Septic shock with acute kidney injury (AKI) carries a high risk of mortality and multi-organ dysfunction. Cytokine adsorption therapy has been proposed as a potential adjunct to continuous renal replacement therapy (CRRT). We aimed to evaluate the association between cytokine adsorption and short-term organ dysfunction as well as in-hospital mortality in patients treated with continuous veno-venous hemodiafiltration (CVVHDF). This single-center retrospective cohort study included 73 adult patients with septic shock and AKI who underwent CVVHDF. Patients receiving additional cytokine adsorption therapy using the HA330 cartridge were compared with those receiving standard treatment. The primary outcome was 72-hour change in SOFA score (ΔSOFA). Secondary outcomes included in-hospital mortality and hemodynamic trends. Multivariable logistic regression and Cox proportional hazards models were applied to adjust for confounding and assess survival. Cytokine adsorption therapy was associated with a significantly greater median ΔSOFA score (5.9 vs. 0.0; p < 0.001). In-hospital mortality was lower in the cytokine group (hazard ratio 0.46; 95% CI 0.23-0.92; p = 0.027). Logistic regression confirmed cytokine adsorption as an independent predictor of survival (OR = 0.006, p = 0.039). The model demonstrated excellent discrimination (ROC AUC = 0.930) with high sensitivity (97.7%) at the 0.5 threshold. Exploratory subgroup analyses suggested that membrane type and microbial profile may modify treatment response. In this retrospective cohort, cytokine adsorption therapy was independently associated with early improvements in organ dysfunction and reduced in-hospital mortality. These findings support its potential therapeutic role, but require confirmation in larger multicenter prospective trials.

Urea cycle disorders represent the most frequent cause of hyperammonemia in the absence of liver failure and may lead to life-threatening elevations in plasma ammonia, particularly when onset is acute and rapidly progressive. Although the etiologies and management principles of acute liver failure have been extensively addressed elsewhere, hyperammonemia must be recognized in critically ill patients as a potential cause of coma, especially when hepatic failure is not present. Non-hepatic causes, including urea cycle disorders, infectious diseases, drug-induced toxicity, and post-transplant complications, are frequently underrecognized. Management requires prompt neuroprotective measures, short-term protein restriction with appropriate nutritional support, and rapid ammonia removal, preferably using high-dose continuous renal replacement therapy. Early intervention is crucial to prevent cerebral edema and to improve neurological outcomes.

Introduction: Hypercapnic respiratory failure is associated with high morbidity and mortality. Low-flow extracorporeal CO2 removal (ECCO2R) has been shown to facilitate lung-protective ventilation or spontaneous breathing. However, three multicenter randomized trials have failed to show benefit which could potentially be a result of patient selection. In this study, we aimed to characterize prognostic scores developed for extracorporeal membrane oxygenation therapy which could potentially assist with the selection of patients for ECCO2R. Methods: A total of 70 patients admitted to the intensive care unit at the University Hospital of Zurich between 10/2009 and 02/2017 with hypercapnic respiratory failure were treated with ECCO2R if pH ≤7.25 and/or PaCO2 ≥ 9 kPa experiencing respiratory exhaustion during spontaneous breathing in obstructive lung disease or reaching the limits of lung protective ventilation (n = 22 and n = 48) in patients with restrictive lung pathologies. Data including baseline characteristics and respiratory parameters were collected prospectively. Scores were calculated retrospectively. Results: The underlying diseases were acute respiratory distress syndrome (n = 27), chronic-obstructive pulmonary disease (n = 12), bronchiolitis obliterans syndrome (BOS; n = 9), cystic fibrosis (n = 10), pulmonary fibrosis (n = 8), and other causes (n = 4). The 180-day mortality was 45.7% with the highest rate observed in PF and BOS patients as well as in patients who had been mechanically ventilated >6 days before initiation of ECCO2R. The modified PRedicting dEath for SEvere hypercapnic respiratory failure on vv-ECCO2R (PRESERVE-CO2) score differentiated well between survivors and non-survivors (4.3 ± 2.2 vs. 6.9 ± 2.6, p < 0.01), whereas the modified Respiratory ECMO Survival Prediction (RESP-CO2) score showed no significant distinction. Receiver operating characteristics analysis of the PRESERVE-CO2 score revealed an area under the curve of 0.78, suggesting a cut-off of 7 points. Conclusion: Careful selection of patients for ECCO2R therapy may help to improve outcomes. The proposed PRESERVE-CO2 score may serve as a guide. A score of 7 points or higher is associated with an unfavorable outcome regarding the 180-day mortality in the specific patient cohort of this study, but future studies to externally validate this score are required.

Introduction: The standard dialysate flow (Qd) for hemodialysis (HD) is currently set at 500 mL/min. One potential, sustainable, and cost-effective solution for eco-friendly HD may involve reducing Qd to limit wastewater. However, the effect of reduced Qd on small molecule and middle molecule (MM) removal remains to be investigated. Methods: In this prospective observational study, 74 patients on different maintenance dialysis modalities with Qd set at 500 mL/min (Qd500) were assigned to receive Qd at 400 mL/min (Qd400) for 3 months. Dialysis adequacy, including small solute removal and MM reduction ratio (RR), was evaluated at enrollment and after 3 months. Results: Compared to Qd500, Qd400 after 3 months achieved similar single-pool Kt/V (1.41 ± 0.30 vs. 1.43 ± 0.33, p = 0.58), equilibrated KT/V, urea RR, creatinine RR, and phosphate RR. Qd400 vs. Qd500 provided significantly higher beta2-microglobulin RR (77.0 [71.4–81.7] vs. 74.7 [68.4–79.4] %, p = 0.009) and lower kappa free light chain (FLC) RR (54.2 [42.1–64.4] vs. 57.6 [41.6–65.0] %, p = 0.03), whereas myoglobin and lambda FLC RR were similar. Qd400 resulted in higher pre-dialysis urea (20.2 ± 5.5 vs. 18.2 ± 6.2 mmol/L, p = 0.002), creatinine (694.0 ± 179.5 vs. 665.6 ± 220.4 µmol/L, p = 0.029), beta2-microglobulin (26.5 [23.0–30.0] vs. 23.5 [20.0–28.0] mg/L, p = 0.0001), and myoglobin (174.0 [122.0–251.0] vs. 159.5 [119.0–195.0] µg/L, p = 0.033) levels. Pre-dialysis levels of albumin, potassium, bicarbonate, phosphate, and calcium were similar between Qd400 and Qd500. Conclusion: Three months of Qd at 400 mL/min appears to provide similar small molecule and MM removal, but with an increase in pre-dialysis urea, creatinine, beta2-microglobulin, and myoglobin levels. Although this strategy could help preserve water, its potential impact on long-term clinical outcomes deserves further evaluation.

Plain Language SummaryExtremely small babies, especially those weighing less than 2.5 kilograms (∼5 pounds), are at high risk of kidney injury and problems with maintaining fluid balance. When too much fluid builds up in the body, it can harm the lungs, brain, and other organs. Doctors sometimes use kidney support treatments, called dialysis, to remove extra fluid, but most current machines are too large for these tiny infants. The Brophy Kit™ is a new manual device that works by gently removing small amounts of blood, passing it through a filter, and then returning it to the body without the requirement of electricity. This study tested whether the device could safely remove fluid in animals that are about the same size and have a similar blood volume as extremely small infants. The Brophy Kit™ was tested in 9 rats. The goal was to remove 5% to 10% of their total blood volume, which is similar to the daily amounts that might need to be removed in sick infants. Eight rats were able to start and complete the procedure safely. Breathing remained steady in nearly all animals, and the amount of fluid removed was close to what was planned. These early results show that the Brophy Kit™ could be a safe and practical way to manage excessive fluid in very small babies, especially in hospitals that do not have access to standard dialysis machines or in limited resource settings. More testing will be needed before the device can be used in newborns.

Introduction: Sleep disturbances are common in hemodialysis (HD) patients. We examined the excessive ultrafiltration rate (UFR), which is associated with poor outcomes, for its possible impact on sleep quality. Methods: Only oligo-anuric patients with a three-times-weekly HD schedule were included in the study. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality and a score >5 indicated poor sleepers. Ultrafiltration values refer to the month preceding the PSQI survey. Patients were divided into three categories: optimal UFR group (<10 mL/kg/h), borderline UFR group (10–13 mL/kg/h), and high UFR group (≥13 mL/kg/h). Results: A total of 102 patients were included, with a median age of 60 (46–67) years. Median dialysis vintage was 44.5 (22–77) months. Average interdialytic weight gain (IDWG) percentage was 4.7 (3.7–5.7) and UFR was 11.6 ± 3.5 mL/kg/h. A total of 37 patients (36.3%) had optimal UFR, 29 patients (28.4%) had borderline UFR, and 36 patients (35.3%) had high UFR. Average PSQI score was 7 (4–10) points and 61 patients (59.8%) was identified as poor sleepers. Mean UFR was 11.7 ± 3.4 mL/kg/h in poor sleepers and 11.5 ± 3.7 mL/kg/h in non-poor sleepers (p = 0.819). PSQI score and poor sleeper prevalence were not significantly different between UFR groups. There was no significant correlation between PSQI and UFR (p = 0.325). In multivariate regression analysis, UFR was not an independent predictor of sleep quality. Additionally, younger age and a long HD vintage were independent predictors of high UFR. Conclusion: Excessive and rapid fluid removal does not constitute a risk for poor sleep quality. Also, current findings underscore the increased frequency and complexity of sleep disorders in dialysis patients.

Background: Regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) has been shown to be safe and effective both in adults and children. The equipment and the solutions available in the pediatric setting are the same as in adults. Summary: Currently three commercially available citrate formulations for RCA during continuous renal replacement therapy CRRT are present: concentrated (4% trisodium citrate, 136 mmol/L), semi-concentrated (anticoagulant dextrose-A, ACD-A, 75 mmol/L) and diluted (Prismocitrate/Regiocit, 18 mmol/L). RCA is delivered as a predilution infusion solution; therefore, its volume in dedicated commercially available citrate solutions impacts continuous renal replacement (CRRT) dose, filtration fraction, circuit pressures, and fluid flow. These aspects represent crucial details in the pediatric setting, and their relevance is more important as the smaller the patient’s body weight is. Thus, when RCA is prescribed in children, the blood pump flow rate, the dose, the load and the concentration of citrate, and the patient’s ability to metabolize citrate should be considered carefully and specifically contextualized by the citrate concentration available in each center. This technical review will describe these practice concepts that should be known in detail by the clinician approaching RCA in the pediatric setting. Key messages: Citrate “dose” is the citrate concentration in the blood running in the CRRT circuit. Citrate “load” represents the mass of citrate that is delivered to the circuit per each treatment hour. For a given citrate dose and blood flow rate, very different CRRT settings, sodium loads, filtration fractions, and dialytic doses are delivered by choosing the different formulations.

Selected s from the 43rd Vicenza Course AKI-CRRT-EBPT and Critical Care Nephrology

Introduction: This study aimed to explore the effectiveness of sodium bicarbonate prereduction during continuous veno-venous hemofiltration (CVVH) with regional citrate anticoagulation (RCA). Methods: Patients undergoing CVVH with RCA were randomly divided into a control group and a prereduction group, with the latter receiving reduced sodium bicarbonate concentration levels to achieve the desired level after 3 h of treatment. The investigation focused on variations in pH, bicarbonate ion levels, and the frequency of sodium bicarbonate dosage adjustments at different intervals during CVVH. Results: The 41 participants (20 in the control group, 21 in the prereduction group) treated from July 2023 to February 2024 had no statistically significant differences in demographic or clinical characteristics. The prereduction group demonstrated significantly lower bicarbonate ion levels in the 4th hour (23.62 ± 2.66 mmol/L) compared with the control group (26.57 ± 2.17 mmol/L, p < 0.05) and required fewer bicarbonate adjustments (0 [0,1] times vs. 2 [1,3] times in the control group, p < 0.05). Conclusion: Sodium bicarbonate prereduction during CVVH using RCA minimises bicarbonate ion fluctuations and reduces the need for dosage adjustments.

Plain Language SummarySepsis is a life-threatening condition where the body’s response to infection causes harm, potentially leading to organ failure. This often involves an excessive release of inflammatory substances. Researchers are exploring ways to help by cleaning the patient’s blood using special filters. This study reviewed previous research on a specific filter called Oxiris. The goal was to see if using this filter to remove inflammatory substances (like one called IL-6) improved health outcomes for critically ill patients with conditions like sepsis or severe COVID-19. The combined results showed that when the Oxiris filter successfully lowered IL-6 levels in the blood, patients experienced significant improvements. They needed less medication to support their blood pressure, their organ function improved, and other signs of infection and inflammation decreased. This suggests that the Oxiris filter could be a valuable tool for managing severe inflammation in critical care. By removing harmful substances, it may help stabilize patients and support their organs. While its effect on survival needs more research, the findings are promising for treating these severe conditions.