Data-driven prediction of continuous renal replacement therapy survival.

Continuous renal replacement therapy (CRRT) is a form of dialysis prescribed to severely ill patients who cannot tolerate regular hemodialysis. However, as the patients are typically very ill to begin with, there is always uncertainty whether they will survive during or after CRRT treatment. Because of outcome uncertainty, a large percentage of patients treated with CRRT do not survive, utilizing scarce resources and raising false hope in patients and their families. To address these issues, we present a machine learning-based algorithm to predict short-term survival in patients being initiated on CRRT. We use information extracted from electronic health records from patients who were placed on CRRT at multiple institutions to train a model that predicts CRRT survival outcome; on a held-out test set, the model achieves an area under the receiver operating curve of 0.848 (CI = 0.822-0.870). Feature importance, error, and subgroup analyses provide insight into bias and relevant features for model prediction. Overall, we demonstrate the potential for predictive machine learning models to assist clinicians in alleviating the uncertainty of CRRT patient survival outcomes, with opportunities for future improvement through further data collection and advanced modeling.

Citrate and low-dose heparin combined anticoagulation in pediatric continuous renal replacement therapy.

There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.

[Observation on the efficacy of continuous veno-venous hemodia-filtration combined with hemoperfusion HA380 in the treatment of 15 cases of heat stroke with multiple organ dysfunction syndrome].

OBJECTIVE: To investigate the clinical efficacy of continuous veno-venous hemodia-filtration (CVVHDF) combined with hemoperfusion (HP) HA380 in the treatment of heat stroke patients with multiple organ dysfunction syndrome (MODS). METHODS: A retrospective and observational study was conducted. A total of 15 patients with heat stroke combined with MODS who were admitted to the department of intensive care unit (ICU) of Suizhou Central Hospital/Hubei University of Medicine from July to September 2022 were selected as the study objects. All 15 patients were treated with CVVHDF combined with HA380 based on the comprehensive management strategy for severe illness. Organ function indicators [including total bilirubin (TBil), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr), cardiac troponin T (cTnT), myoglobin (Myo), MB isoenzyme of creatine kinase (CK-MB), sequential organ failure assessment (SOFA)] and inflammatory indicators [including white blood cell count (WBC), neutrophil count (NEU), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6)] were collected. The improvements of the above indexes at admission, after the first HP, after the second HP, after the third HP, and on the 5th day of treatment were compared. Combined with the clinical outcome of patients, the comprehensive efficacy of CVVHDF combined with HA380 in the treatment of severe heat radiation disease was evaluated. RESULTS: There were 10 males and 5 females among the 15 patients. The average age was (64.5±11.5) years old. There were 6 cases of classical heat stroke and 9 cases of exertional heat stroke. Glasgow coma scale (GCS) was 3-8 at admission; SOFA score was 9-17 within 12 hours after admission; acute physiology and chronic health evaluation II (APACHE II) was 25-45 within 24 hours after admission. After treatment, the IL-6 level and SOFA score gradually decreased, and there were significant differences in the decrease after the second HP compared to admission [IL-6 (ng/L): 48.37 (15.36, 113.03) vs. 221.90 (85.87, 425.90), SOFA: 8.3±3.3 vs. 11.1±2.4, both P < 0.05]. The PCT level reached its peak after the first HP [12.51 (6.07, 41.65) µg/L], and then gradually decreased, and the difference was statistically significant after the third HP [1.26 (0.82, 5.40) µg/L, P < 0.05]. Compared those at admission, Cr level significantly improved after the first HP (µmol/L: 66.94±25.57 vs. 110.80±31.13, P < 0.01), Myo significantly decreased after the second HP [µg/L: 490.90 (164.98, 768.05) vs. 3 000.00 (293.00, 3 000.00), P < 0.05], After the third HP, the CK level also showed significant improvement [U/L: 476.0 (413.0, 922.0) vs. 2 107.0 (729.0, 2 449.0), P < 0.05]. After CVVHDF combined with 3 times HP treatment, the patient's inflammatory response was gradually controlled and organ function gradually recovered. On the 5th day of the disease course, WBC, PCT and IL-6 levels were significantly improved compared to admission, and AST, CK, LDH, Cr, Myo, CK-MB, and SOFA score were significantly corrected compared with those on admission. The 24-hour survival rate of 15 patients was 86.67%, and the 24-hour, 7-day and 28-day survival rates were both as high as 73.33%. The average mechanical ventilation time of 11 surviving patients was (101.8±22.0) hours, the average continuous renal replacement therapy (CRRT) time was (58.8±11.0) hours, the average length of ICU stay was (6.3±1.0) days, and the average total hospitalization was (14.6±5.2) days. CONCLUSIONS: CVVHDF combined with HP HA380 in the treatment of heat stroke patients with MODS can effectively improve organ function and alleviate the inflammatory storm, which is an effective means to improve the rescue rate and reduce the mortality of severe heat stroke patients.

[Construction and external validation of a risk prediction model for unplanned interruption during continuous renal replacement therapy].

OBJECTIVE: To identify the independent factors of unplanned interruption during continuous renal replacement therapy (CRRT) and construct a risk prediction model, and to verify the clinical application effectiveness of the model. METHODS: A retrospective study was conducted on critically ill adult patients who received CRRT treatment in the intensive care unit (ICU) of Zhejiang Hospital from January 2021 to August 2022 for model construction. According to whether unplanned weaning occurred, the patients were divided into two groups. The potential influencing factors of unplanned CRRT weaning in the two groups were compared. The independent influencing factors of unplanned CRRT weaning were screened by binary Logistic regression and a risk prediction model was constructed. The goodness of fit of the model was verified by a Hosmer-Lemeshow test and its predictive validity was evaluated by receiver operator characteristic curve (ROC curve). Then embed the risk prediction model into the hospital's ICU multifunctional electronic medical record system for severe illness, critically ill patients with CRRT admitted to the ICU of Zhejiang Hospital from November 2022 to October 2023 were prospectively analyzed to verify the model's clinical application effect. RESULTS: (1) Model construction and internal validation: a total of 331 critically ill patients with CRRT were included to be retrospectively analyzed. Among them, there were 238 patients in planned interruption group and 93 patients in unplanned interruption group. Compared with the planned interruption group, the unplanned interruption group was shown as a lower proportion of males (80.6% vs. 91.6%) and a higher proportion of chronic diseases (60.2% vs. 41.6%), poor blood purification catheter function (31.2% vs. 6.3%), as a higher platelet count (PLT) before CRRT initiation [×109/L: 137 (101, 187) vs. 109 (74, 160)], lower level of blood flow rate [mL/min: 120 (120, 150) vs. 150 (140, 180)], higher proportion of using pre-dilution (37.6% vs. 23.5%), higher filtration fraction [23.0% (17.5%, 32.9%) vs. 19.1% (15.7%, 22.6%)], and frequency of blood pump stops [times: 19 (14, 21) vs. 9 (6, 13)], the differences of the above 8 factors between the two groups were statistically significant (all P < 0.05). Binary Logistic regression analysis showed that chronic diseases [odds ratio (OR) = 3.063, 95% confidence interval (95%CI) was 1.200-7.819], blood purification catheter function (OR = 4.429, 95%CI was 1.270-15.451), blood flow rate (OR = 0.928, 95%CI was 0.900-0.957), and frequency of blood pump stops (OR = 1.339, 95%CI was 1.231-1.457) were the independent factors for the unplanned interruption of CRRT (all P < 0.05). These 4 factors were used to construct a risk prediction model, and ROC curve analysis showed that the area under the curve (AUC) predicted by the model was 0.952 (95%CI was 0.930-0.973, P = 0.003 0), with a sensitivity of 88.2%, a specificity of 89.9%, and a maximum value of 1.781 for the Youden index. (2) External validation: prospective inclusion of 110 patients, including 63 planned interruption group and 47 unplanned interruption group. ROC curve analysis showed that the AUC of the risk prediction model was 0.919 (95%CI was 0.870-0.969, P = 0.004 3), with a sensitivity of 91.5%, a specificity of 79.4%, and a maximum value of the Youden index of 1.709. CONCLUSIONS: The risk prediction model for unplanned interruption during CRRT has a high predictive efficiency, allowing for rapid and real-time identification of the high risk patients, thus providing references for preventative nursing.

Standard vs. carbone dioxide adapted kidney replacement therapy in hypercapnic ARDS patients: a randomized controlled pilot trial (BigBIC).

BACKGROUND: Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT. METHODS: We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO2-adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment. RESULTS: From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO2-adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group (p = 0.26). CONCLUSION: Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS. TRIAL REGISTRATION: The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed.

Volume control strategy and patient survival in sepsis-associated acute kidney injury receiving continuous renal replacement therapy: a randomized controlled trial with secondary analysis.

Optimal strategy for volume control and the clinical implication of achieved volume control are unknown in patients with sepsis-associated acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). This randomized controlled trial aimed to compare the survival according to conventional or bioelectrical impedance analysis (BIA)-guided volume control strategy in patients with sepsis-associated AKI receiving CRRT. We also compared patient survival according to achieved volume accumulation rate ([cumulative fluid balance during 3 days × 100]/fluid overload measured by BIA at enrollment) as a post-hoc analysis. We randomly assigned patients to conventional volume control strategy (n = 39) or to BIA-guided volume control strategy (n = 34). There were no differences in 28-day mortality (HR, 1.19; 95% CI, 0.63-2.23) or 90-day mortality (HR, 0.99; 95% CI 0.57-1.75) between conventional and BIA-guided volume control group. In the secondary analysis, achieved volume accumulation rate was significantly associated with patient survival. Compared with the achieved volume accumulation rate of ≤ - 50%, the HRs (95% CIs) for the risk of 90-day mortality were 1.21 (0.29-5.01), 0.55 (0.12-2.48), and 7.18 (1.58-32.51) in that of - 50-0%, 1-50%, and > 50%, respectively. Hence, BIA-guided volume control in patients with sepsis-associated AKI receiving CRRT did not improve patient outcomes. In the secondary analysis, achieved volume accumulation rate was associated with patient survival.

Management of pediatric liver failure with therapeutic plasma exchange and continuous renal replacement therapy: A retrospective observational study.

Liver failure represents a critical medical condition, marked by the rapid decline of hepatic functions. Emerging therapies, notably therapeutic plasma exchange (TPE) and continuous venovenous hemodiafiltration (CVVHDF), have demonstrated potential in mitigating these conditions through their roles in detoxification and hepatic support. The utility of these treatments, whether applied individually or in tandem, constitutes a significant area of research concerning the management of liver failure in pediatric patients. This study aims to evaluate the role and efficacy of TPE or TPE combined with CVVHDF in the treatment of liver failure among children. This retrospective study was conducted in a LTICU by reviewing the medical history of pediatric patients aged 1 month to 18 years. Patients were admitted between January 1, 2021 and December 1, 2023 due to acute liver failure or acute-chronic liver failure. The study evaluated those who received TPE or continuous renal replacement therapy combined with TPE. In statistical analyses, a P-value of <.05 was considered statistically significant. The study involved 24 patients with liver failure, comprising 13 males and 11 females. Sixteen patients (66.6%) received only TPE, while 8 patients (33.4%) were treated with TPE and CVVHDF. For patients treated only with TPE, the median INR reduced from 3.1 to 1.26, alanine aminotransferase from 1255 to 148, and aspartate aminotransferase from 2189 to 62. Similar significant reductions were observed in the TPE and CVVHDF group: INR from 3.9 to 1.26, alanine aminotransferase from 1749 to 1148, and aspartate aminotransferase from 1489 to 62. These changes were statistically significant with P-values of .01 for each parameter in both groups. Overall, 14 patients survived without requiring a liver transplant, while 4 patients underwent liver transplantation. Our study on pediatric liver failure treatment shows that both standalone TPE and its combination with CVVHDF are effective, especially as a bridge to transplantation. With 58% transplant-free survival, these therapies demonstrate significant clinical improvements. Future multicentric studies are needed for broader validation of these findings in liver failure management.

Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Acute kidney injury in acute liver failure: A narrative review.

Acute kidney injury (AKI) is a frequent complication of acute liver failure (ALF) and it worsens the already worse prognoses of ALF. ALF is an uncommon disease, with varying etiologies and varying definitions in different parts of the world. There is limited literature on the impact of AKI on the outcome of ALF with or without transplantation. The multifaceted etiology of AKI in ALF encompasses factors such as hemodynamic instability, systemic inflammation, sepsis and direct nephrotoxicity. Indications of renal replacement therapy (RRT) for AKI in ALF patients extend beyond the conventional criteria for dialysis and continuous renal replacement therapy (CRRT) may have a role in transplant-free survival or bridge to liver transplantation (LT). LT is a life-saving option for ALF, so despite somewhat lower survival rates of LT in ALF patients with AKI, LT is not usually deferred. In this review, we will discuss the guidelines' recommended definition and classification of AKI in ALF, the impact of AKI in ALF, the pathophysiology of AKI and the role of CRRT and LT in ALF patients with AKI.

Extra-corporeal non-liver transplant therapies for acute liver failure: Focus on plasma exchange and continuous renal replacement therapy.

The acute inflammatory milieu in patients with acute liver failure (ALF) results in 'toxic' blood in these patients. In vitro experiments have shown that the plasma obtained from ALF patients is toxic to rabbit hepatocytes and inhibits regeneration of rat hepatocytes. Treatments such as plasma exchange and continuous renal replacement therapy to cleanse the blood have improved survival in ALF patients. In the liver microcirculation, the exchange of fluid across fenestrae in liver sinusoidal endothelial cells (LSECs) is vital for proper functioning of hepatocytes. Clogging of the liver filter bed by inflammatory debris and cells ('traffic jam hypothesis') impeding blood flow in sinusoids may in turn reduce the exchange of fluid across LSEC fenestrae and cause dysfunction and necrosis of hepatocytes in ALF patients. In mouse model of paracetamol overdose, disturbances in microcirculation in the liver preceded the development of injury and necrosis of hepatocytes. This may represent a reversible pathophysiological mechanism in ALF which may be improved by the anti-inflammatory effect of plasma exchange. Wider access to urgent plasma exchange is a major advantage compared to urgent liver transplantation to treat ALF patients worldwide, especially so in resource constrained settings. Continuous hemo-filtration or dialysis is used to reduce ammonia levels and treat cerebral edema in ALF patients. In this review, we discuss the different modalities to cleanse the blood in ALF patients, with an emphasis on plasma exchange, from a hepatology perspective.

Safety and Feasibility of Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy With Calcium-Containing Solutions: A Randomized Controlled Trial.

BACKGROUND: Calcium-free (Ca-free) solutions are theoretically the most ideal for regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT). However, the majority of medical centers in China had to make a compromise of using commercially available calcium-containing (Ca-containing) solutions instead of Ca-free ones due to their scarcity. This study was designed to probe into the potential of Ca-containing solution as a secure and efficient substitution for Ca-free solutions. METHODS: In this prospective, randomized single-center trial, 99 patients scheduled for CRRT were randomly assigned in a 1:1:1 ratio to one of three treatment groups: continuous veno-venous hemodialysis Ca-free dialysate (CVVHD Ca-free) group, continuous veno-venous hemodiafiltration calcium-free dialysate (CVVHDF Ca-free) group, and continuous veno-venous hemodiafiltration Ca-containing dialysate (CVVHDF Ca-containing) group at cardiac intensive care unit (CICU). The primary endpoint was the incidence of metabolic complications. The secondary endpoints included premature termination of treatment, thrombus of filter, and bubble trap after the process. RESULTS: The incidence of citrate accumulation (18.2% vs. 12.1% vs. 21.2%) and metabolic alkalosis (12.1% vs. 0% vs. 9.1%) did not significantly differ among three groups (p > 0.05 for both). The incidence of premature termination was comparable among the groups (18.2% vs. 9.1% vs. 9.1%, p = 0.582). The thrombus level of the filter and bubble trap was similar in the three groups (p > 0.05 for all). CONCLUSIONS: In RCA-CRRT for CICU population, RCA-CVVHDF with Ca-containing solutions and traditional RCA with Ca-free solutions had a comparable safety and feasibility. TRIAL REGISTRATION: ChiCTR2100048238 in the Chinese Clinical Trial Registry.

Initial renal replacement therapy (RRT) modality associates with 90-day postdischarge RRT dependence in critically ill AKI survivors.

PURPOSE: Real-world comparison of RRT modality on RRT dependence at 90 days postdischarge among ICU patients discharged alive after RRT for acute kidney injury (AKI). METHODS: Using claims-linked to US hospital discharge data (Premier PINC AI Healthcare Database [PHD]), we compared continuous renal replacement therapy (CRRT) vs. intermittent hemodialysis (IHD) for AKI in adult ICU patients discharged alive from January 1, 2018 to June 30, 2021. RRT dependence at 90 days postdischarge was defined as ≥2 RRT treatments in the last 8 days. Between-group differences were balanced using inverse probability treatment weighting (IPTW). RESULTS: Of 34,804 patients, 3804 patients (from 382 hospitals) had claims coverage for days 83-90 postdischarge. Compared to IHD-treated patients (n = 2740), CRRT-treated patients (n = 1064) were younger; had more admission to large teaching hospitals, surgery, sepsis, shock, mechanical ventilation, but lower prevalence of comorbidities (p < 0.05 for all). Compared to IHD-treated patients, CRRT-treated patients had lower RRT dependence at hospital discharge (26.5% vs. 29.8%, p = 0.04) and lower RRT dependence at 90 days postdischarge (4.9% vs. 7.4% p = 0.006) with weighted adjusted OR (95% CI): 0.68 (0.47-0.97), p = 0.03. Results persisted in sensitivity analyses including patients who died during days 1-90 postdischarge (n = 112) or excluding patients from hospitals with IHD patients only (n = 335), or when excluding patients who switched RRT modalities (n = 451). CONCLUSIONS: Adjusted for potential confounders, the odds of RRT dependence at 90 days postdischarge among survivors of RRT for AKI was 30% lower for those treated first with CRRT vs. IHD, overall and in several sensitivity analyses. SUMMARY: Critically ill patients in intensive care units (ICU) may develop acute kidney injury (AKI) that requires renal replacement therapy (RRT) to temporarily replace the injured kidney function of cleaning the blood. Two main types of RRT in the ICU are called continuous renal replacement therapy (CRRT), which is performed almost continuously, i.e., for >18 h per day, and intermittent hemodialysis (IHD), which is a more rapid RRT that is usually completed in a little bit over 6 h, several times per week. The slower CRRT may be gentler on the kidneys and is more likely to be used in the sickest patients, who may not be able to tolerate IHD. We conducted a data-analysis study to evaluate whether long-term effects on kidney function (assessed by ongoing need for RRT, i.e., RRT dependence) differ depending on use of CRRT vs. IHD. In a very large US linked hospital-discharge/claims database we found that among ICU patients discharge alive after RRT for AKI, fewer CRRT-treated patients had RRT dependence at hospital discharge (26.5% vs. 29.8%, p = 0.04) and at 90 days after discharge (4.9% vs. 7.4% p = 0.006). In adjusted models, RRT dependence at 90 days postdischarge was >30% lower for CRRT than IHD-treated patients. These results from a non-randomized study suggest that among survivors of RRT for AKI, CRRT may result in less RRT dependence 90 days after hospital discharge.

CytoSorb® in burn patients with septic shock and Acute Kidney Injury on Continuous Kidney Replacement Therapy is associated with improved clinical outcome and survival.

BACKGROUND: In burn patients, septic shock and acute kidney injury (AKI) with use of continuous renal replacement therapy (CRRT) severely increase morbidity and mortality. Sorbent therapies could be an adjunctive therapy to address the underlying metabolic changes in inflammatory and anti-inflammatory cytokines dysregulated production. METHODS: A retrospectively observational study of 35 severe burn patients admitted to the Burn Center (Turin, Italy, from January 2017 to December 2022), who underwent CRRT for AKI-associated septic shock. Out of 35 patients, 11 were treated with CytoSorb® as adjunctive therapy to CRRT (Sorbent group) and 24 patients only with CRRT (Control group). RESULTS: The application of CytoSorb® took place in a very dispersed way. Out of 11 patients, 7 started the CRRT together with the sorbent application. The patients of the sorbent group exhibited a significant reduction in norepinephrine use compared to that of the control group. A clinical improvement over the first 4 days of Cytosorb® was observed in both survivors and no survivors of the sorbent group, with significant norepinephrine decreased use on day 4 compared to day 1. In-hospital mortality was 45.4% and 70.8% in the sorbent and control group, respectively, and significantly better at Kaplan-Meier survival analysis at 270 days (p = 0.0445). In both groups, all survivor patients recovered renal function at discharge, whereas no survivors did not. CONCLUSIONS: Adjunctive treatment with CytoSorb® for burn patients with AKI-CRRT and septic shock poorly responsive to standard therapy led to a significant clinical improvement, and was associated with a lower mortality rate compared to CRRT alone.

Hierarchical endpoints in critical care: A post-hoc exploratory analysis of the standard versus accelerated initiation of renal-replacement therapy in acute kidney injury and the intensity of continuous renal-replacement therapy in critically ill patients trials.

PURPOSE: To perform a post-hoc reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) and the Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients (RENAL) trials through hierarchical composite endpoint analysis using win ratio (WR). MATERIAL AND METHODS: All patients with complete information from the STARRT-AKI (which compared accelerated versus standard approaches for renal replacement therapy - RRT initiation) and RENAL (which compared two different RRT doses in critically ill patients) trials were selected. WR was defined as a hierarchical composite endpoint using 90-day mortality, RRT dependency at 90-days, intensive care unit (ICU) length-of-stay (LOS), and hospital LOS (primary analysis); values above the unit represent a benefit of the intervention for the hierarchical composite endpoint. A secondary analysis replacing LOS by days alive and free of RRT was performed. Stratified analyses were performed according to illness severity score, surgical status, and the presence of sepsis. RESULTS: The WR analysis produced 2,141,830 pairs for the STARRT-AKI trial and 536,446 pairs for the RENAL trial, respectively. The WR results for STARRT-AKI and RENAL were 1.04 (95% confidence interval [CI] 0.96-1.13; p = 0.33) and 1.02 (95% CI; 0.90-1.15; p = 0.75) for the primary analysis, and 0.88 (95% CI; 0.79-0.99; p = 0.03) and 1.02 (95% CI; 0.87-1.21; p = 0.77) for the secondary analysis, respectively. The stratified analysis of the primary suggested possible benefit of the accelerated-strategy in the STARRT-AKI trial for non-surgical patients with sepsis, while the secondary analysis suggested possible harm of the accelerated-strategy for surgical patients without sepsis. There was no evidence of heterogeneity in treatment effects in stratified analyses in the RENAL trial. CONCLUSION: WR approach using a hierarchical composite endpoint is feasible for trials in critical care nephrology. The primary re-analyses of the STARRT-AKI and RENAL trials both yielded neutral results; however, there was suggestion of heterogeneity in treatment effect in stratified analyses of the STARRT-AKI trial by surgical status and sepsis. Selection of the endpoints and hierarchical ordering before trial design using the WR approach can have important implications for trial interpretation. TRIAL REGISTRY: ClinicalTrials.gov number NCT02568722 (STARRT-AKI) and NCT00076219 (RENAL).

Factors associated with successful liberation from continuous renal replacement therapy in children and young adults: analysis of the worldwide exploration of renal replacement outcomes collaborative in Kidney Disease Registry.

PURPOSE: Continuous renal replacement therapy (CRRT) is used for supportive management of acute kidney injury (AKI) and disorders of fluid balance (FB). Little is known about the predictors of successful liberation in children and young adults. We aimed to identify the factors associated with successful CRRT liberation. METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease study is an international multicenter retrospective study (32 centers, 7 nations) conducted from 2015 to 2021 in children and young adults (aged 0-25 years) treated with CRRT for AKI or FB disorders. Patients with previous dialysis dependence, tandem extracorporeal membrane oxygenation use, died within the first 72 h of CRRT initiation, and those who never had liberation attempted were excluded. Patients were categorized based on first liberation attempt: reinstituted (resumption of any dialysis within 72 h) vs. success (no receipt of dialysis for ≥ 72 h). Multivariable logistic regression was used to identify factors associated with successful CRRT liberation. RESULTS: A total of 622 patients were included: 287 (46%) had CRRT reinstituted and 335 (54%) were successfully liberated. After adjusting for sepsis at admission and illness severity parameters, several factors were associated with successful liberation, including higher VIS (vasoactive-inotropic score) at CRRT initiation (odds ratio [OR] 1.35 [1.12-1.63]), higher PELOD-2 (pediatric logistic organ dysfunction-2) score at CRRT initiation (OR 1.71 [1.24-2.35]), higher urine output prior to CRRT initiation (OR 1.15 [1.001-1.32]), and shorter CRRT duration (OR 0.19 [0.12-0.28]). CONCLUSIONS: Inability to liberate from CRRT was common in this multinational retrospective study. Modifiable and non-modifiable factors were associated with successful liberation. These results may inform the design of future clinical trials to optimize likelihood of CRRT liberation success.

Association of continuous kidney replacement therapy timing and mortality in critically ill children.

BACKGROUND: Acute kidney injury (AKI) is a common complication of critical illness and associated with high morbidity and mortality. Optimal timing of continuous kidney replacement therapy (CKRT) in children is unknown. We aimed to measure the association between timing of initiation and mortality. METHODS: This is a single-center retrospective cohort study of pediatric patients receiving CKRT from 2013 to 2019. The primary exposure, time to CKRT initiation, was measured from onset of stage 3 AKI during hospitalization (defined using Kidney Disease: Improving Global Outcomes creatinine and urine output criteria) and analyzed as both a continuous and categorical variable. The primary outcome was ICU mortality. RESULTS: Ninety-nine patients met criteria for analysis. Overall mortality was 39% (39/99). Median time from stage 3 AKI onset to CKRT initiation was 1.5 days in survivors and 5.5 days in nonsurvivors (p < 0.001). In multivariable analysis, increased time to CKRT initiation was independently associated with mortality [OR 1.02 per hour (95% CI 1.01-1.04), p < 0.001]. Longer time to CKRT initiation was associated with higher odds of mortality in ascending time intervals. Patients started on CKRT > 2 days compared to < 2 days after stage 3 AKI onset had higher mortality (65% vs. 5%, p < 0.001), longer median ICU length of stay (25 vs. 12 d, p < 0.001), longer median CKRT duration (11 vs. 5 d, p < 0.001), and fewer AKI-free days (0 vs. 14 d, p < 0.001). CONCLUSIONS: Longer time to initiation of CKRT after development of severe AKI is independently associated with mortality. Consideration of early CKRT in this high-risk population may be a strategy to reduce mortality and improve recovery of kidney function. However, there remains significant heterogeneity in the definition of early versus late initiation and the optimal timing of CKRT remains unknown.