The Effect of Combination Use of Hemodialysis and Hemoperfusion on Microinflammation in Elderly Patients with Maintenance Hemodialysis

<b><i>Background:</i></b> Patients with maintenance hemodialysis (MHD) generally have a microinflammatory state. The aim of this study was to investigate the effects of hemodialysis (HD) combined with hemoperfusion (HP) on microinflammatory state in elderly patients with MHD. <b><i>Methods:</i></b> One hundred and fifty elderly patients with MHD were randomly divided into the control group and the observation group. The control group received simple HD treatment, and the observation group received combined HD + HP treatment on the basis of the control group. After 6 months of continuous treatment, the patients were evaluated to compare the quality of life, inflammation, adverse reactions, and nutritional indicators in the 2 groups before and after treatment. <b><i>Results:</i></b> There was no significant difference in the quality of life between the 2 groups before treatment. After treatment, the scores of psychological aspects, physiological aspects, social aspects, environmental aspects, and independent ability in the observation group were higher than those in the control group, with statistical significance (<i>p</i> &#x3c; 0.05). There was no statistical significance in the level of inflammation between 2 groups before treatment. After treatment, the levels of hs-CRP, Hcy, IL-6, and TNF-α in the observation group were significantly lower than those in the control group, with statistical significance (<i>p</i> &#x3c; 0.05). The incidence of dry mouth, skin reaction, neuritis, and subcutaneous tissue fibrosis in the observation group was lower than that in the control group, with statistical significance (<i>p</i> &#x3c; 0.05). There was no statistical significance in nutritional level indexes between 2 groups before treatment (<i>p</i>₁ &#x3e; 0.05). After treatment, the levels of hemoglobin, total protein, albumin, and transferrin in the observation group were significantly higher than those in the control group, with statistical significance (<i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> The clinical effect of HD combined with HP in elderly MHD patients is significant, which can effectively reduce the incidence of adverse reactions and inflammation in the patients and improve the quality of life and nutritional indicators of the patients.

Leakage of Endotoxins through the Endotoxin Retentive Filter: An in vitro Study

<b><i>Introduction:</i></b> Ultrapurification of dialysis fluid has enabled highly efficient dialysis treatments. Online hemodiafiltration is one such treatment that uses a purified dialysis fluid as a supplemental fluid. In this method, an endotoxin retentive filter (ETRF) is used in the final step of dialysis fluid purification, with the aim of preventing leakage of endotoxins. Sodium hypochlorite and peracetic acid are used as disinfecting agents for the dialysis fluid pipes containing the ETRF; however, the effects of these agents on ETRF membrane pores have not been fully clarified. <b><i>Methods:</i></b> Water permeability (flux) and endotoxin permeability were assessed in 3 types of ETRFs made with different membrane materials: polyester polymer alloy (PEPA), polyether sulfone (PES), and polysulfone (PS). High-concentration sodium hypochlorite and 2 types of peracetic acid were used as disinfecting agents, and the changes in flux and the endotoxin sieving coefficient (SC) were measured. <b><i>Results:</i></b> After repeated use of high concentrations of sodium hypochlorite and peracetic acid, the PEPA and PES ETRFs did not permit passage of endotoxins, regardless of their flux. However, in the PS ETRF, the flux and endotoxin SC increased with the number of cleaning cycles. No differences were observed according to the concentration of peracetic acid disinfecting agents. <b><i>Conclusion:</i></b> PEPA and PES ETRFs completely prevent endotoxin leakage and can be disinfected at concentrations higher than the conventionally recommended concentration without affecting pore expansion. Even new PS ETRFs have low levels of endotoxin leakage, which increase after disinfection cycles using sodium hypochlorite and peracetic acid.

Effect of Expanded Hemodialysis with Theranova® in Patients with COVID-19

<b><i>Introduction:</i></b> Cytokine storm control is the main target for improving severe COVID-19 by using immunosuppressive treatment. Effective renal replacement therapy (RRT) could give us an advantage removing cytokines in patients with RRT requirements superimposed on COVID-19. <b><i>Methods:</i></b> This is a prospective observational study in COVID-19 patients who required hemodialysis (HD). Patients were assigned to online hemodiafiltration (OL-HDF) and expanded HD (HDx) according to Brescia group recommendations. We measured several cytokines, β2 microglobulin and albumin levels pre/post-dialysis and on 1st–2nd week. We compared levels among both techniques and control group (HD without COVID-19). <b><i>Results:</i></b> We included 26 patients: 18 with COVID-19 on RRT (5 of them had acute kidney injury [AKI]) and 8 controls. We confirm higher cytokine levels in COVID-19 patients than controls and even higher in patients with AKI than in those with chronic kidney disease. Most cytokines raised during HD session, except IL-10 and TNFα. IL-10 was eliminated by any dialysis technique, while clearance of TNFα was higher in the HDx group. HDx achieved a deeper normalization of cytokines and β2 microglobulin reduction. Mortality was higher in the OL-HDF group than the HDx group. <b><i>Discussion:</i></b> Not all cytokines behave equally along HD session. The following characteristics should be taken into account, such as intrinsic kinetic profile during a HD session. HDx seems to get better performance, probably due to the combination of different factors; however, we did not reach statistical significance due to the small sample size, dropout, and reduction of AKI incidence during the 2nd pandemic wave. <b><i>Conclusion:</i></b> HDx appears to provide better clearance for TNFα and β2 microglobulin during HD session and associates lower mortality. We propose the HDx technique for COVID-19 patients with RRT requirements since it seems to be safe and more effective than OL-HDF. Further studies are still needed, but we hope that our preliminary data may help us in future pandemic waves of SARS-CoV-2 or other viruses still to come.

Dialysis Outcomes in a Middle-Income Country: An Updated Comparison of Patient Mortality between Hemodialysis and Peritoneal Dialysis

<b><i>Introduction:</i></b> Comparisons of survival between dialysis modalities is of great importance to patients with kidney failure, their families, and healthcare systems. <b><i>Objective:</i></b> This study’s objective was to compare mortality of patients on chronic hemodialysis (HD) or peritoneal dialysis (PD) and identify variables associated with mortality. <b><i>Methods:</i></b> This retrospective cohort study included adult incident patients with kidney failure treated with HD or PD by the Baxter Renal Care Services network in Colombia. The study was conducted between January 1, 2008, and December 31, 2013 (recruitment period), with follow-up until December 31, 2018. The outcome was the cumulative mortality rate at 1, 2, 3, 4, and 5 years. Propensity score matching (PSM) and the Gompertz parametric survival model were used to compare mortality in HD versus PD. <b><i>Results:</i></b> The analysis included 12,499 patients, of whom 57.4% were on PD at inception. The overall mortality rate was 14.0 events per 100 patient-years (95% confidence interval [CI], 13.61–14.42). Using an intention-to-treat approach, crude mortality rates were significantly lower in patients receiving HD (HD: 12.3 deaths per 100 patient-years [95% CI, 11.7–12.8] vs. PD: 15.5 [14.9–16.1], <i>p</i> &#x3c; 0.01). Using a Gompertz parametric survival model, dialysis modality was not significantly associated with mortality (hazard ratio HD vs. PD 1.0, 95% CI, 0.9–1.1). After PSM, the mortality cumulative incidence functions between HD and PD were not statistically significantly different (<i>p</i> = 0.88). <b><i>Conclusions:</i></b> The present study in a large cohort of incident dialysis patients with at least 5 years follow-up and using PSM methods showed no differences in cumulative mortality between HD and PD patients. This evidence from a middle-income country may facilitate the process of dialysis modality selection globally.

Peritoneal Vicenza “Short” Catheter Outcomes and Comparison with International Society for Peritoneal Dialysis Guidelines

<b><i>Introduction:</i></b> A well-functioning peritoneal catheter is key to success of peritoneal dialysis (PD). The Vicenza “short” catheter is a modified Tenckhoff catheter with a shorter intraperitoneal segment. The aim of this study was to evaluate the incidence of catheter-related complications and catheter survival rate using the Vicenza “short” catheter, according to the goals suggested by the International Society for Peritoneal Dialysis (ISPD) guidelines. Second, we compared insertion techniques used in our center. <b><i>Methods:</i></b> This is a retrospective cohort, single-center study analyzing incident PD patients undergoing Vicenza “short” peritoneal catheter placement between January 1, 2015, and December 31, 2019. As clinical outcomes, we evaluated catheter patency at 12 months, exit-site/tunnel infection and peritonitis within 30 days of catheter insertion, visceral injury, or significant hemorrhage during the procedure, in accordance with ISPD guidelines. <b><i>Results:</i></b> The percentage of patency at 12 months for all catheter insertion methods was 88.91%, and the percentage for laparoscopic placement was 93.75%. The exit-site/tunnel infection and peritonitis occurring within 30 days of catheter insertion were, respectively, 0.75% and 2.2%; the visceral injury leading to intervention was 0.75%. We did not have any case of significant hemorrhage. All results were in line with ISPD guidelines. <b><i>Conclusion:</i></b> We conclude that the Vicenza “short” catheter is a suitable device for peritoneal access. The implantation procedure is safe and easy to perform, and both nephrologists and surgeons can do it. A confident use and a proper implantation of the Vicenza “short” catheter help achieve the clinical ISPD goals for the PD access procedure in terms of catheter survival and complication rates.

Combined Hemoperfusion and Continuous Veno-Venous Hemofiltration for Carbamazepine Intoxication

<b><i>Introduction:</i></b> Carbamazepine (CBZ) is a widely used anticonvulsant with a low molecular weight that allows for extracorporeal removal of free drug by both dialytic and hemoperfusion techniques, particularly in a massive overdose where serum protein binding is saturated. This report presents a case of CBZ intoxication where we were able to compare the mass removal of CBZ using hemoperfusion, with the mass removal of CBZ achieved with continuous renal replacement therapy (CRRT) during combined treatment. <b><i>Methods:</i></b> The Jafron HA230 resin hemoperfusion cartridge was applied in series with the continuous veno-venous hemofiltration (CVVH) circuit. Baseline and ongoing serum drug levels along with further samples from pre- and post-hemoperfusion cartridges and from CVVH effluent were collected. <b><i>Results:</i></b> Combined CVVH and resin hemoperfusion therapy in series was associated with a 50% reduction in the CBZ level from 16 mg/L to 8 mg/L over 3 h, far more rapid than that observed with CVVH alone or in the absence of extracorporeal drug clearance in the preceding hours. The combination therapy removed close to 35 mg/h of CBZ. <b><i>Conclusion:</i></b> The combination of CRRT and hemoperfusion can be easily deployed, appears safe, and is able to combine the CBZ mass removal achieved with each technique, thus to maximize CBZ extraction.

Cytokine Adsorption Therapy during Extracorporeal Membrane Oxygenation in Adult Patients with COVID-19

Respiratory failure and systemic inflammation are paramount features of severe SARS-CoV-2 disease (COVID-19). Extracorporeal membrane oxygenation (ECMO) therapy has a potential role in patients with refractory disease. An inflammatory response due to blood contact with hemofilters, functioning as a synergic inflammatory stimulus, can lead to a hyperinflammatory state, relatable to cytokine release syndromes. After the first patient succumbed to a refractory vasodilatory shock believed to be due to hyperinflammatory state, a strategy of blood purification through cytokine adsorption therapy (CAT) with CytoSorb® was designed. In this case series, the authors describe the initial experience with such strategy. CAT was employed with no direct complications and helped controlling the inflammatory state, with all patients halting vasopressor support in 72 h and biomarker levels (C-reactive protein, ferritin, and interleukin-6) showing negative trends in most patients. Analysis of inflammatory biomarkers evolution highlighted 2 biomarker profiles related to the presence or absence of superinfection at the time of CAT implementation. In this case series of severe COVID-19 patients, 3 patients died – irreversible lung fibrosis, complications of critical hypoxemia before ECMO induction and complications of systemic anticoagulation were the causes. This case series aimed to contribute to the body of evidence substantiating CAT utilization in hyperinflammatory patients, namely, COVID-19 patients requiring ECMO rescue.

Vascular Access and Clinical Outcomes in Underserved Hemodialysis Patients in Mexico

<b><i>Introduction:</i></b> Central venous catheter (CVC) as vascular access in hemodialysis (HD) associates with adverse outcomes. Early CVC to fistula or graft conversion improves these outcomes. While socioeconomic disparities between the USA and Mexico exist, little is known about CVC prevalence and conversion rates in uninsured Mexican HD patients. We examined vascular access practice patterns and their effects on survival and hospitalization rates among uninsured Mexican HD patients, in comparison with HD patients who initiated treatment in the USA. <b><i>Methods:</i></b> In this retrospective study of incident HD patients at Hospital Civil (HC; Guadalajara, MX) and the Renal Research Institute (RRI; USA), we categorized patients by the vascular access at the first month of HD and after the following 6 months. Factors associated with continued CVC use were identified by a logistic regression model. We developed multivariate Cox proportional hazards models to investigate the effects of access and conversion on mortality and hospitalization over an 18-month follow-up period. <b><i>Results:</i></b> In 1,632 patients from RRI, the CVC prevalence at month 1 was 64% and 97% among 174 HC patients. The conversion rate was 31.7% in RRI and 10.6% in HC. CVC to non-central venous catheter (NON-CVC) conversion reduced the risk of hospitalization in both HC (aHR 0.38 [95% CI: 0.21–0.68], <i>p</i> = 0.001) and RRI (aHR 0.84 [95% CI: 0.73–0.93], <i>p</i> = 0.001). NON-CVC patients had a lower mortality risk in both populations. <b><i>Discussion/Conclusion:</i></b> CVC prevalence and conversion rates of CVC to NON-CVC differed between the US and Mexican patients. An association exists between vascular access type and hospitalization and mortality risk. Prospective studies are needed to evaluate if accelerated and systematic catheter use reduction would improve outcomes in these populations.

Increased Monocyte/Lymphocyte Ratio as Risk Marker for Cardiovascular Events and Infectious Disease Hospitalization in Dialysis Patients

<b><i>Introduction:</i></b> In dialysis patients, cardiovascular disease (CVD) and infectious disease contribute to poor clinical outcomes. We investigated if a higher monocyte/lymphocyte ratio (MLR) is associated with an increased risk of CVD events and infectious disease hospitalizations in incident dialysis patients. <b><i>Methods:</i></b> In an ongoing observational prospective cohort study, 132 Japanese dialysis patients (age 58.7 ± 11.7 years; 70% men) starting dialysis therapy were enrolled and followed up for a median of 48.7 months. Laboratory biomarkers, including white blood cell count and its differential count, were determined at baseline. Event-free time and relative risks (RRs) were calculated using the Kaplan-Meier curves and Cox models, respectively. <b><i>Results:</i></b> When divided into 2 groups according to median MLR (0.35 [range, 0.27–0.46]), the periods without CVD events were significantly shorter in the high MLR group than in the low MLR group (log-rank test = 5.60, <i>p</i> = 0.018). The RR of CVD events, after adjusting for age, sex, and diabetes, was 2.43 (1.22–4.84) in the high MLR group compared to the low MLR group. The periods without infections requiring hospitalization were also shorter (log-rank test = 4.16, <i>p</i> = 0.041). The RR of infections requiring hospitalization was 1.98 (1.02–3.83) after the same adjustments. The number of CVD events was higher in the high MLR group (18.6 events per 100 person-years at risk [pyr]) than the low MLR group (11.1 events per 100 pyr). The duration of infectious disease hospitalization was longer in the high MLR group (6.3 days per pyr) than in the low MLR group (2.8 days per pyr). <b><i>Conclusion:</i></b> A higher MLR is associated with increased risks of both CVD events and infectious disease hospitalization in dialysis patients.

Effects of Medium Cutoff Membranes on Pro-Inflammatory Cytokine and Oxidative Marker Levels in Patients with Sepsis Who Developed Acute Kidney Injury

<b><i>Introduction:</i></b> There is insufficient data on the role of the medium cutoff (MCO) membranes in the clearance of pro-inflammatory cytokines and oxidant radicals in patients with sepsis requiring hemodialysis. <b><i>Methods:</i></b> The study consisted of 38 septic patients who developed acute kidney injury (AKI) and who were scheduled to undergo 2 sessions of hemodialysis. Nineteen patients underwent their first dialysis session with the MCO membrane and 19 patients with the high-flux (HF) membrane. In the second session, the membranes were switched. Pro-inflammatory cytokine and oxidative marker levels were measured in blood samples obtained before and after both dialysis sessions. Reduction ratios were compared for the 2 types of hemodialysis membranes. <b><i>Results:</i></b> After the first session, there was a greater reduction in tumor necrosis factor (TNF)-α with the MCO membrane (28.2 ± 21.1 vs. 8.0 ± 6.6, <i>p</i> = 0.001). After the second session, there was a greater reduction in interleukin (IL)-6 (27.8 ± 26.5 vs. 5.9 ± 13.3, <i>p</i> = 0.003) and IL-1β (20.5 ± 21.1 vs. 4.0 ± 6.5, <i>p</i> = 0.004) with the MCO membrane. When the first and second sessions of all 38 patients were compared, the reductions in TNF-α, IL-6, and IL-1β were consistently greater for MCO than HF (<i>p</i> = 0.001, <i>p</i> = 0.006, <i>p</i> &#x3c; 0.001, respectively). The reductions in total antioxidant status, total oxidant status, and myeloperoxidase were not statistically different for the 2 types of dialysis membranes. <b><i>Conclusions:</i></b> MCO membrane was superior to HF membrane in the removal of cytokines in septic patients with AKI. However, a similar effect was not observed for oxidative stress markers.