Acute Renal Replacement Therapy Research Articles

Acute Renal Replacement Therapy in Intensive Care Units versus Outside Intensive Care Units: Are They Different?

IntroductionAcute renal replacement therapy (RRT) is indicated when metabolic and fluid demands exceed total kidney capacity, and demand for kidney function is determined by non-renal comorbidities, severity of acute disease and solute and fluid burden; therefore, the criteria for commencing RRT and dialysis in intensive care units (ICUs) may be different to those outside ICUs.ObjectiveWe investigated whether criteria for commencing acute RRT and dialysis outside ICU were different to those in ICU and whether these differences affected patient mortality in either setting.MethodsWe performed a retrospective observational study evaluating acute kidney injury (AKI), Kidney Disease Improving Global Outcome 3 (KDIGO3) in adult patients undergoing RRT “in and outside” ICU from 2012 to 2018, in a Brazilian teaching hospital.ResultsWe evaluated 913 adults with AKI KDIGO3 undergoing RRT; 629 (68.9%) outside ICU and 284 (31.1%) in ICU. Infections were the main cause of hospitalisation (34.4%). Septic and ischaemic AKI were the main aetiologies of AKI (50.8% and 32.9%, respectively), metabolic and fluid demand to capacity imbalance were the main indications for dialysis (69.7%), and intermittent haemodialysis (IHD) was the primary dialysis method (59.2%). The general mortality rate after 30 days was 59%. There were no differences in gender, age and main diagnosis between groups. Both groups were different in acute tubular necrosis index specific scores (ATN-ISS), AKI aetiology, elderly population, indications for dialysis, dialysis methods and mortality rates. In ICU, patients older than 65 years old, with septic AKI were more prevalent (49.1 versus 41.4%, and 55.1 versus 37.5%, respectively), while ischaemic and nephrotoxic AKI were less frequent (24.3 versus 37 and 10.2 versus 16.3%, respectively), and ATN-ISS was higher (0.74 ± 0.31 versus 0.58 ± 0.16). Similarly, metabolic and fluid demand to capacity imbalance as an indication for acute RRT, prolonged intermittent haemodialysis (PIRRT) and continuous renal replacement therapy (CRRT) were more frequent, while peritoneal dialysis (PD) was less frequent (74.6 versus 69.7%, 31.6 versus 22.4%, and 5.3 versus 17.8%, respectively), and mortality was higher (69 versus 54.7%, respectively). Logistic regression revealed that age, septic AKI and being “in” ICU were factors associated with death.ConclusionThe criteria for commencing RRT and dialysis in ICU were different to those outside ICU; however, they did not impact on patient outcomes.

The Association Between Rhabdomyolysis, Acute Kidney Injury, Renal Replacement Therapy, and Mortality.

BackgroundWe examined the association between creatine phosphokinase level in rhabdomyolysis patients and risk of acute kidney injury, renal replacement therapy, and death within 30 days.MethodsThe cohort included patients admitted with rhabdomyolysis from November 1, 2011 to March 1, 2014. Rhabdomyolysis was defined as a creatine phosphokinase level higher than 1000 U/L. Information on laboratory variables was obtained from a laboratory database. Medical data were obtained from registries. Acute kidney injury was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. The 30-day risk of outcomes was estimated using the cumulative incidence method. Spline regression applied to imputed datasets with adjustment for baseline variables was used to assess the appropriateness of the categorization chosen for creatine phosphokinase (1000–5000 U/L, 5001–15,000 U/L, and 15,000+ U/L).ResultsThe study included 1027 patients (58.2% male) with a median age of 73.5 years. The median creatine phosphokinase level at rhabdomyolysis diagnosis was 2257 U/L (interquartile range=1404–3961 U/L). The 30-day risks of acute kidney injury according to the three creatinine phosphokinase levels were 42% (95% CI=38–45%), 44% (95% CI=36–52%), and 74% (95% CI=57–85%), respectively, and the risks of renal replacement therapy for the three levels were 3% (95% CI=2–5%), 4% (95% CI=2–7%), and 11% (3–23%), respectively. The 30-day risk of death was 17% (95% CI=14–20%), 16% (95% CI=11–22%), and 11% (95% CI=3–23%), respectively. With increasing creatine phosphokinase levels, the spline plots supported the increasing risk of acute kidney injury and renal replacement therapy, as well as a decreasing risk of death. However, the risk estimates for renal replacement therapy and death were imprecise.ConclusionElevated initial creatine phosphokinase values were associated with an increased risk of acute kidney injury, while estimates of the risk of renal replacement therapy and death were imprecise.

Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy

Background: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. Objective: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. Methods: Observational study in a tertiary care hospital in Milan, Italy. Results: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. Conclusions: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis.

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury. Although haematuria is a risk factor for the development of renal disease, no previous study has analyzed the significance of haematuria in ATIN. Retrospective, observational analysis of 110 patients with biopsy-proven ATIN was conducted. Results: Haematuria was present in 66 (60%) ATIN patients. A higher percentage of ATIN patients with haematuria had proteinuria than patients without haematuria (89.4% vs. 59.1%, p = 0.001) with significantly higher levels of proteinuria (median (interquartile range) protein:creatinine ratio 902.70 (513–1492) vs. 341.00 (177–734) mg/g, p <0.001). Moreover, those patients with more haematuria intensity had a higher urinary protein:creatinine ratio (1352.65 (665–2292) vs. 849.60 (562–1155) mg/g, p = 0.02). Those patients with higher proteinuria were more likely to need renal replacement therapy (22.7 vs. 0%, p = 0.03) and to suffer relapse (4 vs. 0%, p = 0.03). At the end of follow up, haematuric ATIN patients had higher serum creatinine levels (3.19 ± 2.91 vs. 1.91 ± 1.17 mg/dL, p = 0.007), and a trend towards a higher need for acute dialysis (7 vs. 1%, p = 0.09) and renal replacement therapy (12.1 vs. 2.3%, p = 0.12). Haematuria is common in ATIN and it is associated with worse renal function outcomes.

Perioperative risk factors for delirium development after elective cardiovascular surgery

Aim. This study was conducted to determine the incidence of delirium after cardiac surgery and its effect on the length of the patient’s stay in the ICU and to identify the perioperative risk factors.Methods. This research was a retrospective assessment of 1941 medical records and the course of the perioperative period in patients subjected to elective cardiac surgery.Results. Delirium developed in 193 cases (9.94%); whereas, hyperactive, hypoactive and mixed delirium was observed in 13%, 43% and 44% of the patients, respectively. Most often (26% of the cases), delirium occurred after complex combined surgeries. Independent risk factors for the development of delirium were older age (OR 1.041, 95% CI [1.002–1.081], p = 0.038), EuroSCORE II score (OR 1.286, 95% CI [1.093–1.731], p = 0.025), acute kidney injury (OR 1.306, 95% CI [1.107–1.942], p = 0.0018) and renal replacement therapy (OR 1.399 95% CI [1.361–2.792], p = 0.001). Cardiopulmonary bypass duration and time of clamping of the aorta, postoperative serum creatinine level, need for blood transfusions and duration of mechanical ventilation and duration of ICU stay were identified as predictors and were also significantly higher in the delirium group. Delirium was closely associated with critical illness polyneuropathy (OR 9.201, 95% CI [2.13–38.826], p &lt; 0.001) and neurogenic dysphagia (OR 7.48, 95% CI [1.12–56.07], p = 0.022).Conclusion. The key factors for delirium development in the postoperative period include advanced age, high EuroSCORE II scale and acute kidney injury requiring continuous renal replacement therapy. Delirium significantly increases the duration of mechanical ventilation and the duration of ICU stay.Received 30 January 2020. Revised 18 March 2020. Accepted 24 March 2020.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Author contributionsConception and design: V.V. Pasyuga, I.N. LeidermanData collection: D.A. Demin, E.V. Demina, I.L. Nudel, V.V. Pasyuga Data analysis: V.V. Pasyuga, I.N. Leiderman, D.A. Demin, D.G. TarasovDrafting the article: V.V. Pasyuga, D.A. DeminCritical revision of the article: I.N. Leiderman, A.V. KadykovaFinal approval of the version to be published: V.V. Pasyuga, D.A. Demin, I.L. Nudel, E.V. Demina, A.V. Kadykova, D.G. Tarasov, I.N. Leiderman

Predicting Acute Kidney Injury After Cardiac Surgery Using a Simpler Model

To develop a simple model for the prediction of acute kidney injury (AKI) and renal replacement therapy (RRT) that could be used in clinical or research risk stratification. Retrospective analysis. Multi-institutional. All cardiac surgery patients from September 2016 to December 2018. Observational. The study cohort was divided into a development set (75%) and validation set (25%). The following 2 data epochs were used: preoperative data and immediate postoperative data (within 4 h of intensive care unit admission). Univariate statistics were used to identify variables associated with AKI or RRT. Stepwise logistic regression was used to develop a parsimonious model. Model discrimination and calibration were evaluated in the test set. Models were compared with previously published models and with a more comprehensive model developed using the least absolute shrinkage and selection operator. The study included 22,731 patients at 33 hospitals. The incidences of AKI (any stage) and RRT for the present analysis were 5,829 patients (25.6%) and 488 patients (2.1%), respectively. Models were developed for AKI, with an area under the receiver operating curve (AU-ROC) of 0.67 and 0.69 preoperatively and postoperatively, respectively. Models for RRT had an AU-ROC of 0.77 and 0.80 preoperatively and postoperatively, respectively. These models contained between 3 and 5 variables. Comparatively, comprehensive least absolute shrinkage and selection operator models contained between 21 and 26 variables, with an AU-ROC of 0.71 and 0.72 for AKI and 0.84 and 0.87 for RRT respectively. In the present study, simple, clinically applicable models for predicting AKI and RRT preoperatively and immediate postoperatively were developed. Even though AKI prediction remained poor, RRT prediction was good with a parsimonious model.

Questionnaire survey on the prescription of renal replacement therapy for acute phase patients on maintenance dialysis who developed cerebrovascular disease.

There is limited information about acute phase renal replacement therapy (RRT) for maintenance hemodialysis patients after the onset of cerebrovascular disease. This study aimed to investigate which modality of renal replacement therapy is currently selected in practice. We conducted a mail-based survey in 317 dialysis facilities that were certified by three academic societies that focus on dialysis, neurology, and neurosurgery in Japan. We received responses from 103 facilities (32.5%). In cases of cerebral infarction (CI) and intracerebral hemorrhage (ICH), more than 80% of the facilities selected only intermittent RRT, and 22.3% (CI)/8.7% (ICH) of the facilities selected intermittent HD which is the same setting in normal conditions. Although continuous hemodiafiltration and peritoneal dialysis are recommended in the Japanese guidelines, these were selected in only a few facilities: 16.5% and 0% in CI, 16.5% and 1% in ICH, respectively. RRT on the day of onset tended to be avoided, irrespective of the duration following the last HD session. Furthermore, physicians preferred to modify anticoagulants and reduce dialysis performance in the acute phase. This questionnaire survey uncovered a gap between guidelines and actual practice, even in hospitals accredited as educational facility, which is a novel and important finding. Further studies with larger sample sizes are needed to determine the optimal modality of RRT for the acute phase of cerebrovascular disease.

Furosemide stress test as a predictive marker of acute kidney injury progression or renal replacement therapy: a systemic review and meta-analysis

BackgroundThe use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed.MethodsIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated.ResultsWe identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74–0.87) and 0.88 (95% CI 0.82–0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96–7.50), the pooled negative LR was 0.26 (95% CI 0.19–0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00–51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72–0.91) and 0.77 (95% CI 0.64–0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06–4.86) and 0.25 (95% CI 0.14–0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74–32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1–2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51–13.33).ConclusionThe FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.

Preoperative Use of Intra-Aortic Balloon Pump Support Reduced 30-Day Mortality in a Population with LVEF >35% and High Surgical Risk after Coronary Artery Bypass Graft Surgery

Introduction: The intra-aortic balloon pump (IABP) is used to prevent complications after coronary artery bypass grafting (CABG) surgery, although some results are controversial and basal ventricular function may play a role. This study assessed the benefit of preoperative use of IABP, as stratified by the ventricular function, in a population submitted to high-surgical-risk CABG. Methods: Patients >18 years old, with multiple coronary artery disease and thus candidates for CABG, were included. Cardiogenic shock, acute myocardial infarction (AMI), acute ventricle mechanical dysfunction, severe aortic regurgitation, tachyarrhythmia, massive pulmonary embolism, coagulopathy, or low life expectancy were exclusion criteria. Results: One hundred and twenty-nine patients aged 65 years old with hypertension, dyslipidemia, type 2 diabetes mellitus, and mean left ventricular ejection fraction (LVEF) 46% constituted the study population. No difference was observed at 30-day mortality endpoint (IABP vs. no IABP, 17 vs. 24%, OR 0.63, p = 0.20; AMI 25 vs. 31%, OR 0.75, p = 0.29). After LVEF stratification, the subgroup of 48 (75%) patients under IABP support and LVEF >35% had a reduced 30-day mortality risk (LVEF ≤35% vs. LVEF >35%, 37.5 vs. 10.4%, OR 0.3, p = 0.03), independently from potential confounders and showing an interaction with European System for Cardiac Operative Risk Evaluation-II (EuroSCORE-II). At secondary endpoints, IABP use was associated with a lower prevalence of acute renal failure and renal replacement therapy, but with a longer stay in the intensive care unit and longer hospitalization time. Conclusion: The preoperative use of IABP was associated with an independent reduction of 30-day mortality risk in cases with LVEF >35% in a population submitted to high-surgical-risk CABG. Likewise, the use of IABP was associated with a lower risk of postoperative renal complications.

Fluid management in continuous renal replacement therapy

The purpose of intravenous fluid administration is to increase cardiac output. Excessive fluid administration can lead to accumulation of interstitial fluid, worsening hypoperfusion and hence develop organic dysfunction. Therefore, fluid overload is a poor prognostic factor for hospitalized patients and those admitted to the Intensive Care Unit (ICU). A resuscitation strategy divided in four phases has been described; the last phase consists in the elimination of those fluids that have been administrated in the previous phases. When fluid overload is complicated by acute kidney injury renal replacement therapy may be used for this purpose. A successful fluid treatment of a patient depends on a proper, accurate and frequent evaluation, and in the correct understanding of the basic principles and clear objectives of the treatment. In the continuous renal replacement therapy, the rate of the fluid eliminated can be adjusted safely according to each patient needs and it allows additional support of other complications. The ideal strategy to guide the elimination rate is unknown. This review presents the basic principles for an optimum fluid management in the continuous renal replacement therapy.

SUN-054 A CASE WITH ASCITES, PROTEINURIA AND OLIGURIA FOLLOWING POST-PARTUM HELLP SYNDROME TREATED BY EXTRACORPOREAL ULTRAFILTRATION: RENAL CONGESTION AS THE 4TH CATEGORY OF ACUTE KIDNEY INJURY

Heart failure often causes acute kidney injury (AKI) and the relationship is called cardiorenal syndrome. Not only low cardiac output, but also renal congestion is increasingly considered as the major cause of AKI among heart failure patients. Renal congestion may be also caused by other pathologic conditions such as liver cirrhosis and hypoalbuminemia. Decongestion by diuretics can improve cardiorenal syndrome, but it is difficult to prove that the kidney rather than the heart was the main site of action. In the present report, a patient developed severe HELLP syndrome immediately after delivery of a baby. Thrombocytopenia and elevated liver enzymes were largely improved within a week, but anuria and severe ascites continued, which were resistant to oral or iv diuretics. We believe this was a unique case with purely mechanical renal congestion, not associated with heart failure or liver dysfunction. N/A. The case was a 27-year-old woman. Ascites appeared during pregnancy and a baby was delivered by emergency caesarean section at 38 weeks. At that time, there was no hypertension and proteinuria. At 3 days after delivery (D3), hypertension (160/90 mmHg), thrombocytopenia (18,000/uL), liver dysfunction (AST 1,928 U/L, ALT 622 U/L, LDH 2,352 U/L), and indirect bilirubin-dominated jaundice developed (TBIL 3.6 mg/dL, DBIL 0.9 mg/dL). HELLP syndrome was diagnosed. Abdominal fullness, edema, punctate hemorrhage, gross hematuria, proteinuria (2.4 g/gCr) were observed, but renal function was normal (serum Cr 0.68 mg/dL). Carperitide (atrial natriuretic peptide), antihypertensive, loop diuretic and tolvaptan were started for hypertension, fluid retention, edema and oliguria. Thrombocytopenia and liver dysfunction gradually improved, but weight gain (62 → 69 kg) and renal function worsening (D11, Cr 6.6 mg/dL) were observed. It seemed difficult to correct fluid excess by drug treatment, and hemodialysis and ultrafiltration were performed for 3 consecutive days on D11-13, resulting in an increase in urine output and improvement of proteinuria (to 0.4 g/gCr). The patient was discharged on D24 at 59 kg, and Cr was improved to 1.0 mg/dL on D28. HELLP syndrome may cause intra organ bleeding and renal failure, potentially resulting in a severe clinical outcome. In this case, although the primary disease seemed to be improving, ascites resulted in oliguria likely due to an increase in the abdominal pressure, and the level of ascites appeared to exceed the limit of natural recovery. Only 3 days of acute renal replacement therapy with ultrafiltration was sufficient to trigger resolution of all the clinical abnormalities such as ascites, oliguria and proteinuria. There were no signs of prerenal, renal parenchymal or post-renal AKI. This was a unique AKI case caused purely by reversible renal congestion, suggesting that renal congestion is the fourth, independent category of AKI.

Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis

BackgroundOptimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock.MethodsA total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into very-early (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A risk-adjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h.ResultsPatients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0–510] vs. 1500[650–2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500–1900] vs. 2600[1600–3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17–0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h.ConclusionA very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.

Incidence, underlying conditions, and outcomes of patients receiving acute renal replacement therapies in tertiary cardiac intensive care units: An analysis from the Critical Care Cardiology Trials Network Registry

The prevalence of renal disease in cardiac intensive care units (CICUs) is increasing, but little is known about the utilization, concurrent therapies, and outcomes of patients requiring acute renal replacement therapy (RRT) in this specialized environment. In the Critical Care Cardiology Trials Network, 16 centers submitted data on CICU admissions including acute RRT (defined as continuous renal replacement therapy and/or acute intermittent dialysis). Among 2,985 admissions, 178 (6.0%; interhospital range 1.0%-16.0%) received acute RRT. Patients receiving RRT, versus not, were more commonly admitted for cardiogenic shock (15.7% vs 4.2%, P < .01), cardiac arrest (9.6% vs 3.7%, P < .01), and acute general medical diagnoses (10.7% vs 5.8%, P < .01), whereas acute coronary syndromes (16.9% vs 32.1%, P < .01) were less frequent. Variables independently associated with acute RRT included diabetes, heart failure, liver disease, severe valvular disease, shock, cardiac arrest, hypertension, and younger age. In patients receiving acute RRT, versus not, advanced therapies including mechanical ventilation (55.6% vs 18.0%), vasoactive support (73.0% vs 35.2%), invasive hemodynamic monitoring (59.6% vs 29.2%), and mechanical circulatory support (27.5% vs 8.4%) were more common. Acute RRT was associated with higher in-hospital mortality (42.1% vs 9.3%, adjusted odds ratio 3.74, 95% CI, 2.52-5.53) and longer median length of stay (10.0 vs 5.3 days, P < .01). In conclusion, acute RRT in contemporary CICUs was associated with the provision of other advanced therapies and lower survival. These data underscore the risks associated with the provision of renal support in patients with primary cardiovascular problems and the need to develop standardized indications and potential futility measures in this specialized population.

Protein Profiles of Pretransplant Grafts Predict Early Allograft Dysfunction After Liver Transplantation From Donation After Circulatory Death.

Predicting the development of early allograft dysfunction (EAD) following liver transplantation (LT) remains challenging for transplant clinicians. The objectives of this study are to investigate the potential relationship between the protein profiles of pretransplant grafts and the onset of EAD, and then combine with clinical parameters to construct a mathematically predictive model. Clinical data of 121 LT procedures from donation after circulatory death at the authors' center were analyzed. The expression levels of 7 studied proteins were determined by immunohistochemistry. Another independent cohort of 37 subjects was designed for further validation of the predictive model. With an incidence of 43.0% (52/121), EAD was linked to significantly increased risk of acute kidney injury and renal replacement therapy, as well as reduced 6-month patient and liver graft survival. Allograft weight and high intrahepatic vascular endothelial growth factor (VEGF) expression were identified as independent risk factors of EAD and survival outcomes. Liver grafts with high VEGF expression exhibited delayed functional recovery within the first postoperative week. The combination of VEGF overexpression and EAD yielded the highest frequency of renal dysfunction and the worst survival. Based on allograft weight and intrahepatic VEGF expression, an EAD risk assessment model was developed. The incidence of EAD differed significantly between grafts with risk scores ≥-1.72 and <-1.72. The model functioned well in the validation cohort. Pretransplant intrahepatic protein profiling contributes to the estimation of early graft performance and recipient outcomes following LT. The predictive model could allow for an accurate prediction of EAD.

Nephrotoxicity of Antimicrobials and Antibiotics.

Medication-induced nephrotoxicity remains one of the most common causes of acute kidney injury (AKI) among hospitalized patients. Within the extensive group of medications associated with AKI, antibiotics and other antimicrobials are well recognized triggers of structural and functional renal impairment. Clinical manifestations range from mild forms of tubular injury to significant deterioration of kidney function requiring acute renal replacement therapy. Several mechanisms are described, although the most frequent are acute interstitial nephritis, acute tubular necrosis, intratubular crystal deposition, and proximal/distal tubulopathy with electrolyte wasting abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease, and concomitant use of medication with nephrotoxic potential. Prevention and early recognition of AKI represent the standard approach to mitigate AKI and avoid morbidity.

Severe clinical spectrum with high mortality in pediatric patients with COVID-19 and multisystem inflammatory syndrome

OBJECTIVES:To assess the outcomes of pediatric patients with laboratory-confirmed coronavirus disease (COVID-19) with or without multisystem inflammatory syndrome in children (MIS-C).METHODS:This cross-sectional study included 471 samples collected from 371 patients (age<18 years) suspected of having severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study group comprised 66/371 (18%) laboratory-confirmed pediatric COVID-19 patients: 61 (92.5%) patients tested positive on real-time reverse transcription-polymerase chain reaction tests for SARS-CoV-2, and 5 (7.5%) patients tested positive on serological tests. MIS-C was diagnosed according to the criteria of the Center for Disease Control.RESULTS:MIS-C was diagnosed in 6/66 (9%) patients. The frequencies of diarrhea, vomiting, and/or abdominal pain (67% vs. 22%, p=0.034); pediatric SARS (67% vs. 13%, p=0.008); hypoxemia (83% vs. 23%, p=0.006); and arterial hypotension (50% vs. 3%, p=0.004) were significantly higher in patients with MIS-C than in those without MIS-C. The frequencies of C-reactive protein levels >50 mg/L (83% vs. 25%, p=0.008) and D-dimer levels >1000 ng/mL (100% vs. 40%, p=0.007) and the median D-dimer, troponin T, and ferritin levels (p<0.05) were significantly higher in patients with MIS-C. The frequencies of pediatric intensive care unit admission (100% vs. 60%, p=0.003), mechanical ventilation (83% vs. 7%, p<0.001), vasoactive agent use (83% vs. 3%, p<0.001), shock (83% vs. 5%, p<0.001), cardiac abnormalities (100% vs. 2%, p<0.001), and death (67% vs. 3%, p<0.001) were also significantly higher in patients with MIS-C. Similarly, the frequencies of oxygen therapy (100% vs. 33%, p=0.003), intravenous immunoglobulin therapy (67% vs. 2%, p<0.001), aspirin therapy (50% vs. 0%, p<0.001), and current acute renal replacement therapy (50% vs. 2%, p=0.002) were also significantly higher in patients with MIS-C. Logistic regression analysis showed that the presence of MIS-C was significantly associated with gastrointestinal manifestations [odds ratio (OR)=10.98; 95%CI (95% confidence interval)=1.20-100.86; p=0.034] and hypoxemia [OR=16.85; 95%CI=1.34-211.80; p=0.029]. Further univariate analysis showed a positive association between MIS-C and death [OR=58.00; 95%CI=6.39-526.79; p<0.0001].CONCLUSIONS:Pediatric patients with laboratory-confirmed COVID-19 with MIS-C had a severe clinical spectrum with a high mortality rate. Our study emphasizes the importance of investigating MIS-C in pediatric patients with COVID-19 presenting with gastrointestinal involvement and hypoxemia.

Report of the first AKI Round Table meeting: an initiative of the ESICM AKI Section

PurposeCritical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research.MethodsInternational Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: “AKI diagnosis and evaluation”, “Medical management of AKI” and “Renal Replacement Therapy for AKI.” Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research.ResultsThe following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria; (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT).Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT.Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities.ConclusionConsensus was reached on a future research agenda for the AKI section of the ESICM.

Acute kidney injury is independently associated with mortality and resource use after emergency general surgery operations

IntroductionThe incidence of severe perioperative renal dysfunction in high-acuity patients has not been well-explored at the national level. The present study aimed to evaluate the trends in the incidence of perioperative acute kidney injury and renal replacement therapy as well as associated mortality among patients undergoing an emergency general surgery operation. MethodsThis was a retrospective cohort study using the National Inpatient Sample to identify all adult patients (>18 y) without chronic kidney disease who underwent an emergency general surgery procedure from 2008 to 2016. The study cohort was stratified based on presence of acute kidney injury and need for renal replacement therapy postoperatively. A multivariable logistic regression model was developed to predict the odds of mortality and composite morbidity. Nonparametric trend analyses of acute kidney injury and renal replacement therapy incidence and associated mortality were performed. ResultsOf an estimated 5,862,657 patients who underwent an emergency general surgery procedure during the study period, 7.4% patients developed an acute kidney injury and 0.48% patients required renal replacement therapy. Overall, the incidence of acute kidney injury (5.3%–19.4%) and renal replacement therapy (0.43%–0.93%) increased (P < .0001) over the study period. Even without need for renal replacement therapy, acute kidney injury was associated with greater odds of mortality and composite morbidity (adjusted odds ratio 5.2, 95% confidence interval [CI] 5.1–5.3) and mortality (adjusted odds ratio = 2.20, 95% CI 2.3–2.4), as well as greater costs of hospitalization and duration of stay. ConclusionIn this national study, we found that the incidence of acute kidney injury and renal replacement therapy after an emergency general surgery operation has increased. Both acute renal failure and hemodialysis were associated with much greater odds of morbidity and mortality. The apparent increase in the rate of acute kidney injury and renal replacement therapy warrant further investigation of mechanisms for monitoring and limiting the impact of organ malperfusion associated with emergency general surgery operations.

Illicit drug use and acute kidney injury in patients admitted to hospital with rhabdomyolysis.

Severe rhabdomyolysis is associated with acute kidney injury, but it is unclear if patients developing rhabdomyolysis after illicit drug use have a higher risk of acute kidney injury compared to other causes. To provide a descriptive analysis of patients admitted with rhabdomyolysis, with a focus on illicit drug use, and to determine if illicit drug use was an independent predictor for acute kidney injury or renal replacement therapy. We conducted a 5-year cohort study of patients admitted to Monash Health, a tertiary referral hospital network. We identified adult patients with muscle injury from ICD-10 AM codes, serum creatine kinase level greater than 1000 U/mL, and a clinical history consistent with rhabdomyolysis. We determined the prevalence and type of illicit drug involved and determined the association between illicit drug use and renal outcomes by logistic regression. Of 643 patients, illicit drug use was identified in 12%. Acute kidney injury developed in 51%, and 5% required renal replacement therapy. Compared to the rest of the cohort, patients who used illicit drugs were younger and had higher peak serum creatine kinase, and developed a higher severity of acute kidney injury. In multivariable analysis, the factors associated with acute kidney injury were illicit drug use, peak creatine kinase, cardiovascular disease, concurrent sepsis and a clinically-evident pressure injury. Chronic kidney disease and need for fasciotomy were additional risk factors for renal replacement therapy. Illicit drug use was associated with acute kidney injury and renal replacement therapy independent of creatine kinase levels.

Antibiotic Exposure Profiles in Trials Comparing Intensity of Continuous Renal Replacement Therapy.

To determine whether the probability of target attainment over 72 hours of initial therapy with beta-lactam (cefepime, ceftazidime, piperacillin/tazobactam) and carbapenem (imipenem, meropenem) antibiotics were substantially influenced between intensive and less-intensive continuous renal replacement therapy groups in the Acute Renal Failure Trial Network trial and The RENAL Replacement Therapy Study trial. The probability of target attainment was calculated using pharmacodynamic targets of percentage of time that free serum concentrations (fT): 1) were above the target organism's minimum inhibitory concentration (≥ fT > 1 × minimum inhibitory concentration); 2) were above four times the minimum inhibitory concentration (≥ % fT > 4 × minimum inhibitory concentration); and 3) were always above the minimum inhibitory concentration (≥ 100% fT > minimum inhibitory concentration) for the first 72 hours of antibiotic therapy. Demographic data and effluent rates from the Acute Renal Failure Trial Network and RENAL Replacement Therapy Study trials were used. Optimal doses were defined as the dose achieving greater than or equal to 90% probability of target attainment. Monte Carlo simulations using demographic data from Acute Renal Failure Trial Network and RENAL Replacement Therapy Study trials. Virtual critically ill patients requiring continuous renal replacement therapy. None. The pharmacodynamic target of fT greater than 1 × minimum inhibitory concentration led to similarly high rates of predicted response with antibiotic doses often used in continuous renal replacement therapy. Achieving 100% fT greater than minimum inhibitory concentration is a more stringent benchmark compared with T greater than 4 × minimum inhibitory concentration with standard antibiotic dosing. The intensity of effluent flow rates (less intensive vs intensive) did not substantially influence the probability of target attainment of antibiotic dosing regimens regardless of pharmacodynamic target. Antibiotic pharmacodynamic target attainment rates likely were not meaningfully different in the low- and high-intensity treatment arms of the Acute Renal Failure Trial Network and RENAL Replacement Therapy Study Investigators trials.