A case of hyperviscosity syndrome associated with Waldenström macroglobulinemia treated with membrane plasma exchange without predilution.

A 75-year-old man with blurred vision and nasal bleeding was diagnosed with hyperviscosity syndrome and central retinal vein occlusion secondary to Waldenström macroglobulinemia. Serum total protein and IgM levels were undetectable. Because of the severe symptoms, we determined that immediate plasma-exchange treatment was required to decrease the blood viscosity. The initial plasma exchange was performed using the membrane isolation method with a predilution standby. A saline predilution replacement was prepared to decrease the total membrane pressure (TMP); however, the predilution protocol was not used because the planned treatment volume could be achieved without increasing the TMP. After two consecutive days of membrane plasma exchange, all serum biochemical tests were measurable, and IgM was below 4000 mg/dL. After chemotherapy, his visual symptoms improved, and he was discharged. Since it is difficult to assess the risk of elevated TMP prior to initial plasma exchange, membrane plasma exchange with a predilution standby may be a useful strategy for initial plasma exchange for hyperviscosity syndrome in terms of safety and efficiency.

Comparison of citrate dialysate in pre- and post-dilution online hemodiafiltration: effect on clot formation and adequacy of dialysis in hemodialysis patients.

BACKGROUND: Citrate dialysate (CD) has been successfully used in conventional hemodialysis and continuous renal replacement therapy; however, no study has compared pre- and post-dilution online hemodiafiltration (oL-HDF). Therefore, we aimed to investigate the efficacy of citrate anticoagulation for oL-HDF and the metabolic changes and quality of life of patients on hemodialysis treated using both modes. METHOD: Eight dialysis patients were treated with CD containing 0.8 mmol of citric acid for 4 weeks in each phase. Visual clotting scores were investigated as the primary endpoints. Adequacy of dialysis, laboratory parameters, and quality of life were measured as secondary objectives. RESULTS: The mean clotting scores in the pre-dilution mode were significantly lower than those in the post-dilution mode and in all phases except the heparin-free phase (p < 0.001 in the baseline phase, p = 0.001 in phase 1, and p = 0.023 in phase 2). The values of Kt/V in both modalities were comparable except during the baseline phase, in which the values of pre-dilution were significantly greater than post-dilution (2.36 ± 0.52/week vs. 1.87 ± 0.33/week;95% CI -0.81 to -0.19, p = 0.002). The patient's quality of life regarding their physical activity level was significantly higher in the post-dilution mode than in the pre-dilution mode at baseline and in phase 1 (p = 0.014 and 0.004 at baseline and in phase 1, respectively). Metabolic changes did not differ between the two modes. CONCLUSION: Citrate dialysate decreased or prevented anticoagulation in both pre- and post-dilution modes of oL-HDF without significant side effects and had comparable adequacy of dialysis.

Comparison of the pre-dilution and post-dilution methods for online hemodiafiltration.

Online hemodiafiltration (OL-HDF) is a treatment modality using diffusion and ultrafiltration. There are two types of dilution methods in OL-HDF: pre-dilution, which is commonly provided in Japan, and post-dilution, which is commonly provided in Europe. The optimal OL-HDF method for individual patients is not well studied. In this study, we compared the clinical symptoms, laboratory data, spent dialysate, and adverse events of pre- and post-dilution OL-HDF. We conducted a prospective study of 20 patients who underwent OL-HDF between January 1, 2019 and October 30, 2019. Their clinical symptoms and dialysis efficacy were evaluated. All patients underwent OL-HDF every 3 months in the following sequence: first pre-dilution, post-dilution, and second pre-dilution. We evaluated 18 patients for the clinical study and 6 for the spent dialysate study. No significant differences in spent dialysates regarding small and large solutes, blood pressure, recovery time, and clinical symptoms were observed between the pre- and post-dilution methods. However, the serum α1-microglobulin level in post-dilution OL-HDF was lower than that in pre-dilution OL-HDF (first pre-dilution: 124.8 ± 14.3 mg/L; post-dilution: 116.6 ± 13.9 mg/L; second pre-dilution: 125.8 ± 13.0 mg/L; first pre-dilution vs. post-dilution, post-dilution vs. second pre-dilution, and first pre-dilution vs. second pre-dilution: p = 0.001, p < 0.001, and p = 1.000, respectively). The most common adverse event was an increase in transmembrane pressure in the post-dilution period. Compared to pre-dilution, the post-dilution method decreased the α1-microglobulin level; however, there were no significant differences in clinical symptoms or laboratory data.

A systematic examination of anti-drug antibody titer estimation: Applied recommendations.

Biologic drugs (therapeutic proteins or peptides) have become one of the most important therapeutic modalities over the past few decades. Drug-induced immunogenicity is a significant concern as it may affect safety, tolerability, and efficacy. With more sensitive and drug-tolerant screening assays in use today, reliable estimation of anti-drug-antibody (ADA) titer has become more important for understanding clinically relevant ADA levels. Titer is commonly defined as the dilution factor resulting in an assay signal equal to a pre-specified cut point factor. Given its influence on the resulting titer precision, the choice of a titer cut point factor warrants careful consideration. In this paper, we discuss the theoretical dilution model, investigate how titer variability depends on the cut point factor and propose a standardized cut point factor to increase precision of titer estimates. Additionally, we demonstrate that non-linear regression-based titer estimation provides both improved precision and implementation efficiency relative to commonly used estimation approaches.

Experience with pre-diluted plasma exchange therapy for hyperviscosity syndrome.

INTRODUCTION: Plasma exchange therapy (PE) is useful for patients with primary macroglobulinemia and multiple myeloma who present with hyperviscosity syndrome. However, hyperviscous blood may coagulate in the circuit during treatment, and in that case necessitate discontinuation of the treatment. This time, we report that we were able to prevent coagulation in the circuit by adding some ideas during the membrane separation method. METHODS: Physiological saline is injected in front of the plasma separation membrane to pre-dilute the blood, followed by filtration through the plasma separation membrane. RESULTS: As a result of pre-diluting with physiological saline to reduce the viscosity entering the separation membrane, it was possible to process the planned target amount. CONCLUSION: In patients with hyperviscosity syndrome who showed intracircuit coagulation during plasma exchange therapy, devising a predilution method should be considered as one of the ways to continue treatment.

Removal performance of pre- and post-dilution online hemodiafiltration using identical hemodiafilters in the same patients.

Online hemodiafiltration (OHDF) for renal replacement therapy has two modes: pre- (pre-OHDF) and post-dilution OHDF (post-OHDF). To elucidate the precise differences between the two modes, a clinical study was performed using the same polysulfone hemodiafilters in the same patients. Eight patients were treated with ABH™-22PA for 6 weeks: 3 weeks of pre-OHDF (with substitution volumes of 24, 36, and 48 L) and 3 weeks of post-OHDF (6, 8, and 10 L). The reduction ratios of urea, uric acid (UA), creatinine (CRE), inorganic phosphorus (iP), beta-2-microglobulin (ß2-MG), and alpha-1-microglobulin (α1-MG) were evaluated. The removal amounts of ß2-MG, α1-MG, and albumin were also evaluated by analyzing the spent dialysis fluids. The types and numbers of adverse events (AEs) and device malfunctions were recorded. The reduction ratios of urea, UA, CRE, iP, and ß2-MG were comparable among all conditions, while that of α1-MG tended to be slightly higher in post-OHDF than in pre-OHDF. The removal amounts of α1-MG and albumin in pre-OHDF and post-OHDF were significantly greater with the maximum substitution volume than with the minimum volume. However, the selective removal indices, which were obtained by dividing the amount of α1-MG removed by the albumin level, tended to be slightly higher in pre- than in post-OHDF. No device-related AEs or device malfunctions occurred in either mode. No significant differences in inflammatory responses, evaluated by high-sensitivity C-reactive protein and interleukin-6, were observed. This study provides removal performance and safety data regarding the application of ABH-22PA for pre- and post-OHDF.

Convection volume, ß2-microglobulin and α1-microglobulin reduction ratios, and body composition in pre-dilution online haemodiafiltration.

AIM: The effect of convection volume (CV) in patients on pre-dilution online haemodiafiltration (Pre-OL-HDF) was evaluated. METHODS: We conducted a retrospective, cross-sectional study in 126 patients on Pre-OL-HDF. Dialysis conditions, laboratory data, and same day post-dialysis body composition measurements using bioimpedance spectroscopy were assessed. Patients were divided into two groups according to their CV: ≥ median value and < median value. Linear regression analyses for reduction ratios (RRs) of ß2-microglobulin and α1-microglobulin, and body composition, were conducted. RESULTS: Age, dialysis vintage, and CVs of the study patients were 64 ± 12 years, 81 (48-154) months, and 43.2 (38.5-55.9) L/session, respectively. The higher CV (≥ 43 L/session) group (n = 66) had significantly higher RRs of ß2-microglobulin and α1-microglobulin, lean tissue index, body cell mass index, total body water (TBW), extracellular water (ECW), and intracellular water (ICW) compared with the lower CV (< 43 L/session) group (n = 60, p <  .01). Serum albumin and fat tissue index were not significantly different between the groups. CV/ECW, CV/TBW, and CV/ICW but not un-adjusted CV, were significant determinants for ß2-microglobulin and α1-microglobulin RRs (p <  .05). Lean tissue and body cell mass indexes, but not the fat tissue index, showed significant associations with CV, and RRs of ß2-microglobulin and α1-microglobulin (p < kb.05). CONCLUSIONS: Among patients on Pre-OL-HDF, higher values in the lean tissue index and body cell mass index were observed in those with higher CV versus lower CV, and CV adjusted to body water may be useful to prescribe individualized conditions for Pre-OL-HDF.

Continuous intradialytic amino acid infusion from the start of dialysis is better to avoid catabolism under the high-volume pre-dilution on-line HDF.

It was reported that amino acid infusion during hemodialysis is useful for improving nutritional status. The optimal administration method of amino acid infusion under the high-volume pre-dilution on-line HDF (HVPO-HDF) was analyzed in this study. Subjects were 10 patients on maintenance dialysis at our clinic. We performed high-volume pre-dilution on-line HDF. We investigated two methods for administration of Neoamiyu® 200-ml total amino acid (TAA) infusion for patients with renal failure: (1) continuous infusion into the dialysis circuit for 4 h from the start of dialysis to its completion (infusion rate 50 ml/h) and (2) continuous infusion started 1 h before completion of dialysis (infusion rate 200 ml/h), and compared pre- and post-dialysis blood concentrations and leakage of TAA, essential amino acids (EAA), and nonessential amino acids (NEAA) between these methods. Pre-dialysis blood concentrations of amino acids showed no difference between both the groups. Post-dialysis blood concentrations of amino acids were higher in all concentrations were significantly higher with continuous infusion starting 1 h before completion of dialysis. Leakage of amino acids showed no difference between both the groups. The continuous intradialytic amino acid infusion from the start of dialysis is better to avoid catabolism under high-volume pre-dilution on-line HDF.

Comparison of the effects of pre-dilution and post-dilution online hemodiafiltration on the levels of inflammatory markers, lymphocytes, and platelets.

Online hemodiafiltration (OL-HDF) is a blood purification therapy based on diffusion and ultrafiltration and is classified into two types according to the mode of addition of the substitution fluid: pre-dilution OL-HDF (pre-HDF) and post-dilution OL-HDF (post-HDF); we previously reported that pre-HDF is more biocompatible. However, we used lower blood and substitution flow rates in that study and may not have accurately simulated the treatment conditions used in Europe. In this study, we compared the biocompatibilities of the treatment conditions of pre-HDF, commonly used in Japan, and post-HDF, commonly used in Europe, to determine the most biocompatible treatment conditions. We compared the biocompatibilities of pre-HDF and post-HDF using high blood flow rates and high substitution fluid volumes, and also compared the results with those of our previous study. We enrolled six stable patients undergoing maintenance dialysis at our clinic for this study. After the patients underwent hemodialysis (HD), post-HDF, and pre-HDF treatment, the biocompatibilities (based on the serum levels of high-sensitivity C-reactive protein, interleukin-6, pentraxin-3, ß-thromboglobulin, and soluble P-selectin, and the results of the lymphocyte blastogenesis test using phytohemagglutinin and concanavalin A as mitogens) and removal performances (removal performance for urea, creatinine, ß2-microglubulin [MG], and α1-MG, and albumin leakage) were determined. There were no significant differences in the biocompatibility parameters evaluated among the three treatment modes. Post-HDF was associated with significantly higher removal rates of ß2-MG than HD. Post-HDF was associated with significantly higher removal rate of α1-MG, and also significantly higher albumin leakage, than HD and pre-HDF.

Amino acid losses are lower during pre-dilution on-line HDF than HD of the same Kt/V for urea.

In this study, we investigated differences in amino acid losses between HD and pre-dilution on-line HDF with equal Kt/V for urea to determine which modality removes less amino acids from extravascular pools and ensures better nutrition. The subjects were patients receiving pre-dilution on-line HDF (n = 10) or HD (n = 10) at this hospital. Dialysis time was 4 h for all patients. In patients on HD, the blood flow rate was 200 mL/min and the dialysate flow rate was 463 ± 29.3 mL/min. In patients on pre-dilution on-line HDF, the blood flow rate was 240 ± 20 mL/min, the dialysate flow rate was 565.0 ± 42.5 mL/min, and the substitution flow rate (substitution volume) was 252.8 ± 26.4 mL/min (57.0 ± 6.0 L). Kt/V for urea was comparable between patients on HD and patients on pre-dilution on-line HDF (1.46 ± 0.25 vs. 1.46 ± 0.31). Amino acid loss and clear space were evaluated. Patients on pre-dilution on-line HDF lost significantly less glutamine and arginine (p < 0.01 and p = 0.032) and significantly less nonessential amino acids (NEAAs) than patients on HD (p = 0.013). They also had significantly lower clear space of total amino acids (TAAs), NEAAs, essential amino acids (EAAs), and branched-chain amino acids (BCAAs) than patients on HD (Total AA p = 0.019, NEAA p = 0.018, EAA p = 0.024, BCAA p = 0.042). When Kt/V for urea is equal, pre-dilution on-line HDF ensures better nutrition than does HD.

Comparison of Solute Removal Properties Between High-Efficient Dialysis Modalities in Low Blood Flow Rate.

Blood flow (Qb) is one of the dialysis parameters most strongly influencing the performance of dialysis modalities. However, few studies have compared different dialysis modalities in patients with low Qb. We conducted a prospective, single-center study in 21 patients. Each patient underwent four dialysis sessions with routine dialysis parameters: high-flux hemodialysis (HD), predilution hemodiafiltration (pre-HDF), expanded HD (HDx), and postdilution HDF (post-HDF). The removal ratios (RR) of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, free kappa and lambda immunoglobulin light chains (kFLC and λFLC), α1 -acid glycoprotein, and albumin were compared intraindividually. A proportional part of the dialysate was collected to quantify albumin loss. There were no differences in urea and creatinine RRs. The ß2 -microglobulin RR was higher in pre-HDF and post-HDF. Myoglobin and prolactin RRs were higher with HDx and post-HDF. The α1 -microglobulin and α1 -acid glycoprotein RRs were significantly higher with post-HDF than with other treatments, and RRs obtained with HDx were higher than obtained with HD and pre-HDF. Free kFLC and λFLC RRs showed the following results in ascending order: HD, pre-HDF, HDx, and post-HDF, most of them with statistical significance. Albumin loss varied from 0.45 g with HD to 3.5 g with post-HDF. The global removal score values were 41.0 ± 4.8% with HD, 44.0 ± 5.2% with pre-HDF, 49.5 ± 4.6% with HDx, and 54.8 ± 5.3% with post-HDF, with significant differences between all treatment modalities. In conclusion, this study confirms the superiority of post-HDF over high-flux HD, pre-HDF, and HDx in patients with low Qb. HDx was the closest alternative to post-HDF and was clearly superior to HD and pre-HDF. Finally, pre-HDF was also superior to HD. With this Qb, there was a higher risk of underdialysis, both diffusive and convective, especially in patients with a session duration of less than 5 h.

Hemodialysis without anticoagulation: Less clotting in conventional hemodialysis than in predilution hemodiafiltration.

INTRODUCTION: Hemodialysis patients with contraindication to systemic anticoagulation require a heparin-free hemodialysis technique. Among several alternatives to heparin, predilution hemodiafiltration (HDF) is often used, albeit without any confirmation of its effectiveness. METHODS: Patients hospitalized in a nephrology ICU and hemodialysed for stage 5 CKD or AKI and with contraindication to systemic anticoagulation were randomized to either standard HD with a polysulfone membrane, or to predilution HDF with the same membrane. Coagulation activation was evaluated clinically by the need for premature termination and by the measurement of D-dimers. FINDINGS: Two hundred dialysis sessions were performed in 155 patients. Survival curves showed better circuit survival in HD (P = 0.046). In HD, 12% of sessions were interrupted for coagulation versus 23% in predilution HDF (P = 0.04). DISCUSSION: Predilution HDF was associated with more premature clotting than conventional HD without improvement in dialysis duration or performance epuration indices. When aiming for a 4-hour duration session, conventional heparin-free hemodialysis can be safely proposed in most patients with high bleeding risk.

Prevalence of Carnitine Deficiency and Decreased Carnitine Levels in Patients on Hemodialysis.

BACKGROUND: Patients on hemodialysis (HD) are known to be at risk of carnitine deficiency. The aims of this study were to investigate the prevalence of carnitine deficiency in patients on dialysis and to compare the likelihood of a reduction in the serum carnitine level on HD with that on hemodiafiltration (HDF). METHODS: The prevalence of carnitine deficiency, defined as a serum free carnitine level < 20 µmol/L, and that of carnitine insufficiency, defined as an acyl/free carnitine ratio > 0.4, was investigated in 150 patients on dialysis. The reduction rate of serum carnitine was then compared between HD and HDF. RESULTS: The prevalence of carnitine deficiency and that of carnitine insufficiency was 25.3 and 86.7%, respectively. Patients at high risk of carnitine deficiency accounted for 64.7%. Multivariate regression identified an association of duration of dialysis with the free serum carnitine level. The reduction rates of serum free carnitine in HD and HDF were 64 ± 4 and 75 ± 7%, respectively (p < 0.0001). CONCLUSION: The prevalence rates of carnitine deficiency and carnitine insufficiency were high in patients on dialysis. The serum carnitine reduction rate was greater with HDF than with HD.

Predilution On-Line Hemodiafiltration Improves Albumin Redox in Maintenance Hemodialysis Patients.

BACKGROUND/AIM: In this study, we compared the dialysis efficiency, oxidative stress, and nutritional conditions between predilution on-line hemodiafiltration (pre-OL-HDF) and conventional hemodialysis (HD) using a super-flux dialyzer (CHD). METHOD: This was a crossover study of 38 maintenance HD patients. All patients were treated with CHD for the first 4 months (1st CHD period), then were switched to pre-OL-HDF for 4 months (pre-OL-HDF period), and were returned to CHD for the next 4 months (2nd CHD period). RESULTS: We found no significant difference in the removal ratio of small uremic substances or the indices of inflammation or nutritional states between the pre-OL-HDF and CHD periods. However, we found higher removal of ß2 micro-globulin in the pre-OL-HDF period, and the human mercapto-albumin (Alb)/human serum Alb ratio was significantly higher in the pre-OL-HDF period. CONCLUSION: Treatment with pre-OL-HDF enabled enhanced removal of middle molecule uremic toxins and better Alb redox than did CHD.

Restless legs syndrome effectively treated with constant-pressure predilution online hemodiafiltration.

BACKGROUND: We encountered a case of unstable predilution online HDF due to elevated transmembrane pressure (TMP) when performing constant-speed predilution online hemodiafiltration (HDF) as treatment for restless legs syndrome (RLS) in a dialysis patient. We report the effectiveness of incorporating a newly developed constant-pressure predilution online HDF system as a preventive measure against unstable online HDF and frequent adjustment of settings when treating dialysis patients with RLS. CASE PRESENTATION: A 55-year-old man had suffered from RLS and been undergoing constant-speed online HDF with 45 L target predilution and an ABH-21P hemodiafilter. The symptoms of RLS rated 10 on the International Restless Legs Syndrome Rating Scale (IRLS). The α1-microglobulin (α1-MG) removal rate was only 27.8%, so the hemodiafilter was subsequently replaced with a PEPA hemodiafilter. However, episodes of elevated TMP exceeding 250 mmHg occurred frequently after the replacement and were managed by reducing dialysate flow rate. Therefore, we incorporated a constant-pressure predilution online HDF that maintains TMP below 200 mmHg. The amount of replacement was maintained at approximately 43.5 ± 6.98 L and the α1-MG removal rate was 39.5%, with no need to manually reduce the flow rate. The Alb leakage in dialysate waste was 7.9 g. The patient has maintained an IRLS rating of 0 with no RLS symptoms for the past 4 years. CONCLUSIONS: Using the constant-pressure mode enabled achieved the clinical endpoint, namely, resolution of RLS with no need to manually reduce the flow rate.

Predilution online hemodiafiltration is associated with improved survival compared with hemodialysis.

On-line hemodiafiltration is an increasingly common alternative to chronic hemodialysis in some countries, based on the results of randomized controlled trials of post-dilution on-line hemodiafiltration. There are now more than 60,000 patients treated with on-line hemodialfiltration in Japan, over 95% of whom use predilution on-line hemodiafiltration; however, large-scale data on clinical outcomes with this modality are lacking. We created a propensity-matched cohort of 5,000 pairs of patients treated with conventional hemodialysis or predilution on-line hemodiafiltration, using the Japanese Society for Dialysis Therapy Renal Data Registry database from December 31, 2012 to December 31, 2013. One-year all-cause and cardiovascular mortality were compared between the groups. Predilution on-line hemodiafiltration was associated with improved overall survival compared to hemodialysis (hazard ratio for all cause-mortality 0.83, 95% confidence interval 0.705-0.986), with a trend towards improved cardiovascular survival. Among patients treated with predilution on-line hemodiafiltration, those treated with high substitution volumes (≥40.0 L per session) had improved all-cause and cardiovascular survival compared to those treated with low substitution volumes (<40.0 L per session) or those on hemodialysis. The optimal substitution volume associated with improved overall survival was estimated to be 50.5 L [95% confidence interval 39.0-63.5 L]. This observational study suggests that predilution on-line hemodiafiltration, especially with high substitution volumes, may improve all-cause and cardiovascular survival, but randomized controlled trials are needed.

Removal of large middle molecules via haemodialysis with medium cut-off membranes at lower blood flow rates: an observational prospective study.

BACKGROUND: Online haemodiafiltration (OL-HDF) may improve middle molecular clearance in contrast to conventional haemodialysis (HD). However, OL-HDF requires higher convective flows and cannot sufficiently remove large middle molecules. This study evaluated the efficacy of a medium cut-off (MCO) dialyser in removing large middle molecular uraemic toxins and compared it with that of conventional high-flux (HF) dialysers in HD and predilution OL-HDF. METHODS: Six clinically stable HD patients without residual renal function were investigated. Dialyser and treatment efficacies were examined during a single midweek treatment in three consecutive periods: 1) conventional HD using an HF dialyser, 2) OL-HDF using the same HF dialyser, and 3) conventional HD using an MCO dialyser. Treatment efficacy was assessed by calculating the reduction ratio (RR) for ß2-microglobulin (ß2M), myoglobin, κ and λ free light chains (FLCs), and fibroblast growth factor (FGF)-23 and measuring clearance for FLCs. RESULTS: All three treatments showed comparable RRs for urea, phosphate, creatinine, and uric acid. MCO HD showed greater RRs for myoglobin and λFLC than did HF HD and predilution OL-HDF (myoglobin: 63.1 ± 5.3% vs. 43.5 ± 8.9% and 49.8 ± 7.3%; λFLC: 43.2 ± 5.6% vs. 26.8 ± 4.4% and 33.0 ± 9.2%, respectively; P <  0.001). Conversely, predilution OL-HDF showed the greatest RR for ß2M, whereas MCO HD and HF HD showed comparable RRs for ß2M (predilution OL-HDF vs. MCO HD: 80.1 ± 4.9% vs. 72.6 ± 3.8%, P = 0.01). There was no significant difference among MCO HD, HF HD, and predilution OL-HDF in the RRs for κFLC (63.2 ± 6.0%, 53.6 ± 15.5%, and 61.5 ± 7.0%, respectively; P = 0.37), and FGF-23 (55.5 ± 20.3%, 34.6 ± 13.1%, and 35.8 ± 23.2%, respectively; P = 0.13). Notably, MCO HD showed improved clearances for FLCs when compared to HF HD or OL-HDF. CONCLUSIONS: MCO HD showed significantly greater RR of large middle molecules and achieved improved clearance for FLCs than conventional HD and OL-HDF, without the need for large convection volumes or high blood flow rates. This would pose as an advantage for elderly HD patients with poor vascular access and HD patients without access to OL-HDF. TRIAL REGISTRATION: Clinical Research Information Service (CRIS): KCT 0003009. The trial was prospectively registered on the 21 Jul 2018.

Evaluation of pre- and post-dilution continuous veno-venous hemofiltration on leukocyte and platelet function in patients with sepsis.

OBJECTIVE:: We investigated the differences in biocompatibility pre- and post-dilution during continuous veno-venous hemofiltration in patients with sepsis, focusing on leukocyte and platelet function. PATIENTS AND METHODS:: Subjects were 12 patients with septic shock who underwent veno-venous hemofiltration for acute kidney injury between March 2016 and September 2017. The first six patients received pre-dilution veno-venous hemofiltration, and the next six patients received post-dilution veno-venous hemofiltration. The blood flow rate and filtration flow rate for veno-venous hemofiltration using a polysulfone hemofilter were set to 150 and 35 mL/min, respectively. Leukocyte and platelet counts were determined at 0 and 24 h after veno-venous hemofiltration commencement. Serum interleukin-6 and interleukin-10 levels, the induction rates of regulatory T cells, the expression rate of monocyte HLA-DR, neutrophil phagocytic and sterilizing ability, and platelet P-selectin expression rate were determined at 0, 6, and 24 h after veno-venous hemofiltration commencement. RESULTS:: There were no significant differences in patient characteristics between the two groups. Serum interleukin-6 decreased over time during pre- and post-dilution veno-venous hemofiltration. Serum interleukin-10 levels decreased during pre-dilution veno-venous hemofiltration, but remained unchanged during post-dilution veno-venous hemofiltration. The Treg and platelet P-selectin expression rates significantly increased at 24 h compared to 0 h during post-dilution veno-venous hemofiltration. Neutrophil phagocytic ability at 24 h was significantly decreased compared to that at 0 h during post-dilution veno-venous hemofiltration. No significant changes in leukocyte and platelet function were observed during pre-dilution veno-venous hemofiltration. CONCLUSION:: Pre-dilution veno-venous hemofiltration demonstrates superior biocompatibility in terms of decreased leukocyte function and platelet activation in septic shock patients with acute kidney injury.

The Hematocrit Affects the Volume of Plasma Treated With Coupled Plasma Filtration and Adsorption With Predilution.

Coupled plasma filtration and adsorption (CPFA) is an extracorporeal blood purification technique proposed for the treatment of septic-shock. By removing pro- and anti-inflammatory mediators from plasma, CPFA is supposed to have a therapeutic effect on the abnormal inflammatory response seen in this condition. Recently, blood predilution with citrate solution has been adopted to prevent clotting in the CPFA circuit-one of the main problems of the technique. Taking into account the patient's hematocrit, we worked out a formula for the volume of plasma effectively treated by CPFA after predilution. Neglecting this effect, as is commonly done, introduces significant distortions in the estimation of the volume, possibly causing under-treatment. The distortion is stronger when the hematocrit and the predilution fraction are large and weaker when both values shrink. By correctly indicating the daily dose of plasma adsorption received by patients, this formula is essential for assessing the therapeutic efficacy of CPFA and, subsequently, establishing its optimal doses.

Performance evaluation of developed polysulfone membrane hemodiafilters, ABH-F and ABH-P, in post- and pre-dilution hemodiafiltration.

ABH-F and ABH-P have been developed for hemodiafiltration (HDF) therapy. In this study, we evaluated the solute removal characteristics of the hemodiafilters in a bovine blood in vitro study. The hemodiafilters were examined for 120 min at various filtration flow rates (Q F) (31.2-250 mL/min) under a constant blood flow rate of 250 mL/min and constant dialysate flow rates of 500/250 mL/min in pre-dilution HDF (pre-HDF) and post-dilution HDF (post-HDF). Creatinine clearance in pre-HDF was approximately 85% of that in post-HDF because it was removed by molecular diffusion dominantly. The initial clearances of ß2-microglobulin and α1-microglobulin increased with Q F and these values slightly and steeply decreased with time due to membrane fouling. Under a same Q F of 62.5 mL/min, higher clearance values in post-HDF were obtained compared with those in pre-HDF. All clearance values of ABH-P were higher than those of ABH-F under the same Q F. It seems that the ABH-P has a larger pore size of membrane than that in ABH-F. The creatinine and α1-microglobulin clearance values were obtained as highest at post-Q F62.5, the ß2-microglobulin clearance values and transmembrane pressure were obtained as highest at pre-Q F250. Large solute clearances such as α1-microglobulin and albumin decreased with time in all HDF experiments. Time decay of large solute clearance values was observed in the HDF modality that had a higher clearance of the solute at 5 min later after the start of experiment.