Transient Acute Kidney Injury Research Articles

#1934 Association between transient AKI and all-cause mortality in critically ill patients according to baseline BUN/SCr ratio and diuretics use

Abstract Background and Aims Previous studies have yielded inconsistent results regarding the prognosis of transient acute kidney injury (AKI). We aimed to assess the risk of mortality and kidney outcomes in critically ill patients with transient AKI according to BUN/SCr ratio (BCR) level and diuretics treatment at baseline. Method We conducted a multicentre retrospective cohort study of critically ill patients, including 131,034 patients from China (CRDS) and 9,778 patients from US (MIMIC-IV) spanning from 2012 to 2021. Transient AKI was defined as AKI that recovered within two days. Study outcomes included one-year all-cause mortality and the occurrence of major adverse kidney events (MAKE). The associations between transient AKI and study outcomes were compared in patients stratified by BCR level and diuretics use at baseline. Results Of 140,812 eligible patients, 3,863 were diagnosed with AKI according to KDIGO criteria and classified as having transient AKI. In patients with a baseline BCR level ≤ 20 (N = 79,883), transient AKI was associated with 42% and 58% increased risk of mortality and MAKE, respectively, compared to those without AKI. However, these associations were not significant in those with a BCR level > 20 (N = 60,929) (P for interaction < 0.05). Similar modified effects of diuretics on the outcomes of transient AKI were also observed. The associations of transient AKI with mortality and MAKE were both significantly different in patients with (N = 26,140) or without (N = 114,672) diuretics treatment before AKI (P for interaction < 0.05). Conclusion The effects of transient AKI on mortality and kidney outcomes in critically ill patients were modified by the BCR level and diuretics use before AKI.

Machine learning derived serum creatinine trajectories in acute kidney injury in critically ill patients with sepsis

BackgroundCurrent classification for acute kidney injury (AKI) in critically ill patients with sepsis relies only on its severity-measured by maximum creatinine which overlooks inherent complexities and longitudinal evaluation of this heterogenous syndrome. The role of classification of AKI based on early creatinine trajectories is unclear.MethodsThis retrospective study identified patients with Sepsis-3 who developed AKI within 48-h of intensive care unit admission using Medical Information Mart for Intensive Care-IV database. We used latent class mixed modelling to identify early creatinine trajectory-based classes of AKI in critically ill patients with sepsis. Our primary outcome was development of acute kidney disease (AKD). Secondary outcomes were composite of AKD or all-cause in-hospital mortality by day 7, and AKD or all-cause in-hospital mortality by hospital discharge. We used multivariable regression to assess impact of creatinine trajectory-based classification on outcomes, and eICU database for external validation.ResultsAmong 4197 patients with AKI in critically ill patients with sepsis, we identified eight creatinine trajectory-based classes with distinct characteristics. Compared to the class with transient AKI, the class that showed severe AKI with mild improvement but persistence had highest adjusted risks for developing AKD (OR 5.16; 95% CI 2.87–9.24) and composite 7-day outcome (HR 4.51; 95% CI 2.69–7.56). The class that demonstrated late mild AKI with persistence and worsening had highest risks for developing composite hospital discharge outcome (HR 2.04; 95% CI 1.41–2.94). These associations were similar on external validation.ConclusionsThese 8 classes of AKI in critically ill patients with sepsis, stratified by early creatinine trajectories, were good predictors for key outcomes in patients with AKI in critically ill patients with sepsis independent of their AKI staging.

Prognostic impact and predictors of persistent renal dysfunction in acute kidney injury after percutaneous coronary intervention for acute myocardial infarction.

This study aimed to evaluate the prognostic impact and predictors of persistent renal dysfunction in acute kidney injury (AKI) after an emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). A total of 877 patients who underwent emergency PCI for AMI were examined. AKI was defined as serum creatinine (SCr) ≥ 0.3mg/dL or ≥ 50% from baseline within 48h after PCI. Persistent AKI was defined as residual impairment of SCr ≥ 0.3mg/dL or ≥ 50% from baseline 1month after the procedure. The primary outcome was the composite endpoints of death, myocardial infarction, hospitalization for heart failure, stroke, and dialysis. AKI and persistent AKI were observed in 82 (9.4%) and 25 (2.9%) patients, respectively. Multivariate Cox proportional hazards analysis demonstrated that persistent AKI, but not transient AKI, was an independent predictor of primary outcome (hazard ratio, 4.99; 95% confidence interval, 2.30-10.8; P < 0.001). Age > 75years, left ventricular ejection fraction < 40%, a high maximum creatinine phosphokinase MB level, and bleeding after PCI were independently associated with persistent AKI. Persistent AKI was independently associated with worse clinical outcomes in patients who underwent emergency PCI for AMI. Advanced age, poor cardiac function, large myocardial necrosis, and bleeding were predictors of persistent AKI.

Renal arterial resistive index versus novel biomarkers for the early prediction of sepsis-associated acute kidney injury

Acute kidney injury (AKI) is a critical complication of sepsis. There is a continuous need to identify and validate biomarkers for early detection. Serum and urinary biomarkers have been investigated, such as neutrophil gelatinase associated lipocalin (NGAL) and cystatin C (Cys C), but their reliability in the intensive care unit (ICU) remains unknown. Renal hemodynamics can be investigated by measuring the renal resistive index (RRI). This study aimed to compare the performance of RRI, serum NGAL (sNGAL), urinary NGAL (uNGAL), and serum Cys C levels as early predictors of the diagnosis and persistence of sepsis-associated AKI. A total of 166 adult patients with sepsis syndrome were enrolled immediately after ICU admission. Biomarkers were measured directly (T1) and on day 3 (T3). RRI was measured directly (T1) and 24 h later (T2). Patients were categorized (according to the occurrence and persistence of AKI within the first 7 days) into three groups: no AKI, transient AKI, and persistent AKI. The incidence rate of sepsis-associated AKI was 60.2%. Sixty-six patients were categorized as in the no AKI group, while another 61 were in transient AKI and only 39 were in persistent AKI. The RRI value (T1 ≥ 0.72) was the best tool for predicting AKI diagnosis (area under the receiver operating characteristic curve, AUROC = 0.905). Cys C (T1 ≥ 15.1 mg/l) was the best tool to predict the persistence of AKI (AUROC = 0.977). RRI (T1) was the best predictive tool for sepsis-associated AKI, while Cys C was the best predictor of its persistence and 28-day mortality.

Clinical profile and outcome of acute kidney injury in children admitted to paediatric intensive care unit: A prospective observational study

Introduction: Acute kidney injury (AKI) is a commonly encountered problem in the paediatric intensive care unit (PICU). There are limited reports on paediatric AKI from the Indian subcontinent. Objective: To determine the incidence, aetiology and outcome in paediatric AKI using Acute Kidney Injury Network (AKIN) criteria. Method: This prospective observational study was conducted in the PICU of a teaching hospital in Western Maharashtra, India, from July 2016 to June 2017 on patients aged 1 month to 17 years. Results: The incidence of AKI was 18.8% (80/426). The mean age was 70 ± 60 months. Most (66.3%) cases had stage I AKI and 54% developed AKI within 72 hours. Sepsis (35%), pneumonia (25%) and tropical febrile illnesses (18.7%) were the common aetiologies. Complete recovery (CR) was seen in 79% and partial recovery (PR) in 21%. CR was highest in stage I (91%) as compared to stages II and III (p=0.005). Mortality was 22% (18/80). Mortality significantly increased with the stage of AKI (p=0.003). Mechanical ventilation, inotrope support, shock and the stage of AKI had a significant association with mortality on bivariate analysis. Mechanical ventilation was found to be a significant independent predictor of mortality (p= 0.011). Renal replacement therapy was needed in 6 (8%) cases. Conclusions: About one-fifth of children admitted to ICU developed AKI and most experienced mild transient AKI. Moderate to severe AKI carried high mortality suggesting a dose-response effect. Infections remain the commonest cause and mechanical ventilation was an independent predictor of mortality.

Transient acute kidney injury after chimeric antigen receptor T-cell therapy in patients with hematological malignancies.

Acute kidney injury (AKI) occurs in 30% of patients infused with chimeric antigen receptor (CAR) T-cells. The purpose of this study was to identify risk factors and long-term outcomes after AKI in patients who received CAR T-cell therapy. Medical records of 115 adult patients with R/R hematological malignancies treated with CD19-targeted CAR T-cells at Vall d'Hebron University Hospital between July 2018 and May 2021. Baseline demographic data including age, gender, ethnicity, body mass index (BMI), and co-morbidities, as well as the type of hematological neoplasia and prior lines of therapy were collected. Laboratory parameters including serum creatinine and whole blood hemoglobin were retrospectively reviewed and values were gathered for days +1, +7, +14, +21, and +28 post-infusion. A total of 24/115 (21%) patients developed AKI related to CAR T-cell therapy; 6/24 with AKI over chronic kidney disease (CKD). Two patients had AKI in the context of lymphodepleting (LD) chemotherapy and the other 22 after CAR T-cell infusion, starting at day+1 in 3 patients, day+7 in 13 patients, day +14 in 1 patient, day+21 in 2 patients, and day+28 in 3 patients. Renal function was recovered in 19/24 (79%) patients within the first month after infusion. Male gender, CKD, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with AKI. Male gender, CKD, ICANS grade ≥3 and CRS grade ≥2 were identified as independent risk factors for AKI on multivariable analysis. In terms of the most frequent CAR T-cell related complications, CRS was observed in 95 (82%) patients and ICANS in 33 (29%) patients. Steroids were required in 34 (30%) patients and tocilizumab in 37 (32%) patients. Six (5%) patients were admitted to the intensive care unit (1 for septic shock, 4 for CRS grade ≥2 associated to ICANS grade ≥2, and 1 for CRS grade ≥3). A total of 5 (4.4%) patients died in the first 30 days after CAR T-cell infusion for reasons other than disease progression, including 4 cases of infectious complications and 1 of heart failure. Our results suggest that AKI is a frequent but mild adverse event, with fast recovery in most patients.

Acute kidney injury and renal recovery following Fontan surgery

ObjectivesAcute kidney injury has been described after Fontan surgery, but the duration and outcomes are unknown. We sought to describe the incidence of and risk factors for acute kidney injury and the phenotype of renal recovery, and evaluate the impact of renal recovery phenotype on outcomes. MethodsAll children who underwent a Fontan operation at a single center between 2009 and 2022 were included. Data collected included Fontan characteristics, vasopressor use, all measures of creatinine, and postoperative outcomes. Logistic regression models were used to assess predictors of acute kidney injury and the association between acute kidney injury and outcomes. ResultsWe enrolled 141 children (45% female). Acute kidney injury occurred in 100 patients (71%). Acute kidney injury duration was transient (<48 hours) in 77 patients (55%), persistent (2-7 days) in 15 patients (11%), more than 7 days in 4 patients (3%), and unknown in 4 patients (3%). Risk factors for acute kidney injury included higher preoperative indexed pulmonary vascular resistance (odds ratio, 3.90; P = .004) and higher postoperative inotrope score on day 0 (odds ratio, 1.13, P = .047). Risk factors for acute kidney injury duration more than 48 hours included absence of a fenestration (odds ratio, 3.43, P = .03) and longer duration of cardiopulmonary bypass (odds ratio, 1.22 per 15-minute interval, P = .01). Acute kidney injury duration more than 48 hours was associated with longer length of stay compared with transient acute kidney injury (median 18 days [interquartile range, 9-62] vs 10 days [interquartile range, 8-16], P = .006) and more sternal wound infections (17% vs 4%, P = .049). ConclusionsAcute kidney injury after the Fontan operation is common. The occurrence and duration of acute kidney injury have significant implications for postoperative outcomes.

Risk stratification of acute kidney injury (AKI) following ureteral stent insertion for colorectal surgery.

Ureteral stents have long been utilized during colorectal resections to assist in the identification of ureters intraoperatively and mitigate risk of ureteral injury. As these procedures have shifted toward robot-assisted laparoscopic methods, lighted stents have increasingly been used. The incidence of acute kidney injury (AKI) following bilateral ureteral stent placement has been reported to be as high as 41.9%. We sought to identify our single-institution risk and determine the extent to which age, sex, and stent type affected incidence of AKI. A retrospective analysis was performed at a single community hospital of all open and robotic-assisted laparoscopic colorectal surgeries from October 2012 to April 2022. If requested, ureteral stents were placed bilaterally by a urologist and later removed by the surgeon. Non-lighted stents used were 5 Fr whistle-tip (BARD); lighted stents were 6 Fr with a fiberoptic core (STRYKER). Kidney failure was described as a rise of creatinine to ≥ 1.5 times the preoperative value, per KDIGO guidelines. 633 consecutive colorectal surgeries were evaluated, with no stents placed in 237 cases, non-lighted stents placed in 137 cases, and lighted stents placed in 259 cases. No ureteral injuries were observed. Overall incidence of AKI for non-stented surgeries was 0.8% vs 5.8% for non-lighted stents and 5.8% for lighted stents. Patient age was the most significant factor in AKI incidence: for patients under 60, there was no statistical difference in AKI incidence for stented vs non-stented procedures (2.2% vs 1.1%). For patients over 60, the risk of AKI was 10.5% for stented vs 0.7% for non-stented. Female patients had statistically significant risk differences, with AKI incidence of 7.1% stented vs 0.0% non-stented. AKI completely resolved in all cases, regardless of cohort. In patients under age 60, the use of stents was not associated with an increased risk of AKI. For women and those over 60, stents pose a higher risk of transient AKI. Overall incidence of AKI in our larger and single-institution community hospital population was significantly lower than reported in other studies. No statistical difference was observed, overall, in AKI incidence between lighted and non-lighted stents.

#3372 HOST RESPONSE CHANGES ASSOCIATED WITH PERSISTENT ACUTE KIDNEY INJURY IN CRITICALLY ILL PATIENTS WITH COVID-19

Abstract Background and Aims In sepsis, the dysregulated host response has been, at least in part, linked to development of acute kidney injury (AKI) and its duration. Data on the host response to COVID-19 and development of persistent-AKI (duration &amp;gt; 48 h) in critically ill patients are scarce. We hypothesized that COVID-19 infected patients who develop persistent-AKI have different host response aberrations. To address this hypothesis, we sequentially measured host immune response biomarkers in critically ill patients admitted to the intensive care unit (ICU). Method We included patients admitted to the ICU from two tertiary hospitals and one primary care hospital between March and July 2020 (first wave). All patients had PCR-confirmed COVID-19. Excluded were readmitted patients, transfers from another ICU, and patients with chronic kidney disease (CKD stage 3 or higher). The presence of AKI was assessed by using hourly urine output and daily serum creatinine levels, and classified into 3 stages according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. In a subset of patients admitted to the two tertiary hospitals (n=113), 41 plasma protein biomarkers were sequentially measured using a Luminex platform or ELISA, and categorized into five pathophysiological domains: systemic inflammation, endothelial cell activation and dysfunction, coagulation activation, kidney dysfunction, and lung dysfunction. Mixed effects models were used to analyse longitudinal data. Results Of 185 ICU admissions enrolled, 8 were excluded because of existing CKD. Of the remaining 177 patients, 106 patients (59.9%) had AKI within the first 48 h of admission; of these, 76 patients (71.7%) had persistent AKI and 30 patients (28.3%) transient AKI. Patients with persistent AKI more often were obese and had a history of hypertension. A higher disease severity – as determined by the sequential organ failure assessment (SOFA) score - was observed in the persistent AKI group, which was driven by the renal component as the non-renal SOFA score was similar between no-AKI, transient-, and persistent AKI. Sequential protein biomarker analyses revealed that five biomarkers were significantly elevated in persistent-AKI compared to transient-AKI in the first four days, mainly related to inflammation (triggering receptor expressed on myeloid cells-1 [TREM-1], p=.003; tumour necrosis factor receptor 1 [TNF-RI], p &amp;lt; 0.001); lung dysfunction (clara cell secretory protein [CC16], p &amp;lt; 0.001), and kidney dysfunction (Cystatin C [p &amp;lt; 0.001]; neutrophil gelatinase-associated lipocalin [NGAL], p &amp;lt; 0.001). Plasma protein biomarkers reflective of endothelial cell- and coagulation activation were not different in patients with persistent-AKI as compared to patients with transient-AKI. No differences in plasma biomarkers were observed between transient AKI and no-AKI. Conclusion Transient AKI and no-AKI revealed little to no differences, while the persistent AKI group demonstrated stronger host response anomalies across the pathophysiological domains of inflammation and lung dysfunction. In contrast to what has been observed in non-COVID-19-related sepsis, endothelial injury and coagulation activation markers were not associated with AKI trajectories. These findings suggest that COVID-19 can induce a robust immune response that contributes to persistence of AKI, largely mediated through inflammatory responses.

#5569 ASSOCIATION OF URINARY CCL14 WITH PLASMA PROTEIN BIOMARKERS IN CRITICALLY ILL SEPSIS PATIENTS WITH PERSISTENT ACUTE KIDNEY INJURY

Abstract Background and Aims The urinary concentration of CC chemokine ligand 14 (CCL14) – a chemoattractant for T-cells and monocytes – has recently been identified as a strong predictor of persistence of severe acute kidney injury (AKI). The mechanisms by which CCL14 mediates persistent severe AKI are not yet completely understood. With sepsis being the most frequent cause of AKI, we wanted to externally validate whether urinary CCL14 concentration can differentiate sepsis patients with and without persistence of AKI, and its association with plasma protein biomarkers reflective of three pathophysiological pathways. Method Patients admitted with sepsis to the intensive care unit (ICU) were categorized according to the evolution of AKI (no-AKI, transient-AKI, and persistent-AKI, defined as lasting &amp;gt; 48h), and matched to a 1:1:1 ratio. AKI was assessed prospectively and daily, using the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification. Transient- and persistent-AKI patients had at least injury or failure (severe) RIFLE stages. Urine samples collected at ICU admission were analyzed for CCL14 level; in the same patient cohort we measured 9 plasma biomarkers reflective of systemic inflammation and cytokine responses, endothelial cell activation, and loss of endothelial barrier function. We applied a recently proposed cutoff of 1.3 ng/mL for high CCL14 for the identification of patients at high risk for persistent severe AKI. Results of 211 sepsis patients enrolled, 72 patients did not have AKI, 71 had transient AKI and 68 had persistent AKI. Majority of patients with high CCL14 had a persistent AKI (23 out of 31; 74.2%). CCL14 showed good discrimination between persistent-AKI and no-AKI (Area Under the ROC Curve [AUC], 0.82, 95%CI 0.75-0.89), and moderate discrimination between persistent-AKI and transient-AKI (AUC 0.71, 95%CI 0.55-0.87). High CCL14 was associated with higher disease severity as measured by APACHE-IV score, and source of infection being the urinary tract, and skin. The plasma protein analysis revealed that high urinary CCL14 was associated with more prominent systemic (anti-)inflammatory and cytokine responses, and signs of disrupted endothelial barrier function (shown by elevated interleukin [IL]-8 and IL-10, and decreased angiopoietin-1 [P = .005; P = .004; P = .009, respectively]). Within the persistent-AKI group, baseline characteristics (age, chronic comorbidities, and disease severity) did not differ between CCL14 groups, and high CCL14 was only associated with decreased angiopoietin-1 (P = .003). Conclusion External validation of urinary CCL14 showed good discrimination in critically ill sepsis patients between persistent AKI and no-AKI, and moderate discriminative ability to separate transient-AKI. High urinary CCL14 identifies persistent-AKI sepsis patients with more profound dysregulation of inflammatory pathways coupled with loss of endothelial barrier function. This could guide future therapeutic strategies targeting subgroups within the AKI population.

Update on persistent acute kidney injury in critical illnesses.

Acute kidney injury (AKI) affects about half of patients admitted to the intensive care unit (ICU), and worsens their short- and long-term outcomes. Apparently self-limiting AKI episodes initiate a progression toward chronic kidney disease (CKD) through cellular and molecular mechanisms that are yet to be explained. In particular, persistent AKI, defined in 2016 by the Acute Dialysis Quality Initiative as an AKI which lasts more than 48h from its onset, has been correlated with higher morbidity and mortality, and with a higher progression to acute kidney disease (AKD) and CKD than transient AKI (i.e. AKI with a reversal within 48h). This classification has been also used in the setting of solid organ transplantation, demonstrating similar outcomes. Due to its incidence and poor prognosis and because prompt interventions seem to change its course, persistent AKI should be recognized early and followed-up also after its recovery. However, while AKI and CKD are well-described syndromes, persistent AKI and AKD are relatively new entities. The purpose of this review is to highlight the key phases of persistent AKI in ICU patients in terms of both clinical and mechanistic features in order to offer to clinicians and researchers an updated basis from which to start improving patients' care and direct future research.

Acute Charcot neuropathy: A devastating consequence of diabetes mellitus

Abstract Introduction Acute Charcot neuropathy (ACN) is a complication of diabetes mellitus. The prevalence of ACN may be up to 13% in diabetic individuals. ACN has a complex etiology. Although it mostly affects middle of the foot, hind-foot joints, the ankle, and forefoot joints; upper limp may also be affected. Here, we present a case with ACN, whose diagnosis was hard to differentiate and manage. Clinical Case A fifty-nine-year-old female admitted to our emergency department with a complaint of pain, numbness, swelling, edema and erythema on left arm. When questioned, she had a history of type 2 diabetes for 22 years and had impaired glycemic regulation with 12.2% HbA1c level. She had all macro and micro vasculary complications of diabetes. On physical examination, her left arm was swollen, pulses were not palpabl. With a suspicion of acute thromboembolism, doppler ultrasound was performed and USG showed no arterial occlusion, but thrombosis from the basilic vein to the proximal brachial vein was seen. She initiated anticoagulant therapy with heparin. After 2 weeks, her complaints increased and pallor, coldness, and pain with passive movements on the left arm were added. She admitted to our intensive care unit with a diagnosis of compartment syndrome. She was followed in ICU with stable hemodynamics and without oxygen supplementation. She had transient acute kidney injury due to rhabdomyolysis but resolved without hemodialysis. Despite fasciotomy, myonecrosis developed on left arm and transhumeral resection was performed. After this devastating result, the patient transferred to endocrinology clinic. Intensive insulin therapy and appropriate antibiotic treatment were continued. During her stay in our clinic, she had the same complaints and physical examination findings on her left foot. Imaging studies (X-ray, bone scintigraphy) showed no osteomyelitis but acute charcot arthropathy was seen. Her glucose levels were regulated, and antibiotics completed. The physical strengthening and ROM exercises for lower extremity and oral total calorie intake was adjusted. Her HbA1c level was decreased to 6.2% without hypoglycemia and she is stable on follow-up. Conclusion ACN is a devastating complication of diabetic neuropathy with its consequences. The diagnosis may mislead clinicians to cellulitis, acute venous thrombosis, arthritis or gout. Misdiagnosis or delay in diagnosis may result in serious consequences such as infection, ulceration even amputation as in our case. A multidisciplinary approach and close monitoring of the findings may provide huge benefit for the patient.

Mortality and Cumulative Kidney Score are Associated with Transient and Persistent Acute Kidney Injury in Septic Patients: A Retrospective Study Based on MIMIC-IV.

Acute kidney injury (AKI) is frequently caused by sepsis. Recently, the Acute Disease Quality Initiative (ADQI) workgroup further classified AKI as transient or persistent. Oliguria and increased serum creatinine represent two different kinds of renal impairment. The aim of the study was to assess mortality and cumulative AKI score associated with transient and persistent AKI in septic patients. Septic patients were stratified according to the presence and AKI development (considered persistent when remaining >48 h) were included. An adjusted logistic regression model was used to determine hospital mortality. In addition, we calculated an AKI score by combining both Kidney Disease: Improving Global Outcomes (KDIGO) criteria of urine output and creatinine AKI stages. The relationship between the cumulative AKI score and persistent AKI was further examined using the logistic regression model and receiver operating characteristic (ROC) curve analysis. 12928 septic patients were enrolled in the study. AKI occurred in 73.7% of septic patients, in 39.5% was transient and in 60.5% was persistent. Patients with persistent AKI had higher severity scores and more severe renal dysfunction upon admission. Persistent AKI, but not transient AKI, was associated with increased intensive care units (ICUs) and hospital mortality. Then we found that the cumulative AKI score was associated with an increased risk of persistent AKI. This association was consistent across three original KDIGO severity stages and subgroup analyses. It was found that persistent AKI was independently associated with mortality in septic patients. Furthermore, serum creatinine and urine output criteria had cumulative effects on KDIGO AKI staging and provided more information about the relationship between AKI and outcomes.

EndoSuture aneurysm repair versus fenestrated aneurysm repair in patients with short neck abdominal aortic aneurysm.

The aim of this study was to compare midterm results of EndoAnchors in EndoSuture aneurysm repair (ESAR) versus fenestrated endovascular aneurysm repair (FEVAR) in short neck abdominal aortic aneurysm (AAA). All patients who underwent an ESAR procedure for a short neck AAA at our center between September 2017 and May 2020 were considered for analysis. To form the control group, preoperative computed tomography angiography of patients who underwent FEVAR for juxtarenal AAA between April 2012 and May 2020 were reviewed and patients who met short neck criteria selected. A propensity-matched score on neck length and neck diameter was calculated, resulting in 18 matched pairs. AAA shrinkage, type Ia endoleaks (EL), AAA-related reinterventions, and AAA-related deaths were compared. The median AAA diameter was 54mm (interquartile range [IQR], 52-61mm) versus 58mm (IQR, 53-63mm) with a median neck length of 8mm (IQR, 6-12mm) vs 10mm (IQR, 6-13mm) in ESAR and FEVAR patients, respectively. Technical success was 100% in both groups. Procedural success was 94% in the ESAR group versus 100% in the FEVAR group. The median procedure duration was 138mm (IQR, 113-182mm) vs 240mm (IQR, 199-293mm) ( P< .001) and the median length of stay was 2days (IQR, 2-3days) vs 7days (IQR, 6-7days) (P< .001) in ESAR and FEVAR patients, respectively. No major hospital complications were observed in ESAR patients compared with two in FEVAR patients (11%) with one transient acute kidney injury and one transient paraplegia. The median follow-up was 23months (IQR, 19-33months) vs 36months (IQR, 22-57months) with 67% versus 61% AAA shrinkage in the ESAR and FEVAR groups, respectively (P= .73). No type Ia EL, proximal neck-related reinterventions, or AAA-related deaths were observed in either group. No AAA-related reintervention was observed in the ESAR group versus three reinterventions in the FEVAR group (P= .23). ESAR seems to be a safe technique with no major postoperative complications or reinterventions observed during follow-up. It seems to offer similar midterm results as FEVAR in terms of type Ia EL, aneurysm shrinkage, and aneurysm-related mortality. ESAR seems to be a good off-the-shelf alternative to FEVAR in case of technical constraints.

Transient vs In-Hospital Persistent Acute Kidney Injury in Patients With Acute Coronary Syndrome

BackgroundThe occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ. ObjectivesThe aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS. MethodsIn the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5 mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding. ResultsPersistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95% CI: 1.48-3.64; P < 0.001; NACE: adjusted HR: 2.29; 95% CI: 1.48-3.52; P < 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95% CI: 2.03-5.82; P < 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria. ConclusionsAmong patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627)

Evaluation of Predictors, Kinetics of Renal Recovery and Outcomes of COVID-19 Patients with Acute Kidney Injury Admitted to Intensive Care Unit: An Observational Study.

The incidence of acute kidney injury (AKI) is greater than 50% among coronavirus disease-2019 (COVID-19) patients admitted to the intensive care unit (ICU). However, the literature on predictors and kinetics of renal recovery remains unclear. This observational study was conducted in a 30-bedded mixed ICU of a tertiary care center from May 2020 to July 2021. A total of 200 consecutive adult COVID-19 patients who had AKI in ICU were included. Using logistic regression with the best subset selection, predictors of renal recovery were identified. Outcomes and kinetics of AKI recovery were determined. Among 200 patients, 67 recovered from AKI, of which 38, 17, and 12 patients had transient AKI, persistent AKI, and acute kidney disease (AKD), respectively. A total of 25 patients had AKI relapse, primarily associated with hospital-acquired infections. Results of logistic regression showed that the combination of Acute Physiology and Chronic Health Evaluation (APACHE II) {odds ratio (OR) 1.1 [p < 0.001; 95% confidence interval (CI) 1.06-1.16]}, day onset of AKI [OR 1.6 (p = 0.001; 1.24-2.24)] and severity of AKI [OR 2.9 (p < 0.001; 2.03-4.36)] were the predictors associated with poor renal recovery. This model had sufficient discrimination with the area under the curve (AUC) of 0.86. Renal replacement therapy requirement and mortality among COVID-AKI patients were 68 and 84%, respectively. A higher APACHE II at admission, a longer time to onset of AKI, and the severity of AKI during ICU stay predicted poor renal recovery. Study results emphasize the need for stepping-up dialysis resources in the likely case of future waves of COVID-19. The relapse of AKI was associated with sepsis, and mortality rates were substantially high. Gudivada KK, Narayan SK, Narasimha A, Krishna B, Muralidhara KD. Evaluation of Predictors, Kinetics of Renal Recovery and Outcomes of COVID-19 Patients with Acute Kidney Injury Admitted to Intensive Care Unit: An Observational Study. Indian J Crit Care Med 2022;26(12):1293-1299.

Long-Term Effects of Acute Kidney Injury Following Endovascular Femoropopliteal Intervention: Insights From a Multicenter Trial.

To examine the association between acute kidney injury (AKI) severity and duration with cardiovascular mortality, following endovascular treatment of femoropopliteal disease, and whether it is AKI in itself that confers an increased risk of cardiovascular mortality. A retrospective analysis of prospectively collected data obtained between 2014 and 2019 from 3 vascular centers. Renal function was followed up for a minimum of 90 days. Electronic records were queried to establish a cause of death, where applicable. Patients were excluded if unable to provide written informed consent or if presenting with acute limb ischemia. Primary outcomes were the hazard ratios for cardiovascular death (AKI patients vs no AKI; no AKI vs stage 1 AKI vs stage 3 AKI; and no AKI vs transient AKI vs established AKI). Propensity score-matched analysis was used to establish whether developing AKI, in patients with similar demographics and procedural characteristics, is associated with a higher risk of cardiovascular death. Overall 239 patients developed AKI, and this was associated with an increased risk of cardiovascular mortality (hazard risk [HR]: 4.3, 95% confidence intervals [CIs]: 2.1-6.8, pairwise comparison p value=0.006]. This was dependent on the severity of the AKI stage (HR 5.4, 95% CI: 2.4-7.3, pairwise comparison p value=0.01) and duration (HR 4.2, 95% CI: 2.3-6.2, pairwise comparison p value=0.04). The propensity score-matched analysis showed that even when patients are matched for comorbidity and procedural characteristics, AKI confers an increased risk of mortality (p=0.04). Acute kidney injury is common after femoropopliteal endovascular therapy. It confers an increased risk of long-term cardiovascular mortality, which is still present when renal decline is transient, and highest for patients with established decline in renal function. This is the first study in the setting of peripheral arterial disease to show that acute kidney injury has an adverse effect on cardiovascular mortality, in the long-term, that is dependent on its severity, and present even when the AKI is transient. We have also shown that this difference in cardiovascular mortality becomes more pronounced from the medium-term, and thus closer follow-up of these patients is required.

Is Renal Function Equally Impacted By Hypomethylating Agents during Acute Myelogenous Leukemia Induction Therapy?

Background: Hypomethylating agents (HMA), such as azacitidine (AZA) /decitabine (DAC) plus BCL2 inhibitors are increasingly used as acute myelogenous leukemia (AML) therapy. However, side effects such as neutropenic fever, tumor lysis syndrome and acute kidney injury (AKI) are described. Although AKI induced by HMAs is infrequent, severity can result in permanent renal damage. Previous reports suggest that kidneys clear more than 50% of AZA with renal tubular acidosis and electrolytes abnormalities developing after drug exposure. To date, it is unknown whether concurrent comorbid conditions increase risk of AKI in AML patients. This study aimed to evaluate renal function overtime in patients receiving a HMAs plus venetoclax to determine each agent's ability to induce AKI. Methods: A single center retrospective, descriptive study from January 2018 to March 2022 was conducted at Baylor St. Luke's Medical Center. Patients with a confirmed diagnosis of AML, who received at least 1 cycle of venetoclax and a HMA, who were not eligible for intensive chemotherapy were included. Primary objective was incidence of AKI in AZA vs DAC during first week induction. Given potential additive impact of BCL2 inhibition on renal function, secondary objective was a subgroup analysis of patients in AZA group receiving venetoclax ≤ or >14 days. Descriptive and paired-t-test comparing baseline and daily sequential creatinine and glomerular filtration rate (GFR) were analyzed using SAS. Results: 40 AML patients were included. 25/40 (62.5%) and 15/40 (37.5%) received AZA and DAC. Baseline patient characteristics were well balanced between groups, except for differential absolute lymphocyte count (ALC) expression [3.4 K/uL vs 1.3 K/uL, in AZA treated vs DAC, p=0.01]. Patients receiving AZA developed significantly higher incidence of AKI from day 1 to day7. DAC was associated with transient significant AKI detectable only during day 5 (Fig 1A). At last follow up, incidence of irreversible renal failure was observed in 1/40 (2.5%) of AML patients. In further subgroup analysis, we sought to understand the possible nephrotoxic BCL2- inhibitor effect while combining with AZA. Patients exposed >14 days of BCL2- inhibitors developed sustained AKI throughout day 3 to day 7 [p=<0.05 for all time points], as compared to those receiving ≤14 days. No detectable differences on incidence of diabetes, heart failure, infections, and use of diuretics were found in patients exposed or not to 14 days of BCL-2 inhibitor. Conclusions: Our study demonstrates more severe and sustained worsening renal function in patients exposed to AZA than those receiving DAC. While our report recapitulates similar previous observations, we describe an important synergistic BCL-2 inhibitor effect on renal function when combined with AZA. It would be interesting to investigate whether higher than expected ALC cooperates to induce renal damage via enhanced T-cell immunity. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

OA19 A case of severe refractory lupus enteritis and nephritis that remitted with Obinutuzumab

Introduction/BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease that can affect almost any organ system but gastrointestinal (GI) involvement is very rare. Obinutuzumab is a humanised type II anti-CD20 monoclonal antibody that is licensed to treat haematological malignancies. It has been used in a small number of SLE patients with secondary non-depletion non-response (2NDNR) to Rituximab and appears to be effective in lupus nephritis (LN) as outlined in the NOBILITY trial. We present a case of refractory lupus enteritis (LEn) and LN in a patient with 2NDNR to repeated Rituximab cycles that achieved remission with Obinutuzumab.Description/MethodA 19-year-old African woman was diagnosed with SLE in 2018 after presenting with polyarthritis without systemic involvement. Blood tests showed leucopenia, positive antinuclear antibody, anti-double-stranded DNA >200 IU/ml and hypocomplementaemia. Prednisolone and Methotrexate were commenced. However, one month later she presented to hospital with generalised abdominal pain, vomiting and diarrhoea. CT abdomen demonstrated significant small bowel wall thickening with mucosal hyperenhancement. Multidisciplinary team (MDT) input confirmed likely LEn. She was treated successfully with intravenous Methylprednisolone and Rituximab. Total parenteral nutrition was required for two weeks.Unfortunately, four further hospital admissions followed over the next six months due to GI symptoms, transient acute kidney injury and moderate proteinuria. Small bowel oedema persisted on MRI, three months after the CT. Renal biopsy demonstrated class 2 LN. Intravenous methylprednisolone helped and further Rituximab was given but she had infusion reactions. Six months later she re-presented with abdominal pain, synovitis and had nephrotic range proteinuria. She was treated again for LEn after gastroenterology input. Further Rituximab was given (MabThera instead of Truxima) but reactions still occurred and her B cells were non-deplete. Repeat renal biopsy confirmed class 4 LN and intravenous Cyclophosphamide (Euro-Lupus regimen) was commenced. This was repeated seven months later due to persisting high disease activity and proteinuria despite a short trial of intravenous Belimumab. However, she was admitted to hospital with colitis on CT after completing the second course of Cyclophosphamide. MDT decision was to treat with Obinutuzumab. Since commencing treatment eighteen months ago, her SLE has dramatically improved and she feels well for the first time. SLEDAI-2K score is 2 (16 pre-treatment), renal function has recovered with mild proteinuria. Anti-double-stranded DNA has reduced from >200 to 52.9 IU/ml and complements normalised. She remains on Prednisolone 5mg daily and Tacrolimus and a third maintenance dose of Obinutuzumab is planned.Discussion/ResultsLEn has been reported in only 0.2-5.8% of SLE cases. It is defined by the British Isles Lupus Assessment Group (BILAG 2004) by either vasculitis or inflammation of the small bowel supported by imaging or histology. Its pathogenesis is poorly understood but thought to be related to immune complex deposition and complement activation resulting in intestinal capillary leak and submucosal oedema. Symptoms are non-specific and a review by Janssens et al. (2013) suggested abdominal pain (97%), ascites (78%), nausea (49%), vomiting (42%) and diarrhoea (32%) were the most common symptoms in patients with LEn. They reported the ileum and jejunum were most commonly affected in LE (84% and 83% respectively), followed by colon (19%), duodenum (17%) and rectum (4%).Abdominal CT is considered to be the first line investigation and ‘classic’ radiological findings are bowel wall oedema (“target sign”), engorgement/increased number of mesenteric vessels (“comb sign”) and increased attenuation of the mesenteric fat (Ha et al. 2000, and Kim et al. 2006). These were all demonstrated on our patient’s initial CT abdomen which showed engorgement of the mesenteric vessels from the proximal jejunum to the proximal ileum.LEn seldom occurs in isolation and usually presents in the context of high disease activity and other systemic involvement. It is often responsive to glucocorticoids and bowel rest but further immunosuppression with Cyclophosphamide or Rituximab might be warranted in refractory cases as in our patient’s case.Obinutuzumab has been shown to be safe, effective and steroid-sparing in renal and non-renal SLE patients with 2NDNR to Rituximab from a case series of 9 patients by Arnold et al. (2022). This applied to LN in our patient and we believe this to be the first case where refractory LEn was treated successfully with Obinutuzumab.Key learning points/ConclusionAlthough very rare, have a high index of suspicion of LEn in SLE patients who present with GI symptoms and typical radiological findings.LEn often occurs with other systemic manifestations including LN and it is important to assess for these at the time of diagnosis of LEn.Obinutuzumab is an emerging treatment for severe SLE particularly 2NDNR to Rituximab and can improve both LN and LEn. We eagerly await results from the current REGENCY and ALLEGORY clinical trials which are assessing Obinutuzumab in renal and non-renal SLE patients respectively.

POS-136 MANAGEMENT AND OUTCOMES OF SEPSIS ASSOCIATED ACUTE KIDNEY INJURY IN CRITICALLY ILL PATIENTS

Sepsis-associated acute kidney injury (AKI)remains a major cause of mortality in patients with critical illness and has an especially high health-related burden in developping countries. However, only a few clinical studies have focused on the clinical characteristics and prognosis of septic AKI, especially in low-income settings. Therefore, the aim of our study was to describe the clinical profile, management and outcome of critically ill patients with sepsis associated AKI. A retrospective observational study of critically ill patients with septic AKI was performed from March 2020 to June 2021 at our university hospital. Sepsis was diagnosed clinically by the presence of acute infection and new organ dysfunction.The presence of AKI was evaluated using the Acute Kidney Injury Network (AKIN) criteria. Patients with preexisting ESRD and those who did not fulfill at least one predefined criterion for AKI were excluded. A total of 105 patients with a median age of 58.9 years (31-78) were enrolled, including 69 and 36 patients with persistent and transient AKI, respectively. The mean SAPS II score was 51.8 (38-77). The primary source of sepsis was mainly abdominal (42.8%). AKI was defined by oliguria in 18 patients (17.1%), by creatinine elevation in 65 patients (61.9%), and by both criteria in 22 patients (21%). Septic AKI was associated with great aberrations in hemodynamics, with 71 patients (67.6%) requiring vasoactive therapy and 65 patients (61.9%) requiring mechanical ventilation. AKI severity according to the AKIN classification scheme was determined to be stage 1 in 32 patients (30.5%), stage 2 in 22 patients (20.9%), and stage 3 in 51 patients (48.6%). Overall, 75.2% of the cohort required renal replacement therapy (RRT). Hospital survival was 63.8% (n = 23) in patients with transient AKI and 43.5% (n =30) in patients with persistent AKI. Sepsis is the main cause of AKI in intensive care units, accounting for up to 50% of cases. Our results suggest that septic AKI is associated with higher disease severity scores at admission, requirement of vasoactive drugs, need for mechanical ventilation and increased hospital mortality. Further studies are required, especially in developping countries, to implement more preventive measures and therapeutic interventions to decrease CKD progression and mortality in these patients.