines responsible for systemic inflammatory response syndrome (SIRS).

Tumor necrosis factor-α, IL-1 and IL-6 are the most important cytokines released in IRI and seem to play a pivotal role in the onset of AKI in SIRS and sepsis.

The development of AKI after hypoxia/ischemia of the graft, as observed more frequently in the population of recipients from donors after cardiocirculatory death (DCD) compared to donation after brain death (DBD), confirms this pathogenetic mechanism.

Aim of the study is to evaluate AKI occurrence among liver transplanted patients and its relationship with IRI and cytokines systemic release.

Method

Data of 78 patients (62 males, 79.5%) undergone liver transplantation (2007-2011) were retrieved.

Results

The following clinical investigations were performed:

AKI patients demonstrated a progressive increasing of IL-6 after liver transplantation (AKI 34.4-37.8-88.2 ng/ml vs no AKI 30.5-21.6-23.3 ng/ml).

Conclusion

Patients who experienced greater ischaemia-reperfusion injury of the liver graft developed more frequently AKI. Patients with AKI experienced an increased release and circulation of IL-6, that probably is involved in AKI development with interesting implications in future therapy.
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

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 >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) > 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 <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

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 = <0.001) and AKI progression to stage 3 (OR 0.59, 95% CI 0.49-0.71, p = <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

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

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

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<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<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

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 >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

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<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<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<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<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

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

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.
MO554THE EFFECT OF HEMOGLOBIN CHANGES AND THE SEVERITY OF CHRONIC KIDNEY DISEASE IN PHYSICAL FUNCTION IN ELDERLY PATIENTS WITH HEART FAILURE
Authors: Noda Takumi , Kamiya Kentaro , Hamazaki Nobuaki , Nozaki Kohei , Ichikawa Takafumi , Yamashita Masashi , Uchida Shota , Yoshikoshi Shun , Maekawa Emi , Yamaoka-Tojo Minako , Matsunaga Atsuhiko , Ako Junya
Published: May 2021

Background and Aims

Anemia is frequently observed in patients with heart failure (HF) and causes increased hospitalization and mortality rates. Anemia is also associated with and is a major risk factor of impaired physical function and frailty. On the other hand, a high percentage of elderly patients with HF have chronic kidney disease (CKD), which is an aggravating factor for anemia, and the combination of anemia and CKD has been reported to increase physical dysfunction and mortality. However, the relationship between hemoglobin (Hb) changes and physical function during hospitalization in elderly patients with HF is unclear, and the impact of CKD severity on these relationships is also unclear. This study aimed to examine the relationship between Hb changes and physical function during hospitalization in elderly patients with HF. We further examined the relationship when stratified by CKD severity.

Method

Seven hundred and thirty-seven elderly patients with HF, who underwent changes in Hb and physical function test (leg strength, gait speed, and 6-min walking distance [6MWD]), were included in this study. Using a multiple linear regression model, associations between Hb changes and physical function were assessed. In addition, using a generalized linear mixed model, we divided the HF patients into three groups with eGFR ≥60, 30–60, and <30, and examined whether the severity of CKD was related to the Hb change and physical function.

Results

The median age of the subjects in this study was 77 years (interquartile range 72–82). Changes in Hb during hospitalization were independent determinants of physical function (leg strength, β: 0.158, P < 0.001; gait speed, β: 0.023, P < 0.001; 6MWD, β: 13.039, P < 0.001), even after accounting for factors related to severity of HF. Moreover, the group with more severe CKD showed significantly lower physical function, although Hb improved (P < 0.001) with respect to leg strength and 6MWD compared with the group with lower CKD stage.

Conclusion

Hb change during hospitalization was an independent determinant of physical function in patients with HF. Patients with a more severe CKD showed lower leg strength values and 6MWD even if Hb improved.