Hemodiafiltration with endogenous reinfusion for uremic toxin removal in patients undergoing maintenance hemodialysis: a pilot study.

OBJECTIVE: To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance hemodialysis (MHD). METHODS: Patients who have been on MHD for a period of at least 3 months were enrolled. Each subject underwent one HFR and one hemodiafiltration (HDF) treatment. Blood samples were collected before and after a single HFR or HDF treatment to test uremic toxin levels and to calculate clearance rate. The primary efficacy endpoint was to compare uremic toxin levels of indoxyl sulfate (IS), λ-free light chains (λFLC), and ß2-microglobulin (ß2-MG) before and after HFR treatment. Secondary efficacy endpoints was to compare the levels of urea, interleukin-6 (IL-6), P-cresol, chitinase-3-like protein 1 (YKL-40), leptin (LEP), hippuric acid (HPA), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), fibroblast growth factor 23 (FGF23) before and after HFR treatment. The study also undertook a comparative analysis of uremic toxin clearance between a single HFR and HDF treatment. Meanwhile, the lever of serum albumin and branched-chain amino acids before and after a single HFR or HDF treatment were compared. In terms of safety, the study was meticulous in recording vital signs and the incidence of adverse events throughout its duration. RESULTS: The study enrolled 20 patients. After a single HFR treatment, levels of IS, λFLC, ß2-MG, IL-6, P-cresol, YKL-40, LEP, HPA, TMAO, ADMA, TNF-α, and FGF23 significantly decreased (p < 0.001 for all). The clearance rates of λFLC, ß2-MG, IL-6, LEP, and TNF-α were significantly higher in HFR compared to HDF (p values: 0.036, 0.042, 0.041, 0.019, and 0.036, respectively). Compared with pre-HFR and post-HFR treatment, levels of serum albumin, valine, and isoleucine showed no significant difference (p > 0.05), while post-HDF, levels of serum albumin significantly decreased (p = 0.000). CONCLUSION: HFR treatment effectively eliminates uremic toxins from the bloodstream of patients undergoing MHD, especially protein-bound toxins and large middle-molecule toxins. Additionally, it retains essential physiological compounds like albumin and branched-chain amino acids, underscoring its commendable safety profile.

Clinical Efficacy and Long-term Prognosis of High Flux Hemodialysis Combined with Different Frequency Hemodiafiltration in the Treatment of Middle-Aged and Elderly Patients with Uremia.

INTRODUCTION: To analyze the clinical efficacy and long-term prognosis of high flux hemodialysis (HFHD) combined with different frequency hemodiafiltration (HDF) in uremic patients. METHODS: 86 middle-aged and elderly patients with uremia were divided into the HF group (HFHD combined with high-frequency HDF) and the LF group (HFHD combined with low-frequency HDF). The changes between the two groups in various indicators after 12 months of dialysis and the survival rate at 5 years of follow-up were compared. We used SPSS 25.0 software for data analysis. RESULTS: The differences of the levels of serum albumin, hemoglobin and transferrin in HF Group was significantly higher than LF Group before and after treatment (P < .05). The differences of the levels and clearance rate of calcium, phosphorus, parathyroid hormone, ß2-microglobulin and cysteine protease inhibitor C in the patients' blood after dialysis were significantly higher in HF Group than in LF Group (P < .05). The all-cause mortality rate, new cardiovascular event rate, new cerebrovascular event rate, and new infection event rate of HF Group were significantly lower than those of LFHD group, respectively (P < .05). The LF Group had a significantly higher risk of all-cause mortality events, new cardiovascular cerebrovascular and infectious events than the HF Group (P < .05). CONCLUSION: 1 week/time HDF combined with HFHD can more effectively eliminate the vascular related toxins in middle-aged and elderly patients with uremia, improve their nutritional status, treatment effect, and long-term prognosis.  DOI: 10.52547/ijkd.7864.

Acute myeloma kidney and SARS-COV2 infection with dialysis need: never say never - a case report.

BACKGROUND: Older individuals with multiple comorbidities and especially patients with multiple myeloma are at higher risk of contracting SARS-CoV-2. When patients with multiple myeloma (MM) are also affected by SARS-CoV-2 the time to start immunosuppressants is still a clinical dilemma especially when urgent hemodialysis is required for acute kidney injury (AKI). CASE PRESENTATION: We present a case of an 80-year-old woman who was diagnosed with AKI in MM. The patient began hemodiafiltration (HDF) with free light chain removal combined with bortezomib and dexamethasone. The reduction of free light chains concurrently was obtained by means of HDF using poly ester polymer alloy (PEPA) high-flux filter: 2 PEPA filters were used in series during each 4-h length HDF session. A total of 11 sessions was carried out. The hospitalization was complicated with acute respiratory failure caused by SARS-CoV-2 pneumonia successfully treated with both pharmacotherapy and respiratory support. Once the respiratory status stabilized MM treatment was resumed. The patient was discharged in stable condition after 3 months of hospitalization. The follow up showed significant improvement of the residual renal function which allowed interruption of hemodialysis (HD). CONCLUSIONS: The complexity of patients affected by MM, AKI, and SARS-CoV-2 should not discourage the attending physicians to offer the adequate treatment. The cooperation of different specialists can lead to a positive outcome in those complicated cases.

The high-volume haemodiafiltration vs high-flux haemodialysis registry trial (H4RT): a multi-centre, unblinded, randomised, parallel-group, superiority study to compare the effectiveness and cost-effectiveness of high-volume haemodiafiltration and high-flux haemodialysis in people with kidney failure on maintenance dialysis using linkage to routine healthcare databases for outcomes.

BACKGROUND: More than a third of the 65,000 people living with kidney failure in the UK attend a dialysis unit 2-5 times a week to have their blood cleaned for 3-5 h. In haemodialysis (HD), toxins are removed by diffusion, which can be enhanced using a high-flux dialyser. This can be augmented with convection, as occurs in haemodiafiltration (HDF), and improved outcomes have been reported in people who are able to achieve high volumes of convection. This study compares the clinical- and cost-effectiveness of high-volume HDF compared with high-flux HD in the treatment of kidney failure. METHODS: This is a UK-based, multi-centre, non-blinded randomised controlled trial. Adult patients already receiving HD or HDF will be randomised 1:1 to high-volume HDF (aiming for 21+ L of substitution fluid adjusted for body surface area) or high-flux HD. Exclusion criteria include lack of capacity to consent, life expectancy less than 3 months, on HD/HDF for less than 4 weeks, planned living kidney donor transplant or home dialysis scheduled within 3 months, prior intolerance of HDF and not suitable for high-volume HDF for other clinical reasons. The primary outcome is a composite of non-cancer mortality or hospital admission with a cardiovascular event or infection during follow-up (minimum 32 months, maximum 91 months) determined from routine data. Secondary outcomes include all-cause mortality, cardiovascular- and infection-related morbidity and mortality, health-related quality of life, cost-effectiveness and environmental impact. Baseline data will be collected by research personnel on-site. Follow-up data will be collected by linkage to routine healthcare databases - Hospital Episode Statistics, Civil Registration, Public Health England and the UK Renal Registry (UKRR) in England, and equivalent databases in Scotland and Wales, as necessary - and centrally administered patient-completed questionnaires. In addition, research personnel on-site will monitor for adverse events and collect data on adherence to the protocol (monthly during recruitment and quarterly during follow-up). DISCUSSION: This study will provide evidence of the effectiveness and cost-effectiveness of HD as compared to HDF for adults with kidney failure in-centre HD or HDF. It will inform management for this patient group in the UK and internationally. TRIAL REGISTRATION: ISRCTN10997319 . Registered on 10 October 2017.

Comparative efficacy between hemodialysis using super high-flux dialyzer with hemoperfusion and high-volume postdilution online hemodiafiltration in removing protein bound and middle molecule uremic toxins: A cross-over randomized controlled trial.

BACKGROUND: Hemodialysis (HD) using super high-flux dialyzer (HD + SHF) comparably removed uremic toxins to high-volume postdilution online hemodiafiltration (olHDF). Integration of hemoperfusion (HP) to HD + SHF (HD + SHF + HP) might provide superior uremic toxin removing capability to high-volume postdilution olHDF. METHOD: The present study was conducted in thrice-a-week HD patients to compare the efficacy in removing indoxyl sulfate (IS), beta-2 microglobulin (ß2 M), and urea between high-volume postdilution ol-HDF and HD + SHF + HP, comprising HD + SHF as the main treatment plus HD + SHF + HP 1/week in the first 4 weeks and 1/2 weeks in the second 4 weeks. RESULTS: Ten prevalent HD patients with blood flow rate (BFR) above 400 ml/min were randomized into two sequences of 8-week treatment periods of HD + SHF + HP and later high-volume postdilution olHDF or vice versa. When compared with high-volume postdilution olHDF (convective volume of 26.02 ± 1.8 L/session), HD + SHF + HP provided comparable values of percentage reduction ratio of IS (52.0 ± 11.7 vs. 56.3 ± 7.5%, p = 0.14) and ß2 M (83.7 ± 4.9 vs. 84.0 ± 4.3%, p = 0.37) and slightly lower urea reduction ratio. Despite greater dialysate albumin loss (p = 0.008), there was no significant change in serum albumin level in HD + SHF + HP group. CONCLUSIONS: HD + SHF + HP could not provide superior efficacy in removing uremic toxins to high-volume postdilution olHDF. The use of low BFR of 200 ml/min during the first 2 h of HD + SHF + HP session, according to the instruction of manufacturer, might impair the efficacy of the HD + SHF part in removing uremic toxins.

Management of acute kidney injury in frail patients with biopsy-proven cast nephropathy: a combined approach with chemotherapy plus Supra-hemodiafiltration with post-adsorption endogenous reinfusion.

BACKGROUND: Patients with multiple myeloma often have kidney involvement with acute kidney injury which is frequently due to cast nephropathy. Hemodiafiltration with endogenous reinfusion (HFR) allows removal from the circulation of significant amounts of free light chains (FLCs) responsible for tubular damage. METHODS: Between 2014 and 2018, 13 patients affected by multiple myeloma (64% λ chain and 36% k), including 10 cases with biopsy-proven cast nephropathy, were treated with this technique. Each patient had high free light chains levels at diagnosis: median 8586 mg/l for λ and 4200 mg/l for k, and stage III acute kidney injury (median serum creatinine 7.5 mg/dl). We initially performed daily HFR-Supra sessions and then modulated them based on renal response (mean 10 sessions/patient). At the same time, the patients also received various chemotherapy regimens, depending on their hematological criteria. RESULTS: Forty-six percent of patients showed at least partial renal function recovery within the third month, thus allowing dialysis discontinuation; 38% remained on dialysis. Two patients died. The mean reduction rate of free light chains at the end of the HFR-Supra cycle was 85% (k) and 40% (λ), respectively. Serum albumin remained stable during the whole treatment. DISCUSSION: In our experience, the synergistic effect of chemotherapy and HFR-Supra led to a recovery of renal function in 6 out of 13 patients presenting with severe dialysis-requiring acute kidney injury. HFR-Supra allowed stable albumin levels, with high free light chains removal rate, at a relatively low costs.

Citrate high volume on-line hemodiafiltration modulates serum Interleukin-6 and Klotho levels: the multicenter randomized controlled study "Hephaestus".

BACKGROUND: Studies addressing the anti-inflammatory properties of citrate dialysate enrolled patients in both hemodialysis (HD) and hemodiafiltration (HDF), the latter not adjusted for adequate convective exchange. This is a potential source of confounding in that HDF itself has anti-inflammatory effects regardless of the buffer, and optimal clinical outcomes are related to the amount of convection. METHODS: To distinguish the merits of the buffer from those of convection, we performed a 6-month, prospective, randomized, crossover AB-BA study. Comparisons were made during the 3-month study period of on-line HDF with standard dialysate containing three mmol of acetic acid (OL-HDFst) and the 3-month of OL-HDF with dialysate containing one mmol of citric acid (OL-HDFcit). Primary outcome measure of the study was interleukin-6 (IL-6). Klotho, high sensitivity C-reactive protein (hsCRP), fetuin and routine biochemical parameters were also analyzed. RESULTS: We analyzed 47 patients (mean age 64 years, range 27-84 years) enrolled in 10 participating Nephrology Units. Convective volumes were around 25 L/session with 90 percent of sessions > 20 L and ß2-microglobulin reduction rate 76% in both HDFs. Baseline median IL-6 values in OL-HDFst were 5.6 pg/ml (25:75 interquartile range IQR 2.9:10.6) and in OL-HDFcit 6.6 pg/ml (IQR 3.4:11.4 pg/ml). The difference was not statistically significant (p 0.88). IL-6 values were lower during OL-HDFcit than during OL-HDFst, both when analyzed as the median difference of overall IL-6 values (p 0.02) and as the median of pairwise differences between the baseline and the 3-month time points (p 0.03). The overall hsCRP values too, were lower during OL-HDFcit than during OL-HDFst (p 0.01). Klotho levels showed a time effect (p 0.02) and the increase was significant only during OL-HDFcit (p 0.01). CONCLUSIONS: Citrate buffer modulated IL-6, hsCRP and Klotho levels during high volume OL-HDF. These results are not attributable to differences in the dialysis technology that was applied and may suggest a potential biological effect of citrate on CKD-associated inflammatory state. ClinicalTrials.gov identifier NCT02863016.

Dialysis patients who smoke are more hypertensive, more fluid overloaded and take more antihypertensive medications than nonsmokers.

Background: Smoking remains a powerful risk factor for death in end-stage renal disease (ESRD) and so is the presence of fluid overload. The relationship between smoking, blood pressure (BP) control and volume overload is insufficiently explored in patients on maintenance dialysis.Methods: This is a retrospective cross-sectional cohort study, utilizing existing patients' data generated during routine ESRD care, including bimonthly protocol bioimpedance fluid assessment of the volume status.Results: We analyzed the data of 63 prevalent patients receiving thrice weekly maintenance hemodiafiltration treatments at one rural dialysis unit in Hungary. The cohort's mean ± SD age was 61.5 ± 15.3 years; 65% male, 38% diabetic, with a mean arterial blood pressure (MAP) 99.5 ± 16.8 mmHg and Charlson score 3.79 ± 2.04. Of these, 38 patients were nonsmokers and 25 smokers. The nonsmokers' MAP was 94.3 ± 14.0 versus smokers' 105.9 ± 18.9 mmHg (p: .002); nonsmokers took an average 0.73 ± 0.92 antihypertensive medications vs. 1.73 ± 1.21 for smokers (p: .0001). The distribution of taking more antihypertensive medications is skewed toward a higher number among the smokers (2x5 chi square p: .004). By bioimpedance spectroscopy, nonsmokers had an average 10.93 ± 7.65 percent overhydration (OH) over the extracellular space compared to 17.63 ± 8.98 in smokers (p: .005).Conclusions: Smoking may be a significant mediator of not only BP but also of chronic fluid overload in ESRD patents. Additional, larger studies are needed to explore the mechanistic link between smoking and volume overload.

Differences and Effects of Metabolic Fate of Individual Amino Acid Loss in High-Efficiency Hemodialysis and Hemodiafiltration.

OBJECTIVE: The objective of the study was to quantify the loss and arterial blood concentration of the three main classes of amino acids (AAs)-nonessential amino acids (NEAAs), essential amino acids (EAAs), and branched-chain amino acids-as resulting from high-efficiency hemodialysis (HED) and hemodiafiltration (HDF). We moreover aimed to identify the different fates and metabolic effects manifested in patients undergoing hemodialysis and the consequences on body composition and influence of nutritional decline into protein energy wasting. DESIGN AND METHODS: Identical dialysis monitors, membranes, and dialysate/infusate were used to ensure consistency. Ten patients were recruited and randomized to receive treatment with on-line modern HED and HDF. Arterial plasma concentrations of individual AAs were compared in healthy volunteers and patients undergoing hemodialysis, and AA levels outflowing from the dialyzer were evaluated. Baseline AA plasma levels of patients undergoing hemodialysis were compared with findings obtained 1 year later. RESULTS: A severe loss of AA with HED/HDF was confirmed: a marked loss of total AAs (5 g/session) was detected, corresponding to more than 65% of all AAs. With regard to individual AAs, glutamine displayed a consistent increase (+150%), whereas all other AAs decreased after 12 months of HD/HDF. Only a few AAs, such as proline, cysteine, and histidine maintained normal levels. The most severe metabolic consequences may result from losses of EAAs such as valine, leucine, and histidine and from NEAAs including proline, cysteine, and glutamic acid eliciting the onset of hypercatabolism threatening muscle mass loss. CONCLUSION: Dialysis losses, together with the effect of chronic uremia, resulted in a reduction of fundamental EAAs and NEAAs, which progressively led our patients after 12 months to a deterioration of lean mass toward sarcopenia. Therefore, the reintroduction of a correctly balanced AA supplementation in patients undergoing HD to prevent or halt decline of hypercatabolism into cachexia is recommended.

Ultrafiltration Rate Effects Declines in Residual Kidney Function in Hemodialysis Patients.

BACKGROUND: High ultrafiltration rate (UFR) has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of UFR on decline of residual kidney function (RKF) has not been elucidated among patients receiving conventional HD. METHODS: We performed a retrospective cohort study of 7,753 patients who initiated conventional HD from 2007 to 2011 and survived the first year of dialysis with baseline UFR and renal urea clearance (KRU) data at baseline and 1 year (5th patient-quarter). The primary exposure was average UFR at the 1st patient-quarter from dialysis initiation (<4, 4 to <6, 6 to <9, 9 to <13, and ≥13 mL/h/kg). Decline in RKF was defined as the percent change in KRU and decline in urine output during the first year after initiation of dialysis. We used a logistic regression model for rapid decline in RKF and a linear regression model for change in urine volume. RESULTS: In our HD cohort, mean baseline UFR was 7.0 ± 3.1 mL/h/kg, and median (interquartile range) baseline KRU was 3.5 (2.1-5.3) mL/min/1.73 m2. There was a graded association between UFR and a rapid decline in RKF; the expanded case mix-adjusted ORs and 95% CIs were 1.21 (1.04-1.40), 1.34 (1.16-1.55), 1.73 (1.46-2.04), and 1.93 (1.48-2.52) for baseline UFR 4 to <6, 6 to <9, 9 to <13, and ≥13  mL/h/kg, respectively (reference: <4 mL/h/kg). KRU trajectories showed a greater KRU decline over time in higher UFR categories. Higher UFR was also associated with a greater decline in urine output after 1 year. CONCLUSION: Higher UFR was associated with a rapid decline in RKF among conventional HD patients. Further clinical trials are needed to elucidate a causal effect of UFR on RKF among HD patients.

Albumin losses during hemodiafiltration: all dialyzers are not created equal - a case report.

BACKGROUND: Online hemodiafiltration (OL-HDF) is associated with better removal of both small and middle molecules and might improve survival compared to conventional hemodialysis (HD). Nevertheless, hemodiafiltration (HDF) can lead to an increase in albumin loss across the dialyzer, especially with high permeability membrane and high convective volume (CV). We present the case of a patient treated by OL-HDF who developed severe hypoalbuminemia resulting from massive albumin loss into dialysate. CASE PRESENTATION: A 71-year-old woman with ESRD started renal replacement therapy in December 2016. She was treated by high volume post-dilution OL-HDF, 4 h, 3 times per week. The dialyzer was the Phylther HF20SD (a 2.0m2 heat sterilized high flux (HF) polyphenylene membrane from Bellco). At the initiation of dialysis, the serum albumin was 4.0 g/dl. During the following months, the patient developed severe hypoalbuminemia. The lowest value observed was 2.26 g/dl in July 2017. Diagnostic workup excluded nephrotic syndrome, hepatic failure and malabsorption. The patient was shifted from OL-HDF to standard HF HD, keeping the same dialyzer and dialysis schedule. During the following months, we observed a progressive correction of the hypoalbuminemia (3.82 g/dl at last follow-up). To precise the impact of the epuration technique on the albumin losses in this patient, we measured the amount of albumin in dialysate during one session with the Phylther HF20SD on OL-HDF and one session with the same filter but on standard HD. The CV was 29.0 l for the HDF session. The total albumin losses were 23.6 g on OL-HDF and 4.6 g on HD. CONCLUSION: OL-HDF can lead to significant albumin loss into the dialysate, especially with high permeability membrane and high CV. When prescribing post-dilutional OL-HDF, the choice of the dialyzer membrane should be made with caution. Users of the steam sterilized polyphenylene membrane, the Phylther SD, should be informed of the risk of large albumin loss with this membrane during post-dilution OL-HDF.

High-permeability alternatives to current dialyzers performing both high-flux hemodialysis and postdilution online hemodiafiltration.

Most high-flux dialyzers can be used in both hemodialysis (HD) and online hemodiafiltration (OL-HDF). However, some of these dialyzers have higher permeability and should not be prescribed for OL-HDF to avoid high albumin losses. The aim of this study was to compare the safety and efficacy of a currently used dialyzer in HD and OL-HDF with those of several other high permeability dialyzers which should only be used in HD. A prospective, single-center study was carried out in 21 patients. Each patient underwent 5 dialysis sessions with routine dialysis parameters: 2 sessions with Helixone (HD and postdilution OL-HDF) and 1 session each with steam sterilized polyphenylene, polymethylmethacrylate (PMMA), and medium cut-off (MCO) dialyzers in HD treatment. The removal ratios (RR) of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. A proportional part of the dialysate was collected to quantify the loss of various solutes, including albumin. Urea and creatinine RRs with the Helixone-HDF and MCO dialyzers were higher than with the other 3 dialyzers in HD. The ß2 -microglobulin, myoglobin and prolactin RRs with Helixone-HDF treatment were significantly higher than those obtained with all 4 dialyzers in HD treatment. The ß2 -microglobulin value obtained with the MCO dialyzer was also higher than that obtained with the other 3 dialyzers in HD treatment. The myoglobin RR with MCO was higher than those obtained with Helixone and PMMA in HD treatment. The prolactin RR with Helixone-HD was significantly lower than those obtained in the other 4 study sessions. The α1 -microglobulin and α1 - acid glycoprotein RRs with Helixone-HDF were significantly higher than those obtained with Helixone and PMMA in HD treatment. The albumin loss varied from 0.54 g with Helixone-HD to 3.3 g with polyphenylene. The global removal score values ((UreaRR + ß2 -microglobulinRR + myoglobinRR + prolactinRR + α1 -microglobulinRR + α1 -acid glycoproteinRR - albuminRR )/6) were 43.7% with Helixone-HD, 47.7% with PMMA, 54% with polyphenylene, 54.8% with MCO and 59.6% with Helixone-HDF, with significant differences. In conclusion, this study confirms the superiority of OL-HDF over HD with the high-flux dialyzers that allow both treatments. Although new dialyzers with high permeability can only be used in HD, they are in an intermediate position and some are very close to OL-HDF.

The effect of high-flux hemodialysis and post-dilution hemodiafiltration on platelet closure time in patients with end stage renal disease.

INTRODUCTION: We aimed to compare prospectively the effect of high-flux hemodialysis and post-dilution hemodiafiltration on platelets. METHODS: Twenty-two hemodialysis patients were treated with one high-flux hemodialysis and one post-dilution hemodiafiltration procedure. PFA-100 closure times (collagen/epinephrine-CEPI and collagen/adenosine diphosphate-CADP) were measured before and after the procedure, as well as platelet count, hemoglobin, hematocrit, and red blood cell count. All pre-dialysis and post-dialysis samples were taken from the afferent line. FINDINGS: The platelet count after vs. before hemodialysis did not change significantly (229.3 ± 55.0 x109 /L vs. 233.6 ± 55.8 × 109 /L; P = 0.269), but was significantly lower after post-dilution hemodiafiltration (215.5 ± 51.7 × 109 /L vs. 245.3 ± 59.9 × 109 /L; P < 0.0001). CEPI after vs. before hemodialysis was not significantly prolonged (192.9 ± 60.8 s vs. 173.4 ± 52.5 s; P = 0.147), and the same applied to CADP (143.6 ± 40.3 s vs. 142.6 ± 38.4 s; P = 0.897). CEPI after vs. before post-dilution hemodiafiltration was significantly prolonged (268.3 ± 41.3 s vs. 176.4 ± 54.0 s; P < 0.0001) as was CADP (221.0 ± 53.9 s vs.133.9 ± 31.1 s; P < 0.0001). DISCUSSION: Only after post-dilution hemodiafiltration, we found a lower platelet count and prolonged platelet closure times.

A single dialysis session of hemodiafiltration with sorbent-regenerated endogenous ultrafiltrate reinfusion (HFR) removes hepcidin more efficiently than bicarbonate hemodialysis: a new approach to containing hepcidin burden in dialysis patients?

BACKGROUND: Most hemodialysis patients have high Hepcidin-25 levels, which may be involved in the pathogenesis of several uremic complications related to an altered iron biology. The hemodialysis procedure itself can influence Hepcidin-25 levels by removing Hepcidin-25 and maybe stimulating its production due to a pro-inflammatory effect. METHODS: To assess the relationship between dialysis-related inflammation and intradialysis changes in Hepcidin-25, we performed a crossover trial in 28 hemodialysis patients to compare the effects on serum levels of Hepcidin-25 and inflammatory markers activated during dialysis [Tumor Necrosis Factor-α (TNF-α), Interleukin-6, C-reactive protein (CRP), Pentraxin-3] of a single dialysis session using a technique capable of reducing inflammation, HFR (Hemo Filtrate Reinfusion: a hemodiafiltration system combining convection, diffusion and adsorption) or bicarbonate-dialysis using either the same low-flux membrane as in the diffusion stage of HFR (LFBD) or a high-flux membrane (HFBD). RESULTS: HFR achieved a greater reduction in Hepcidin-25 levels than both LFBD [-72% (95% CI: -11 to -133), p = 0.022] and HFBD [-137% (95% CI: -2 to -272), p = 0.047], conceivably due to both a greater removal (because of its convective/adsorptive component) and a lower inflammation-related Hepcidin-25 production. HFR also led to a greater decrease in TNF-α than LFBD [-277% (95% CI: -59 to -494), p = 0.014], while the two methods induced similar changes in Interleukin-6, CRP and Pentraxin-3 levels. CONCLUSIONS: Our findings suggest that a single bicarbonate-dialysis session can upregulate Hepcidin-25 synthesis and that HFR can fully overcome this effect, enabling a greater Hepcidin-25 removal during dialysis. Adequately-designed studies are needed, however, to establish whether the beneficial effect of HFR emerging from our study could reduce Hepcidin-25 (and TNF-α) burden and improve clinically-relevant outcomes. TRIAL REGISTRATION: ISRCTN15957905.

Variables affecting darbepoetin resistance index in hemodialysis patients.

Erythropoietin resistance index calculation has been used as a tool to evaluate anemia response to erythropoietin therapy. Very little has been reported in its use when using darbepoetin and factors influencing in Arab patients. Darbepoetin resistance index (DRI) was calculated in all our patients using darbepoetin. This was correlated to demographic, clinical, and laboratory parameters. Of the 250 patients, 40.4% were diabetic, 71.1% on hemodialysis, and 28.6% on hemodiafiltration), 23.9% with PermCaths (PC), and 76.1 % with arteriovenous fistula (AVF). The mean DRI was 10.96 ± 12.9 I. Females had 45% higher DRI than males (P = 0.005), and patients with PC had a 66% higher DRI than those with AVF (P = 0.029). Patients with Vitamin D level below the 50th percentile had 55.9% higher DRI than those above it (P = 0.05). DRI was negatively correlated with age (P = 0.018), dialysis vintage (P = 0.039), interdialytic weight gain P = 0.007), Vitamin D level, and serum albumin (P = 0.005) and positively correlate with parathyroid hormone (PTH) level (P = 0.000). No impact was seen by the mode of dialysis, being diabetic, using anti-hypertensive therapy, body mass index, Kt/V, serum iron, total iron binding capacity, transferrin saturation, ferritin, C-reactive protein, Ca, or P. DRI in our Arab patients was comparable to erythropoietin resistance indices reported in other communities. Higher DRI was observed in females, PC users, lower serum albumin, lower Vitamin D, and shorter dialysis vintage. A negative correlation existed between DRI and age, dialysis vintage, interdialytic weight, and serum albumin and a positive correlation with PTH level.

A Randomized, Single-Blind, Crossover Trial of Recovery Time in High-Flux Hemodialysis and Hemodiafiltration.

BACKGROUND: The choice between hemodiafiltration (HDF) or high-flux hemodialysis (HD) to treat end-stage kidney disease remains a matter of debate. The duration of recovery time after treatment has been associated with mortality, affects quality of life, and may therefore be important in informing patient choice. We aimed to establish whether recovery time is influenced by treatment with HDF or HD. STUDY DESIGN: Randomized patient-blinded crossover trial. SETTINGS & PARTICIPANTS: 100 patients with end-stage kidney disease were enrolled from 2 satellite dialysis units in Glasgow, United Kingdom. INTERVENTION: 8 weeks of HD followed by 8 weeks of online postdilution HDF or vice versa. OUTCOMES: Posttreatment recovery time, symptomatic hypotension events, dialysis circuit clotting events, and biochemical parameters. MEASUREMENTS: Patient-reported recovery time in minutes, incidence of adverse events during treatments, hematology and biochemistry results, quality-of-life questionnaire. RESULTS: There was no overall difference in recovery time between treatments (medians for HDF vs HD of 47.5 [IQR, 0-240] vs 30 [IQR, 0-210] minutes, respectively; P=0.9). During HDF treatment, there were significant increases in rates of symptomatic hypotension (8.0% in HDF vs 5.3% in HD; relative risk [RR], 1.52; 95% CI, 1.2-1.9; P<0.001) and intradialytic tendency to clotting (1.8% in HDF vs 0.7% in HD; RR, 2.7; 95% CI, 1.5-5.0; P=0.002). Serum albumin level was significantly lower during HDF (3.2 vs 3.3g/dL; P<0.001). Health-related quality-of-life scores were equivalent. LIMITATIONS: Single center; mean achieved HDF convection volume, 20.6L. CONCLUSIONS: Patients blinded to whether they were receiving HD or HDF in a randomized controlled crossover study reported similar posttreatment recovery times and health-related quality-of-life scores.

Biocompatibility of Hemodiafilters.

BACKGROUND: Biocompatibility and the efficiency of solute removal are important considerations in blood purification therapy. Improvement of biocompatibility is expected to lead to the prevention of dialysis-related complications (e.g. amyloidosis, arteriosclerosis, and malnutrition) and to the delay of disease progression by alleviating microinflammation. SUMMARY: The biocompatibility of dialyzers is greatly influenced by the interaction between blood and the treatment materials, in which the chemical and physical characteristics of membrane materials play important roles. In hemodiafiltration (HDF), treatment characteristics such as dilution modes are also considered to greatly affect this interaction between blood and materials. Studies have reported that the levels of C-reactive protein are decreased in patients receiving HDF. Thus, the improvement of biocompatibility is an important factor in HDF. Key Messages: To improve the biocompatibility of HDF, it is essential to improve the biocompatibility of hemodiafilters. This article outlines the importance of biocompatibility and related factors in HDF.

Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study.

Hemodiafiltration with endogenous reinfusion (HFR) after ultrafiltrate passage through a resin cartridge combines adsorption, convection, and diffusion. Our prospective single-center crossover study compared HFR and online-hemodiafiltration (OLHDF) effects on two uremic toxins and 13 inflammatory, endothelial status, or oxidative stress markers. After an 8-week run-in period of high-flux hemodialysis, 17 eligible stable dialysis patients (median age 65 years, 10 male) without overt clinical inflammation were scheduled for four 8-week periods in the sequence: HFR/OLHDF/HFR/OLHDF. Relative to OLHDF, HFR was associated with greater indoxyl sulfate removal and lesser abnormalities in all other study variables, namely circulating interleukin-6, tumor necrosis factor-alpha, proportions of activated proinflammatory (CD14+CD16+, CD14++CD16+) monocytes, endothelial progenitor cells, apoptotic endothelial microparticles, vascular endothelial growth factor, vascular cellular adhesion molecule, angiopoietins 2 and 1, annexin V, and superoxide dismutase. Differences were significant (P < 0.05) in median values of 13/15 variables. Study period comparisons were generally consistent with dialysis technique comparisons, as were data from the subgroup completing all study periods (n = 9). Our investigation provides hypothesis-generating results suggesting that compared with OLHDF, HFR improves protein-bound toxin removal, inflammatory and endothelial status, and oxidative stress.

Feasibility of intermittent back-filtrate infusion hemodiafiltration to reduce intradialytic hypotension in patients with cardiovascular instability: a pilot study.

BACKGROUND: Intradialytic hypotension (IDH) is one of the major problems in performing safe hemodialysis (HD). As blood volume depletion by fluid removal is a major cause of hypotension, careful regulation of blood volume change is fundamental. This study examined the effect of intermittent back-filtrate infusion hemodiafiltration (I-HDF), which modifies infusion and ultrafiltration pattern. METHODS: Purified on-line quality dialysate was intermittently infused by back filtration through the dialysis membrane with a programmed dialysis machine. A bolus of 200 ml of dialysate was infused at 30 min intervals. The volume infused was offset by increasing the fluid removal over the next 30 min by an equivalent amount. Seventy-seven hypotension-prone patients with over 20-mmHg reduction of systolic blood pressure during dialysis or intervention-requirement of more than once a week were included in the crossover study of 4 weeks duration for each modality. In a total of 1632 sessions, the frequency of interventions, the blood pressure, and the pulse rate were documented. RESULTS: During I-HDF, interventions for symptomatic hypotension were reduced significantly from 4.5 to 3.0 (per person-month, median) and intradialytic systolic blood pressure was 4 mmHg higher on average. The heart rate was lower during I-HDF than HD in the later session. Older patients and those with greater interdialytic weight gain responded to I-HDF. CONCLUSIONS: I-HDF could reduce interventions for IDH. It is accompanied with the increased intradialytic blood pressure and the less tachycardia, suggesting less sympathetic stimulation occurs. Thus, I-HDF could be beneficial for some hypotension-prone patients. UMIN REGISTRATION NUMBER: 000013816.

Microcirculatory alterations during continuous renal replacement therapy in ICU: A novel view on the 'dialysis trauma' concept.

OBJECTIVE: The purpose of this study was to evaluate microcirculation over 24 h renal replacement therapy (CRRT) in critically ill patients. METHODS: We conducted a single-center, prospective, observational study, measuring microcirculation parameters, monitored by near infrared spectroscopy (NIRS) before hemodiafiltration onset (H0), and at six (H6) and 24 h (H24) during CRRT in critically ill patients. Serum Cystatin C (sCysC) and soluble (s)E-selectin levels were measured at the same time points. Twenty-eight patients [19 men (68%)] were included in the study. RESULTS: Tissue oxygen saturation (StO2, %) [76.5 ± 12.5 (H0) vs 75 ± 11 (H6) vs 70 ± 16 (H24), p = 0.04], reperfusion rate, indicating endothelial function (EF, %/sec) [2.25 ± 1.44 (H0) vs 2.1 ± 1.8 (H6) vs 1.6 ± 1.4 (H24), p = 0.02] and sCysC (mg/L) [2.7 ± 0.8 (H0) vs 2.2 ± 0.6 (H6) vs 1.8 ± 0.8 (H24), p < 0.0001] significantly decreased within the 24 h CRRT. Change of EF positively correlated with changes of sCysC within 24 h CRRT (r = 0.464, p = 0.013) while in patients with diabetes the change of StO2 correlated with dose (r = − 0.8, p = 0.01). No correlation existed between hemoglobin and temperature changes with the deteriorated microcirculation indices. sE-Selectin levels in serum were elevated; no difference was established over the 24 h CRRT period. A strong correlation existed between the sE-Selectin concentration change at H6 and H24 and the mean arterial pressure change in the same period (r = 0.77, p < 0.001). CONCLUSIONS: During the first 24 h of CRRT implementation in critically ill patients, deterioration of microcirculation parameters was noted. Microcirculatory alterations correlated with sCysC changes and with dose in patients with diabetes.