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Background: Intermittent infusion hemodiafiltration is a recently developed convective method of renal replacement therapy using cyclic back-filtration infusion. Quick and regular infusion prevents intradialytic hypotension. However, the optimal dose of bolus dialysate infusion required to stabilize blood pressure has not been reported. Here, we investigated the relationship between the dose of bolus dialysate infusion and blood pressure., Summary: A total of 77 patients on maintenance hemodialysis were enrolled in this study. Dialysate was infused rapidly by backward filtration at a rate of 150 mL/min at 30-min intervals using an automated dialysis machine. The effects with two bolus infusion volumes (100 and 200 mL) were compared, each for an observation period of 2 weeks. Systolic blood pressure (SBP) was measured at the start and at the end of each dialysis session, and the highest SBP and lowest SBP measurements were also recorded. Patients were divided according to dry weight into a <52 kg group and a ≥52 kg group, and various parameters were compared between the 100 and 200 mL bolus infusion volumes in each group. Among patients in the <52 kg group, SBP did not vary at any of the time points. However, for patients in the ≥52 kg group, SBP at the end of treatment was significantly lower in the 100-mL group than in the 200-mL group (141 ± 20 vs. 144 ± 21 mm Hg, p = 0.041), and the minimum SBP was also lower in the 100-mL group than in the 200-mL group (127 ± 17 vs. 131 ± 18 mm Hg, p = 0.010). Key Messages: Among patients with a dry weight of ≥52 kg, blood pressure was more stable when a bolus fluid volume of 200 mL was used, compared with a volume of 100 mL. However, for patients with a dry weight of <52 kg, the significance of the difference in bolus fluid volumes disappeared. Thus, the replacement fluid volume might be better determined based on the patient's dry weight., Trial Registration: UMIN 000028145, Registered July 10, 2017., (© 2019 S. Karger AG, Basel.)

Background: Intradialytic hypotension (IDH) is a major challenge to safely performing haemodialysis. Blood volume depletion due to fluid removal is a major cause of hypotension, so more emphasis should be placed on finding alternative modalities to traditional constant rate ultrafiltration., Summary: Intermittent back-filtrate infusion haemodiafiltration (I-HDF) utilises purified online quality dialysate with an automated dialysis machine. A bolus of 200 mL of dialysate is repetitively infused at 30-min intervals. A pilot study with 68 hypotension-prone patients revealed that I-HDF can reduce the frequency of IDH interventions, particularly in elderly patients and patients with large interdialytic weight gain (IDWG). This was typically accompanied by an increase in intradialytic blood pressure and decreased tachycardia in the latter half of the session, suggesting reduced sympathetic stimulation during I-HDF. Protective mechanisms involved in the pathophysiology of IDH could be explained in part by the findings obtained in this pilot study. Intermittent increases in blood pressure during I-HDF may prevent venous pooling (i.e., the DeJager-Krogh phenomenon), and reduced sympathetic stimulation may maintain a physiological state less likely to induce the cardio-vagal reflex (i.e., the Bezold-Jarisch reflex). The plasma refilling rate (PRR), evaluated as the refilling fraction (RF), is unexpectedly smaller in I-HDF. However, in patients who respond, the RF is well achieved, which suggests that adequate PRR is the central physiology for preventing IDH. Patients for whom I-HDF is effective are characteristically relatively elderly and show increased IDWG. Blood pressure increment and reduced sympathetic activation in I-HDF may be a mechanism for prevention of IDH. Key Messages: Evaluating relative changes in blood volume during I-HDF will provide a new perspective for exploring appropriate ultrafiltration modification that circumvents IDH., (© 2019 S. Karger AG, Basel.)

Background: The extracorporeal removal of mediators is a rescue strategy for septic shock patients, which is still under investigation. Several techniques are available: coupled plasma filtration and adsorption (CPFA) combines plasma processing with renal replacement therapy., Methods: The study aimed to elucidate the role of both timing of initiation and intensity of treatment on the outcome, for which we retrospectively studied 52 patients. We collected the overall pre-CPFA time interval, starting from the first episode of hypotension in the wards and the volume of processed plasma (Vp), which we used as a proxy for intensity of treatment., Results: Timing of initiation did not significantly differ between survivors and non-survivors (25 vs. 27 h), while the Vp did (0.25 vs. 0.17 L/kg/session, p < 0.05). The significance of Vp was confirmed by a multiple logistic regression model., Conclusion: Our study confirms that intensity of CPFA, but not its timing of initiation, correlates with survival of septic shock patients., (© 2018 S. Karger AG, Basel.)

Aims: This study aimed to assess risk factors of intradialytic hypotension (IDH) and the association of prognosis and IDH among maintenance hemodialysis (MHD) patients., Methods: Among 293 patients, 117 were identified with IDH (more than 4 hypotensive events during 3 months). The association between IDH and survival was evaluated., Results: The incidence of IDH was 39.9%. Age, ultrafiltration rate, N-terminal pro-B-type natriuretic peptide (NT-proBNP), albumin, β2-microglobulin (β2MG), and aortic root inside diameter (AoRD) were independently associated with IDH. During the 5-year follow-up, 84 patients died with a mortality rate 5.2 per 100 person-year. IDH-prone patients had a higher all-cause mortality rate. IDH and left ventricular mass index were independent risk factors for death (HR 1.655, 95% CI 1.061-2.580; HR 1.008, 95% CI 1.001-1.016)., Conclusion: IDH is an independent risk factor for long-term mortality in MHD patients. Patients with older age, high ultrafiltration rate, high level of serum NT-proBNP and β2MG, hypoalbuminemia, and shorter AoRD are at high risk of IDH., (© 2018 S. Karger AG, Basel.)

Aims: High cut-off (HCO) continuous veno-venous hemodialysis (CVVHD) was compared to high-flux membrane (HFM) continuous veno-venous hemodiafiltration (CVVHDF) in intensive care unit (ICU) acute kidney injury (AKI) in terms of efficiency, hemodynamic tolerance, medium-sized molecules removal, albumin loss, and inflammatory system activation., Methods: In a prospective cross-over randomized study, 10 AKI patients underwent successively HCO (Ultraflux EmiC2: β2-microglobulin [β2M] sieving coefficient [SC]: 0.9) CVVHD and HFM (Ultraflux AV1000S: β2M SC: 0.65) -CVVHDF., Results: Over the 20 sessions, hypotensive and febrile episodes, reduction rates of urea, creatinine, and β2M were similar in both modalities. Though dialysis dose was higher with CVVHDF (36 ± 4 vs. 21 ± 6 mL/Kg/h), urea, creatinine, and β2M instantaneous and plasmatic clearances did not differ except for urea at 12 h. Protein loss, superoxide anion production, cytokines, and growth factors variations were also comparable., Conclusion: HCO CVVHD is well tolerated and is as effective as HFM CVVHDF in clearance of solutes and removal of β2M. It induces neither protein loss nor overproduction of superoxide anion. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=489082., (© 2018 S. Karger AG, Basel.)

Background/aims: To evaluate the balance between arginine-vasopressin (AVP) and apelin during hemodialysis and its role in hypotension onset and in the inflammation status., Methods: We enrolled 50 patients chronically treated with hemodialysis. We assessed plasmatic osmolality, AVP, apelin, mean blood pressure (BP), high-sensitivity C-reactive protein (hsCRP) and β(2)-microglobulin., Results: Apelin rises during dialytic treatment (from 0.68 ± 0.34 to 1.89 ± 0.56 pg/ml, p < 0.0001), while plasmatic osmolality (from 325 ± 4.54 to 311 ± 1.20 mosm/kg H(2)O, p < 0.0001), AVP (from 4.28 ± 1.12 to 2.48 ± 0.50 pg/ml, p < 0.0001) and mean BP (from 124 ± 6 to 110 ± 7 mm Hg, p < 0.0001) decrease. At multivariate regression with respect to apelin, only mean BP remains (r = -0.95, p < 0.0001). We also correlated the AVP/apelin ratio with BP. Moreover, apelin is inversely related to hsCRP (r = -0.79, p < 0.0001)., Conclusions: The AVP/apelin balance changes with plasmatic osmolality variations induced by hemodialytic sessions and could represent a physiopathological marker of arterial hypo- and hypertension. Finally, apelin appears inversely related to inflammation markers., (Copyright © 2012 S. Karger AG, Basel.)

Background and Aim: Leukocytapheresis (LCAP) is an extracorporeal leukocyte removal therapy that removes immunocompetent leukocytes from the peripheral blood. Nafamostat mesilate (NM) is the most commonly used anticoagulant for LCAP due to various benefits associated with its use, such as a reduced likelihood of bleeding and minimization of adverse reactions caused by contact between blood and the LCAP device. However, adverse reactions have also been reported with NM administration. We reviewed the safety of anticoagulants other than NM, from the perspective of bradykinin production and the consequent drop in blood pressure during treatment., Methods: For each of 10 patients with ulcerative colitis, we used four types of anticoagulants sequentially [NM (30-50 mg), heparin, low-molecular-weight heparin (LMWH) and NM (1 mg), and LMWH] for LCAP. We then examined the changes in the blood bradykinin concentrations from the perspective of adverse reactions during LCAP., Results: The bradykinin production levels from Cellsorba EX varied, depending on the type of anticoagulant used. NM alone (30-50 mg) or LMWH + NM (1 mg) inhibited bradykinin production, whereas heparin alone or LMWH alone significantly accelerated it. However, an excessive fall of blood pressure was not noted in any of the cases. Use of LMWH alone was frequently associated with pressure elevations in the column., Conclusions: Given the significant benefits of minimized adverse reactions of LCAP and of continuation of LCAP, we suggest that an appropriate selection of the anticoagulant(s) may allow safer execution of LCAP., (Copyright 2007 S. Karger AG, Basel.)

Carnitine is a metabolic cofactor which is essential for normal fatty acid metabolism. Patients with chronic kidney disease on dialysis have been shown both to suffer from disordered fatty acid metabolism and to have a significant deficiency in plasma and tissue carnitine. Aberrant fatty acid metabolism has been associated with a number of cellular abnormalities such as increased mitochondrial permeability (a promoter of apoptosis), insulin resistance, and enhanced generation of free radicals. These cellular abnormalities have, in turn, been correlated with pathological clinical conditions common in dialysis patients including cardiomyopathy with attendant hypotension and resistance to the therapeutic effect of recombinant human erythropoietin (EPO). In 1999, the Food and Drug Administration approved levocarnitine injection for the prevention and treatment of carnitine deficiency in patients on dialysis based on documentation of free plasma carnitine levels in dialysis patients similar to other serious carnitine deficiency states for which treatment was required. Data analysis performed by expert panels convened by both the American Association of Kidney Patients and, subsequently, the National Kidney Foundation recommended a trial of levocarnitine therapy for specific subsets of dialysis patients including those with EPO resistance, dialysis-related hypotension, cardiomyopathy and muscle weakness. In 2003, the Centers for Medicare and Medicaid services convened a Medical Advisory Committee which established reimbursement on a national level for carnitine-deficient dialysis patients who had either dialysis-related hypotension or EPO resistance. Recently, a correlation between reductions in hospitalization rates of dialysis patients receiving levocarnitine therapy has been demonstrated in a large retrospective study. Despite data-based recommendations and national reimbursement, only a small minority of dialysis patients have been prescribed a therapeutic trial of levocarnitine. Whereas the reasons for the reluctance of nephrologists to prescribe this therapeutic trial are unclear, possible explanations include a lack of appreciation of the pivotal role played by carnitine in cellular metabolism and the strength of evidence for a substantial deficiency of carnitine in dialysis patients, an underestimation of the prognostic import of EPO resistance and dialysis-related hypotension, inadequate dissemination of the clinical trial data supporting the use of levocarnitine in dialysis patients, and the heterogeneous clinical response of dialysis patients to levocarnitine therapy. Difficulties in documenting both initial eligibility and evidence of improvement as a result of therapy may also be a contributing factor. This paper discusses the biological role of carnitine and its particular relevance to dialysis patients. Clinical trial data concerning an effect of therapy on EPO resistance and dialysis-related hypotension are summarized along with a discussion of the logic behind the use of levocarnitine in dialysis. Finally, the difficulties posed by a reimbursement policy based on clinical as opposed to laboratory endpoints and a heterogeneous response to therapy are addressed., (Copyright 2006 S. Karger AG, Basel.)

The database for carnitine supplements in dialysis includes no large-scale randomized trials and no registered trials. Medical practitioners prefer to make treatment decisions based on the outcome of randomized clinical trials, with appropriate controls. Furthermore, registered trials provide a further level of integrity, since trial registration avoids publication bias by ensuring that all outcomes are reported, including trials that are not completed. Positive effects reported from carnitine administration in dialysis patients include decreased erythropoietin dose, increased hematocrit, less intradialytic hypotension, and less fatigue. The evidence for carnitine effectiveness is limited to trials that are mostly open-label and that include no more than a total of 1,000 patients. An analysis of recent carnitine administrations to patients in a large dialysis practice database indicates no overall change in hemoglobin or erythropoietin dose following 6 months of carnitine administration. As outcomes of controlled trials with appropriate power to examine for the benefits of carnitine are not yet available, the dialysis practitioner cannot justify the administration of carnitine., (Copyright 2006 S. Karger AG, Basel.)

Background: To clarify the effects of post-treatment with direct hemoperfusion using a CTR column on the mortality and inflammatory responses to endotoxin-induced shock in rats., Methods: Thirty-six male rats were randomly assigned to 1 of 3 groups (n = 12/group): the endotoxemic group, receiving intravenous Escherichia coli endotoxin (15 mg/kg over 2 min); the control column group, treated without CTR for 120 min at 2 h after endotoxin injection, and CTR-post-treatment group, treated with CTR for 120 min at 2 h after endotoxin injection. Hemodynamics, arterial blood gases, and mortality were recorded for the 8-hour observation period, and plasma cytokine concentrations were measured every 4 h., Results: The mortality rates were 83, 83 and 33% for the endotoxemic, control column, and CTR post-treatment groups, respectively. The increases in IL-6 concentrations were less for the CTR post-treatment group than the other 2 groups., Conclusion: The present study shows that CTR post-treatment inhibited hypotension and elevations in IL-6 concentrations, reducing the mortality rate of rats with endotoxin-induced shock.

Background: Intradialytic hypotension (IH) has been long recognized as a common complication during hemodialysis (HD) therapy, but few studies have discussed IH-related myocardial injuries and the long-term prognosis of patients prone to IH (HP)., Methods: We conducted a prospective study on 70 chronic HD patients who had no recent occurrences of acute coronary artery syndrome. The patients were divided into two groups: HP (n = 29) and IH resistant (n = 41). While they underwent HD therapy, we monitored and evaluated their baseline data and their patterns of cardiac troponin I (cTnI), creatine kinase, and creatine kinase isoenzyme MB., Results: The HP and IH-resistant patients had similar baseline cardiac marker levels that did not seem to be influenced by uneventful HD therapy. However, if during HD therapy the patients experienced an episode of symptomatic IH, they were found to have significant increases in the creatine kinase MB activity at the end of HD therapy and in the cTnI levels 44 h following HD. After 12 months, the HP patients with baseline cTnI levels > or =0.20 ng/ml were more likely to experience cardiovascular events or death (adjusted odds ratio 15.0, p = 0.012)., Conclusions: Our study showed that, after symptomatic IH episodes, the HP patients were more likely to suffer occult myocardial injuries. HP patients who have high cTnI levels should be closely monitored for cardiovascular diseases.