Continuous Replacement Research Articles

Extracorporeal Elimination of Pro- and Anti-inflammatory Modulators by the Cytokine Adsorber CytoSorb® in Patients with Hyperinflammation: A Prospective Study.

The release of pro-inflammatory cytokines in critically ill patients with sepsis leads to endothelial dysfunction resulting in cardiocirculatory insufficiency. Their extracorporeal elimination using the cytokine adsorber CytoSorb® (CS) (adsorption of especially hydrophobic molecules < 60kDa) might be promising, but data about the adsorption capacity as well as a potential harmful adsorption of anti-inflammatory cytokines are missing so far. The prospective Cyto-SOLVE-study included 15 patients with sepsis or other hyperinflammatory conditions (interleukin 6 > 500pg/ml), continuous kidney replacement therapy, and the application of CS. Various cytokines and chemokines were measured pre- and post-CS as well as in patients' blood at predefined timepoints. Significant changes in the concentrations were detected with the Wilcoxon test with associated samples. Clearance of the adsorber (ml/min) was calculated with: RESULTS: Most of the inflammatory mediators showed a high initial extracorporeal clearance of 70-100ml/min after CS installation, which dropped quickly to 10-30ml/min after 6h of treatment. No difference in clearance was observed between pro- and anti-inflammatory cytokines. Despite extracorporeal adsorption, a significant (p < 0.05) decrease in the blood concentration after 6h was only observed for the pro-inflammatory cytokines tumor necrosis factorα (TNF-α) (median 284 vs. 230pg/ml), vascular endothelial growth factor (VEGF) (median 294 vs. 252pg/ml), macrophage inflammatory protein 1a (MIP-1a) (median 11.1 vs. 9.0pg/ml), and regulated upon activation, normal T cell expressed and secreted (RANTES) (median 811 vs. 487pg/ml) as well as the anti-inflammatory cytokines interleukin 4 (median 9.3 vs. 6.4pg/ml), interleukin 10 (median 88 vs. 56pg/ml), and platelet-derived growth factor (PDGF) (median 177 vs. 104pg/ml). A significant (p < 0.05) decrease in patients' blood after 12h was only detected for interleukin 10. CS can adsorb pro- as well as anti-inflammatory mediators with no relevant difference regarding the adsorption rate. A fast saturation of the adsorber resulted in a rapid decrease of the clearance. The potential clinical benefit or harm of this unspecific cytokine adsorption needs to be evaluated in the future. ClinicalTrials.gov NCT04913298, registration date June 4, 2021.

Large/small eddy simulations: A high-fidelity method for studying high-Reynolds number turbulent flows

Direct numerical simulations (DNS) are one of the main ab initio tools to study turbulent flows. However, due to their considerable computational cost, DNS are primarily restricted to canonical flows at moderate Reynolds numbers, in which turbulence is isolated from the realistic, large-scale flow dynamics. In contrast, lower fidelity techniques, such as large eddy simulations (LES), are employed for modeling real-life systems. Such approaches rely on closure models that make multiple assumptions, including turbulent equilibrium, small-scale universality, etc., which require prior knowledge of the flow and can be violated. We propose a method, which couples a lower-fidelity, unresolved, time-dependent calculation of an entire system (LES) with an embedded small eddy simulation (SES) that provides a high-fidelity, fully resolved solution in a sub-region of interest of the LES. Such coupling is achieved by continuous replacement of the large SES scales with a low-pass filtered LES velocity field. The method is formulated in physical space, with no assumptions of equilibrium, small-scale structure, and boundary conditions. A priori tests of both steady and unsteady homogeneous, isotropic turbulences are used to demonstrate the method's accuracy in recovering turbulence properties, including spectra, probability density functions of the intermittent quantities, and sub-grid dissipation. Finally, SES is compared with two alternative approaches: one embedding a high-resolution region through static mesh refinement and a generalization of the traditional volumetric spectral forcing. Unlike these methods, SES is shown to achieve DNS-level accuracy at a fraction of the cost of the full DNS, thus opening the possibility to study high-Re flows.

Self-sustaining antifouling coating for underwater solar cells

If not protected, underwater solar cells are encrusted with biological organisms, such as algae and barnacles, which lower the electrical or operational efficiency and are expensive to remove. We engineered a self-sustaining antifouling coating using ultra-low concentrations of nano-sized, seawater-soluble pigments, specifically cuprous oxide (Cu2O) and zinc oxide (ZnO), combined with an organic booster biocide and a fast-polishing binder material. This coating maintained high levels of visible light transmission for three months in tropical seawater without requiring human intervention, such as mechanical cleaning. Field tests demonstrated the coating's effectiveness in preventing biofouling, while preserving transparency. We anticipate that these self-sustaining antifouling coatings can be applied to thin, transparent, and interchangeable substrates for continual replacement on solar-powered autonomous underwater vehicles or solar cell platforms, thereby ensuring long-term operational efficiency.

Cystatin C and Kidney Function Recovery in Patients Requiring Continuous KRT for Acute Kidney Injury.

Plasma cystatin C is a reliable marker to estimate kidney function; however, it is unknown whether this remains true in patients receiving continuous kidney replacement therapy (CKRT). Herein, we tested the hypothesis that lower concentrations of plasma cystatin C during the first three days of CKRT would predict kidney function recovery. We performed a retrospective observational study of 72 patients from a 126-patient, single-center CKRT study. We studied two a priori defined cohorts of patients without advanced CKD who had acute kidney injury requiring CKRT (AKI-CKRT): 1) with early kidney function recovery defined as liberation from KRT within seven days of CKRT initiation versus 2) with delayed kidney function recovery defined as receipt of KRT for >21 days or death while on KRT. Subsequent analysis included patients with advanced CKD and intermediate kidney function recovery (liberation between 8 and 21 days). Cystatin C was then measured on stored plasma, urine, and dialysis effluent collected prior to CKRT initiation and on days 1, 2, and 3 of CKRT. Plasma cystatin C was significantly lower in patients with early kidney function recovery in comparison to patients with delayed kidney function recovery on days 1 (1.79 vs. 2.39mg/L), 2 (1.91 vs. 2.38mg/L) and 3 (2.04 vs. 2.67mg/L) of CKRT. Sieving coefficient and CKRT clearance of cystatin C were similar for patients with early and delayed kidney function recovery. The lowest plasma cystatin C concentration on days 1-3 of CKRT predicted early kidney function recovery with an area under the receiver operating curve of 0.77 (P = 0.002), positive likelihood ratio of 5.60 for plasma cystatin C <1.30mg/L, and negative likelihood ratio of 0.17 for plasma cystatin C ≥1.88mg/L. Lower plasma cystatin C concentrations during the first three days of CKRT are associated with early kidney function recovery.

Characteristics and outcomes of children ≤ 10 kg receiving continuous kidney replacement therapy: a WE-ROCK study.

Continuous kidney replacement therapy (CKRT) is often used for acute kidney injury (AKI) or fluid overload (FO) in children ≤ 10kg. Intensive care unit (ICU) mortality in children ≤ 10kg reported by the prospective pediatric CRRT (ppCRRT, 2001-2003) registry was 57%. We aimed to evaluate characteristics associated with ICU mortality using a contemporary registry. The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry is a retrospective, multinational, observational study of children and young adults aged 0-25years receiving CKRT (2015-2021) for AKI or FO. This analysis included patients ≤ 10kg at hospital admission. ICU mortality and major adverse kidney events at 90days (MAKE-90) defined as death, persistent kidney dysfunction, or dialysis within 90days, respectively. A total of 210 patients were included (median age 0.53years (IQR, 0.1, 0.9)). ICU mortality was 46.5%. MAKE-90 occurred in 150/207 (72%). CKRT was initiated at a median 3days (IQR 1, 9) after ICU admission and lasted a median 6days (IQR 3, 16). On multivariable analysis, pediatric logistic organ dysfunction score (PELOD-2) at CKRT initiation was associated with increased odds of ICU mortality (aOR 2.64, 95% CI 1.68-4.16), and increased odds of MAKE-90 (aOR 2.2, 95% CI 1.31-3.69). Absence of comorbidity was associated with lower MAKE-90 (aOR 0.29, 95%CI 0.13-0.65). We report on a contemporary cohort of children ≤ 10kg treated with CKRT for acute kidney injury and/or fluid overload. ICU mortality is decreased compared to ppCRRT. The extended risk of death and morbidity at 90days highlights the importance of close follow-up.

Vitamin D and metabolic bone disease in prolonged continuous kidney replacement therapy: a prospective observational study

BackgroundComplications of prolonged continuous kidney replacement therapy (CKRT) have not been well described. Our objective was to describe mineral metabolism and bone findings in children who required prolonged CKRT.MethodsIn this single center prospective observational study, we enrolled 37 patients who required CKRT for ≥ 28 days with regional citrate anticoagulation. Exposure was duration on CKRT and outcomes were 25-hydroxy vitamin D and osteopenia and/or fractures.ResultsThe prevalence of vitamin D deficiency and insufficiency was 17.2% and 69.0%, respectively. 29.7% of patients had radiographic findings of osteopenia and/or fractures. There was no association between vitamin D deficiency or insufficiency with age or ethnicity. Time on CKRT and intact PTH levels were not predictive of vitamin D levels. Children with chronic liver disease were more likely to have osteopenia and/or fractures compared children with other primary diagnoses, odds ratio (3.99 (95%CI, 1.58–2.91), p = 0.003) after adjusting for age and time on CKRT.ConclusionVitamin D deficiency and/or insufficiency, and osteopenia and/or fractures are prevalent among children who require CKRT for a prolonged period. The risk for MBD may be higher with chronic liver disease. Higher doses of vitamin D may be required to maintain normal levels while on CKRT.

Severity-adjusted evaluation of initial dialysis on short-term health outcomes in urea cycle disorders

ObjectiveIn individuals with urea cycle disorders (UCDs) and neonatal disease onset, extracorporeal detoxification by continuous kidney replacement therapy is considered the therapeutic method of choice in addition to metabolic emergency treatment to resolve hyperammonemic decompensation. However, the indications for the initiation of dialysis are heterogeneously implemented transnationally, thereby hampering our understanding of (optimal) short-term health outcomes. MethodsWe performed a retrospective comparative analysis evaluating the therapeutic effects of initial dialysis on survival as well as neurocognitive outcome parameters in individuals with UCDs in comparison to a severity-adjusted non-dialyzed control cohort. Overall, 108 individuals with a severe phenotype of male ornithine transcarbamylase deficiency (mOTC-D), citrullinemia type 1 (CTLN1) and argininosuccinic aciduria (ASA) were investigated by stratification based on a recently established and validated genotype-specific disease prediction model. ResultsMortality is associated with the height of initial peak plasma ammonium concentration, but appears to be independent from treatment with initial dialysis in mOTC-D. However, improved survival after initial dialysis was observed in CTLN1, while there was a trend towards improved survival in ASA. In survivors, annual frequency of (subsequent) metabolic decompensations did not differ between the dialyzed and non-dialyzed cohorts. Moreover, treatment with initial dialysis was not associated with improved neurocognitive outcomes. InterpretationThe present severity-adjusted comparative analysis reveals that general practice of initial dialysis is neither associated with improved survival in individuals with mOTC-D nor does it differ with regard to the neurocognitive outcome for the investigated UCD subtypes. However, initial dialysis might potentially prove beneficial for survival in CTLN1 and ASA.Clinical trial registration: The UCDC database is recorded at the US National Library of Medicine (https://clinicaltrials.gov).

Continuous Kidney replacement Therapy Dosage and Mortality in Critically Ill Patients: a Retrospective Cohort Study using Marginal Structural Model.

Continuous kidney replacement therapy (CKRT) is a crucial intervention for hemodynamically unstable patients with acute kidney injury (AKI). Despite the recommendations to offer a CKRT dose of 20-25 mL/kg/h, the optimal CKRT dose remains uncertain, especially whether low-dose CKRT is associated with poor outcomes. This study investigated the association between low CKRT dosage and 90-day mortality using a marginal structural model (MSM). Using the MIMIC-IV database, adult patients who received CKRT for more than 24 hours were included. Data on time-fixed and time-dependent variables were collected. Patients were categorized based on CKRT dose thresholds of 13 and 20 ml/kg/h. Among the 1,329 patients, the 90-day mortality rate was 49.6%. The median age of the patients was 62 years (IQR: 52-72). Changes in CKRT dosing during treatment were frequent. Patients with a reduced delivered CKRT dose (<20 and < 13 ml/kg/h) generally exhibited low values during the initial days of CKRT, with an increase in the delivered CKRT dose. After adjusting only for baseline variables (traditional Cox regression model), patients receiving CKRT doses <13 ml/kg/h had significantly greater 90-day mortality (HR: 1.70, 95% CI 1.16-2.49) than those receiving CKRT doses ≥13 ml/kg/h. However, after adjusting for time-dependent variables, the CKRT dose was not significantly associated with mortality at either the 13 or 20 ml/kg/h threshold. Additionally, there were no significant associations between the delivered CKRT dose and 90-day mortality within the range of 5 to 40 ml/kg/h. This study highlights the impact of methodological approaches on the association between CKRT dose and mortality and that with personalized adjustments, there may not be a lower limit of the unsafe CKRT dose. However, lower CKRT doses were initially associated with higher mortality, and adjusting for time-dependent variables nullified this association.

Factors influencing circuit lifetime in paediatric continuous kidney replacement therapies – results from the EurAKId registry

BackgroundContinuous kidney replacement therapy (CKRT) has recently become the preferred kidney replacement modality for children with acute kidney injury (AKI). We hypothesise that CKRT technical parameters and treatment settings in addition to the clinical characteristics of patients may influence the circuit lifetime in children.MethodsThe study involved children included in the EurAKId registry (NCT 02960867), who underwent CKRT treatment. We analysed patient characteristics and CKRT parameters. The primary end point was mean circuit lifetime (MCL). Secondary end points were number of elective circuit changes and occurrence of dialysis-related complications.ResultsThe analysis was composed of 247 children who underwent 37,562 h of CKRT (median 78, IQR 37–165 h per patient). A total of 1357 circuits were utilised (3, IQR 2–6 per patient). MCL was longer in regional citrate anticoagulation (RCA), compared to heparin (HA) and no anticoagulation (NA) (42, IQR 32-58 h; 24, IQR 14-34 h; 18, IQR 12-24 h, respectively, p < 0.001). RCA was associated with longer MCL regardless of the patient’s age or dialyser surface. In multivariate analysis, MCL correlated with dialyser surface area (beta = 0.14, p = 0.016), left internal jugular vein vascular access site (beta = -0.37, p = 0.027), and the use of HA (beta = -0.14, p = 0.038) or NA (beta = -0.37, p < 0.001) vs. RCA. RCA was associated with the highest ratio of elective circuit changes and the lowest incidence of complications.ConclusionAnticoagulation modality, dialyser surface, and vascular access site influence MCL. RCA should be considered when choosing first-line anticoagulation for CKRT in children. Further efforts should focus on developing guidelines and clinical practice recommendations for paediatric CKRT.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Wheat yield and grain-filling characteristics due to cultivar replacement in the Haihe Plain in China.

The Haihe Plain plays an important role in wheat production and food security in China and has experienced continuous cultivar replacement since the 1950s.This study assessed the evolution of the yield and grain-filling characteristics of the main winter wheat cultivars in the Haihe Plain over the last seven decades (1950s to date). Cultivar characterization indicated that the increase in yield was negatively affected by spike number and positively affected by the number of kernels per spike before the 2000s and kernel weight after the 2000s. Field trials were conducted across two ecological zones over two consecutive wheatgrowing seasons. The results showed that genetic gains in grain yield, spike number, and kernel weight during 1955 to 2021 were 0.629%, 0.574%, and 0.332% year-1 on a relative basis or 39.12 kg ha-1, 24,350 hm-2, and 0.15 g year-1 on an absolute basis, respectively. However, the increase in the kernel number per spike was not significant. Moreover, cultivar replacement explained 25.6%, 12.8%, and 37.5% of the total variance in grain yield, spike number, and kernel weight, respectively. In summary, during the initial grain-filling stage, wheat cultivar replacement led to the shortening of grain-filling duration and rapid grain-filling rate. However, a longer active grain-filling duration was produced by prolonged durations of rapid and late grain-filling. Additionally, the experimental year had a greater effect on the kernel number, which explained 53.2% of the total variance. Ultimately, modern wheat cultivars had a greater kernel weight. Although the increase in kernel weight has affected grain yield during cultivar replacements in the Haihe Plain, the potential for further yield increase through kernel weight enhancement alone is limited. Consequently, future breeding efforts and cultivation practices should focus on improving spike traits and canopy architecture to enhance productivity.

Impact of specialized renal technologists on optimizing delivery of continuous kidney replacement therapy in critical care areas a retrospective study.

Continuous renal replacement therapy (CKRT) is delivered to some of the most critically ill patients in hospitals. This therapy is expensive and requires coordination of multidisciplinary teams to ensure the prescribed dose is delivered. With increased demands on the critical care nursing staff and increased complexities of patients admitted to critical care units, we evaluated the role of specialized renal technologists in ensuring the prescribed dose is delivered. Therefore, the aim of this study is to investigate the impact of supporting intensive care unit nurses with specialized renal technologists on optimizing efficiency of CKRT sessions in the United Arab Emirates. This is a retrospective study that compared critically ill patients on CKRT overseen by specialized renal technologists versus who are non-covered in the year 2021. A total of 331 sessions on 158 patients were included in the study. The mean filter life was longer in specialized renal technologists-covered patients compared to the non-covered group (66 vs. 59 h, p = 0.019). After adjustment by multiple regression analysis for risk factors (i.e., age, gender, mechanical ventilation, sepsis, mean arterial pressure, vasopressors, and SOFA) that may affect CKRT machines' filter life, presence of a specialized renal technologists resulted in significantly longer filter life (co-efficient 0.129; CI 95% 1.080, 11.970; p-value: 0.019). Our study suggests that specialized renal technologists play a vital role in prolonging CKRT machine's filter life span and optimizing CKRT machine's efficiency. Further research should focus on other potential benefits of having specialized renal technologists performing CKRT sessions, and to confirm the finding of this study. Additionally, a cost-benefit analysis could be conducted to determine the economic impact of having specialized teams performing CKRT.

Similarities and differences between intermittent hemodialysis and sustained low-efficiency dialysis

Abstract Acute kidney injury (AKI) is a multifaceted syndrome with diverse etiologies encountered very frequently in all critical care service units. Time and again, multiple researchers have proven its independent contribution to increasing morbidity and mortality in hospitalized children and adults. This undeniable fact has guided the development of newer strategies and logical concepts that have led to new modalities of treating AKI. In the absence of curative medical therapy, kidney replacement therapy (KRT) is considered the primary supportive therapy for AKI, and when initiated at the right time, it has the potential to bridge the gap toward cure. Among all KRT methods, blood-based dialysis occupies a prominent role and has now become the cornerstone of treatment for critically ill children with AKI. Two major methods usually employed are “intermittent hemolysis” (IHD) and “continuous kidney replacement therapy” (CKRT). Currently, a third method called “sustained low-efficiency dialysis (SLED)” is gaining momentum in critical care. It is a hybrid method; in simpler terms, it is a slow and prolonged IHD that may carry a few of the critical merits of CKRT. This narrative review article sheds light on SLED, as well as its comparison to IHD in critical care practice.

Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation, leading to metformin-associated lactic acidosis (MALA). As diabetes mellitus is a common chronic metabolic condition found in critically ill patients, pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit. The aim of this narrative mini review is therefore to update clinicians about MALA, and to provide a practical approach to its diagnosis and treatment. MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis, and confirmed when lactate exceeds 5 mmol/L. Risk factors include those that reduce renal elimination of metformin (renal impairment from any cause, histamine-2 receptor antagonists, ribociclib) and excessive alcohol consumption (as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism). Treatment of MALA involves immediate cessation of metformin, supportive management, treating other concurrent causes of lactic acidosis like sepsis, and treating any coexisting diabetic ketoacidosis. Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy. The optimal time to restart metformin has not been well-studied. It is nonetheless reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin.

Association between systemic inflammation biomarkers and mortality in patients with sepsis-associated acute kidney injury receiving intensive care and continuous kidney replacement therapy: results from the RENERGY (REsearches for NEphRology and epidemioloGY) study.

Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT. This multi-center, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, kidney replacement therapy dependence at discharge, and lengths of intensive care unit (ICU) and hospital stays. When added to the widely accepted Acute Physiology and Chronic Health Evaluation II score, platelet-to-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% confidence interval [CI], 0.00-0.02) and 0.02 (95% CI, 0.01-0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models. Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.

The role of nafamostat mesylate anticoagulation in continuous kidney replacement therapy for critically ill patients with bleeding tendencies: a retrospective study on patient outcomes and safety.

Continuous kidney replacement therapy (CKRT) is crucial in the management of acute kidney injury in intensive care units (ICUs). Nonetheless, the optimal anticoagulation strategy for patients with bleeding tendencies remains debated. This study aimed to evaluate patient outcomes and safety of nafamostat mesylate (NM) compared with no anticoagulation (NA) in critically ill patients with bleeding tendencies who were undergoing CKRT. This retrospective study enrolled 2,313 patients who underwent CKRT between March 2013 and December 2022 at the third affiliated hospital in South Korea. After applying the exclusion criteria, 490 patients were included in the final analysis, with 245 patients in the NM and NA groups each, following 1:1 propensity score matching. Subsequently, in-hospital mortality, incidence of bleeding complications, agranulocytosis, hyperkalemia, and length of hospital stay were assessed. No significant differences were observed between the groups regarding the lengths of hospital and ICU stays or the incidence of agranulocytosis and hyperkalemia. The NM group showed a smaller decrease in hemoglobin levels during CKRT (-1.90 g/dL vs. -2.39 g/dL) and less need for blood product transfusions than the NA group. Furthermore, the NM group exhibited a survival benefit in patients who required transfusion of all three blood products. NM is an effective and safe anticoagulant for CKRT in critically ill patients, especially those requiring transfusion of all three blood products. Although these findings are promising, further multicenter studies are needed to validate them and explore the mechanisms underlying the observed benefits.

Phosphate level predicts mortality in acute kidney injury patients undergoing continuous kidney replacement therapy and has a U-shaped association with mortality in patients with high disease severity: a multicenter retrospective study.

This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21-1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78-2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09-1.99; p = 0.01) but not among those with low disease severity. High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

Plasma presepsin for mortality prediction in patients with sepsis-associated acute kidney injury requiring continuous kidney replacement therapy.

The reliability of presepsin as a biomarker of sepsis may be reduced in patients with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT). This study analyzed the utility of plasma presepsin values in predicting mortality in patients with AKI requiring CKRT, particularly those with sepsis-associated AKI. This single-center retrospective study included 57 patients who underwent CKRT, with plasma presepsin measurements, from April 2022 to March 2023; 35 had sepsis-associated AKI. The predictive values of plasma presepsin, as well as Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, for 28-day mortality were analyzed using receiver operating characteristic curves. Multivariate Cox regression analysis was performed to identify risk factors for 28-day mortality in the sepsis-associated AKI subgroup. Overall, plasma presepsin showed a lower area under the curve value (0.636; 95% confidence interval [CI], 0.491-0.781) than the APACHE II (0.663; 95% CI, 0.521-0.804) and SOFA (0.731; 95% CI, 0.599-0.863) scores did. However, in sepsis-associated AKI, the area under the curve increased to 0.799 (95% CI, 0.653-0.946), which was higher than that of the APACHE II (0.638; 95% CI, 0.450-0.826) and SOFA (0.697; 95% CI, 0.519-0.875) scores. In the multivariate Cox regression analysis, a high presepsin level was an independent risk factor for 28-day mortality in sepsis-associated AKI (hazard ratio, 3.437; p = 0.03). Presepsin is a potential prognostic marker in patients with sepsis-associated AKI requiring CKRT.

#1970 Mortality prediction of plasma presepsin in sepsis-associated acute kidney injury patients requiring continuous kidney replacement therapy

Abstract Background and Aims Presepsin has recently introduced as a more specific biomarker for sepsis. Presepsin is greatly affected by kidney function, so its reliability may be reduced in acute kidney injury (AKI) patient, especially requiring continuous kidney replacement therapy (CKRT). For this reason, there has been no study to date analyzing presepsin in AKI patients requiring CKRT. This study analyzed the usefulness of plasma presepsin for predicting mortality in AKI patients requiring CKRT, especially in sepsis-associated AKI (SA-AKI). Method This single-center, retrospective study included the patients who underwent CKRT with plasma presepsin measurement from April 2022 to March 2023. A total of 57 patients were enrolled, of which 35 were SA-AKI. 28-day mortality predictive values of plasma presepsin, Acute Physiology and Chronic Health Evaluation-II (APACHE-II), and Sequential Organ Failure Assessment (SOFA) scores were analyzed using receiver operating characteristics (ROC) curve analysis. Multivariate Cox regression analysis was performed to identifying risk factors for 28-day mortality in the SA-AKI subgroup. Results In the overall cohort, plasma presepsin showed the lower area under the ROC (AuROC) value of 0.636 than those of APACHE-II (0.663) and SOFA (0.731) scores. However, in SA-AKI subgroup, AuROC value of plasma presepsin was much increased to 0.799, which was the higher than those of APACHE-II (0.651) and SOFA (0.697) scores. Moreover, in multivariate Cox regression analysis, high presepsin was observed as an independent risk factor for 28-day mortality in the SA-AKI subgroup (HR 6.868, P=0.005). Conclusion Presepsin can be used as a good prognostic marker in SA-AKI patients requiring CKRT. The usefulness of plasma presepsin in the patients undergoing CKRT needs to be further studied in the future.

#226 Outcome of intermittent hemodialysis vs. continuous kidney replacement therapy for acute kidney injury: observational prospective multi-center study

Abstract Background and Aims Continuous hemodialysis in hemodynamically stable acute kidney injury (AKI) patients may impact outcome differently compared to intermittent hemodialysis, although this issue is controversial. We look at differences in AKI outcomes between patients treated with intermittent hemodialysis (IHD) and patients treated with continuous kidney replacement therapy (CKRT) modalities in in Kuwait. Method Clinically and hemodynamically stable adult inpatients with native kidneys (i.e., did not need inotropic support or mechanical ventilation) who received IHD or CKRT for AKI, in seven public hospitals in Kuwait between 1/January to 31/December 2021 were recruited. CKRT was selected due to lack of access to water treatment in patients wards in some of the participating hospitals. Demographics, comorbidities, dialytic and non-dialytic management data, and 30-day kidney and patient outcome data for, were prospectively collected and analyzed. Results Total number of AKI patients not on inotropic support and not mechanically ventilated who received dialysis during study period was 229 (age: 59.9 years; males: 60.3%; baseline eGFR: 56 ml/min). IHD (group 1) was performed in 27.1% of the cohort whereas CKRT (group 2) was performed in 72.9%. There was no statistically significant difference between the two groups in age (58.4 for IHD and 59.9 for CKRT, p=0.6), baseline eGFR (55 ml/min for IHD and 56.4 for CKRT, p=0.8), sex ratio, incidence of diabetes, hypertension or cardiovascular disease, or cause of AKI. However, renin angiotensin aldosterone system inhibitors (RAASi) were precipitating factors for AKI more significantly in the IHD group (25.8% vs. 6% for CKRT, P ≤ 0.001). Intensive care unit (ICU) contributed 21% of cases (14.5% for IHD and 23.4% for CKRT, insignificant p value of 0.1). Also, there was no statistically significant difference in receiving intravenous fluids between the two groups (71% for IHD vs. 71.5% for CKRT, p=0.8), however, more patients in the IHD group received diuretics (62.9% vs 43.1% for CKRT, p=0.008). Dialysis vascular access was right internal jugular vein in 59% (75.8% FOR IHD vs. 52.7% for CKRT) followed by femoral vein in 35% of cases (19.4%). Extracorporeal membrane oxygenation (ECMO) was used in only two cases in the CKRT group. Of the total cohort, 21.8% died, with no difference between the two groups (16.1% for IHD vs 24% for CKRT, p=0.2). Partial recovery was higher in IHD group (30.8% vs.17.3%, p=0.046) and complete recovery higher in CKRT group 33.1% vs 13.5%, p=0.009). eGFR at 30 days was 53.2 ml/min with no statistically significant difference between the two groups (44.6 for IHD vs 56.1 for CKRT, p=0.15). Conclusion The IHD group and the CKRT group were statistically similar in basic characteristics and received similar lines of management, except for the diuretics. At 30 days, they had similar death rates but CKRT group had higher rates of complete recovery than the IHD group. This is in line with published literature that suggest CKRT may not improve mortality but may improve kidney recovery.

#916 Outcomes of renal replacement therapy in ICU adult patients with acute kidney injury: a retrospective cohort study

Abstract Background and Aims Continuous renal replacement therapy (CRRT) and sustained low-efficiency dialysis (SLED) are usually used for critically ill patients with acute kidney injury when indicated. Most studies done throughout the years showed no statistically significant difference in outcomes between the two modalities. Thus, this study aims to determine the outcomes and associated factors of both CRRT and SLED in patients with AKI. Hence, this will allow us to determine our competency as an institution in using CRRT and SLED to formulate recommendations and protocols in the future. Method We conducted a retrospective cohort study of patients who developed acute kidney injury and underwent either SLED or CRRT in the ICU of a tertiary hospital in Makati City, Metro Manila. Patients who are on maintenance hemodialysis, who underwent both sustained low-efficiency dialysis and continuous replacement therapy, and who did not complete or tolerate 1 session of SLED or 24 hours of CRRT were excluded in the study. Key outcomes investigated were all-cause mortality at 30 days and dialysis dependence at 30 days after initiation of treatment. Results Eighty-four patients who were initiated with either SLED (N=48) or CRRT (N=36). There was a significant difference in terms of all-cause mortality between modalities 20 (42%) for SLED and 33 (92%) for CRRT, p-value=0.000). Among variables used in the study, higher vasopressor requirement (aOR 2.78, 95% CI: 1.47-5.25, p=0.002) and age (aOR 2.21, 95% CI: 1.13-4.33, p=0.021) at initiation were associated with higher likelihood of mortality across modalities. Thirteen patients (28%) who underwent SLED were dependent on dialysis at 30 days. Baseline serum creatinine (aOR 3.21 95% CI: 1.17-8.79, p=0.023) and serum creatinine at initiation (aOR 4.11, 95% CI: 1.43-22.56, p=0.014) were identified to be associated with dialysis dependence. Sub-analysis of the CRRT group showed continuous veno-venous hemodialysis (CVVHD) (aOR 16.57, 95% CI: 3.54-77.49, p&amp;lt;0.001) was associated with higher likelihood of mortality among CRRT modalities. Conclusion Increased mortality was seen in patients who underwent CRRT especially CVVHD and was associated with age and number of vasopressors present during initiation of renal replacement therapy.