Time Of Continuous Renal Replacement Therapy Initiation Research Articles

Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-Associated Acute Kidney Injury: A Comprehensive Review and Future Directions

This review examines the application of continuous renal replacement therapy (CRRT) in patients with sepsis-associated acute kidney injury (S-AKI), with a particular focus on the timing of CRRT initiation. This review addresses the controversy surrounding initiation timing and proposes future research directions. Through a systematic review of recent literature on CRRT for S-AKI, working principles, therapeutic mechanisms, initiation timing of CRRT, and related meta-analyses were summarized. Current studies indicate that the optimal timing for CRRT initiation in S-AKI patients remains inconclusive, with ongoing debate regarding whether early initiation significantly improves patient survival and renal function. This lack of consensus reflects the heterogeneity of the S-AKI patient population and the limitations of existing research methodologies. Future studies should focus on advancing the application of precision medicine in S-AKI and developing individualized treatment strategies by integrating multidimensional information to optimize CRRT utilization and improve patient outcomes.

Characteristics of initiation timing and anticoagulation of continuous renal replacement therapy in patients following cardiac surgery: A retrospective analysis of 28 patients.

Continuous renal replacement therapy (CRRT) used in cardiac surgery-associated acute kidney injury (CSA-AKI) may have different characteristics from other diseases. We reviewed the medical records of patients with CSA-AKI requiring CRRT who underwent cardiac surgery from January 2020 to September 2021. Patients with AKI caused by other reasons who received CRRT during the same period were also evaluated. A total of 28 patients with CSA-AKI and 12 patients with AKI caused by other reasons were enrolled in this study. Compared with AKI patients caused by other reasons, patients with CSA-AKI were found to have lower mean arterial pressure, higher level of bilirubin, higher vasoactive-inotropic score, and larger daily diuretic dosage. The patients with CSA-AKI were prescribed CRRT earlier than the patients with AKI caused by other reasons. There was a significant difference in the CRRT anticoagulation method between patients with CSA-AKI and patients with AKI caused by other reasons. Six patients with CSA-AKI were treated with regional citrate anticoagulation (RCA), and the other 22 patients were treated with low molecular weight heparin or without anticoagulants. The timing of CRRT initiation in patients with CSA-AKI is earlier than that in patients with AKI caused by other reasons. Although RCA is recommended as the preferred anticoagulant for patients without contraindications, patients with CSA-AKI often have circulatory dysfunction and severe liver damage, so the risk of citrate accumulation is greater, whether to use RCA should be determined according to the individual condition of the patient.

A New Dosing Frontier: Retrospective Assessment of Effluent Flow Rates and Residual Renal Function Among Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

In 2020, cefiderocol became the first Food and Drug Administration-approved medication with continuous renal replacement therapy (CRRT) dosing recommendations based on effluent flow rates (QE). We aimed to evaluate the magnitude and frequency of factors that may influence these recommendations, that is, QE intrapatient variability and residual renal function. Retrospective observational cohort study. ICUs within Hartford Hospital (890-bed, acute-care hospital) in Connecticut from 2017 to 2023. Adult ICU patients receiving CRRT for greater than 72 hours. CRRT settings including QE and urine output (UOP) were extracted from the time of CRRT initiation (0 hr) and trends were assessed. To assess the impact on antibiotic dosing, cefiderocol doses were assigned to 0 hour, 24 hours, 48 hours, and 72 hours QE values per product label, and the proportion of antibiotic dose changes required as a result of changes in inpatient's QE was evaluated. Among the 380 ICU patients receiving CRRT for greater than 72 hours, the median (interquartile range) 0 hour QE was 2.96 (2.35-3.29) L/hr. Approximately 9 QE values were documented per patient per 24-hour window. QE changes of greater than 0.75 L/hr were observed in 21.6% of patients over the first 24 hours and in 7.9% (24-48 hr) and 5.8% (48-72 hr) of patients. Approximately 40% of patients had UOP greater than 500 mL at 24 hours post-CRRT initiation. Due to QE changes within 24 hours of CRRT initiation, a potential cefiderocol dose adjustment would have been warranted in 38% of patients (increase of 21.3%; decrease of 16.6%). QE changes were less common after 24 hours, warranting cefiderocol dose adjustments in less than 15% of patients. Results highlight the temporal and variable dynamics of QE and prevalence of residual renal function. Data also demonstrate a risk of antibiotic under-dosing in the first 24 hours of CRRT initiation due to increases in QE. For antibiotics with QE-based dosing recommendations, empiric dose escalation may be warranted in the first 24 hours of CRRT initiation.

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults

In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown. To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90). This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023. The primary exposure was time to CRRT initiation from intensive care unit admission. The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]). Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]). In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.

The benefits of early continuous renal replacement therapy in critically ill patients with acute kidney injury at high-altitude areas: a retrospective multi-center cohort study

Severe hypoxia would aggravate the acute kidney injury (AKI) in high-altitude areas and continuous renal replacement therapy (CRRT) has been used to treat critically ill patients with AKI. However, the characteristics and outcomes of CRRT in critically ill patients at AKI in high altitudes and the optimal timing of CRRT initiation remain unclear. 1124 patients were diagnosed with AKI and treated with CRRT in the ICU, comprising a high-altitude group (n = 648) and low-altitude group (n = 476). Compared with the low-altitude group, patients with AKI at high altitude showed longer CRRT (4.8 vs. 3.7, P = 0.036) and more rapid progression of AKI stages (P < 0.01), but without any significant minor or major bleeding episodes (P > 0.05). Referring to the analysis of survival and kidney recovery curves, a higher mortality but a lower possibility of renal recovery was observed in the high-altitude group (P < 0.001). However, in the high-altitude group, the survival rate of early CRRT initiation was significantly higher than that of delayed CRRT initiation (P < 0.001). The findings showed poorer clinical outcomes in patients undergoing CRRT for AKI at high altitudes. CRRT at high altitudes was unlikely to increase the adverse events. Moreover, early CRRT initiation might reduce the mortality and promote renal recovery in high-altitude patients.

HMGB1 Is a Prognostic Factor for Mortality in Acute Kidney Injury Requiring Renal Replacement Therapy

Instruction: High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine that reportedly causes kidney injury and other organ damage in rodent acute kidney injury (AKI) models. However, it remains unclear whether HMGB1 is associated with clinical AKI and related outcomes. This study aimed to evaluate the association with HMGB1 and prognosis of AKI requiring continuous renal replacement therapy (CRRT). Methods: AKI patients treated with CRRT in our intensive care unit were enrolled consecutively during 2013–2016. Plasma HMGB1 was measured on initiation. Classic initiation was defined as presenting at least one of the following conventional indications: hyperkalemia (K ≥6.5 mEq/L), severe acidosis (pH <7.15), uremia (UN >100 mg/dL), and diuretics-resistant pulmonary edema. Early initiation was defined as presenting no conventional indications. The primary outcome was defined as 90-day mortality. Results: A total of 177 AKI patients were enrolled in this study. HMGB1 was significantly associated with the primary outcome (hazard ratio, 1.06; 95% CI, 1.04–1.08). When the patients were divided into two-by-two groups by the timing of CRRT initiation and the HMBG1 cutoff value obtained by receiver operating curve (ROC) analysis, the high HMGB1 group (>10 ng/mL) with classic initiation was significantly associated with the primary outcome compared with the others, even after adjusting for other factors including the nonrenal serial organ failure assessment (SOFA) score. Conclusion: HMGB1 was associated with 90-day mortality in AKI patients requiring CRRT. Notably, the highest mortality was observed in the high HMGB1 group with classic initiation. These findings suggest that CRRT should be considered for AKI patients with high HMGB1, regardless of the conventional indications.

Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK)

Continuous renal replacement therapy (CRRT) is used for the symptomatic management of acute kidney injury (AKI) and fluid overload (FO). Contemporary reports on pediatric CRRT are small and single center in design. Large international studies evaluating CRRT practice and outcomes are lacking. Herein, we describe the design of a multinational collaborative. The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) is an international collaborative of pediatric specialists whose mission is to improve short- and long-term outcomes of children treated with CRRT. The aims of this multicenter retrospective study are to describe the epidemiology, liberation patterns, association of fluid balance and timing of CRRT initiation, and CRRT prescription with outcomes. We included children (n= 996, 0-25 years) admitted to an intensive care unit (ICU) and treated with CRRT for AKI or FO at 32 centers (in 7 countries) from 2018 to 2021. Demographics and clinical characteristics before CRRT initiation, during the first 7 days of both CRRT, and liberation were collected. Outcomes include the following: (i) major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction), and (ii) functional outcomes (functional stats scale). The retrospective WE-ROCK study represents the largest international registry of children receiving CRRT for AKI or FO. It will serve as a broad and invaluable resource for the field of pediatric critical care nephrology that will improve our understanding of practice heterogeneity and the association of CRRT with clinical and patient-centered outcomes. This will generate preliminary data for future interventional trials in this area.

Hyperlactatemia is a predictor of mortality in patients undergoing continuous renal replacement therapy for acute kidney injury

BackgroundHyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury.MethodsA total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1–7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score-based models.ResultsA total of 802 (48.3%) and 542 (32.6%) patients had moderate and high lactate levels, respectively. The moderate and high lactate groups had a higher risk of mortality than the low lactate group, with HRs of 1.64 (1.22–2.20) and 4.18 (2.99–5.85), respectively. The lactate-enhanced models had higher AUROCs than the models without lactates (0.764 vs. 0.702 for SOFA score; 0.737 vs. 0.678 for APACHE II score).ConclusionsHyperlactatemia is associated with mortality outcomes in patients undergoing CRRT for acute kidney injury. Serum lactate levels may need to be monitored in this patient subset.

The association between albumin corrected anion gap and ICU mortality in acute kidney injury patients requiring continuous renal replacement therapy

The relationship between albumin corrected anion gap (ACAG) and mortality in acute kidney injury (AKI) patients who received continuous renal replacement therapy (CRRT) has not been investigated in any previous studies. This study aimed to investigate the relationship between ACAG at CRRT initiation and all-cause mortality among these patients in the intensive care unit (ICU). Patients diagnosed with AKI and treated with CRRT in the ICU from the Medical Information Mart for Intensive Care-IV version 1.0 (MIMIC IV) database and Huzhou Central Hospital were retrospectively enrolled. Participants were divided into two groups: the normal ACAG group (12–20 mmol/L) and high ACAG group (> 20 mmol/L). The Kaplan–Meier method and log-rank test were used to compare the survival rate between the two groups. Restricted cubic spine (RCS) and Cox proportional-hazards models were utilized to analyze the relationship between ACAG at CRRT initiation and ICU all-cause mortality of these patients. A total of 708 patients met the inclusion criteria in the study. The all-cause mortality of these patients during ICU hospitalization was 41.95%. Patients in the high ACAG group exhibited significantly higher ICU all-cause mortality rate than patients in the normal ACAG group (all P < 0.001). The Kaplan–Meier survival curves showed that the normal ACAG group had a higher ICU cumulative survival rate than the high ACAG group (log-rank test, χ12 = 13.620, χ22 = 12.460, both P < 0.001). In the multivariate COX regression analyses, patients with higher ACAG (> 20 mmol/L) levels at the time of CRRT initiation in the MIMIC IV database and Huzhou Central Hospital were significantly correlated with ICU all-cause mortality after adjusting multiple potential confounding factors with hazard ratios of 2.852 (95% CI 1.718–4.734) and 2.637(95% CI 1.584–4.389), respectively. In critically AKI patients who undergo CRRT, higher ACAG (> 20 mmol/L) level at the initiation of CRRT was significantly correlated with ICU all-cause mortality. Therefore, clinicians should pay more attention to those patients with a higher ACAG value.

Risk Factors Associated with 30-day Mortality in Patients with Postoperative Acute Kidney Injury Who Underwent Continuous Renal Replacement Therapy in the Intensive Care Unit

Purpose: To evaluate the risk factors associated with 30-day mortality in patients with postoperative acute kidney injury who underwent continuous renal replacement therapy (CRRT).Methods: Retrospective analysis of the medical charts of patients with postoperative acute kidney injury who underwent CRRT in the intensive care unit between April 2012 and May 2019 was conducted.Results: There were 71 patients whose average age was 64.8 years, and average Acute Physiology and Chronic Health Evaluation 2 score was 26.2. There were 37 patients who had non-trauma emergency surgery, 16 who required trauma surgery, and 18 who had elective major surgery. In most patients, CRRT was started based on Stage 3 Acute Kidney Injury Network criteria, and the mean creatinine level at the time of CRRT initiation (3.62 mg/dL). The median period from surgery to CRRT was 3 days, and the median CRRT application was 4 days. Forty-seven patients died within 30 days of receiving CRRT. Age, elective major surgery, creatinine level on initiation of CRRT, use of norepinephrine upon the initiation of CRRT, and average daily fluid balance/body weight for 3 days following the initiation of CRRT were associated with increasing 30-day mortality in univariate analysis. In multivariate analysis, age, major elective surgery, and norepinephrine use upon initiation of CRRT were identified as independent risk factors for 30-day mortality.Conclusion: Surgical patients who underwent CRRT postoperatively had a poor prognosis. The risk of death in elderly patients who have undergone major elective surgery, or are receiving norepinephrine upon initiation of CRRT should be considered.

Explainable Machine Learning-Based Risk Prediction Model for In-Hospital Mortality after Continuous Renal Replacement Therapy Initiation.

In this study, we established an explainable and personalized risk prediction model for in-hospital mortality after continuous renal replacement therapy (CRRT) initiation. This retrospective cohort study was conducted at Changhua Christian Hospital (CCH). A total of 2932 consecutive intensive care unit patients receiving CRRT between 1 January 2010, and 30 April 2021, were identified from the CCH Clinical Research Database and were included in this study. The recursive feature elimination method with 10-fold cross-validation was used and repeated five times to select the optimal subset of features for the development of machine learning (ML) models to predict in-hospital mortality after CRRT initiation. An explainable approach based on ML and the SHapley Additive exPlanation (SHAP) and a local explanation method were used to evaluate the risk of in-hospital mortality and help clinicians understand the results of ML models. The extreme gradient boosting and gradient boosting machine models exhibited a higher discrimination ability (area under curve [AUC] = 0.806, 95% CI = 0.770–0.843 and AUC = 0.823, 95% CI = 0.788–0.858, respectively). The SHAP model revealed that the Acute Physiology and Chronic Health Evaluation II score, albumin level, and the timing of CRRT initiation were the most crucial features, followed by age, potassium and creatinine levels, SPO2, mean arterial pressure, international normalized ratio, and vasopressor support use. ML models combined with SHAP and local interpretation can provide the visual interpretation of individual risk predictions, which can help clinicians understand the effect of critical features and make informed decisions for preventing in-hospital deaths.

Body temperature trends of critically Ill patients on continuous renal replacement therapy: A single-center retrospective study

BackgroundInterpretation of human body temperature in patients on continuous renal replacement therapy (CRRT) is challenging. Clinicians currently use definitions of ‘normal’ temperature derived from healthy patients over a century ago and apply these definitions to patients on continuous renal replacement therapy (CRRT). There is a significant opportunity to refine temperature definitions to apply to the increasing population of critically ill patients on CRRT. MethodsA total of 1361 critically ill patients admitted to the hospital between 12/1/2006 and 11/31/2015 and requiring CRRT were studied. Temperature data were summarized (median, IQR) and compared during time periods that patients were on CRRT and time periods that they were not on CRRT using paired comparisons. Additionally, analyses were performed to compare temperature dynamics between patients who died during their hospitalization with those who did not. ResultsThe median body temperature change was −0.6 °C (95% CI −1.3, −0.6) from 12 h before CRRT to 12 h after CRRT (p < .001), and an increase of 0.6 °C (95% CI 0.2, 0.6) from 12 h before CRRT end to 12 h after CRRT end (p < .001). Temperature significantly increased by a median 0.3 °C from the start to the end of CRRT. ConclusionsThere are significant body temperature changes in critically ill patients on CRRT with cooling at the time of CRRT initiation and warming at the time of CRRT cessation.

3 Continuous Renal Replacement Therapy for the Treatment of Burn Shock: A Post Hoc Analysis

IntroductionBurn shock is a consequence of burns that cover ≥20% TBSA and may be complicated by acute kidney injury, which is commonly treated with continuous renal replacement therapy (CRRT). However, early initiation of CRRT has not been clinically evaluated for the treatment of burn shock.MethodsData were obtained from the Renal Replacement Therapy in Severe Burns: A Multicenter Observational Study. In that study, baseline (t0) measurements were taken at the time of CRRT initiation and ~24 (t1) and ~48 (t2) hours thereafter. Patients were included in this analysis if they had ≥20% TBSA and began CRRT within 2 days of injury. Patients were categorized as Group A (began CRRT on same day as injury), Group B (began CRRT on day 1 postburn), and Group C (began CRRT on day 2 postburn). Outcomes measured at t0, t1, and t2 and hospital and ICU length of stay (LOS) were analyzed using generalized linear mixed models. Cox proportional hazards models were used to assess survival to hospital discharge (HD). All models were adjusted, e.g. for age, % full thickness, etc. Burn center was included as a random effect.ResultsMore than half of the 48 patients included were treated at just 2 burn centers. Timing of CRRT initiation varied by center, with all patients at one center starting CRRT on either the day of injury or the day after injury. Nearly 96% of patients had AKI at CRRT start and, of those, 22 were at stage 1 or 2. Patients generally had severe burns; Group A had more inhalation injuries and higher %TBSA, % full thickness, and Baux scores than Groups B and C. Shock index (SI) was persistently elevated across all 3 time points and did not vary by timing of CRRT initiation (p=0.37). Vasopressor dependency index (VDI) was also not associated with timing of CRRT initiation (p >0.99), although mean VDI for Groups B and C declined over time. For all 3 groups, fluid balance decreased from t0, but there were no differences among the groups (all p >0.30). Survival to HD was better for patients with lower TBSA (i.e. 20-49%) compared to those with TBSA ≥50% (hazard ratio=0.37; 95% CI=0.15-0.91). In contrast, timing of CRRT initiation was not associated with survival (p=0.73). Among patients that survived to HD, the mean hospital LOS was shorter for Groups A (13 days; p=0.01) and B (39 days; p=0.03) compared to Group C (131 days). Mean ICU LOS was also shorter for Groups A (13 days; p=0.01) and B (52 days; p=0.03) than for Group C (168 days).ConclusionsIn this analysis, earlier initiation of CRRT did not improve survival to hospital discharge. Nonetheless, starting patients on CRRT early may be advantageous for reducing ICU and hospital LOS for those patients that do survive.

Early Implementation of Renal Replacement Therapy after Lung Transplantation Does Not Impair Long-Term Kidney Function in iPAH Patients

<h3>Purpose</h3> In patients suffering from idiopathic pulmonary arterial hypertension (iPAH), cardiac function can be impaired in the early postoperative phase after lung transplantation as the chronically untrained left ventricle is prone to fail. Thus, restrictive fluid management is pivotal to unload the left heart. In our institution, continuous renal replacement therapy (CRRT) is implemented liberally, whenever a patient cannot be balanced negatively. It remains unclear whether such strategy impairs long-term kidney function. <h3>Methods</h3> iPAH patients transplanted between 2000 and 2018 were included in this retrospective study. The influence of hemofiltration in the peri-operative phase on long-term outcomes was investigated. <h3>Results</h3> A total of 87 iPAH lung transplant recipients were included in this analysis. In 38 patients (44%) CRRT was started in the early postoperative period for a median of 16 days (3-45). In this group, urine production had significantly decreased and patients began to acquire a positive fluid balance, however, hemostatic functions of the kidney were still preserved at the time of CRRT initiation. All patients were successfully weaned from CRRT and fully recovered their kidney function at the time of hospital discharge (Figure 1). No difference in kidney function was found between CRRT and non-CRRT patients at 1, 3, and 5 years. Long-term survival was excellent with 10-year survival rates of 75%. <h3>Conclusion</h3> Early implementation of CRRT for perioperative volume management does not impair long-term kidney function in iPAH recipients. Our data suggest that such a strategy leads to excellent long-term outcomes.

Target value of mean arterial pressure in patients undergoing continuous renal replacement therapy due to acute kidney injury

BackgroundAlthough patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI) frequently have instability in mean arterial pressure (MAP), no consensus exists on the target value of MAP related to high mortality after CRRT.MethodsA total of 2,292 patients who underwent CRRT due to AKI in three referral hospitals were retrospectively reviewed. The MAPs were divided into tertiles, and the 3rd tertile group served as a reference in the analyses. The major outcome was all-cause mortality during the intensive care unit period. The odds ratio (OR) of mortality was calculated using logistic regression after adjustment for multiple covariates. The nonlinear relationship regression model was applied to determine the threshold value of MAP related to increasing mortality.ResultsThe mean value of MAP was 80.7 ± 17.3 mmHg at the time of CRRT initiation. The median intensive care unit stay was 5 days (interquartile range, 2–12 days), and during this time, 1,227 (55.5%) patients died. The 1st tertile group of MAP showed an elevated risk of mortality compared with the 3rd tertile group (adjusted OR, 1.28 [1.03–1.60]; P = 0.029). In the nonlinear regression analysis, the threshold value of MAP was calculated as 82.7 mmHg. Patients with MAP < 82.7 mmHg had a higher mortality rate than those with ≥ 82.7 mmHg (adjusted OR, 1.21 [1.01–1.45]; P = 0.037).ConclusionsLow MAP at CRRT initiation is associated with a high risk of mortality, particularly when it is < 82.7 mmHg. This value may be used for risk classification and as a potential therapeutic target.

Dyschloremia is associated with failure to restore renal function in survivors with acute kidney injury: an observation retrospective study

Dyschloremia is common in critically ill patients. However, little is known about the effects of dyschloremia on renal function in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). A total of 483 patients who received CRRT for AKI were selected and divided into three groups according to their serum chloride concentrations at the time of CRRT initiation. At 90 days after initiating CRRT, renal outcome, i.e., non-complete renal recovery, or renal failure, was assessed in the three groups. The hypochloremia group (serum chloride concentrations < 96 mEq/L, n = 60), the normochloremia group (serum chloride concentrations, 96–111 mEq/L, n = 345), and the hyperchloremia group (serum chloride concentrations > 111 mEq/L, n = 78) were classified. The simplified acute physiology score III was higher in the hyperchloremia and hypochloremia groups than in the normochloremia group. Multivariate logistic regression analyses showed that hypochloremia (odds ratio, 5.12; 95% confidence interval [CI], 2.56–10.23; P < 0.001) and hyperchloremia (odds ratio, 2.53; 95% CI, 1.25–5.13; P = 0.01) were significantly associated with non-complete renal recovery. Similar trends were observed for renal failure. This study showed that dyschloremia was independently associated with failure in restoring renal function following AKI.

Filter Clotting with Continuous Renal Replacement Therapy in COVID-19

Background: Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). The incidence, clinical features, and treatment strategies to address severe filter clotting in patients with COVID-19 is unknown.Aim: We aimed to characterize the burden of CRRT filter clotting in patients with COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing.Methods: Consecutive patients with confirmed COVID-19 infection admitted between March 16, 2020 and April 27, 2020 who required CRRT were included in this multi-center retrospective study. Severe clotting was defined as >2 filter losses in 48 hours or one filter loss <8 hours into CRRT. Primary outcome was time to CRRT filter loss. Due to the unreliability of PTT levels in patients with COVID-19, a COVID-specific CRRT anticoagulation protocol (referred to as protocol henceforth) which dosed systemic unfractionated heparin (UFH) by anti-factor Xa levels was piloted at one center starting April 13, 2020.Given that there was no difference in the treatment plan from CRRT initiation to first filter loss between the two anticoagulation approaches, this period served as a run-in period. Time from first to second filter loss (where protocol patients were exposed to low systemic UFH dosing) and time from second to third filter loss (where protocol patients were exposed to high systemic UFH dosing) were analyzed with a log-rank test.Results: Sixty-five patients were analyzed, with 17 using the anti-factor Xa protocol to guide systemic heparin dosing whereas 48 were treated with standard of care anticoagulation dosed by PTT . There were no major differences between groups in age, sex, race, ethnicity, body mass index, or baseline medications. Fifty-seven out of 65 patients (88%) initiated CRRT for AKI, whereas 8/65 patients (12%) had end stage renal disease. At the time of CRRT initiation, 64/65 patients (98%) were mechanically ventilated, 22/65 patients (34%) required prone ventilation, and 59/65 patients (91%) were on intravenous vasopressors. Patients spent a median of 6 [2, 13] days on CRRT.Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 [2.5, 33.5] hours. There was no difference between groups in percentage who lost their first filter (88% vs. 81%), or second filter (73% vs. 72%). However, fewer patients in the protocol group lost their third filter (55% vs. 93%) resulting in a longer median third filter survival time (24 [15.1, 54.2] vs. 17.3 [9.5, 35.1] hours, p = 0.04), Figure 1.Conclusions: The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is a reasonable approach to anticoagulation in this population.DisclosuresRosovsky:Bristol-Myers Squibb: Consultancy, Research Funding; Portola: Consultancy; Janssen: Consultancy, Research Funding; Dova: Consultancy. Sise:EMD-Serono: Research Funding; Abbvie: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Bioporto: Consultancy. Steele:HealthReveal: Consultancy; Blackstone Life Sciences: Consultancy. Czarnecki:Alexion: Consultancy; Reata: Consultancy. Allegretti:Mallinckrodt Pharmaceuticals: Consultancy.

Modification of the Renal Angina Index for identifying the need for renal replacement therapy in critically ill pediatric patients

Severe Acute Kidney Injury (AKI) is a common, serious problem affecting critically ill children that lacks effective treatment options. Currently, there are no treatment options for AKI other than supportive care. Continuous renal replacement therapy (CRRT) is employed to reduce Fluid Overload (FO) burden and treat metabolic disturbances in AKI. Identifying patients upon admission who may require CRRT has potential clinical care implications. The aim of this study was to determine if the RAI had diagnostic capabilities to identify patients who would require CRRT. The analytic cohort consisted of patients who required CRRT and illness severity score matched controls who did not require CRRT at a single center. Patients who required CRRT had higher mortality rates, length of stay, and use of ventilatory and inotropic support. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) assessed and compared the discriminatory accuracy of three scores: 1) the renal angina index (RAI), 2) serum-creatinine (sCr) based AKI on day 0 and 3) modified RAI created with an additional RAI injury tranche that corresponded to severe stage 3 AKI sCr elevation. Compared to Day0AKI (AUC 0.78, 0.70-0.87; sensitivity 0.63, 0.45-0.79; specificity 0.93, 0.870.97) and RAI (AUC 0.76, 0.69-0.82; sensitivity 0.94, 0.81-0.99; specificity 0.57, 0.47-0.66), the modified RAI had the highest AUC (0.79; 0.72-0.85) with a high sensitivity (0.91; 0.77-0.98) and moderate specificity (0.65; 0.56-0.75) for prediction of CRRT requirements. As a more accurate tool for discriminating patients in need of CRRT, a modified RAI has numerous potential implications. Identifying patients who ultimately require CRRT at an earlier timepoint may influence timing of CRRT initiation in an attempt to avoid further FO, or may influence nephrotoxin administration. The diagnostic capabilities of the modified RAI may be refined by the addition of urinary biomarkers. These findings should be validated in a larger cohort.

Continuous renal replacement therapy in critically ill patients with acute on chronic liver failure and acute kidney injury: A retrospective cohort study .

Incident acute kidney injury (AKI) in critically ill patients with acute on chronic liver failure (ACLF) is associated with poor prognosis. The role of continuous renal replacement therapy (CRRT) is not well established for patients with ACLF and AKI. We conducted a retrospective cohort study to examine clinical outcomes in 66 patients with ACLF and AKI requiring CRRT. All-cause hospital mortality was 89.4%. Five (7.6%) patients were listed for liver transplantation, of whom 1 (1.5%) was eventually subjected to transplantation. Etiology of AKI included type 1 hepatorenal syndrome (HRS) with or without some degree of acute tubular necrosis (ATN) in 20 (30.3%) patients, and primarily ATN in 46 (69.7%) patients. When evaluated at the time of CRRT initiation, Child-Pugh-Turcotte (CPT) and Model for End-stage Liver Disease (MELD) (area under the receiver operating characteristics curve (AUROC) 0.67 for both) had fair performance for prediction of mortality, whereas Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure (CLIF)-SOFA performed better for the prediction of mortality (AUROC 0.87 for both). SOFA and CLIF-SOFA also performed well when determined at the time of ICU admission (AUROC 0.86 and 0.85, respectively). Etiology of liver disease or AKI did not influence prognosis. Critically ill patients with ACLF and AKI requiring CRRT have poor hospital survival, even with provision of extracorporeal support therapy. SOFA and CLIF-SOFA are good prognostic tools of mortality in this susceptible population.

Optimal timing of initiating continuous renal replacement therapy in septic shock patients with acute kidney injury

Acute kidney injury (AKI) in patients with septic shock is associated with high mortality, but the appropriate timing for initiating continuous renal replacement therapy (CRRT) is controversial. We retrospectively enrolled 158 septic shock patients with AKI in the medical intensive care unit (ICU) from July 2016 to April 2018. The time from AKI onset to CRRT initiation was compared according to ICU mortality using Cox proportional hazard, receiver operating characteristic, and Kaplan-Meier survival analyses. At the time of ICU discharge, the mortality rate was 50.6% (n = 80). It took longer to initiate CRRT in non-survivors than in survivors (hazard ratio 1.009; 95% confidence interval [CI] 1.003–1.014; P = 0.002). The cut-off time from AKI onset to CRRT initiation for ICU mortality was 16.5 hours (area under the curve 0.786; 95% CI 0.716–0.856; P < 0.001). The cumulative mortality rate was significantly higher in patients in whom CRRT was initiated beyond 16.5 hours after AKI onset than in those in whom CCRT was initiated within 16.5 hours (log-rank test, P < 0.001). Several clinical situations must be considered to determine the optimal timing of CRRT initiation in these patients. Close observation and CRRT initiation within 16.5 hours after AKI onset may help improve survival.