Continuous Dialysis Research Articles

Vancomycin Sequestration in ST Filters: An In Vitro Study.

Sequestration of vancomycin in ST® filters used in continuous renal therapy is a pending question. Direct vancomycin-ST® interaction was assessed using the in vitro NeckEpur® technology. ST150® filter and Prismaflex dialyzer, Baxter-Gambro, were used. Two modes were assessed in duplicate: (i) continuous diafiltration (CDF): 4 L/h, (ii) continuous dialysis (CD): 2.5 L/h post-filtration. The mean initial vancomycin concentration in the central compartment (CC) was 51.4 +/- 5.0 mg/L. The mean percentage eliminated from the CC over 6 h was 91 +/- 4%. The mean clearances from the CC by CDF and CD were 2.8 and 1.9 L/h, respectively. The mean clearances assessed using cumulative effluents were 4.4 and 2.2 L/h, respectively. The mean percentages of the initial dose eliminated in the effluents from the CC by CDF and CD were 114 and 108% with no detectable sequestration of vancomycin in both modes of elimination. Significant sequestration adds a clearance to that provided by CDF and CD. The study provides multiple evidence from the CC, the filter, and the effluents of the lack of an increase in total clearance in comparison with the flow rates without significant sequestration in the ST® filter comparing cumulative effluents to the initial dose in the CC. There is no evidence ST® filters directly sequestrate vancomycin.

Designing adsorptive membranes for removing protein-bound uremic toxins via π-π and cation-π interaction

Protein-bound uremic toxins (PBUTs) are recently thought to critically influence overall organ dysfunction, morbidity, and mortality of chronic kidney disease (CKD) patients. However, traditional hemodialysis and/or hemoperfusion processes fail to remove PBUTs efficiently due to their strong affinity with albumins. Herein, we fabricated a novel adsorptive membrane incorporating amine/polyphenol/bimetal ions complexation in the polysulfone membrane substrate, which has a higher affinity with hippuric acid, p-cresol sulfate, and indoxyl sulfonate. The complexation is a synergy of polyelectrolyte (polyethyleneimine-tannic acid) and metal-phenolic (tannic acid/metals) networks. The adsorption behavior of those three uremic toxins on the optimized adsorptive membrane was investigated by kinetic and adsorption isotherm studies. From X-ray photoelectron spectroscopy analysis assisted by Fourier transform infrared reflection spectrum, we attribute the high adsorption capacity to π-π and/or cation-π interaction with aromatic ring groups of uremic toxins. The adsorptive membrane could effectively remove albumin bounded uremic toxins and water-soluble urea through a continuous dialysis process. Besides, the membrane showed excellent hemocompatibility and minimized immune responses by suppressing complement activation. The above results showed the potential clinical application of adsorptive membranes.

Single-Center Experience With the Seraph-100® Microbind® Affinity Blood Filter in Patients With SARS-CoV-2 Infection and Septic Shock at a Military Treatment Facility.

Coronavirus disease 2019 (COVID-19) infection is characterized by a dysregulated inflammatory response, which may result in severe hemodynamic instability and septic shock. The Seraph-100® Microbind® Affinity Blood Filter is a commercially available extracorporeal pathogen absorbent device with the ability to bind pathogens and cytokines present within the blood. Our study aimed to evaluate the efficacy of the Seraph-100® for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and septic shock. A retrospective review was performed to evaluate the use of the Seraph-100® blood filter at a Single Center tertiary-care facility at Brooke Army Medical Center from 2020 to 2021. Nine patients (11 treatments) were completed with the Seraph-100® blood filter in patients with SARS-CoV-2 infection and septic shock. The Seraph-100® blood filter was used in combination with continuous renal replacement therapy and slow low-efficiency dialysis or directly in parallel with the extracorporeal membrane oxygenation circuit. Within this cohort, there was a statistically significant improvement in the following clinical parameters comparing values to before and after treatment with the Seraph-100® blood filter: Mean arterial pressure (mmHg) (64.2 ± 2.36 vs. 76.2 ± 2.68; P < .001), heart rate (beats per minute) (128 ± 6.6 vs. 100.3 ± 6.07; P < .001), administered fraction of oxygen (%) (74.4 ± 10.58 vs. 60.3 ± 10.35; P < .001), serum lactate (mmol/L) (6.14 ± 1.25 vs. 2.8 ± 1.14; P = .0095), and pH (7.29 ± 0.03 vs. 7.39 ± 0.04; P = .0203). There were statistically significant improvements in vasopressor requirements: norepinephrine (mcg/min) (36.3 ± 4.74 vs. 8.3 ± 3.92; P < .001), vasopressin (units/min) (0.04 ± 0.004 vs. 0.02 ± 0.003; P < .001), dobutamine (mcg/kg/min) (2.3 ± 1.00 vs. 0.2 ± 0.75; P = .006) and angiotensin II (ng/kg/min) (34.5 ± 6.4 vs. 3.3 ± 5.26; P < .001). The use of the Seraph-100® blood filter was associated with statistically and clinically significant improvements in hemodynamic parameters and decreased vasopressor requirements in patients with septic shock and SARS-CoV-2 infection.

Development and validation of a dosing nomogram for continuous infusion cloxacillin in infective endocarditis.

Cloxacillin is the first-line treatment for methicillin-susceptible staphylococcal infective endocarditis (IE). The recommended dose is 12 g per day regardless of the patient characteristics, despite the importance of renal function on its pharmacokinetics. We sought to build a population pharmacokinetics model of continuous infusion cloxacillin in IE patients to evaluate the influence of multiple covariates and then develop a nomogram based on significant covariates for individual adaptation. We included patients of a local IE cohort who were treated with cloxacillin administered by continuous infusion, excluding those who received intermittent or continuous dialysis, extracorporeal membrane oxygenation or extracorporeal circulation. The population pharmacokinetic analysis was performed using Pmetrics. The influence of weight, ideal weight, height, body mass index, body surface area, glomerular filtration rate (GFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration formula (both expressed in mL/min/1.73 m² and in mL/min) and serum protein level on cloxacillin pharmacokinetics was assessed. Accounting for relevant covariates, a dosing nomogram was developed to determine the optimal daily dose required to achieve a steady-state plasma concentration range of 20-50 mg/L with a probability ≥0.9. A total of 114 patients (331 plasma concentrations) were included. A one-compartment model including GFR expressed in mL/min as a covariate was chosen. Using the nomogram, achieving the cloxacillin concentration target requires a daily dose ranging from 3.5 to 13.1 g for a GFR ranging from 20 to 125 mL/min. This work provided a practical tool for cloxacillin dose adjustment in IE according to renal function.

Clinical value of the renal pathologic scoring system in complement-mediated thrombotic microangiopathy

Objectives This study was initiated to establish a renal thrombotic microangiopathy (TMA) scoring system based on clinical needs and investigate its predictive value for patients’ long-term outcomes. Methods Kidney biopsy-proven Complement-mediated TMA (C-TMA) patients from January 2000 to December 2017 in Peking University First Hospital were retrospectively studied. Both acute and chronic TMA-related lesions, including 15 pathologic indices, were semiquantitatively scored. The interobserver and intraobserver reproducibility and correlation between the pathologic indices and clinical parameters were analyzed. Furthermore, the patients were divided into 2 groups by dialysis use at baseline, and the association of these pathologic indices with their prognostic outcomes was assessed between the two groups. Results Ninety-two patients with renal biopsy-proven C-TMA were enrolled. All fifteen included pathology indices showed good or moderate interobserver and intraobserver reproducibility and correlated well with several clinical parameters. Several clinicopathological indices were worse in the dialysis group than in the nondialysis group, such as serum creatinine, hemoglobin, platelet count, and estimated glomerular filtration rate. Moreover, morphologic features in the dialysis group presented with more severe vascular lesions. Interstitial fibrosis and chronic tubulointerstitial lesions were related to a trend of high risk of continuous dialysis in the dialysis group. Based on univariate and multivariable Cox regression analysis, more severe glomerular lesions, including glomerular mesangiolysis, glomerular basement membrane double contours and glomerular mesangial proliferation, were identified as risk factors predicting worse prognosis. Conclusions Our renal C-TMA semiquantitative scoring system is reliable with good reproducibility and prognostic value in clinical practice, which needs further validation.

From monomer to micelle: a facile approach to the multi-step synthesis of block copolymers via inline purification.

A one-pass continuous flow strategy to form block copolymer nanoaggregates directly from monomers is presented. A key development towards such a sophisticated continuous flow setup is a significant improvement in continuous flow dialysis. Often impurities or solvent residues from polymerizations must be removed before block extensions or nanoaggregate formation can be carried out, typically disrupting the workflow. Hence, inline purification systems are required for fully continuous operation and eventual high throughput operation. An inline dialysis purification system is developed and exemplified for amphiphilic block copolymer synthesis from thermal and photoiniferter reversible addition fragmentation chain transfer (RAFT) polymerization. The inline dialysis system is found to be significantly faster than conventional batch dialysis and the kinetics are found to be very predictable with a diffusion velocity coefficient of 4.1 × 10-4 s-1. This is at least 4-5 times faster than conventional dialysis. Moreover, the newly developed setup uses only 57 mL of solvent for purification per gram of polymer, again reducing the required amount by almost an order of magnitude compared to conventional methods. Methyl methacrylate (MMA) or butyl acrylate (BA) was polymerized in a traditional flow reactor as the first block via RAFT polymerization, followed by a 'dialysis loop', which contains a custom-built inline dialysis device. Clearance of residual monomers is monitored via in-line NMR. The purified reaction mixture can then be chain extended in a second reactor stage to obtain block copolymers using poly(ethylene glycol) methyl ether acrylate (PEGMEA) as the second monomer. In the last step, nano-objects are created, again from flow processes. The process is highly tuneable, showing for the chosen model system a variation in nanoaggregate size from 34 nm to 188 nm.

PS-R06-1: A CASE OF PATIENT WITH END-STAGE KIDNEY DISEASE INTRODUCED HEMODIALYSIS AFTER CEREBRAL HEMORRHAGE.

A 46-year-old male had been treated for end-stage kidney disease due to diabetic nephropathy and adaptive FSGS, and underwent surgery of arteriovenous fistula 3 weeks before the admission. He was scheduled to be introduced hemodialysis, but was urgently hospitalized due to cerebral hemorrhage. The head CT scan showed a subcutaneous hematoma of about 45 ml in the left frontal lobe, and the patient had impaired consciousness and worsening respiratory status. There were no surgical indications for cerebral hemorrhage, we initiated blood pressure control with nicardipine. Hyperkalemia was also seen, but urgent dialysis was not necessary, and we planned to introduce dialysis the next day or later. The next day hemodialysis was introduced, but soon after hemodialysis completed, worsening of respiratory condition and dilated pupil were observed. The head CT scan showed worsening cerebral edema compared to pre-dialysis CT scan on the same day. Thereafter, respiratory and general condition did not improve, and he died 11 days after the admission. It is recommended that dialysis should be avoided within 24 hours of the onset of cerebral hemorrhage because of the high risk of hematoma expansion. In addition, in the acute phase of cerebral hemorrhage, it is considered to choose a dialysis method that causes less intracranial pressure increase, such as peritoneal dialysis or continuous hemodiafiltration dialysis, if possible. Administration of hypertonic glycerol may also be helpful. When a patient with end-stage kidney disease is introduced hemodialysis soon after cerebral hemorrhage, control of blood and intracranial pressure should be cared.

607. Establishing Pharmacokinetic Profile of β -lactams in Critically Ill Patients on Continuous Sustained Low-efficiency Dialysis (C-SLED)

Abstract Background Critically ill patients have altered pharmacokinetic (PK) due to severity of illness and multi-organ failure. The lack of pharmacokinetic and pharmacodynamic data in Continuous Sustained Low-efficiency Dialysis (C-SLED) further perpetuates the uncertainty of efficacy with current antimicrobial dosing strategies. The objective of this study is to evaluate patient-specific PK of various β-lactams antibiotics in critically ill patients on C-SLED to assess if the current dosing strategy leads to therapeutic drug levels. Methods This prospective observational cohort study was performed at an academic medical center from November 2021 to June 2022. It included patients age &amp;gt; 18 years and on β-lactam antibiotics while on C-SLED. Therapeutic drug monitoring (TDM) was performed by checking two levels (peak and trough). These levels were used to calculate patient-specific elimination rate constant (k), half-life, and the fraction of time above MIC (fT&amp;gt;MIC). Other data collected included demographics, β-lactam regimens, source of infection, microbiology data, mortality on days 7 and 30, and length of stay. Descriptive statistics were used for data analysis. Results There were 11 patients included in the study with a median age of 55 and 82% (n = 9) of patients were male. β-lactam daily regimen was dosed as creatinine clearance (CrCl) &amp;gt; 50mL/min in 71.4% of patients (n = 10), CrCl 30-50 mL/min in 28.5% (n = 4), and &amp;lt; 30mL/min in 0% of patients. An extended infusion dosing strategy was used in 35.6% of patients (n = 5). The therapeutic drug target (50%fT &amp;gt; MIC for penicillins, 60%fT &amp;gt; MIC for cephalosporins, 40%fT &amp;gt; MIC for carbapenems) was achieved in 100% (n=14) of patients. Dose adjustment was not needed in all 14 cases. However, 100%fT &amp;gt; MIC was only achieved in 64% (n=9) patients. The median hospital length of stay was 60 days. Mortality on days 7 and 30 was 9% (n=1) and 27% (n=3), respectively. Conclusion Preliminary analysis shows that β-lactam daily dose based on CrCl of &amp;gt;30mL/min leads to therapeutic drug levels in patients on C-SLED. Disclosures All Authors: No reported disclosures.

Improved Cell-Free Transcription–Translation Reactions in Microfluidic Chemostats Augmented with Hydrogel Membranes for Continuous Small Molecule Dialysis

Increasing the protein production capacity of the PURE cell-free transcription-translation (TX-TL) system will be key to implementing complex synthetic biological circuits, and to establishing a fully self-regenerating system as a basis for the development of a synthetic cell. Under steady-state conditions, the protein synthesis capacity of the PURE system is likely at least one order of magnitude too low to express sufficient quantities of all PURE protein components. This is in part due to the fact that protein synthesis cannot be sustained during the entire dilution cycle, especially at low dilution rates. We developed a microfluidic chemostat augmented with semipermeable membranes that combines steady-state reactions and continuous dialysis as a possible solution to enhance protein synthesis at steady-state. In batch operation, the continuous dialysis of low molecular weight components via the membranes extended protein synthesis by over an order of magnitude from 2 h to over 30 h, leading to a 7-fold increase in protein yield. In chemostat operation, continuous dialysis enabled sustained protein synthesis during the entire dilution cycle even for low dilution rates, leading to 6-fold higher protein levels at steady state. The possibility to combine and independently manipulate continuous dialysis and chemostat operation renders our dialysis chemostat a promising technological basis for complex cell-free synthetic biology applications that require enhanced protein synthesis capacity.

Gout among Patients with Dialysis: Prevalence, Associated Factors, Treatment Patterns, and Outcomes-Population-Based Retrospective Cohort Study.

Key Points Population-based retrospective cohort study to evaluate clinical correlates of gout and its impact on patients undergoing chronic dialysis.13.5% of US dialysis-dependent patients had gout and were older and male, with a higher prevalence of hypertension and cardiovascular disease.Gout diagnosis was associated with a higher incidence of cardiovascular conditions, levels of anemia, hospitalization, and mortality. Background An association between gout and nondialysis chronic renal disease has long been recognized, yet limited research exists regarding prevalence, treatment, anemia management, and outcomes in patients with ESKD undergoing dialysis. Methods Using data from United States Renal Data System, we conducted a population-based retrospective cohort study in adult patients covered by Medicare and on dialysis in 2017. Multivariate logistic regression models were used to estimate potential factors and odds of gout diagnosis. Antigout medications and impact on anemia management were assessed and compared between gout and nongout dialysis patients using descriptive and regression analyses. Associations for all-cause mortality and cardiovascular-related hospitalizations during 1 year of study follow-up were compared between gout and nongout patients using multivariate Cox regression models. Results Of 231,841 ESKD Medicare patients in 2017 undergoing continuous dialysis, 31,300 (13.5%) had one or more gout diagnostic code(s). Increased odds of having a gout diagnosis were independently associated with older age, male sex, Asian race, obesity, hypertension, and cardiovascular disease. Gout diagnosis was associated with higher prevalence for anemia as indicated by increased erythropoietin-stimulating agent requirements (odds ratio=1.18 for high versus low erythropoietin-stimulating agent dose, 95% confidence interval [95% CI], 1.14 to 1.22) and likelihood of blood transfusions (odds ratio=1.34, 95% CI, 1.30 to 1.38). During the 1-year study follow-up, mortality among gout versus nongout patients was higher by 3% (95% CI, 0 to 6) and a composite association of mortality and cardiovascular disease hospitalization was higher by 6% (95% CI, 3 to 9) after adjusting for comorbid conditions. Conclusions A gout diagnosis was found in 13.5% of US dialysis-dependent patients and was associated with a higher burden of comorbid cardiovascular conditions as well as an elevated incidence of hospitalization and mortality. These observations improve our current understanding of gout among the dialysis population and highlight the importance of new and better treatments to improve outcomes.

Enhanced Antibacterial Activity of Highly Biocompatible Polymeric Core-Shell Levofloxacin Gold Nanocomposite Formulation Against Pseudomonas aeruginosa.

Using natural and synthetic polymers as the components for the core-shell nanocomposite preparation has received recent attention in biomedicine due to their high biocompatibility, high efficacy, and biodegradability. In this present investigation, chitosan-polyvinyl alcohol core-shell gold nanocomposite was synthesised adopting green science principles followed by fabrication with fluoroquinolone antibiotic levofloxacin (LE-CS-PVA-AuNC). Core-shell nanocomposite was prepared from biogenic gold nanoparticles, chitosan, polyvinyl alcohol polymer mixture, and levofloxacin under optimum conditions, and the synthesised nanocomposite exhibited a highly stable nanoarchitecture. Enhancement of antibacterial activity of the nanocomposite was evaluated against the clinical strain of Pseudomonas aeruginosa by determination of growth inhibition, survival rate parameters, and biofilm inhibition rate. Levofloxacin-fabricated core-shell nanocomposite brought about higher growth inhibition than the free levofloxacin, which was confirmed by a notable zone of inhibition, growth inhibition at a lower concentration, rapid biofilm inhibitory rate, and changes in survival growth parameters. In vitro drug release pattern was studied by continuous dialysis, which reveals that the nanocomposite exhibited controlled, sustained release pattern and cumulative release reached almost 98.0% at 72h. Biocompatibility was studied with human keratinocytes (HaCaT cell line), which was studied by measuring cell viability, oxidative stress marker protein, and genotoxicity. The tested nanocomposite was not inducing any sign of toxicity which was confirmed by no marked impact on cell viability, intracellular reduced glutathione, lipid peroxidase, and lactate dehydrogenase activity. In addition, the nanocomposite has not shown any toxic effect on DNA, and all findings indicate that the synthesised nanocomposite was compatible with human keratinocytes. LE-CS-PVA-AuNC synthesised in the present system adopting green science principles can be used in modern biomedicine as an effective and safe antimicrobial agent due to its high antimicrobial action against wound infection pathogens and its best compatibility with human keratinocytes.

Impact of Fluid Overload on Patients Receiving Continuous Dialysis for AKI

Impact of Fluid Overload on Patients Receiving Continuous Dialysis for AKI

Pharmacological Interventions to Prevent Clotting in Extracorporeal Circuits During Continuous Renal Replacement Therapy

What are the risks and benefits of pharmacological interventions to prevent clotting in extracorporeal circuits during continuous renal replacement therapy (CRRT)?Patients who are critically ill in an intensive care unit often develop kidney complications related to multiple factors such as infection, hypotension, and necessary medications. Acute kidney injury occurs in approximately 11% to 18% of hospitalized patients and contributes to an estimated 1.7 million deaths every year.1 Because these patients are hemodynamically unstable, they cannot tolerate standard dialysis, which is typically a 3- to 4-hour procedure. Instead, continuous dialysis is the treatment of choice, and critically ill patients often tolerate it better. This continuous treatment, known as CRRT, provides opportunities for the health care team to introduce treatment modalities that would otherwise cause waste products and fluid to accumulate within the injured kidneys.2Standard practice is to run CRRT continuously for 24 hours; however, the therapy is often inadvertently stopped for periods of time because of clotting in the circuits. When such clotting occurs, the circuits must be changed immediately. The need to change the circuits not only delays treatment but also takes staff time and adds costs. To maintain the full therapeutic effect of CRRT, reducing any interruptions to therapy is essential.2During CRRT, blood contacts the circuit system, which can activate the coagulation pathway. Pharmacological approaches to avoid clotting in CRRT circuits involve several medications including intravenous anticoagulants (eg, unfractionated heparin [UFH], low-molecular-weight heparin, argatroban, citrate), oral anticoagulants (warfarin), and antiplatelet agents.3 The purpose of this systematic review was to assess the benefits and harms of pharmacological interventions for preventing clotting in extracorporeal circuits during CRRT.This systematic review, conducted by Tsujimoto et al,4 included 34 randomized controlled trials (and some quasi-experimental trials) comprising 1960 adult participants. The main primary outcomes investigated included major bleeding, successful prevention of clotting (defined as not needing a circuit change during the first 24 hours), and death from any cause at day 28. The included studies evaluated many different pharmacological comparisons; the most common were heparin derivatives and citrate. Because citrate and UFH are the most commonly used medications to prevent clotting during CRRT,2 this summary describes only the comparison of these 2 interventions.Tsujimoto et al4 independently assessed the risk of bias for each study, including selection, performance, detection, attrition, reporting, and publication biases. They resolved any disagreements by reviewing the data together and through discussion. For dichotomous outcomes, risk ratios (RRs) with 95% CIs were used as measures of treatment effect between various comparisons and outcomes. The authors also used the internationally approved Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to determine the certainty of evidence—high, moderate, low, or very low—for each outcome5: This review showed that, when comparing citrate with UFH to prevent clotting during CRRT, moderate-certainty evidence supports citrate resulting in less major bleeding and having slightly more success at the prevention of clotting.4 The findings from this systematic review align with those of other studies showing that citrate, when compared with UFH, more effectively prolongs the duration of CRRT circuits and reduces the risk of bleeding.6 Currently, several ongoing studies could, once completed or published, be included in similar assessments in future systematic reviews.4The evidence from this systematic review can affect clinical care teams’ decisions when they are creating treatment plans for patients in this population. As nurses caring for critically ill patients, advocating for the best evidence-based treatment remains an important piece of our role. We must always consider the best available evidence and understand the feasibility, appropriateness, meaningfulness, and effectiveness of any intervention to determine whether it is most appropriate to implement in our individual context.

MO298: Predictors of Renal Function Recovery in Critically ill Patients With Acute Kidney Injury

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a frequent and serious complication in critically ill patients admitted in intensive care unit (ICU). The development of acute kidney damage is associated with various adverse outcomes, such as prolonged stay in the ICU, the development of chronic kidney disease (CKD), increased mortality and increased treatment costs. The aim of this study was to determine the predictors of renal function recovery in critically ill patients with AKI who were treated with continuous renal replacement therapy (CRRT). METHOD We performed a single-centre retrospective study of 440 adult surgical and non-surgical patients with AKI or AKI episode in CKD who were admitted to the ICU between 2014 and 2018 and treated with CRRT. Demographic, clinical and laboratory parameters [urea, creatinine, C-reactive protein (CRP), procalcitonin (PCT), quick sequential organ failure assessment (qSOFA) score], comorbidities, the need for vasopressor therapy and mechanical lung ventilation on the day of confirmed AKI, as well as CRRT modalities were analysed. Renal recovery was defined by renal replacement therapy discontinuation within 90 days of its start. Patients with the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 AKI and/or volume overload have had an ‘early’ start of CRRT within 24 h of the AKI diagnosis; patients with poor response to conservative treatment or evidence of clinical complications associated with AKI have had a ‘late’ start of CRRT. The patients were divided into two groups: patients with recovered renal function (RRF group) and patients who had not recovered renal function (NRRF group). RESULTS Out of a total of 440 patients, 242 (55%) recovered renal function. RRF versus NRRF group did not differ significantly by gender (males: 64.5% versus 69.7%) and age (mean age of 60.93 years versus 64.5 years). Cardiovascular diseases were the most common comorbidity in both groups of patients, and CKD was significantly more prevalent in the NRRF groups (88 versus 352, P &amp;lt; .001). There were no significant differences in examined laboratory parameters in the RRF and NRRF group (urea 27.28 versus 26.68 mmol/L; creatinine 401.43 versus 373.7 μmol/L; CRP 144.38 versus 143.52 mg/L; PCT 23.07 versus 22.44 ng/L). No significant difference was found in relation to mechanical lung ventilation (234 in the RRF group versus 206 in the NRRF group; P = .18) and vasopressor therapy (221 in the RRF group versus 219 in the NRRF group; P = 0.94). Values of the qSOFA score were significantly lower (P &amp;lt; .001) in patients with recovered renal function (Fig. 1). In the RRF group, the most commonly used CRRT modality was CVVHD (165; 37.6%), while in the NRRF group it was CVVHDF (181; 40.9%). Predictors of renal recovery in critically ill patients who were treated with CRRT were: age &amp;lt;65 years (P = .044), an ‘early’ start of RRT (P = .043), absence of mechanical ventilation (P = .044) and absence of earlier CKD (P = .005) (Table 1). Predictors of renal recovery in septic critically ill patients with AKI treated with CRRT were: age &amp;lt;65 years (P = .002), the absence of diabetes mellitus (P = .023) and previous CKD (P = .045) and CRP &amp;lt; 100 mg/L (P = .033), while in critically ill patients without sepsis, the predictor of renal function recovery was the absence of previous kidney disease (P = .035). CONCLUSION Previous kidney disease is the most significant factor for the prediction of renal function recovery in critically ill patients with AKI treated with CRRT. Individual consideration of potential predictors of renal recovery, as well as a timely decision to initiate continuous dialysis, will prevent complications and improve the outcome of critically ill patients with AKI.

Risky Business: Angiotensin II Use In A Heartmate 3 LVAD Patient In The Setting Of Refractory Vasoplegia

Introduction :Vasoplegia is a well-described post-operative complication, defined as hypotension due to a decline in systemic vascular resistance in the setting of normal cardiac output and filling pressures. Angiotensin II is a vasoconstrictor with a potential for thrombosis. We present a case of vasoplegia refractory to standard therapy in a patient status post Left Ventricular Assist Device (LVAD) placement in which angiotensin II was utilized successfully. Case Description A 44-year-old African American man with history of stage D idiopathic dilated cardiomyopathy and chronic kidney disease status post HeartMate 3 (HM3) LVAD placement three months ago, complicated by right ventricular failure requiring home milrinone infusion, presented to clinic for follow-up. He was found to have Class IV heart failure symptoms and anasarca, despite an increase in his home diuretic regimen, requiring hospital admission. He denied fever, productive cough or infectious exposures, LVAD alarms, or changes in urine output. Despite an increase of his milrinone and addition of dobutamine, epinephrine, bumetanide, and intravenous chlorothiazide on admission, his hemodynamics on right heart catheterization revealed elevated biventricular filling pressures and a low systemic vascular resistance (SVR) without evidence of right ventricular failure on these therapies (Table 1). The patient maintained poor urine output and required continuous dialysis. However, due to continued vasoplegia, fluid removal was not possible despite maximizing ionotropic and pressor support. A trial of angiotensin II was attempted after discussion with the patient and family about the associated thrombotic risk to HM3. With optimized dosing of angiotensin II, SVR improved (Table 1), and fluid was successfully removed with continuous dialysis. Ionotropic and pressor support was then weaned. The patient did not develop any thromboembolic events or pump thrombosis of the LVAD. The patient was discharged home and one month later underwent a successful heart and kidney transplantation. Conclusion : Angiotensin II use carries significant thromboembolic risk for some patients, with the ATHOS-3 trial showing 12.9% risk versus 5% for placebo. Although this can raise concerns among patients with mechanical circulatory support, significant hemodynamic improvement can be achieved with those facing refractory vasoplegia. Clinicians should be aware of the risks of angiotensin II use and be prepared to utilize the medication in the appropriate patient following a discussion of the potential risks and benefits. :Vasoplegia is a well-described post-operative complication, defined as hypotension due to a decline in systemic vascular resistance in the setting of normal cardiac output and filling pressures. Angiotensin II is a vasoconstrictor with a potential for thrombosis. We present a case of vasoplegia refractory to standard therapy in a patient status post Left Ventricular Assist Device (LVAD) placement in which angiotensin II was utilized successfully. A 44-year-old African American man with history of stage D idiopathic dilated cardiomyopathy and chronic kidney disease status post HeartMate 3 (HM3) LVAD placement three months ago, complicated by right ventricular failure requiring home milrinone infusion, presented to clinic for follow-up. He was found to have Class IV heart failure symptoms and anasarca, despite an increase in his home diuretic regimen, requiring hospital admission. He denied fever, productive cough or infectious exposures, LVAD alarms, or changes in urine output. Despite an increase of his milrinone and addition of dobutamine, epinephrine, bumetanide, and intravenous chlorothiazide on admission, his hemodynamics on right heart catheterization revealed elevated biventricular filling pressures and a low systemic vascular resistance (SVR) without evidence of right ventricular failure on these therapies (Table 1). The patient maintained poor urine output and required continuous dialysis. However, due to continued vasoplegia, fluid removal was not possible despite maximizing ionotropic and pressor support. A trial of angiotensin II was attempted after discussion with the patient and family about the associated thrombotic risk to HM3. With optimized dosing of angiotensin II, SVR improved (Table 1), and fluid was successfully removed with continuous dialysis. Ionotropic and pressor support was then weaned. The patient did not develop any thromboembolic events or pump thrombosis of the LVAD. The patient was discharged home and one month later underwent a successful heart and kidney transplantation. : Angiotensin II use carries significant thromboembolic risk for some patients, with the ATHOS-3 trial showing 12.9% risk versus 5% for placebo. Although this can raise concerns among patients with mechanical circulatory support, significant hemodynamic improvement can be achieved with those facing refractory vasoplegia. Clinicians should be aware of the risks of angiotensin II use and be prepared to utilize the medication in the appropriate patient following a discussion of the potential risks and benefits.

Creatinine] can change in an unexpected direction due to the volume change rate that interacts with kinetic GFR: Potentially positive paradox.

[Creatinine] was proved to change in the opposite direction of the kinetic GFR (GFRK), but does the [creatinine] also change in the opposite direction of the volume rate? If volume is administered and the [creatinine] actually goes up, then the two changes move in the same direction and their ratio is positive, paradoxically. The equation that describes [creatinine] as a function of time was differentiated with respect to the volume rate. This partial first derivative has a global maximum that can be positive under definable conditions. Knowing what makes the maximum positive informs when the derivative will be positive over some continuous domain of volume rate inputs. The first derivative versus volume rate curve has a maximum and a minimum point depending on the GFRK. If GFRK is below a calculable value, then the curve's minimum vanishes, letting it descend to ‐∞ and not allowing the derivative to ever be positive. If GFRK lies between a lower and a higher calculable value, then the curve's maximum vanishes, letting the derivative diverge to +∞, though the clinical scenario is unrealistic. If GFRK is above the higher calculable value, then the curve's absolute maximum can become positive by decreasing the creatinine generation rate or increasing the initial [creatinine]. The derivative is potentially positive under these clinically realizable circumstances. The combination of parameters above can align in septic patients (low creatinine generation rate) with kidney failure (high initial [creatinine]) who are put on continuous dialysis (high GFRK). If a first derivative is positive, removing more volume can improve the [creatinine] and, dismayingly, giving more volume can worsen the [creatinine]. This paradox is explained by a covert interplay between the ambient [creatinine] and GFRK that excretes creatinine faster than its volume of distribution declines.

Hospitalization in patients with dialysis in Taiwan: A nationwide population-based observational study

The hospitalization rate is higher in patients with end-stage kidney disease (ESKD) than in the general population. However, the national estimates in Taiwan remain unclear. Therefore, we investigated the hospitalization rates of ESKD patients in a disease-specific manner from 2010 to 2018 in Taiwan. This population-based study was conducted using data from the National Health Insurance Research Database. We analyzed the hospitalization rates of patients with ESKD, defined as continuous dialysis for at least three successive months. The first diagnosis at discharge for each hospitalization was defined as the main diagnosis of hospitalization. The hospitalization rate in a certain year was calculated as the number of hospitalizations divided by the number of patients undergoing chronic dialysis in the respective year. Hospitalization occurred in half of all prevalent ESKD patients, with an increasing trend over time. The hospitalization rate increased from 964.1 per 1000 person-years in 2010 to 1037.9 per 1000 person-years in 2018. ESKD patients who were male, aged over 75 years, and receiving hemodialysis had higher hospitalization rates. Infection-related hospitalization was the main cause of hospitalization, followed by cardiovascular disease. The 30-day re-admission rate was 19%, and the in-hospital mortality rate was 9%. Hospitalization rates continued to increase from 2010 to 2018. The high hospitalization rates for infection-related diseases and hemodialysis patients call for further strategies to be developed that reduce the hospitalization burden.

Antiviral treatment and prognosis in patients undergoing maintenance hemodialysis due to hepatitis C virus.

Maintenance hemodialysis (MHD) is one of the important renal replacement therapies for patients with end-stage renal disease. Hepatitis C virus (HCV) infection is a serious global public health problem. The proportion of MHD patients complicated with HCV infection and the risk of adverse prognosis are higher than those in the general population. Active antiviral treatment and prevention of reinfection is a combined treatment by nephrology and infection physicians. It is a widely accepted preventive measure to set hemodialysis buffer area for patients in treating HCV infection, but its effectiveness and safety still need to be further explored. Thus, the aim of this study is to explore the antiviral treatment and prognosis of MHD patients with HCV infection during hemodialysis. A retrospective analysis for renal disease patients at 10 end-stage with long-term hemodialysis in the HCV area of the Blood Purification Center of Xiangya Hospital, Central South University. After standard antiviral drug treatment, the patient reached the cure standard for HCV infection. The buffer zone was set up in the Blood Purification Center by the Department of Nephrology of Xiangya Hospital since April 2017. Patients cured of HCV infection were transferred from the HCV area to the buffer zone for continuous dialysis, accompanied by monitoring serum HCV-RNA, anti-HCV antibody levels and changes in clinical biochemical indicators following the status of reinfection. Ten patients with HCV infection were finally cured after antiviral treatment, and there were no significant changes in clinical biochemical indicators before and after treatment. In the followed-up period after the transfer, the patient continued to be negative for HCV-RNA and positive for anti-HCV antibody. Direct antiviral therapy is safe and effective in MHD patients with HCV infection. Active antiviral therapy and transferring to the buffer area for dialysis are new and effective treatment modes for HCV patients during MHD.

The effect of pre-ESRD care program on potentially inappropriate medication in advanced CKD patients

Abstract Background Due to the multiple comorbidities and the associated complications among advanced CKD population, assessing potentially inappropriate medications (PIM) in these patients is an important task for physicians and multidisciplinary care team members. This study aimed to investigate the impact of the national pre-ESRD pay-for-performance (P4P) program on prescribing quality in Taiwan. Methods We conducted a retrospective cohort study using data from National Health Insurance Research Database (NHIRD) maintained by the Health and Welfare Data Science Center, Ministry of Health and Welfare (HWDC, MOHW). The incidents of CKD in year 2010 were observed until the end of 2017. Adult patients who initiated maintenance dialysis therapy were enrolled. To identify the use of PIM that should be avoided in advanced CKD patients, the Beers 2019 criteria and latest Taiwan Manual of Renal Injury Prevention and Drug Safety were applied. We measured PIM use in one year before starting long-term dialysis. Results Among 7,828 participants underwent continuous dialysis treatment, 2,119 (27.1%) were P4P patients. Most (90.4%) participants were prescribed one or more PIMs before ESRD initiation. After adjusted age, sex, Charlson Comorbidity Index (CCI) and the number of nephrologist visits, the logistic regression showed lower probability of PIM use in the P4P enrollees (OR = 0.56, 95% CI = 0.47-0.66). The effect of P4P on PIM was more prominent in the subgroups of patients who were female and CCI≤3. Conclusions The implementation of the pre-ESRD P4P program might reduce PIM use among CKD patients. Our results underline the strategy of financial incentives in the payment design to improve prescribing patterns. Key messages Prescribing potentially inappropriate medications is common among patients who were approaching ESRD. The study highlights the importance of implementing the pre-ESRD P4P program to reduce PIM use in advanced CKD patients.

Safety and effectiveness of left atrial appendage occlusion in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis

Objective: To evaluate the safety and effectiveness of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis. Methods: Six patients with AF and end-stage renal disease(ESRD)on long term hemodialysis who underwent LAAO from March 2017 to March 2021 in Beijing Anzhen Hospital were enrolled. Baseline characteristics such as age, sex, types of arrhythmia, stroke and bleeding score, and continuous dialysis time were collected. Four patients underwent LAAO, two patients underwent the combined procedure of catheter ablation and LAAO. Perioperative treatment and serious complications were recorded. Transesophageal echocardiography was repeated at 45 days and 60 days after the procedure. Telephone follow-up was conducted at 3, 6 and 12 months after the procedure, and every 6 months thereafter. Thromboembolism and major bleeding events and survival were evaluated. Results: The average age was (66.7±17.0) years old, and 5 were male (5/6). There were 4 patients with paroxysmal AF (4/6), and 2 patients with persistent AF (2/6). The mean CHA2DS2-VASc score was (4.8±1.5), and the HAS-BLED score was (3.5±1.4). The duration of hemodialysis was 2.6 (1.1, 8.3) years. Successfully Watchman implantation was achieved in all patients. There were no severe perioperative complications, and no device related thrombosis or leaks were observed by transesophageal echocardiography. During a mean of 22.0 (12.0, 32.0) months follow-up, there was no thromboembolism or major bleeding events. A total of 2 patients died, one from sudden cardiac death, and another one from heart failure. Conclusions: LAAO may be a safe and effective therapeutic option for prevention of thromboembolism in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis, further studies with larger patient cohort are needed to confirm our results.