Blood Purification最新文献

Background: Antibiotic dosing in critically ill patients receiving continuous renal replacement therapy (CRRT) is challenging due to altered pharmacokinetics, variability in CRRT delivery, and limited dosing guidance. Optimizing therapy is essential, as underdosing may drive resistance and overdosing may increase toxicity, including cefepime-associated neurotoxicity.

Methods: We conducted a retrospective single-center study of ICU patients who received CRRT and at least one dose of cefepime, meropenem, or piperacillin-tazobactam between 2016 and 2020. Delivered CRRT dose was calculated from effluent rates. Daily antibiotic doses across CRRT phases were summarized, and resistance development was evaluated for Pseudomonas aeruginosa and Enterobacter cloacae using logistic regression.

Results: Of 954 eligible ICU patients, 661 met inclusion criteria. Median delivered CRRT dose was 29.5 mL/kg/h (IQR 25.0-33.5); 57.7% received ≥30 mL/kg/h, while only 9.6% were within the KDIGO-recommended 20-24.9 mL/kg/h. Median CRRT duration was 144 h (IQR 84-312), initiated a median of 2.3 days after ICU admission. Median daily doses during CRRT were 2.5 g for cefepime, 1.5 g for meropenem, and 10.8 g for piperacillin-tazobactam. Treatment-emergent resistance occurred in 17.6% of P. aeruginosa and 14.3% of E. cloacae isolates, while baseline resistance was common in E. coli (20.5%) and K. pneumoniae (27.3%). In multivariable models, longer treatment duration (OR 1.07/day, 95% CI 1.06-1.08), higher CRRT dose (OR 1.13 per 5 mL/kg/h, 95% CI 1.10-1.16), and lower daily antibiotic dose (OR 0.65 per g/day, 95% CI 0.61-0.70) were independently associated with cefepime resistance (AUC 0.73), with similar findings for meropenem (AUC 0.80).

Conclusion: Antibiotic dosing during CRRT was at the lower end of the therapeutic range and was associated with treatment-emergent resistance in exploratory analyses. These findings highlight the potential importance of CRRT-informed dosing strategies and underscore the need for careful balance between efficacy and toxicity.

Introduction: Socioeconomic and developmental diversity across Latin America (LA) significantly affects the availability of extracorporeal blood purification (EBP) therapies to treat acute kidney injury (AKI) and the training of nephrology fellows in these technologies. This survey assessed the availability of EBP therapies and perceived training needs of nephrologists and intensivists in the region.

Objective: To evaluate the availability of EBP therapies to treat AKI and identify training needs among LA nephrologists and intensivists.

Methods: Between March and December 2024, the AKI and extracorporeal organ support therapy committee of SLANH conducted an online survey targeting nephrologists and intensivists.

Results: 505 responses were collected, with 93% by nephrologists. Participants represented 20 LA countries, primarily from South America (58%), Mexico (23.6%), and the Caribbean (10.1%). Intermittent hemodialysis (IHD) was the most widely available therapy, accessible in 98% of centers. Peritoneal dialysis (PD) was available in 65% of hospitals, while continuous renal replacement therapy (CRRT) in 59% of centers but reported as unavailable in Haiti, Nicaragua, Paraguay, and Venezuela. Therapeutic plasma exchange (TPE) was available in 60% of hospitals, although accessibility varied significantly by country. Multi-organ support therapies showed limited regional availability, including liver support (11.9%), extracorporeal membrane oxygenation (ECMO, 16.7%), extracorporeal CO₂ removal (ECCO₂R, 7%), and hemoadsorption (20.6%). The greatest perceived training needs were identified for ECMO (54.2%), ECCO₂R (51.3%), CRRT (48.7%), and TPE (46.8%), whereas demand for further training in IHD and PD was comparatively lower. These findings underscore substantial disparities in therapy access and highlight urgent regional priorities for advanced EBP training.

Conclusion: This study highlights significant disparities in EBP therapy availability across LA, with advanced modalities like CRRT and multi-organ support inaccessible in several countries. Additionally, there is a high perceived need for training in ECMO, ECCO₂R, CRRT, and TPE. Addressing these gaps requires expanding access to EBP, implementing standardized training programs, establishing regional centers of excellence, and fostering international collaboration, patient outcomes across the region.

Introduction: Some antibiotics are recommended by ISPD for peritonitis treatment but does not have stability and compatibility data in different conditions yet. The current study was to investigate the stability and compatibility of such drugs.

Methods: Levofloxacin, clindamycin phosphate and fluconazole were tested in the study. Three different commercially available peritoneal dialysis solutions were selected. Two were glucose-based (2.5%, Ca 1.25mmol/L, lactate buffered) solution, one with PVC package and the other with non-PVC package. The third solution was icodextrin (non-PVC package). The stability of the three antibiotics were tested in the three different dialysates in different temperature (4 ℃ and 25℃) for 6 hours, 1 days, 2 days and 7 days. For 37℃, the storage stability was tested only for 6 hours. The test antibiotics concentrations were selected as ISPD recommended or based on published data. All conditions were repeated separately in three bags. The antibiotics concentrations were measured by Liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: For clindamycin phosphate and fluconazole, there was no significant change in final concentration over the 7 days study period for both 4 ℃ and 25℃. For 37 ℃, there was also no difference in concentration for clindamycin phosphate and fluconazole. For levofloxacin, there was no significant change in concentration over 7 days for 4 ℃. The concentration of levofloxacin was slightly higher after store in 25℃ and 37℃, while the exact differences were less than 3%. Drug concentrations were generally lower in icodextrin than in glucose-based solutions. The exact differences were less than 10%. The difference between icodextrin and glucose-based solutions was higher than the two glucose-based solutions with different container material (PVC vs non-PVC).

Conclusions: Levofloxacin, clindamycin phosphate and fluconazole were stable and compatible with both glucose-based and icodextrin solutions. They might be stored for up to 7 days at room temperature (25℃). It is not suggested to store the dialysate for long time once warmed up to body temperature.

Introduction: Chronic kidney disease-associated pruritus (CKD-aP) is one of the most prevalent and distressing symptoms experienced by patients with end-stage renal disease (ESRD), significantly impacting their quality of life and the sustainability of hemodialysis (HD) treatment. This systematic review aimed to evaluate the efficacy and safety of difelikefalin (DFK) in treating patients with chronic kidney disease (CKD).

Methods: Electronic databases, including PubMed, Embase, The Cochrane Library, Web of Science, and Scopus, were systematically searched for randomized controlled trials (RCTs) that reported on the efficacy and safety of DFK in patients with ESRD undergoing HD. The search was conducted up to November 19, 2024. The risk of bias in the included studies was assessed using the Cochrane risk of bias tool. Data analysis was performed using Stata version 15.1. Results were reported as RR and MD with 95% confidence interval (CI).

Results: This meta-analysis included five randomized controlled trials with a total of 937 participants, all of whom were undergoing MHD. The results indicated that, in comparison to the control group, DFK significantly reduced the weekly average WI-NRS score (MD: -0.41 [-0.51, -0.31], p = 0.671). Specifically, DFK demonstrated a significant reduction in the weekly mean WI-NRS scores compared with placebo at week 4 (MD: -0.48 [-0.61, -0.35], p = 0.965) and at week 8 (MD: -0.32 [-0.46, -0.17], p = 0.473). Additionally, DFK significantly reduced the total score on the 5-D itch scale (MD: -0.42 [-0.53, -0.31], p = 0.262), the total score on Skindex-10 (MD: -0.42 [-0.58, -0.26], p = 0.221), and the total score on Skindex-16 (MD: -0.16 [-0.23, -0.00], p = 0.287). Furthermore, DFK significantly increased the proportion of participants achieving a weekly average WI-NRS score improvement of ≥3 points (RR: 1.29 [1.04, 1.50], p = 0.034) and ≥4 points (RR: 1.45 [1.10, 1.92], p = 0.047), as well as PGIG (RR: 1.44 [1.15, 1.80], p = 0.007). Additionally, it significantly improved adverse events (RR: 1.26 [1.08, 1.45], p < 0.001). However, no significant differences were observed between the two groups regarding serious adverse events (RR: 1.33, 95% CI [0.94, 1.88], p = 0.134), discontinuation (RR: 1.50, 95% CI [0.90, 2.28], p = 0.108), and mortality (RR: 0.92, 95% CI [0.35, 2.46], p = 0.949).

Conclusion: DFK is an effective medication for the treatment of moderate-to-severe pruritus associated with CKD, in patients with ESRD undergoing HD. However, the use of DFK may also lead to an increase in adverse reactions. This systematic review still acknowledges its limitations and recognizes the need for more comprehensive evidence. Therefore, it is imperative to conduct multicenter, large-scale randomized controlled trials to further validate the efficacy and safety of DFK in alleviating pruritus among HD patients.

Introduction: Sepsis and septic shock frequently lead to acute kidney injury and the need for continuous renal replacement therapy (CRRT). The oXiris hemofilter has cytokine- and endotoxin-adsorptive properties that may improve outcomes, but evidence remains inconclusive. This study compared the clinical outcomes of septic intensive care unit (ICU) patients treated with CRRT using oXiris versus standard filters.

Methods: We conducted a retrospective observational study at a tertiary ICU in Istanbul between January 2019 and June 2024. Adult septic patients requiring CRRT within 24 h of ICU admission were included. Patients were treated with either oXiris or standard CRRT filters (M-100/M-150) for ≥16 h. The primary endpoint was ICU mortality; secondary endpoints included ventilator-free days (VFDs), ICU length of stay, and trends in inflammatory and biochemical markers.

Results: A total of 360 patients were analyzed (133 oXiris, 227 standard filters). Despite higher baseline sequential organ failure assessment (SOFA) scores, c-reactive protein (CRP), procalcitonin (PCT), and lactate in the oXiris group, ICU survival was significantly higher (61.7% vs. 48.9%, p = 0.019). After adjustment, oXiris use remained independently associated with improved survival (odds ratio 1.68, 95% confidence interval 1.09-2.60, p = 0.020). Total CRRT duration was markedly shorter in the oXiris group (56.4 vs. 107.4 h, p < 0.001). VFDs were similar between groups. Inflammatory markers (CRP, PCT) remained elevated in oXiris patients through day 5, while hemodynamic stabilization (lactate decline, norepinephrine reduction) was more pronounced. Platelet counts decreased in both groups without recovery.

Conclusion: Our study demonstrated that patients with sepsis treated using the oXiris filter exhibited significantly higher ICU survival rates, despite higher mechanical ventilation duration and ICU length of stay. However, persistent elevations in CRP and PCT, along with thrombocytopenia, suggest that these markers may not fully reflect therapeutic response. While oXiris use was associated with reduced ICU mortality, further randomized trials are needed to confirm its efficacy and account for potential confounders.

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.

Introduction: Hypophosphataemia is common in acute liver failure (ALF) and may worsen during continuous renal replacement therapy (CRRT) with phosphate-free fluids. We aimed to evaluate the safety and efficacy of Phoxilium®, a phosphate-containing CRRT fluid.

Methods: We conducted a retrospective single-center cohort study of paracetamol-induced ALF patients treated with CRRT between January 2018 and May 2024 as our ICU transitioned from Accusol® to Phoxilium®. We obtained data on demographics, biochemistry, and outcomes. We compared biochemical variables every 6 h up to 48 h post-CRRT initiation and then every 12 h until 168 h. The primary outcome was the occurrence of severe hypophosphataemia (<0.32 mmol/L).

Results: In 38 ALF patients (Phoxilium® = 14 and Accusol® = 24), Phoxilium® was associated with a reduction in the incidence of severe hypophosphataemia (0% vs. 38%; p = 0.014), a reduction in its median burden (proportion of phosphate readings <0.81 mmol/L: 13% [interquartile range: 2-33%] vs. 44% [29-51%]; p = 0.001), and significantly lower phosphate supplementation requirements (median, 45 mmol [20-70 mmol] vs. 100 mmol [60-210 mmol]; p = 0.008). Phoxilium® patients experienced a small but significant decrease in median arterial pH and standard base excess, which remained within normal limits, but lower than with Accusol® (p = 0.018 and p = 0.046, respectively). No significant differences were observed in clinical outcomes.

Conclusion: In paracetamol-induced ALF patients, Phoxilium® was associated with reduced incidence of severe hypophosphataemia, hypophosphataemia burden, and need of phosphate supplementation. Larger studies are needed to further assess its impact on ALF patient outcomes.

Introduction: Renal anemia is a serious complication in patients with chronic kidney disease. Daprodustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, represents a potential therapeutic option for renal anemia; however, its efficacy and safety in patients maintained on peritoneal dialysis (PD) remain unknown. This exploratory study aimed to evaluate the preliminary effects of daprodustat in patients with chronic kidney disease undergoing maintenance PD.

Methods: This single-center, prospective study included 11 patients undergoing maintenance PD who shifted from darbepoetin alfa to daprodustat. Over a 24-week observation period, hematological parameters, iron metabolism markers, cardiac function, and oxidative stress indicators were monitored. Statistical significance was determined using repeated-measures ANOVA with Bonferroni correction for multiple comparisons.

Results: Hepcidin-25 levels (p = 0.0004) and oxidized low-density lipoprotein levels (p = 0.0437) significantly decreased, while total iron-binding capacity (p = 0.0043) and reticulocyte counts (p = 0.0052) significantly increased. Despite these favorable biochemical changes, hemoglobin and hematocrit values showed no significant improvement. Other oxidative stress markers showed downward trends, while cardiac function parameters (N-terminal pro-brain natriuretic peptide, cardiothoracic ratio, left ventricular ejection fraction) remained unchanged.

Conclusion: This pilot study suggests that daprodustat may enhance iron metabolism and mitigate oxidative stress while preserving cardiac function in PD patients. The pronounced reduction in hepcidin-25 levels indicates potential beneficial effects on iron homeostasis. However, the absence of significant hemoglobin improvement, combined with the small sample size (n = 11), lack of control group, and short 24-week follow-up period, significantly limits the clinical relevance and generalizability of these findings. Larger randomized controlled trials with longer follow-up periods are essential to definitively establish the efficacy and safety of daprodustat in this patient population.

Introduction: Far infrared radiation may improve arteriovenous fistula maturation and patency rates in patients on hemodialysis (HD). The mechanism is proposed to involve anti-inflammatory and vasodilatory effects in the arteriovenous fistula. This study examined the impact of far infrared radiation on plasma changes and dialysate excretion of biomarkers of endothelial dysfunction, inflammation, and vasodilation in the arteriovenous fistula during a single HD.

Methods: The study was a randomized, controlled, single-blinded study involving 44 participants on HD with an arteriovenous fistula. Participants were randomized to far infrared radiation or no far infrared radiation (control). Blood samples and dialysate water were drawn before, during, and after 4 h of HD. The change and elimination of biomarkers of endothelial dysfunction, inflammation, and vasodilation was explored in blood and dialysate water, respectively. Changes in plasma levels from the start to the end of HD and the area under the curve for the biomarker concentration were compared between groups by ANCOVA.

Results: There was no difference in the change of biomarkers of endothelial dysfunction, inflammation, and vasodilation between the two groups after and during 4 h of HD. There was a minimal excretion of the biomarkers in the dialysate water. Regardless of the treatment group, 4 h of HD caused a significant decrease in tumor necrosis factor-alpha (-1.30 [-1.70; -1.03] pg/mL, p < 0.001), monocyte chemoattractant protein-1 (-32.50 [-50.50; -8.25] pg/mL, p < 0.001), nitrite and nitrate (-20.00 [-27.75; -14.00] µmol/L, p < 0.001) as well as asymmetric dimethylarginine (-0.24 [-0.28; -0.18] µmol/L, p < 0.001).

Conclusion: Overall, the study is not supportive of a beneficial effect of far infrared radiation on the arteriovenous fistula on biomarkers of endothelial dysfunction, inflammation, or vasodilation during one HD treatment.