Hemodynamic and Metabolic Tolerance of Acetate-Free Biofiltration in Mechanically Ventilated Critically Ill Patients: A Real-Life Study.

Intradialytic hypotension can lead to superimposed organ hypoperfusion and ultimately worsens long-term kidney outcomes in critically ill patients requiring kidney replacement therapy. Acetate-free biofiltration (AFB), an alternative technique to bicarbonate-based hemodialysis (B-IHD) that does not require dialysate acidification, may improve hemodynamic and metabolic tolerance of dialysis. In this study, we included 49 mechanically ventilated patients requiring 4 h dialysis (AFB sessions n = 66; B-IHD sessions n = 62). Whereas more AFB sessions were performed in patients at risk of hemodynamic intolerance, episodes of intradialytic hypotension were significantly less frequent during AFB compared to B-IHD, whatever the classification used (decrease in mean blood pressure ≥ 10 mmHg; systolic blood pressure decrease >20 mmHg or absolute value below 95 mmHg) and after adjustment on the use of vasoactive agent. Diastolic blood pressure readily increased throughout the dialysis session. The use of a bicarbonate zero dialysate allowed the removal of 113 ± 25 mL/min of CO2 by the hemofilter. After bicarbonate reinjection, the global CO2 load induced by AFB was +25 ± 6 compared to +80 ± 12 mL/min with B-IHD (p = 0.0002). Thus, notwithstanding the non-controlled design of this study, hemodynamic tolerance of AFB appears superior to B-IHD in mechanically ventilated patients. Its use as a platform for CO2 removal also warrants further research.

High immunogenicity of a messenger RNA-based vaccine against SARS-CoV-2 in chronic dialysis patients.

BACKGROUND: Patients with chronic kidney disease, dialysis patients and kidney transplant patients are at high risk of developing severe coronavirus disease 2019 (COVID-19). Data regarding the immunogenicity of anti-severe acute respiratory syndrome coronavirus 2 messenger RNA (anti-SARS-CoV-2 mRNA) vaccines in dialysis patients were published recently. We assessed the immunogenicity of anti-SARS-CoV-2 mRNA vaccine in dialysis patients. PATIENTS AND METHODS: One hundred and nine patients on haemodialysis (n = 85) or peritoneal dialysis (n = 24) have received two injections of 30-µg doses of BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) that were administered intramuscularly 28 days apart. Those who were still seronegative after the second dose were given a third dose 1 month later. Anti-SARS-CoV-2 antibodies were tested before and after vaccination. RESULTS: Ninety-one out of the 102 patients who had at least a 1-month follow-up after the second (n = 97) or the third (n = 5) vaccine doses had anti-SARS-CoV-2 antibodies. The seroconversion rate was 88.7% (86 out of 97 patients) among SARS-CoV-2 seronegative patients at the initiation of vaccination. Receiving immunosuppressive therapy was an independent predictive factor for non-response to vaccination. CONCLUSION: Due to high immunogenicity and safety of mRNA vaccines, we strongly recommend prioritizing a two-dose vaccination of dialysis patients. A third dose can be required in non-responders to two doses. When possible, patients waiting for a kidney transplantation should be offered the vaccine before transplantation.

Cost-minimization analysis between intravenous iron sucrose and iron sucrose similar in hemodialysis patients.

OBJECTIVES: Intravenous iron and erythropoiesis-stimulating agents are used to manage anemia in chronic hemodialysis patients. The interchangeability between intravenous iron sucrose preparations is still debated. We evaluated how cost and effectiveness were impacted when chronic hemodialysis patients were switched from an original iron sucrose product to an iron sucrose similar preparation. METHODS: A single center sequential observational retrospective study was conducted at a French hospital. The same patients were followed during two 24-week periods (iron sucrose in period P1; and iron sucrose similar in period P2). Anemia-related treatment costs were assessed in P1 and P2 from a hospital perspective. Sensitivity analyses were performed to assess the robustness of the results. RESULTS: Our study included 109 patients (105 analyzed patients and 4 patients with missing data). The mean hemoglobin level was not different between P1 and P2 (p = 0.92). The mean differential cost per patient was + €13.90 (P2 - P1). The factors with the biggest impact on this result were the prices of epoetin alfa and iron sucrose. CONCLUSION: This cost minimization analysis suggests that for chronic hemodialysis patients, iron sucrose and iron sucrose similar have the same efficacy and that using iron sucrose similar was more expensive in 66.7% of iterations.

No Improvement of Hepatitis B Vaccination Response in Patients Dialysed with a Polymethylmethacrylate Membrane Compared to High-Flux Polysulfone: Results of the HEPADIAL Study.

BACKGROUND: An altered immune response and decreased vaccine response are observed in patients with chronic renal failure. A preliminary study of 15 non-immunised patients, despite appropriate previous hepatitis B vaccination, showed a 60% seroconversion rate after 3 months of dialysis with a polymethylmethacrylate (PMMA) membrane. This response was associated with circulating soluble CD40 (CD40s) decrease, a natural inhibitor of the humoral immune response. The aim of the study is to confirm these results in a randomised study. METHODS: We conducted a multicentre randomised intention-to-treat superiority clinical trial comparing polysulfone and a PMMA membrane in 2 parallel patient groups. The primary end point was the vaccine response rate, as defined by an anti-HBs antibodies titre of >10 IU/L, 1 month after the last vaccination with a double dose of Engerix B20®, performed at weeks 12, 16, 20, and 36. RESULTS: Twenty-five patients were randomised and included in an intention-to-treat analysis. They were dialysed on polysulfone (n = 11) or PMMA (n = 14) for 40 weeks. Fifty percent of the PMMA patients versus 54.5% of the polysulfone patients achieved seroconversion (p = 1.00). The median anti-HBs antibody titre in responders at week 40 was 496 (92-750) versus 395 (43-572) UI/mL for PMMA and polysulfone, respectively (p = 0.46). The median CD40s titre at week 12 was 306 (193-448) versus 491 (281-515) pg/mL (p = 0.21). The CD40s median variation between week 0 and week 12 was 5 (-105 to 90) versus 64 (-63 to 123) pg/mL (p = 0.55). The CD40s level at week 12 in non-responders was slightly inferior to that of the responders: median 193 (168-331) versus 413 (281-512) pg/mL (p = 0.08). CONCLUSION: We did not observe a better vaccine response with the PMMA membrane compared to high-flux polysulfone. The PMMA membrane did not decrease the CD40s more than the polysulfone membrane probably because the titre was previously low in the 2 groups.

Randomised trial on clinical performances and biocompatibility of four high-flux hemodialyzers in two mode treatments: hemodialysis vs post dilution hemodiafiltration.

This prospective multicenter randomized comparative cross-over trial aimed at evaluating the influence of hemodialysis vs post-dilution hemodiafiltration with high-flux dialyzers in solute clearance and biocompatibility profile. 32 patients were sequentially dialyzed with Leoceed-21HX, Polypure-22S+, Rexsys-27H and VIE-21A. Primary outcome was ß2-microglobulin removal. Secondary outcomes were (i) extraction of other uremic solutes (ii) parameters of inflammation and nutrition and (iii) comparative quantification of perdialytic albumin losses (using total 'TDC' vs partial 'PDC' collection of dialysate). Significant increases in removal rates of ß2-microglobulin (84.7 ± 0.8 vs 71.6 ± 0.8 mg/L), myoglobin (65.9 ± 1.3 vs 38.6 ± 1.3 µg/L), free immunoglobulin light chains Kappa (74.9 ± 0.8 vs 55.6 ± 0.8 mg/L), ß-trace protein (54.8 ± 1.3 vs 26.8 ± 1.4 mg/L) and orosomucoid (11.0 ± 1.1 vs 6.0 ± 1.1 g/L) but not myostatin (14.8 ± 1.5 vs 13.0 ± 1.5 ng/mL) were observed in HDF compared to HD when pooling all dialyzers. Rexsys and VIE-A use in both HD and HDF subgroups was associated to a better removal of middle/large-size molecules compared to Leoceed and Polypure, except ß2-microglobulin for Rexsys. Inflammatory parameters were unchanged between dialyzers without any interaction with dialysis modality. Mean dialysate albumin loss was comparable between TDC and PDC (1.855 vs 1.826 g/session for TDC and PDC respectively). In addition, a significant difference in albumin loss was observed between dialyzers with the highest value (4.5 g/session) observed using Rexsys. Use of all dialyzers was associated with good removals of the large spectrum of uremic toxins tested and good biocompatibility profiles, with an additional gain in removal performances with HDF. Larger surface area, thinner wall and resultant very high ultrafiltration coefficient of Rexsys should be taken into account in its clear performance advantages.

The Effectiveness of Topical Cerium Nitrate-Silver Sulfadiazine Application on Overall Outcome in Patients with Calciphylaxis.

BACKGROUND: Calciphylaxis (CPX) is a rare and life-threatening disease characterized by vascular calcification and development of painful and necrotizing skin lesions with a challenging management. Mechanisms of CPX are complex and include an imbalance between vascular calcification promoters and inhibitors, and frequently vitamin K deficiency. OBJECTIVES: To describe the various presentations and identify predictive factors of death in patients with CPX. METHODS: In this multicenter retrospective study, we included 71 CPX patients followed in South-West France (n = 26) and in French Polynesia (n = 45), and who all received sodium thiosulfate (25 g thrice weekly for a median of 61 days). RESULTS: Characteristics at presentation significantly differed between metropolitan and Polynesian French patients. Polynesians were less frequently on regular dialysis at the onset of CPX, had a higher incidence of diabetes mellitus and obesity, more disturbances of calcium-phosphorus metabolism, and received vitamin K antagonists less frequently than patients from South-West France. Despite intensive management, the 1-year mortality rate was 66% and median time to death was 200 days (IQR, 40; 514). The number of body areas involved (i.e., three: OR 2.70 [1.09; 6.65], p = 0.031; four: OR 8.79 [1.54; 50.29], p = 0.015) was the only predictive factor for death, whereas application of topical cerium nitrate-silver sulfadiazine was protective (OR 0.44 [0.20; 0.99], p = 0.046). Surgical debridement, hyperbaric oxygenation therapy, and geographical origin were not associated with overall outcomes. CONCLUSIONS: Cerium nitrate may lead to vascular decalcification and chelation of reactive oxygen species, and prevent infection. Cerium nitrate-silver sulfadiazine was associated with better outcomes and should be tested in a prospective comparative trial in CPX patients.

Cardiac Rhythm Disturbances in Hemodialysis Patients: Early Detection Using an Implantable Loop Recorder and Correlation With Biological and Dialysis Parameters.

OBJECTIVES: The aim of this study was to identify using implantable loop recorder (ILR) monitoring the mechanisms leading to sudden death (SD) in patients undergoing hemodialysis (HD). BACKGROUND: SD accounts for 11% to 25% of death in HD patients. METHODS: Continuous rhythm monitoring was performed using the remote monitoring capability of the ILR device in patients undergoing HD at 8 centers. Clinical, biological, and technical HD parameters were recorded and analyzed. RESULTS: Seventy-one patients (mean age 65 ± 9 years, 73% men) were included. Left ventricular ejection fraction was <50% in 16%. Twelve patients (17%) had histories of atrial fibrillation or flutter at inclusion. During a mean follow-up period of 21.3 ± 6.9 months, 16 patients died (14% patient-years), 7 (44%) of cardiovascular causes. Four SDs occurred, with progressive bradycardia followed by asystole. The incidence of patients presenting with significant conduction disorder and with ventricular arrhythmia was 14% and 9% patient-years, respectively. In multivariate survival frailty analyses, a higher risk for conduction disorder was associated with plasma potassium >5.0 mmol/l, bicarbonate <22 mmol/l, hemoglobin >11.5 g/dl, pre-HD systolic blood pressure >140 mm Hg, the longer interdialytic period, history of coronary artery disease, previous other arrhythmias, and diabetes mellitus. A higher risk for ventricular arrhythmia was associated with potassium <4.0 mmol/l, no antiarrhythmic drugs, and previous other arrhythmias. With ILR monitoring, de novo atrial fibrillation or flutter was diagnosed in 14 patients (20%). CONCLUSIONS: ILR may be considered in HD patients prone to significant conduction disorders, ventricular arrhythmia, or atrial fibrillation or flutter to allow early identification and initiation of adequate treatment. Therapeutic strategies reducing serum potassium variability could decrease the rate of SD in these patients. (Implantable Loop Recorder in Hemodialysis Patients [RYTHMODIAL]; NCT01252823).

Treatment tolerance and patient-reported outcomes favor online hemodiafiltration compared to high-flux hemodialysis in the elderly.

Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and ß2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly.

Transonic, thermodilution, or ionic dialysance to manage vascular access: which method is best?

Regularly monitoring blood flow through a vascular access (Qa) can predict a dysfunction and dramatically reduce the number of thromboses. The aim of our study was to compare two integrated access flow devices, thermodilution (Qa-BTM: BTM(®), Fresenius Medical Care, Bad Homburg, Germany) and ionic dialysance (Qa-ID: OCM(®), Fresenius Medical Care, Bad Homburg, Germany), with the "gold standard" saline dilution (Qa-T: Transonic(®), Systems Inc., Ithaca, NY, USA). Measurements were performed sequentially and were repeated in the first 90 minutes of a single dialysis session in 24 long-term hemodialysis patients with a vascular access. Bland-Altman, linear regression (r(2)), and intraclass correlation coefficients (ICC) assessed reproducibility, correlations, and concordance between the techniques. Average access flow for Qa-T was 1549 (± 844) mL/minute, Qa-BTM was 1530 (± 856) mL/minute (P = NS), and Qa-ID was 1619 (± 1085) mL/minute (P = NS). Respectively, ICC, (r(2)), and bias were 0.99, (0.98), and -19 mL/minute for Qa-BTM, and 0.75, (0.65), and +69 mL/minute for Qa-ID. The limits of agreement were -287 to +250 mL/minute for Qa-BTM and -1647 to +1785 mL/minute for Qa-ID. Reproducibility of thermodilution and ionic dialysance, expressed as relative differences, was not significantly different from saline dilution. Recirculation, measured by saline dilution, was 0% (0-4%), the same as the 0% measured by thermodilution, with correct placement of bloodlines and corrected for cardiopulmonary recirculation. The integrated access flow measurement devices, thermodilution and ionic dialysance, are reasonable alternatives to using saline dilution to measure Qa: Thermodilution showed better precision and correlation. They are reliable, make monitoring of vascular access easier, incur no extra costs, and use no additional consumables.