Acute Kidney Injury Stage Research Articles

Abstract 12852: Transcatheter Aortic Valve Replacement for Aortic Stenosis in Small Aortic Annulus: Medium-Term Follow-Up

Introduction: Small aortic annulus (SAA) is a clinical challenge in managing aortic stenosis (AS). The SAA has been associated with poorer outcomes after surgical AVR with an increased risk of perioperative and overall mortality, suboptimal valvular hemodynamics, and adverse cardiovascular events. Hypothesis: TAVI could be a therapeutic alternative in these patients. Methods: We performed a retrospective analysis of all patients with AS treated with TAVI from 2015 to 2021 in our center, with SAA defined as the aortic annulus of ≤22mm perimeter-derived diameter (PDD), measured by CT. Results: Sixty-eight patients were included (85.3% women, 83.2± 6.5 years) with a mean PDD of 20.7 ± 1.1 mm. The 14.7% had LVEF <50% and 1.4% had bicuspid aortic valve. The Access route was transfemoral in 64 patients (94.2%) and 4 transapical (5.8%). Self-expanding prostheses were used in 78% of the cases, balloon-expandable prostheses in 17.6%, and mechanically-expandable prostheses in 4.4%. The size of the aortic prostheses was 23mm in 82.3% and >23mm in 17.7%. The perioperative implant success rate was 100% defined as single prosthesis implantation with a mean gradient <20mmhg and angiographic paravalvular leak <2. The rate of new permanent pacemaker implantation was 13.2%. The in-hospital complications rate was 5.8% (4 patients): major vascular complication in 1 patient (1.4%), acute kidney injury stage ≥2 in 1 (1.4%), disabling stroke in 2 (2.9%). There were no deaths in the first 30 days of the procedure. At discharge, the TTE máximum gradient was 19.8 ± 9.2mmhg, the mean gradient 9 ± 4.8mmhg, and 4 patients had paravalvular leak grade ≥2 (5.9%). During a mean follow-up of 27.8 ±7.6 months, 45 patients were in NYHA functional class I (66.2%), 19 in NYHA 11 (27.9%), and 3 in NYHA III (4.4%). Eight patients (11.7%) were readmitted due to heart failure, 10 died (14.7%) due to all-cause mortality, and only 3 of them died due to cardiovascular causes (4.4%). Conclusions: Although the optimal approach for treating patients with AS and SAA remains controversial. TAVI is a very attractive option in these patients, allowing the implantation of prostheses with excellent immediate hemodynamic results, a low rate of complications, and significant clinical improvement in the follow-up.

Abstract 127: Urine Output And Mortality In Patients Resuscitated From Out Of Hospital Cardiac Arrest

Background: Urine output (UO) measurement utility after out-of-hospital cardiac arrest (OHCA) survivors who undergo targeted temperature management (TTM) is not well understood. Methods: We included 247 comatose adult patients who underwent TTM after OHCA between 2007 and 2017 and excluded those on maintenance dialysis. Groups were defined based on mean hourly UO during the first 24 hours: Group 1 (<0.5 ml/kg/hr, n=73), Group 2 (0.5-1 ml/kg/hr, n=81) and Group 3 (>1 ml/kg/hr, n=93). Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria were used to define and stage acute kidney injury (AKI). Multivariable analysis was used to evaluate in-hospital mortality. Results: In-hospital mortality decreased as 24-hour mean UO increased (56.2% [41/73] vs 29.6% [24/81] vs 18.3% [17/93] in Groups 1, 2 and 3, respectively; adjusted OR 0.93 per 0.1 ml/kg/h higher, 95% CI 0.87-0.99, p = 0.03), and UO < 0.5 ml/kg/hr was strongly associated with in-hospital mortality (adjusted OR 4.2 [1.6-10.8], p=0.003). In-hospital mortality varied by the KDIGO stage and UO group (Figure), lowest in KDIGO stage 0 and highest in KDIGO stage 3. Both UO (adjusted OR 0.92 per 0.1 ml/kg/h higher, p = 0.002) and KDIGO stage (adjusted OR 1.62 per each stage, p = 0.002) were associated with in-hospital mortality when included in the same model. Among patients with KDIGO stage 0, lower UO portended higher mortality (Figure). Likewise, among patients with low UO (group 1), a higher KDIGO stage predicted higher mortality. Conclusion: Amongst OHCA survivors undergoing TTM, higher UO is incrementally associated with lower in-hospital mortality. The lowest mortality was observed at UO >=1 ml/kg/h, suggesting this as a target for resuscitation in OHCA patients undergoing TTM. Low UO remains associated with in-hospital mortality even when accounting for AKI by creatinine criteria, suggesting that oliguria is a more sensitive prognostic marker in the early post-OHCA phase.

PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose

Abstract Introduction Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, has emerged as an important novel therapy for osteoporosis, hypercalcemia of malignancy (HCM), and other skeletal disorders in adults. While off-label use has been reported in children with these conditions, pediatric data is limited. We report a case of a 35-month old patient who had received Denosumab for management of life-threatening HCM. Case 2-year-old male previously healthy who presented with increase work of breathing, altered mental status, and changes in his voice in the setting of progressive neck swelling over 2-weeks. Initial workup revealed a large mediastinal mass and metabolic anomalies including hypercalcemia (21.6mg/dL), shortened QTc on ECG, and acute kidney injury (AKI) stage 1-2 (eGFR 71 ml/min/1.73m2). Flow cytometry confirmed diagnosis of T-Cell ALL. PTHrP was 8.6pmol/L with a PTH of 7.1Pg/ml and a 25OH vitamin D of 38.9Ng/ml with 1,25OH of 6pg/ml. On admission, patient started maintenance IV fluids, dexamethasone, calcitonin, and denosumab 0.3mg/kg. His calcium normalized by day 2-3 of treatment and eventually started oral calcium supplementation (25mg/kg elemental) with calcitriol to prevent hypocalcemia. Calcium stabilized with the lowest level at 7.6mg/dL on day 7; did not require IV calcium correction during hospitalization and renal function normalized. Patient was discharged on 0.5 mcg of calcitriol daily and 125mg/kg/day of elemental calcium. Discussion HCM develops in less than 1% of pediatric patients with cancer. Most cases are due to systemic parathyroid hormone-related protein, followed by osteolytic metastases leading to inflammatory cytokines locally released and least common via ectopic production of 1,25 dihydroxy vitamin D. HCM is an oncologic emergency. In adults, Denosumab has been used for HCM as a second-line agent after failure to respond to bisphosphonates, or when they are contraindicated. Bisphosphonates have shown to worsen renal function, even in those with normal glomerular filtration. Denosumab has been overall very well tolerated by patients. Initial hypocalcemia that peaks between days 4–10, and rebound hypercalcemia are one of the more feared side effects. Despite Denosumab not been cleared by the kidney, in adult patients with AKI or CKD, they have a higher risk of developing rebound hypercalcemia after receiving the standard 120mg SQ dose; a weight base dose was proposed, 0.3mg/kg for those with renal impairment. The reported dose in pediatrics for HCM has been 120mg, but we decided to do a weight base dose as our patient had AKI at presentation, with increased risk for decompensation once chemotherapy was started. Our patient responded very well to Denosumab with improvement in hypercalcemia, without severe hypocalcemia requiring IV calcium supplementation. Incidentally, to the best of our knowledge, our patient is the youngest patient reported to have received Denosumab for management of HCM. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in Low-risk Patients: A Meta-Analysis Based on a 2-Year Follow-Up.

Previous studies have shown that transcatheter aortic valve implantation is the best alternative therapy to surgical aortic valve replacement in high-risk surgical patients with aortic stenosis. However, it is not clear whether transcatheter aortic valve implantation can be utilized in low-risk surgical patients with aortic stenosis. This studyaimed to evaluate the safety and efficacy of transcatheter aortic valve implantation in low-risk patients. From the outset of our initiative until April 2022, PubMed, EMBASE, and the Cochrane database were thoroughly searched, yielding the selection of 3 randomized controlled trials including 2644 patients with aortic stenosis, to assess outcome measures at distinct follow-up time. The mean Society of Thoracic Surgeons Predicted Risk of Mortality score of patients was 2.2. At the 30-day and 1-year follow-up, transcatheter aortic valve implan- tation was associated with a lower incidence of all-cause mortality, cardiovascular mor- tality, acute kidney injury (stage 2 or 3), life-threatening or significant bleeding, and new atrial fibrillation but an increased risk of permanent pacemaker implantation. At the 2-year follow-up, transcatheter aortic valve implantation only had an advantage in new atrial fibrillation (relative risk, 0.27; 95% CI, 0.14-0.51; P < .0001), with no significant differ- ence in all-cause mortality or cardiovascular mortality. For low-risk surgical patients with aortic stenosis, compared to surgical aortic valve replacement, transcatheter aortic valve implantation was associated with lower all-cause mortality at 30-day follow-up and lower cardiovascular mortality at 1-year follow-up. Except for the advantages in new atrial fibrillation, transcatheter aor- tic valve implantation had no significant impact on mortality at 2-year follow-up.

Acute Kidney Injury in Non-Intensive Care Unit (ICU) Hospitalizations for Coronavirus Disease (COVID-19).

Background: Acute kidney injury (AKI) is a common complication among SARS-CoV-2-positive patients who undergo hospitalization. Abundant evidence exists concerning the epidemiology of AKI in patients hospitalized in the ICU for COVID-19 but limited data are available about the occurrence of AKI in SARS-CoV-2-positive patients being hospitalized in a non-ICU setting. Aim and Methods: We have carried out a retrospective study to evaluate frequency and risk factors for AKI among patients consecutively admitted at a third-level university hospital starting from February 2020 (the beginning of the first wave of the SARS-CoV-2 pandemic); all patients were hospitalized outside the ICU. Results: A total of 387 SARS-CoV-2-positive patients were included in the current study; 372 (96.1%) had SARS-CoV-2-related pneumonia. In-hospital AKI onset was recorded in 119 (30.7%) patients, mainly with AKI stage 1 (n = 74, 62.2%); eighteen (4.6%) patients reported AKI stage 3 and six (1.5%) patients had HD-dependent AKI. There were 235 (60.7%) patients with severe COVID-19, and this was more common in patients developing AKI, 94.5% (86/119) vs. 86.1% (149/268), p = 0.02. Multivariate regression model (n = 144 patients) reported an independent and significant relationship between AKI occurrence and greater levels of ferritin (p = 0.036), IL-6 (p = 0.032), and azotemia at admission (p = 0.0001). A total of 69 (17.8%) SARS-CoV-2-positive patients died and strong predictors of in-hospital death resulted from age (p < 0.0001), serum ferritin (p < 0.0001) and white blood cells (p < 0.001). According to multivariable analysis (n = 163 patients), there was a consistent link between in-hospital death and AKI stage (1) (p = 0.021) and -stage (2) (p = 0.009). Our results support the notion that AKI occurs frequently among hospitalized COVID-19 patients even in a non-ICU setting and plays a pivotal role in the mortality of this population. Further studies are ongoing in order to clearly establish the frequency of AKI in patients with COVID-19; the mechanisms underlying kidney injury in this population are an area of active investigation. These data provide solid evidence to support close monitoring of COVID-19 patients for the development of AKI and measures taken to prevent this.

Development and validation of a nomogram for postoperative severe acute kidney injury in acute type A aortic dissection.

Postoperative acute kidney injury (AKI) is a major complication associated with increased morbidity and mortality after surgery for acute type A aortic dissection (AAAD). To the best of our knowledge, risk prediction models for AKI following AAAD surgery have not been reported. The goal of the present study was to develop a prediction model to predict severe AKI after AAAD surgery. A total of 485 patients who underwent AAAD surgery were enrolled and randomly divided into the training cohort (70%) and the validation cohort (30%). Severe AKI was defined as AKI stage III following the Kidney Disease: Improving Global Outcomes criteria. Preoperative variables, intraoperative variables and postoperative data were collected for analysis. Multivariable logistic regression analysis was performed to select predictors and develop a nomogram in the study cohort. The final prediction model was validated using the bootstrapping techniques and in the validation cohort. The incidence of severe AKI was 23.0% (n = 78), and 14.7% (n = 50) of patients needed renal replacement treatment. The hospital mortality rate was 8.3% (n = 28), while for AKI patients, the mortality rate was 13.1%, which increased to 20.5% for severe AKI patients. Univariate and multivariate analyses showed that age, cardiopulmonary bypass time, serum creatinine, and D-dimer were key predictors for severe AKI following AAAD surgery. The logistic regression model incorporated these predictors to develop a nomogram for predicting severe AKI after AAAD surgery. The nomogram showed optimal discrimination ability, with an area under the curve of 0.716 in the training cohort and 0.739 in the validation cohort. Calibration curve analysis demonstrated good correlations in both the training cohort and the validation cohort. We developed a prognostic model including age, cardiopulmonary bypass time, serum creatinine, and D-dimer to predict severe AKI after AAAD surgery. The prognostic model demonstrated an effective predictive capability for severe AKI, which may help improve risk stratification for poor in-hospital outcomes after AAAD surgery.

Optimal stage of initiating continuous renal replacement therapy in the treatment of neonatal acute kidney injury.

To explore the optimal stage of initiating continuous renal replacement therapy (CRRT) in the treatment of neonatal acute kidney injury (AKI), a total of 25 AKI neonates treated with CRRT were hospitalized at the Department of Neonatology of Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University (Shanghai, China) from November 2016 to June 2021. According to the renal function, the AKI neonates prior to CRRT were divided into two groups as follows: AKI stage 0-1 and AKI stage 2-3. The changes noted in specific indicators including renal function, electrolyte concentration, and acid-base balance index were analyzed at 0, 12, 24 and 48 h, and at the end of the CRRT treatment. Among the 25 neonates with AKI, serum potassium, urea nitrogen and creatinine levels were significantly decreased following 12 h of CRRT treatment and reached the normal range following 24 h of CRRT treatment with a significant increase in the volume of urine. The serum creatinine levels of the neonates in the AKI stage 0-1 group were significantly decreased following 24 h of CRRT treatment and urine output was significantly increased. At 24 h and following CRRT treatment, the levels of serum creatinine of AKI stage 2-3 neonates were higher than those of AKI stage 0-1 neonates (F=3.013, 5.005; P<0.05), and at all time-points, the urine output of AKI stage 0-1 was higher than that of AKI stage 2-3 (F=13.785, 4.008, 0.965; P<0.05). A total of four cases of thrombocytopenia, two cases of obstruction, and two cases of hypotension were noted in the course of CRRT treatment (the occurrence rate was 8/25). Therefore, it was concluded that CRRT could be an effective measure for the treatment of AKI neonates. Thus, ideally CRRT treatment of AKI neonates should be initiated in cases characterized as AKI stages 0-1.

Toll-Like Receptor 4 Is an Early and Sensitive Biomarker to Detect Acute Kidney Injury after Surgery for Type A Aortic Dissection.

Acute kidney injury (AKI) is a relatively common complication after surgery for type A acute aortic dissection (ATAAD) and is associated with a poor prognosis. Preclinical models suggest that toll-like receptor 4 (TLR4) may participate in the pathogenesis of AKI. However, the correlation of serum TLR4 and post-operative AKI has not been studied in ATAAD patients. This study aimed to explore the possibility of using serum TLR4 levels to predict AKI and 30-day mortality in patients undergoing ATAAD surgery. A prospective, single-center cohort study was conducted and enrolled a total of 64 patients undergoing ATAAD surgery. The level of serum TLR4 was measured and compared before and within 24 hours after the completion of surgery. Thirty-five (54.7%) patients developed AKI, including 7 (10.9%) diagnosed with severe AKI (Kidney Disease Improving Global Outcomes (KDIGO) stage 3). TLR4 levels at 0-hour,1-hour, 3-hour, and 6-hour after intensive care unit (ICU) admission were significantly different between patients with or without AKI. Further analysis showed that the difference was most significant at 0-hour after ICU admission which corresponded to an area under the curve (AUC) of 0.886 (95% confidence interval (CI), 0.800 to 0.973). For severe AKI, the AUC of TLR4 was the highest with 0.923 (0.852 to 0.995) at 1-hour after ICU admission. TLR4 levels before surgery and at 0-hour, 1-hour, as well as 3-hour after ICU admission were significantly different between survivors and non-survivors. Furthermore, we found that the serum level of TLR4 upon ICU admission could be used to predict the 30-day mortality with AUC of 0.805 (0.648 to 0.962). Serum TLR4 levels can be used as a biomarker to predict the occurrence of AKI and 30-day mortality in patients undergoing ATAAD surgery. ChiCTR2200057197.

Progression of Kidney Injury with the Combination of Vancomycin and Piperacillin-Tazobactam or Cefepime in Sepsis-Associated Acute Kidney Injury.

The combination of vancomycin/piperacillin-tazobactam is associated with increases in serum creatinine compared to other antibiotic combinations in the treatment of infections for hospitalized patients. However, the available literature is limited to the study of incident acute kidney injury (AKI). The combination has not been evaluated in patients with AKI already present and the degree to which the trajectory of AKI is influenced by this combination is unknown. This was a single center, retrospective cohort study of adult patients with sepsis and AKI present on admission prescribed a combination of vancomycin with either piperacillin-tazobactam or cefepime within the first 3 days of admission. The primary outcome was maximum serum creatinine observed within days 2-7 of the hospital stay. Subsequent kidney outcomes were evaluated at one week and hospital discharge. Of 480 patients with sepsis and AKI who met inclusion criteria, 288 (60%) received vancomycin/piperacillin-tazobactam, and 192 (40%) received vancomycin/cefepime. Patients were well-matched on clinical factors, including severity of illness, stage of AKI, exposure to other nephrotoxins, and durations of antimicrobial therapy. There were no differences in AKI trajectory during the first week as assessed by maximum serum creatinine (2.1 (1.4-3.5) mg/dl vs. 2.1 (1.4-3.0) mg/dl; p=0.459) and AKI progression (24.0% vs. 23.4%; p=0.895). No differences were observed with other kidney related outcomes, including the need for dialysis (14.6% vs. 13.0%; p=0.628) or major adverse kidney events at hospital discharge (48.3% vs. 47.9%; p=0.941). In patients with sepsis and AKI, the combination of vancomycin/piperacillin-tazobactam compared to vancomycin/cefepime was not associated with higher serum creatinine values or AKI progression in the week following ICU admission.

Deceased Donor Kidney Transplantation from Donors with Acute Kidney Injury: Realities and Cost

Introduction: The use of kidneys from deceased donors with acute kidney injury (AKI) is one of the options to expand donor pool. Methods: this is a single center, retrospective study, reviewed the medical records of recipients from January 2016 to November 2021. Outcomes were compared between AKI and non-AKI recipients. Results: Total 380 consecutive deceased donor’s kidney transplantation recipients files were studies. The mean follow up time was 40 months. 129 (34%) kidneys were transplanted from AKI donors and 251 (66%) from non-AKI donors. DGF rate was 33% in AKI group and 25.5% in non-AKI group (P = 0.099). The mean overall cost of transplantation in AKI group were comparable ($253865 vs $253611 in non-AKI group) (P = 0.97). The mean length of stay (LOS) in AKI group was 6 ± 3.94 days and 6.3 ± 6.3 days for non-AKI group (P = 0.64). DGF rate was increased as AKI stage got higher (18% stage 1, 45% stage 2, 36% stage 3 AKI) (P = 0.03) but no significant difference between AKI stages in terms of LOS (5.53 stage 1, 6.15 stage 2, 6.22 stage 3 AKI P = 0.69) and cost ($250290 stage 1, $254892 stage 2 and $255832 stage 3, P = 0.91) was mentioned. Conclusion: Our study shows transplant with donor AKI have comparable outcome in terms of DGF, graft and patient survival rates, hospital charge and length of stay. Our study confirms that grafts from donors with AKI can be used safely and expand donor pool in kidney transplantation without increased cost.

Acute kidney injury requiring kidney replacement therapy in childhood lupus nephritis: a cohort study of the Pediatric Nephrology Research Consortium and Childhood Arthritis and Rheumatology Research Alliance.

Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited. A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure. Fifty-nine patients (mean age 14.3years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure. Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.

Risk Factors and Outcome of Acute Kidney Injury following Acute Myocardial Infarction-A Case Series Study from 2009 to 2019.

Background: Historically, acute kidney injury (AKI) has been a common severe complication of acute myocardial infarction (MI). As percutaneous coronary interventions have become more widely used, AMI outcomes have significantly improved. However, post-AMI AKI epidemiology and its associated factors are not well-understood in the age of interventional cardiology. Materials and methods: This is a retrospective study examining changes in creatinine levels in all patients admitted for AMI in a single medical center between August 2009 and February 2019. KDIGO criteria were used to define the different stages of post-AMI AKI. Results: The study included 1299 eligible cases, among which 213 (16.4%) developed AKI during AMI index admission; and 128 (60.1%), 46 (21.6%), and 39 (18.3%) were classified as KDIGO stages 1, 2, and 3, respectively. Compared with non-AKI subjects, the AKI group had a higher prevalence of non-STEMI (48.4% vs. 29.1%, p < 0.001), higher Killip class (3 or 4), and higher in-hospital mortality (15% vs. 2.5%, p < 0.001). During the index MI hospitalization, 13.6% (29/213) of the post-MI AKI patients received hemodialysis. Baseline abnormal creatinine (≥1.5 mg/dL), dyslipidemia, and more advanced KDIGO stages (2 or 3) were associated with an increased risk of requiring in-hospital hemodialysis. Moreover, a more advanced KDIGO stage (≥2) was correlated with higher all-cause in-hospital mortality. Conclusion: AMI patients remain at risk of AKI, which negatively affects their survival in the modern age.

Factors associated with occurrence and severity of acute kidney injury in patients with Sepsis – A retrospective database study

PurposeSepsis remains the most common cause of acute kidney injury (AKI) and is associated with a high mortality. This study aims to identify laboratory, clinical and demographic factors that are associated with the different stages of AKI in sepsis. MethodsWe studied patients >18 years who met Sepsis-3 criteria between July 10, 2009 and September 7, 2019 using ordinal logistic regression to determine the factors associated with different stages of AKI. Sensitivity analyses for development of any stage vs no AKI and, separately, the factors associated with receipt of kidney replacement therapy were also done. ResultsOf 31,228 patients meeting Sepsis-3 criteria, 4684 (15%) developed AKI. Of the AKI patients, 53% were KDIGO stage 1, 9% stage 2, and 37% stage 3, with 27% of AKI patients receiving kidney replacement therapy (Stage 3b). Several comorbidities, mechanical ventilation, and pre-sepsis creatinine levels were associated with AKI occurrence and severity. Positive blood culture was associated with a higher risk (OR 1.10 [1.06, 1.15], p < 0.001), while positive respiratory, urine, and wound cultures were associated with lower risks of developing AKI and with lower severity. ConclusionPresepsis creatinine levels, mechanical ventilation, comorbidities, and positive blood cultures were associated with AKI.

Aminoglycosides use has a risk of acute kidney injury in patients without prior chronic kidney disease

The outcome of acute kidney injury (AKI) as a result of aminoglycosides (AGs) use remains uncertain in patients without prior chronic kidney disease (CKD). Therefore, we explored the outcomes of AGs use on AKI episodes associated with renal recovery and progress in patients without prior CKD in Taiwan. This was a retrospective cohort study by using the Taipei Medical University Research Database from January 2008 to December 2019. 43,259 individuals without CKD who had received parenteral AGs were enrolled. The exposed and unexposed groups underwent propensity score matching for age, gender, patients in intensive care unit/emergency admission, and covariates, except serum hemoglobin and albumin levels. We identified an exposed group of 40,547 patients who used AGs (median age, 54.4 years; 44.3% male) and an unexposed group of 40,547 patients without AG use (median age, 55.7 years; 45.5% male). There was the risk for AKI stage 1 (adjusted hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.00–1.79; p = 0.05) in patients that used AGs in comparison with the control subjects. Moreover, patients using AGs were significantly associated neither with the progression to acute kidney disease (AKD) stages nor with the progression to end-stage renal disease (ESRD) on dialysis. Further analyzed, there was an increased risk of AKI episodes for serum albumin levels less than 3.0 g/dL and hemoglobin levels less than 11.6 g/dL. Among patients without prior CKD, AGs-used individuals were associated with AKI risks, especially those at relatively low albumin (< 3.0 g/dL) or low hemoglobin (< 11.6 g/dL). That could raise awareness of AGs prescription in those patients in clinical practice.

Safety and Effectiveness of Veno-Venous Extracorporeal Membrane Oxygenation Combined With Continuous Renal Replacement Therapy.

Patients receiving extracorporeal membrane oxygenation (ECMO) often suffer from acute kidney injury (AKI), requiring continuous renal replacement therapy (CRRT). In our clinical practice, we connected the inlet line of a CRRT machine to the postoxygenator Luer port and the outlet line to the inlet Luer port of the oxygenator. In this case series, we analyzed the interaction between the two machines. Between December 31, 2017, and December 31, 2019, we enrolled 15 patients from the ICU of the San Matteo Hospital, Pavia, Italy. All of them suffered from severe acute respiratory distress syndrome and AKI stage 3. We analyzed 570 hours of CRRT combined with venovenous ECMO and collected 261,751 CRRT data. No discontinuation of CRRT occurred before 48 hours. Most of the alarms occurred within 24 hours of the connection: 22/10,831 (0.2%) showed an outranged inlet pressure, 11/10831 (0.11%) showed an outranged transmembrane pressure, 14/10,831 (0.13%) showed an outranged inlet pressure, and 138/10,831 (1.27%) an outranged effluent pressure. The rate per minute set for the ECMO circuit was correlated with the inlet (β = 5.38; CI, 95% 1.42-9.35; p = 0.008), transmembrane (β = 4.6; CI, 95% 1.97-7.24; p = 0.001), effluent (β = 3.02; CI, 95% 1.15-4.90; p = 0.002), and outlet pressures (β = 597; CI, 95% 2.31-9.63; p = 0.001) of the CRRT circuit. We reported that our configuration could be safe and effective, however well-designed studies would be beneficial for determining the potential risks and benefits.

Expert Clinical Management of Severe Immune-Related Adverse Events: Results from a Multicenter Survey on Hot Topics for Management.

There are differences in recommendations for the management of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs). To assess the real-world management of irAEs, three surveys regarding ICI-induced hepatitis (IIH), renal irAEs, and myositis were developed and sent to experts in each area. Fifty-six surveys were completed (17 IIH, 20 renal irAEs, and 19 myositis). All experts agreed on performing imaging in every suspected case of severe IIH. Sixty-five percent agreed on performing a liver biopsy in patients not responding to corticosteroids. The most common indication for corticosteroid use (59%) was for severe IIH not improving after discontinuation of ICIs. Additionally, 60% of the experts agreed on performing a biopsy for stage 2/3 acute kidney injury (AKI), and 70% recommended imaging for any stage of AKI. Thirty-five percent favored corticosteroids in AKI patients with creatinine levels 2–3-fold above baseline. For myositis, 58% would recommend a muscle biopsy in a patient with weakness and creatine kinase levels of 5000 U/L; 47% would also opt for an endomyocardial biopsy when the troponin levels are increased. Fifty-eight percent recommended oral corticosteroids for myositis, and 37% recommended additional therapy, mainly immunoglobulins. These results show substantial differences in expert practice patterns for the management of severe liver, kidney, and muscular irAEs.

Non-recovery of vancomycin-associated nephrotoxicity is related to worsening survival outcomes: Combined retrospective analyses of two real-world databases.

There has been growing concern in worsening survival and renal outcomes following vancomycin-associated nephrotoxicity (VAN) onset, but the factors associated with these phenomena remain unclear. To examine these factors, we performed a retrospective study combining the analysis of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was used to evaluate the relationship between VAN and mortality using odds ratios (ORs) and 95% confidence intervals (CIs). Next, electronic medical records (EMRs) were examined in a more robust cohort for evaluation of the association between renal outcomes and worsening survival using Cox proportional hazards regression models. FAERS analysis revealed a significant correlation between VAN occurrence and increased mortality (OR: 1.30; 95% CI: 1.17-1.46). EMR analysis showed that non-recovery of VAN was associated with increased hospital mortality (hazard ratio [HR]: 4.05; 95% CI: 2.42-6.77) and 1-year mortality (HR: 3.03, 95% CI: 1.98-4.64). The HR for VAN recovery was lower for patients with acute kidney injury (AKI) stage ≥2 (HR: 0.09; 95% CI: 0.02-0.40). Thus, worsening survival outcomes were associated with non-recovery of VAN, whereby AKI stage ≥2 was a significant risk factor. Progression to severe VAN should be prevented for better survival outcomes.

A Machine Learning Approach for the Prediction of Severe Acute Kidney Injury Following Traumatic Brain Injury.

Acute kidney injury (AKI), a prevalent non-neurological complication following traumatic brain injury (TBI), is a major clinical issue with an unfavorable prognosis. This study aimed to develop and validate machine learning models to predict severe AKI (stage 3 or greater) incidence in patients with TBI. A retrospective cohort study was conducted by using two public databases: the Medical Information Mart for Intensive Care IV (MIMIC)-IV and the eICU Collaborative Research Database (eICU-CRD). Recursive feature elimination was used to select candidate predictors obtained within 24h of intensive care unit admission. The area under the curve and decision curve analysis curves were used to determine the discriminatory ability. On the other hand, the calibration curve was employed to evaluate the calibrated performance of the newly developed machine learning models. In the MIMIC-IV database, there were 808 patients diagnosed with moderate and severe TBI (msTBI) (msTBI is defined as Glasgow Coma Score < 12). Of these, 60 (7.43%) patients experienced severe AKI. External validation in the eICU-CRD indicated that the random forest (RF) model had the highest area under the curve of 0.819 (95% confidence interval 0.783-0.851). Furthermore, in the calibration curve, the RF model was well calibrated (P = 0.795). In this study, the RF model demonstrated better discrimination in predicting severe AKI than other models. An online calculator could facilitate its application, potentially improving the early detection of severe AKI and subsequently improving the clinical outcomes among patients with msTBI.

Prevalence and prognostic impact of cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation. AMY-TAVI study

Abstract Background Aortic stenosis (AS) and cardiac transthyretin amyloidosis (CTTRA) are two diseases that are typically associated with aging. In both cases, dyspnea is the main symptom, so the diagnosis of CTTRA in patients with AS is underestimated. Purpose To determine the real prevalence of CTTRA in patients with AS and its influence on prognosis. Methods After implantation, and before hospital discharge, CTTRA screening was carried out by performing a scintigraphy with 99mTc-3,3-diphosphono-1,2-propanedicarboxylic acid, and monoclonal peak in peripheral blood and urine was excluded to rule out CA-AL.According to Perugini's classification, CATTR grades 1, 2 and 3 were established and grade 0 as the absence of CATTR. Result 325 patients were included. The incidence of CTTRA was 11.7% (38 patients). Grade 1 39.4% (15 patients), grade 2 34.2% (13 patients) and grade 3 26.3% (10 patients). Patients with CATTR were more frequently male (female 36.8% vs 54%, p=0.046), had a lower mean transvalvular gradient (43.2±14.0 mmHg vs 50.9±14.7 mmHg, p=0.003), and greater thickness of the interventricular septum (15.4±2.3 mm vs 14.4±2.7 mm, p=0.038). There were no differences in the rest of the clinical or analytical variables, including functional class or NT proBNP levels (3663.3±4343.9 vs 3815.4±7901.7, p=0.912). According to the Valve Academic Research Consortium-3 classification, there were no differences in in-hospital complications between the two groups, stroke (3.1% vs 2.6%, p=0.866), greater bleeding (7.3% vs 15.8%, p=0.202), acute kidney injury stage 3 (2.1% vs 0.9, p=0.566), permanet pacemaker implantation (19.2% vs 13.2%, p=0.370), acute myocardial infarction (0.3% vs 0%), acute heart failure (4.2% vs 2.6%, p=0.647).Mean follow-up time was 19.0±7.4 months (median: 19.2, IQR 12.5–25.7 months). During this time, there was no difference in the appearance of MACE, defined as all-cause mortality, heart failure, acute myocardial infraction and stroke, between patients with and without CTTRA (Figure 1A). Nor when we analyze these events separately. Finally, the evolution in functional class and NT proBNP values six months after implantation were analyzed. Although there was an improvement in functional class in all groups, this was not significant in patients with CTTRA grade 3, going from 30% of patients in NYHA class III–IV at baseline to 22.2% at 6 months (p=0.556). Regarding the NT proBNP values, these decreased in all the groups but they only did so significantly in the patients without CTTRA (Figure 2). Conclusion The coexistence of AS and CTTRA in patients undergoing TAVR is relatively frequent. Although there are no more in-hospital or mid-term follow-up complications than in patients without CTTRA, the degree of symptomatic improvement and normalization of natriuretic peptides is lower in these patients, especially in the more advanced stages, where it will be necessary to assess whether the procedure will be futile or not. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pfizer

Lower serum chloride concentrations are associated with an increased risk of death in ICU patients with acute kidney injury: an analysis of the MIMIC-IV database.

The association between baseline serum chloride levels and mortality in patients with severe acute kidney injury (AKI) is unknown. Our aim was to investigate the relationship between baseline blood chloride levels and 28-day mortality in patients with AKI admitted to the ICU and to detect possible effect modifiers in this population. AKI patients with severe critical illness were extracted from the MIMIC-IV. During ICU admission, chloride levels were measured for the first time. Our primary outcome was 28-day mortality in patients with AKI after 24 hours in the ICU. Multivariable logistic regression was used to examine the association between three groups of chloride levels and 28-day mortality, and logistic regression with restricted cubic spline was applied to detect the non-linear trendy. A total of 24,166 patients with critically ill AKI were included in this retrospective cohort study. The total 28-day mortality rate in the ICU was 15.9%. Overall, there was a U-shaped relationship between baseline serum chloride levels and 28-day mortality (non-linear P<0.001). Accordingly, patients with low serum chloride (<96 mEq/L) had a significantly increased risk of death compared to patients with normal serum chloride (96-108 meq/L) (adjusted OR=1.94, 95% CI: 1.68-2.24, P<0.001). None of the variables, including age, gender, 24-hour fluid intake, continuous renal replacement therapy, ventilation, Atrial fibrillation, Sequential Organ Failure Assessment score, whether to measure lactate and AKI stage, significantly modified the association between lower chloride levels and 28-day mortality. Low serum chloride levels at baseline were associated with death at 28 days in intensive illnesses with AKI.