Blood Purification最新文献

Introduction: Uremic patients exhibit remarkably increased rates of mortality and cardiovascular (CV) events, but risk prediction in this setting remains difficult. Systemic mitochondrial dysfunction is pervasive in end-stage kidney disease and may contribute to CV complications. We tested the clinical significance of circulating MOTS-c, a small mitochondrial-derived peptide, as a biomarker for improving mortality and CV risk prediction in hemodialysis (HD) patients.

Methods: We conducted a prospective, observational, multicenter study on 94 prevalent HD patients. The study endpoint was a composite of all-cause mortality and non-fatal CV events. The diagnostic and prognostic capacities of predictive models based on cohort-related risk factors were tested before and after the inclusion of MOTS-c.

Results: MOTS-c levels were higher in HD patients than in controls (p < 0.001) and even more elevated (p = 0.01) in the 53 individuals experiencing the combined endpoint during follow-up (median duration: 26.5 months). MOTS-c was independently associated with the endpoint at either multivariate logistic (OR 1.020; 95% CI: 1.011-1.109; p = 0.03) or Cox regression analyses (HR 1.004; 95% CI: 1.000-1.025; p = 0.05) and the addition of this biomarker to prognostic models including the other cohort-related risk predictors (age, left ventricular mass, evidence of diastolic dysfunction, diabetes, pulse pressure) significantly improved the calibration, risk variability explanation, discrimination (receiver operating characteristic area under the curve from 0.727 to 0.743; C-index from 0.658 to 0.700), and particularly, the overall reclassification capacity (NRI 15.87%; p = 0.01).

Conclusions: In HD patients, the mitochondrial-derived peptide MOTS-c may impart significant information to refine CV risk prediction, beyond cohort-related risk factors. Future investigations are needed to generalize these findings in larger and more heterogeneous cohorts.

Introduction: Hemoadsorption, an extracorporeal apheresis technique, is reportedly used in severe COVID-19 patients. However, limited evidence from randomized clinical trials supports this practice.

Methods: In this single-center study, severe COVID-19 patients requiring ICU admission were randomly assigned (1:1) to receive HA-330 hemoadsorption in combination with standard treatment or standard therapy alone. Both groups received tocilizumab intravenously if their clinical conditions worsened within 24-48 h. The primary outcome was mortality from any cause within 28 days after randomization. Secondary outcomes included mechanical ventilator-free days, daily C-reactive protein levels, oxygenation (defined by PaO2/FiO2 ratio), daily sequential organ failure assessment score, and severity score of lung infiltration on chest X-rays (CXR RALE score).

Results: A total of 28 patients underwent randomization, with 14 (50%) receiving HA-330 hemoadsorption. Only 9 out of 14 patients (64.3%) in the control group experienced clinical worsening and were subsequently administered intravenous tocilizumab. At 28 days, the mortality rate was significantly lower in the intervention group (28.57% vs. 78.57%, p = 0.021), with a hazard ratio of death of 0.26 (95% CI = 0.08-0.81; p = 0.021). All of secondary outcomes were comparable in both groups.

Conclusion: Based on our pilot randomized trial, the early application of HA-330 hemoadsorption in patients with severe COVID-19 may establish a favorable outcome in term of mortality. These data provide the initial proof of concept for conducting a large-scale study in the future.

Introduction: Exogenous haptoglobin administration may enhance plasma-free hemoglobin (pfHb) clearance during hemolysis and reduce its end-organ damage: we systematically reviewed and summarized available evidence on the use of haptoglobin as a treatment for hemolysis of any cause.

Methods: We included studies describing haptoglobin administration as treatment or prevention of hemolysis-related complications. Only studies with a control group reporting at least one of the outcomes of interest were included in the quantitative synthesis. Primary outcome was the change in pfHb concentration 1 h after haptoglobin infusion.

Results: Among 573 articles, 13 studies were included in the review (677 patients, 52.8% received haptoglobin). Median initial haptoglobin intravenous bolus was 4,000 (2,000, 4,000) IU. Haptoglobin was associated with lower pfHb 1 h (SMD -11.28; 95% CI: -15.80 to -6.75; p < 0.001) and 24 h (SMD -2.65; 95% CI: -4.73 to -0.57; p = 0.001) after infusion. There was no difference in all-cause mortality between haptoglobin-treated patients and control group (OR 1.41; 95% CI: 0.49-4.95; p = 0.520). Haptoglobin was associated with a lower incidence of acute kidney injury (OR 0.64; 95% CI: 0.44-0.93; p = 0.020). No adverse events or side effects associated with haptoglobin use were reported.

Conclusions: Haptoglobin administration has been used in patients with hemolysis from any cause to treat or prevent hemolysis-associated adverse events. Haptoglobin may reduce levels of pfHb and preserve kidney function without increase in adverse events.

Introduction: Autogenous arteriovenous fistula (AVF) is the preferred vascular access in patients undergoing maintenance hemodialysis (MHD). However, complications such as thrombosis may occur. This study aimed to construct and validate a machine learning-based risk-prediction model for AVF thrombosis, hypothesizing that such a model can effectively predict occurrences, providing a foundation for early clinical intervention.

Methods: The retrospective longitudinal study included a total of 270 patients who underwent MHD at the Hemodialysis Center of the Second Affiliated Hospital of Harbin Medical University between March 2021 and December 2022. During this study, baseline data and scale information of patients between March 2020 and December 2021 were collected. We recorded outcome indicators between March 2021 and December 2022 for subsequent analyses. Five machine learning models were developed (artificial neural network, logistic regression, ridge classification, random forest, and adaptive boosting). The sensitivity (recall), specificity, accuracy, and precision of each model were evaluated. The effect size of each variable was analyzed and ranked. Models were assessed using the area under the receiver-operating characteristic (AUROC) curve.

Results: Among the 270 included patients, 105 had AVF thrombosis (55 male and 50 female patients; age range, 29-79 years; mean age, 56.72 years; standard deviation [SDs], ±13.10 years). Conversely, 165 patients did not have AVF thrombosis (99 male and 66 female patients; age range, 23-79 years; mean age, 53.58 years; SD, ± 13.33 years). During the observation period, approximately 52.6% of patients with AVF experienced long-term complications. The most common complications associated with AVF were thrombosis (105; 38.9%), aneurysm formation (27; 10%), and excessively high output flow (10; 3.7%). Fifty-four (20%) patients with AVF required intervention because of complications associated with vascular access. The AUROC curve of the testing set was between 0.858 and 0.903.

Conclusion: In this study, we developed five machine learning models to predict the risk of AVF thrombosis, providing a reference for early clinical intervention.

Introduction: Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin.

Methods: Blood spiked with a lyophilized penKid peptide solved in 20 mm dipotassium phosphate and 6 mm disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated.

Results: Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min).

Conclusion: penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.

Introduction: Despite major advances in the field of dialysis, there are still some unmet needs such as reducing inflammation through adequate depuration. It is well known that the wide spectrum of pro-inflammatory and pro-atherosclerotic uremic toxins are inefficiently removed by current dialysis techniques. Adsorption seems to be an extra tool to remove toxins, but its effect and optimization have not been widely studied. The aim of this report was to present preliminary results regarding the possibility of performing hemodiafiltration with a highly adsorptive polymethylmethacrylate membrane.

Methods: The study was first conducted in 10 patients in which the safety and feasibility of hemodiafiltration with PMMA BG-U 2.1 membrane were tested through measurement of hemolysis indices, transmembrane pressures, and dialysis adequacy. Twenty patients were prospectively observed for 18-month period in which they consecutively underwent standard hemodialysis, standard post-dilution hemodiafiltration, and polymethylmethacrylate-based post-dilution hemodiafiltration. Protein-bound uremic toxins concentrations and inflammatory markers were measured throughout the observed period.

Results: HDF-PMMA was inferior to HDF in convective volume, but KT/V was similar, and no differences were noted in operating pressures during the two treatments. During HDF-PMMA period of treatment, we observed a significant reduction of CPR levels, and HDF-PMMA was superior to all other treatments in hepcidin removal even if this did not significantly affect hemoglobin levels. HDF-PMMA could significantly reduce indoxyl sulfate (indoxyl) concentration over a period of 6 months but not for p-cresyl sulfate (p-cresyl).

Conclusion: PMMA BG-U 2.1 membrane can be safely and efficiently used in hemodiafiltration. Moreover, as these preliminary results show, adding adsorption properties to convection and diffusion enabled an increased removal of indoxyl uremic toxin associated to a reduction in inflammation markers as CRP and hepcidin without any negative impact on albumin levels.

Introduction: This study was designed to assess the association of age and frailty with clinical outcomes in patients with severe acute kidney injury (AKI), according to accelerated and standard renal-replacement therapy (RRT) initiation strategies in the STARRT-AKI trial.

Methods: This was a secondary analysis of an international randomized trial. Older age was defined as ≥65 years. Frailty was assessed using the clinical frailty scale (CFS) score and defined as a score ≥5. The primary outcome was all-cause mortality at 90 days. Secondary outcomes included RRT dependence and RRT-free days at 90 days. We used logistic and linear regression and interaction testing to explore the impact of age and frailty on clinical outcomes.

Results: Of 2,927 patients randomized in the STARRT-AKI trial, 1,616 (55.2%) were aged ≥65 years (median [interquartile range] 73.9 [69.4-78.9]). Older patients had greater comorbid cardiovascular and chronic kidney disease, were more likely to be surgical admissions and to receive vasopressors at baseline. Older patients had higher 90-day mortality (50.4% vs. 35.6%, adjusted-odds ratio (OR), 1.81 [1.53-2.13], p < 0.001). There was no significant difference in RRT dependence at 90 days between older and younger patients (8.7% vs. 7.8%, adjusted-OR, 1.21 [0.82-1.79], p = 0.325). Patients with frailty had higher mortality; but no difference in RRT dependence at 90 days. There was no significant interaction between age and CFS score in relation to mortality, RRT dependence at 90 days, and other secondary outcomes. There was no significant difference in the proportion of patients who received RRT in the standard-strategy stratified by age groups (adjusted-OR, 0.85 [0.67-1.08], p = 0.180).

Conclusion: In this secondary analysis of the STARRT-AKI trial, older and frail patients had higher mortality at 90 days; however, there was no difference in RRT dependence. Mortality and RRT dependence were not modified by RRT initiation strategy in older or frail patients.

Introduction: The main objective of this study was to evaluate the impact of hemoadsorption on the elimination of inflammatory mediators.

Methods: A prospective, bicenter, observational cohort study was conducted between March 2020 and February 2022 to explore the immunomodulatory response, demographic and clinical characteristics of individuals with COVID-19 admitted to the ICU with severe acute respiratory failure and in need of CRRT with Oxiris® with or without AKI.

Results: Sixty-four patients were analyzed. Statistically significant differences were observed between exposed and unexposed groups, in relation to the reduction in D-dimer levels -15,614 (24,848.9) versus -4,136.5 (9,913.47) (p 0.031, d: 1.59, 95% CI: -21,830, -1,126). An increase in PCT was observed 0.47 (2.08) versus -0.75 (2.3) (p 0.044 95% CI: 0.03, 2.44). No differences were found in a decrease in CRP -4.21 (7.29) versus -1.6 (9.02) (p 0.22) nor in the rest of inflammatory parameters fibrinogen, IL-6, ferritin, lymphocytes, and neutrophils. Subgroup analysis in patients exposed to therapy also showed a significant decrease in D-dimer of 55% from baseline: 6,000 (1,984.5-27,750) pre-therapy versus 2,700 (2,119.5-6,145) (95% CI: -23,000, -2,489) post-therapy with a strong effect size (p 0.001, d: 0.65).

Conclusion: The hemoadsorptive therapy in COVID-19 was associated with a significant decrease in D-dimer parameters without showing decreases in the rest of the clinical, inflammatory parameters and severity scales analyzed.

Introduction: Anticoagulants are used in continuous renal replacement therapy (CRRT) to prolong filter life. There are no prior investigations directly comparing epoprostenol to more commonly used forms of anticoagulation in children. Therefore, the primary aim of this study was to assess the efficacy and safety of epoprostenol as compared to heparin and citrate anticoagulation in a pediatric cohort.

Methods: We performed a retrospective analysis of all patients <18 years of age admitted to an academic quaternary care children's hospital from 2017-2022 who received epoprostenol, heparin, or citrate exclusively for CRRT anticoagulation. Efficacy was evaluated by comparing the hours to the first unintended filter change and the ratio of filters used to CRRT days. Safety was assessed by evaluating changes in platelet count and vasoactive-ionotropic score (VIS).

Results: Of 101 patients, 44 received epoprostenol (43.6%), 38 received heparin (37.6%), and 19 received citrate (18.8%). The first filter change was more commonly planned in patients receiving anticoagulation with epoprostenol (43%) as compared to citrate (11%) or heparin (29%) (p = 0.034). Of those patients where the first filter change was unintended (n = 33), there were greater median hours until the filter was replaced in those receiving epoprostenol (29) when compared to citrate (21) (p = 0.002) or heparin (18) (p = 0.003). There was a smaller median ratio of filters used to days on therapy in the patients that received epoprostenol (0.53) when compared to citrate (1) (p = 0.003) or heparin (0.75) (p = 0.001). For those receiving epoprostenol, there was no significant decrease in platelet count when comparing values prior to CRRT initiation through 7 days of therapy. There was no significant difference in VIS when comparing values prior to CRRT initiation through the first 2 days of CRRT.

Conclusions: Epoprostenol-based anticoagulation is effective when compared to other anticoagulation strategies used in pediatric CRRT with a favorable side effect profile.