Increased Dialysis Efficiency Research Articles

Switching from acetate to citrate dialysate in a central concentrate delivery system for high-volume online hemodiafiltration: a retrospective cohort study

Interest in citrate-based dialysate (Cit-D) is growing due to its benefits, including anticoagulation and dialysis efficacy. However, research on safety and efficiency of Cit-D in high-volume hemodiafiltration (HDF) via central concentrate delivery system (CCDS) is scarce. This study aimed to investigate the safety and efficacy of Cit-D when switching from acetate-based dialysate (Acet-D) in high-volume HDF via CCDS. This is a retrospective analysis of 28 patients who underwent post-dilution online HDF via CCDS, who switched from Acet-D to Cit-D. The study period was divided into 3 periods for analysis: 12 weeks using Acet-D (AD period), the first 12 weeks using Cit-D (CD-1 period), and the second 12 weeks using Cit-D (CD-2 period). We collected the laboratory, dialysis, and safety parameters in each period from electrical medical records. After switching from Acet-D to Cit-D, heparin dosage decreased by 17%, whereas the incidence of complications did not increase. Kt/VBUN and urea reduction ratio increased by 4.6% and 2.1%, respectively. Pre-dialysis beta2-microglobulin concentration decreased after using Cit-D. The corrected calcium levels decreased in the CD-1 period compared to the AD period, but in CD-2, they subsequently increased to levels similar to those observed during the AD period. Symptomatic hypocalcemia did not occur, and there was no significant difference in the incidence of hyperparathyroidism. Endotoxin levels and the bacterial culture of ultrapure dialysate were unremarkable throughout all periods. These results might suggest that Cit-D could potentially offer advantages over Acet-D, such as reducing the heparin dose and increasing dialysis efficiency, in patients undergoing high-volume HDF using CCDS.

#857 How low can we go with dialysate flow? Does that mean we can make nephrology green?

Abstract Background and Aims Green nephrology encompasses all initiatives in kidney care that have a positive impact on the climate and environment. We know that environmental impact of dialysis is particularly high, considering water consumption and disposable waste production during each session. All that suggests a great opportunity where many improvements should be made. To prepare the dialysate 240 liters of water are needed for one four-hour session with a dialysate flow (Qd) set at 500 ml/min. Including additional water needed to rinse and sterilize the system, this gives approximately 500 liters of water used for one hemodialysis. Lower dialysate flow rate is associated with a significant reduction in the amount of water used for the hemodialysis procedure. An increase in Qd from 500 ml/min to 800 ml/min has been recommended to increase dialysis efficiency. It's benefit was not confirmed in in vivo studies which suggested that increasing the dialysate flow rate offers no benefit in terms of delivered Kt/V. Similarly, studies with a Qd of 400 ml/min showed comparable efficiency. If hemodialysis could be performed equally effectively with less dialysate consumption, water could be significantly saved. The aim of this study was to check whether change of dialysate flow from 500 ml/min to 300 ml/min has a significant impact on dialysis adequacy (measured by Kt/V). Method The study was a retrospective analysis. During the COVID19 surge in January 2022 due to administrative issues in a satellite dialysis center the dialysate flow was reduced to 300 ml/min. The center again increased Qd to 500 ml/min in February 2022. We analyzed laboratory data from 3 months before dialysate flow reduction, in the month with reduced Qd to 300 ml/min, and from 3 months thereafter with Qd set at 500 ml/min. Results 26 patients (10 men and 16 women – all dialysis patients from a satellite dialysis center) were enrolled in the study. Two of them died during observation, therefore 24 people were included in final analysis. Their median age was 72 (66-78) years. ANOVA with repeated measures showed lack of differences between three time points in terms of Kt/V (Qd 500 ml/min - 1.285±0.202, Qd 300 ml/min - 1.275±0.192 and Qd 500 ml/min - 1.337±0.199; p=0.093). Change in serum potassium during hemodialysis did not depend on dialysate flow (ΔK Qd 500ml/min - 1.5±0.5 mmol/l, Qd 300 ml//min - 1.7±0.5 mmol/l, Qd 500 ml/min - 1.6±0.4 mmol/l; p=0.197). Serum phosphorus was comparable between three time points (Qd 500 ml/min - 5.99±1.68 mg/l, Qd 300 ml/min - 5.65±1.4mg/l, Qd 500 ml/min - 6.01±1.67 mg/l; p=0.066). Conclusion Reduction in dialysate flow rate to 300 ml/min is safe for the patients and probably does not cause any short-term negative effects. Thus we can achieve the same therapeutic effect saving water consumption. Larger, long-term studies are needed to confirm the efficacy of this approach.

The Effect of Dialysate Flow Rate on Dialysis Efficiency

End-stage renal failure is a debilitating condition with a high level of mortality. One of the most effective approaches for ameliorating these conditions is hemodialysis. It saves hundreds of thousands of patients every year from premature death. Increasing dialysis efficiency is a core proponent of hemodialysis. Accordingly, an increase in dialysis efficiency means that hemodialysis is improved. A number of approaches have been taunted as effective in improving dialysis efficiency. One of these approaches is increasing the dialysate flow rate. The research, however, on the effect of dialysis flow rate on dialysis efficiency is not conclusive because some studies suggest that an increase in dialysis flow rate increases dialysis efficiency, while other researches point out that an increase in Qd has minimal to no impact on dialysis efficiency.

Improved dialysis removal of protein-bound uremic toxins by salvianolic acids

BackgroundIndoxyl sulfate (IS) and p-cresyl sulfate (pCS) are two key protein-bound uremic toxins that accumulate in patients with end-stage renal disease. IS and pCS cannot be efficiently removed by conventional hemodialysis because they are highly bound to proteins. One promising means to optimize the removal of protein-bound uremic toxins involves using binding competitors to liberate uremic toxins from protein-binding partners. PurposeIn this study, we try to identify potential binding competitors that can enhance the dialysis removal of IS and pCS in natural compounds of phytomedicine. MethodsWe employed microdialysis to evaluate whether Danhong injection (DHI) and its salvianolic acids can increase the free fractions of IS and pCS and thus improve their dialysis efficiency in vitro. Furthermore, we confirmed the positive effects of DHI and salvianolic acids in vivo on chronic kidney disease model rats in which IS and pCS had heavily accumulated. ResultsDHI significantly increased the dialysis efficiency of IS and pCS by 99.13% and 142.00% in vitro (10-fold dilution), respectively, and by 135.61% and 272.13% in vivo (4.16 ml/kg). Salvianolic acids including lithospermic acid (LA), salvianolic acid A (SaA), tanshinol (DSS), caffeic acid (CA), salvianolic acid B (SaB), protocatechuic aldehyde (PA) and rosmarinic acid (RA) significantly enhanced the dialysis removal of IS and pCS in a concentration-dependent manner. LA, the best competitor of the tested salvianolic acids, increased dialysis efficiency levels of IS and pCS by 197.23% and 198.31% in vitro (400 μM), respectively, and by 119.55% and 127.56% in vivo (24.69 mg/kg). ConclusionThe removal of protein-bound uremic toxins IS and pCS using DHI or salvianolic acids as protein-bound competitors is superior to previously reported strategies and drugs and may contribute to clinical hemodialysis therapeutic practice.

Insomnia, muscular cramps and pruritus have low intensity in hemodialysis patients with good dialysis efficiency, low inflammation and arteriovenous fistula.

Insomnia, muscular cramps, pruritus and postdialysis recovery time (RT) are quality-of-life parameters that affect hemodialysis (HD) patients physically and mentally. We included 171 end-stage renal disease patients: 115 on high-flux HD and 56 on online hemodiafiltration (HDF). Patients were asked "How long does it take you to recover from a dialysis session?" and they evaluated intensity (absent, mild, medium and severe) of insomnia, muscular cramps and pruritus in the past 4weeks. We sought associations of RT, insomnia, muscular cramps and pruritus with themselves and age, dialysis vintage, sex, body mass index, hemoglobin, albumin, C-reactive protein (CRP), Daugirdas single-pool Kt/V (Kt/V), ultrafiltration volume, blood processed volume and vascular access type. Insomnia absence correlated with muscular cramps absence (p=0.01), arteriovenous fistula (AVF) presence (p=0.02) and lower CRP (p=0.003). Muscular cramps absence associated pruritus absence (p=0.007) and AVF (p=0.001). Absent pruritus patients were younger (p=0.04), had higher Kt/V (p=0.01) and more AVF (p=0.02). Men insomnia was more severe in HD than HDF and albumin related (p=0.007), while CRP was lower in absent pruritus. Women insomnia associated with muscular cramps (p=0.04) and vascular access (p=0.03), as was pruritus (p=0.03). RT had no relations with any parameter. HD patients with AVF have less insomnia, muscular cramps and pruritus. Insomnia is associated with muscular cramps and inflammation. Pruritus is worse in older patients, is diminished with increased dialysis efficiency and is associated with higher CRP in men. There is no difference between HD and HDF patients, except more severe insomnia for HD in men.

MP604INSOMNIA, MUSCULAR CRAMPS AND PRURITUS ARE ABSENT IN HEMODIALYSIS PATIENTS WITH GOOD DIALYSIS EFFICIENCY, LOW INFLAMMATION AND ARTERIOVENOUS FISTULA

Introduction and Aims: Insomnia, muscular cramps, pruritus and recovery time after hemodialysis are still controversial quality of life (QoL) parameters in hemodialysis patients. Methods: This was a single center, prospective, transversal and observational study which included 171 end-stage renal disease patients (age: 59.5±15.2 years and dialysis vintage: 89.7±125.6 months). One hundred fifteen patients were on high-flux hemodialysis (HD) and 56 patients were treated with on-line hemodiafiltration (HDF). Patients were asked “How long does it take you to recover from a dialysis session?” and they evaluated the intensity (absent, mild, medium and severe) of insomnia, muscular cramps and pruritus in the past 4 weeks. We studied associations of postdialysis recovery time, insomnia, muscular cramps and pruritus with themselves and age, dialysis vintage, sex, body mass index, hemoglobin, albumin, C-reactive protein (CRP), Daugirdas single-pool Kt/V (Kt/V), ultrafiltration volume, blood processed volume and vascular access type. Results: Absence of insomnia was significantly associated with absence of muscular cramps (p=0.01) and with dialysis on arteriovenous fistula (AVF) (p=0.01). The absence of muscular cramps was associated with the absence of pruritus (p=0.007) and with AVF (p=0.007). Low albumin level was predictive for severe insomnia (p=0.008) and severe pruritus (p=0.04), while CRP was significantly higher in severe vs. absent insomnia (p=0,002). Severe pruritus was associated with significantly lower Kt/V compared to absent pruritus (p=0.01). Conclusions: HD patients with AVF had less insomnia, muscular cramps and pruritus. Inflammation (low albumin and high CRP levels) was associated with severe insomnia and pruritus. Increased dialysis efficiency improved pruritus. Recovery time after HD had no significantly relations with any studied parameter. There was no difference of studied QoL features between HD and HDF patients.

Peritoneal Dialysis Tailored to Pediatric Needs

Consideration of specific pediatric aspects is essential to achieve adequate peritoneal dialysis (PD) treatment in children. These are first of all the rapid growth, in particular during infancy and puberty, which must be accompanied by a positive calcium balance, and the age dependent changes in body composition. The high total body water content and the high ultrafiltration rates required in anuric infants for adequate nutrition predispose to overshooting convective sodium losses and severe hypotension. Tissue fragility and rapid increases in intraabdominal fat mass predispose to hernia and dialysate leaks. Peritoneal equilibration tests should repeatedly been performed to optimize individual dwell time. Intraperitoneal pressure measurements give an objective measure of intraperitoneal filling, which allow for an optimized dwell volume, that is, increased dialysis efficiency without increasing the risk of hernias, leaks, and retrofiltration. We present the concept of adapted PD, that is, the combination of short dwells with low fill volume to promote ultrafiltration and long dwells with a high fill volume to improve purification within one PD session. The use of PD solutions with low glucose degradation product content is recommended in children, but unfortunately still not feasible in many countries.

Innovation in the Treatment of Uremia: Proceedings from the Cleveland Clinic Workshop: More of the Same: Improving Outcomes Through Intensive Hemodialysis

The typical dialysis patient faces both a poor quality of life and a significantly shortened survival. This is often blamed on "uremia." However, defining the clinical entity of uremia is surprisingly difficult. It represents the clinical sequelae of the effects of retention products, other effects of renal disease, and the effects of other comorbid conditions. The list of retention products that could act as uremic toxins is lengthy, but it would appear that urea itself does not contribute significantly to the uremic state. Larger molecular weight substances are likely the major contributors to the uremic milieu. Regardless of the causes, the uremic state persists in many patients who are reaching their dialysis adequacy targets as defined by urea clearance. This raises the possibility that more intensive hemodialysis could improve patient outcomes. Hemodialysis can be intensified by increasing dialysis efficiency without changing duration or frequency. Alternatively, hemodialysis duration, frequency, or both can be increased. All intensification methods increase small solute removal, but the removal of larger molecular weight retention products depends more upon treatment time. Modalities such as short daily hemodialysis, long intermittent hemodialysis, and quotidian nocturnal hemodialysis have been associated with a variety of clinical improvements, as well as improvements in quality of life and a lower standardized mortality ratio. However, the HEMO study approach of intensifying small solute clearance without significant modifications of the dialysis schedule does not appear to be effective. Future research will help to define the optimal treatment duration and frequency in hemodialysis patients.

Risk Factors for Cardiovascular Calcifications in Non-Diabetic Caucasian Haemodialysis Patients

Background/Aims: Dialysis patients display an increased mortality which is associated with cardiovascular calcifications. Diabetes mellitus and ethnicity are known factors that affect the extent of cardiovascular calcifications. However, most studies have investigated mixed cohorts with diabetics and/or mixed ethnicity. Methods: Cardiovascular calcifications were assessed in non-diabetic Caucasian haemodialysis patients by the semiquantitative Adragao calcification score (X-ray pelvis and hands) and a novel composite calcification score encompassing the Adragao score as well as calcifications detected by X-ray of the fistula arm, echocardiography of heart valves and carotid ultrasound. Results: Using multivariate analysis, age, male gender, dialysis vintage, lower Kt/V, calcium-phosphate product, smoking and high-sensitivity CRP were independent risk factors for cardiovascular calcifications as assessed by the Adragao or the composite score. Pulse wave velocity was independently related to both calcification scores. Body mass index, cholesterol, triglycerides, iPTH and serum levels of fetuin-A and uncarboxylated matrix Gla protein were not associated with cardiovascular calcifications. Conclusions: In our cohort of non-diabetic Caucasian haemodialysis patients, age, male gender, dialysis vintage, smoking, calcium-phosphate product, high-sensitivity CRP and lower Kt/V were independent risk factors for cardiovascular calcifications. Whether lowering the calcium-phosphate product and increasing dialysis efficiency can reduce cardiovascular calcifications in dialysis patients remains to be determined.

Pilot study to assess increased dialysis efficiency in patients with limited blood flow rates due to vascular access problems

In the last few years, the number of hemodialysis patients with inadequate blood flow (Qb) rates has increased due to vascular access problems. To avoid a clinical status of underdialysis, these patients need long-lasting dialysis sessions. However, other factors aimed to optimize the dialysis dose have to be considered. High-efficiency convective therapies, such as online hemodiafiltration (HDF), are claimed to be superior to high-flux hemodialysis (HF-HD) in improving the dialysis efficacy, but treatment efficacy is strongly related to blood flow rate and infusion volumes. Online mid-dilution (HDF-MD) with the Nephros OL-pure MD190 represents a new HDF concept to increase the removal of middle molecules. In a cross-over clinical trial, 8 patients, with Qb eff <300 mL/min, received either online HDF-MD or HF-HD; Qd was 700 mL/min, the time duration was 240 min, and the filtration volume in HDF-MD was 112+/-7 mL/min. No differences were found for Kt/V, urea, and creatinine clearances. Clearance of both small phosphate (P) large beta(2)-microglobulin (beta(2)m), and leptin (L) solutes was significantly greater for MD (P 217+/-32, beta(2)m 85.5+/-10, L 42.6+/-18 mL/min) than for HF-HD (P 178+/-32, beta(2)m 71.9+/-13, L 32.1+/-12 mL/min). The results of this study indicate that HDF remains the best means of providing increased removal of large-molecular weight solutes even in patients with vascular access problems.

Uraemic itching: do polymethylmethacrylate dialysis membranes play a role?

Patients undergoing chronic renal replacement therapy by haemodialysis (HD) suffer from chronic itching, the prevalence of which is very high. Many of the available treatment options are ineffective, but, as it has been shown that Polymethylmethacrylate based dialysis membranes (PMMA) membranes remove a wide range of 'middle molecules' and improve such long-term complications of HD as carpal tunnel syndrome and malnutrition, they may also have an effect on uraemic itching. This prospective study enrolled eight patients undergoing standard HD with low-flux synthetic membranes and suffering from chronic itching. The strength and duration of itching was evaluated by the patients themselves at each study time-point using a visual analogue scale (VAS). After a baseline evaluation, the patients were switched to a PMMA membrane for 6 months during which their pre-dialysis haemoglobin, haematocrit, total protein, albumin, urea, creatinine, phosphate, intact parathyroid hormone (i-PTH), serum bile acid, beta2-microglobulin, C-reactive protein (CRP) levels, and eKt/V were measured, and any general complaints were recorded. The self-assessed VAS itching strength scores decreased by 15% after 1 month, 30% after 2 months, and 55% after 6 months, and itching duration decreased by, respectively, 10, 22 and 44% at the same time; 2 months after the end of the study, both scores had slightly increased. There were no statistically significant differences in the pre-dialysis blood chemistry values or eKt/V at the four study time-points, but beta2-microglobulin levels significantly decreased (P < 0.03); the decrease in CRP levels was not significant (P < 0.06). Furthermore, four patients showed a trend towards a lower incidence of intradialytic hypotension. These findings support the hypothesis that a PMMA dialyser may improve renal itching in ESRD patients. This effect is not mediated by increased dialysis efficiency or an improvement in other biochemical parameters, but we can speculate that ionic substances may be directly or indirectly adsorbed into the polymer composition of BG-U series (PMMA membrane dialyser). We are currently undergoing further studies using a proteomic approach.

Daily Hemodialysis: The Time Has Come? - Pro

IN RECENT YEARS there has been great interest in studying the effect of dialytic dose on patient outcomes. This interest is based on the concept that a greater dialytic dose results in greater toxin removal, which in turn results in improved patient outcomes. Attempts to increase dose delivery in conventional thrice weekly hemodialysis (HD) by increasing dialysis efficiency with higher blood flow rates and high-flux membranes did not result in improved overall survival in the HEMO Study. 1 Eknoyan G. Beck G.J. Cheung A.K. et al. Hemodialysis (HEMO) Study GroupEffect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002; 347: 2010-2019 Crossref PubMed Scopus (1559) Google Scholar This clearly indicated that the currently accepted single-treatment target dose was not just that necessary for dialysis adequacy but is also the optimal affordable by such an intermittent therapy. Thus, interest has turned to the possible effect of increasing dialysis frequency; this interest appears to be growing worldwide. Short-duration, high-efficiency (SDHD) and long-duration, slow daily nocturnal hemodialysis (NHD) regimens are the 2 most common forms in use. Occasionally hybrid or combinations of SDHD and NHD are employed. Most reports describe SDHD and NHD as home-based therapies; SDHD has also been used in dialysis centers.

News and Traditional Indications from Short Daily Dialysis: Different Schemes to Optimized ESF Response

Interest in quotidian (daily) hemodialysis (DHD) seems to be growing. DHD improves quality of life, blood pressure control, and nutrition, and decreases the need of medications, including erythropoiesis stimulating factors (ESF). We evaluate the short daily dialysis (SDHD) efficacy in 14 patients in conventional hemodialysis (HD) (3 weekly sessions/4 h), mean age 52.1 years, range 25–75, 10 males and 4 females, and found that they needed to increase dialysis efficiency by different medical indications: in 11 cases traditional indications – 5 cases with hypertensive myocardiopathy and severe LVH (2 of them with low left ventricle ejection fraction), 2 cases with symptomatic, ischemic cardiopathy 2 patient with big body‐surface area and elevated phosphorus levels, and 2 patients by inadequate dialysis (infradialysis conditioning malnutrition status) secondary to HD with permanent catheter. In one female (25 yr old), SDHD was prescribed to improve cardiac toxicity secondary to chemotherapy for acute promyelocytic leukemia. The index resistance of ESF decreased since the first month, and the Aranesp doses decreased by more than 40%. 1 male (49 years) with nephrogenic fibrosing dermopathy showed skin lesions with osteoblastic transformation. The skin lesions were improving since the first week, obtaining a decrease of the index resistance ESF higher than 60% in the first month. 1 male with symptomatic obstructive hypertrophic myocardiopathy showed improvement of symptoms and quality of life since the first weeks, as well as echocardiograpic signs and improvement in Hb levels and decreasing dose of ESF. The schedule in all of them was 5–6 days/week sessions between 2.15 h and 3 h, depending on body‐surface area. To obtain a weekly Kt/V nearest to 4, HD sessions were realized in the hospital (7 pts) or in satellite unit (7 pts). The time remaining in this schedule was between 1 and 42 months. All the patients showed clinical improvement, subjective and objective, since the first week of start of SDHD. 3 patients could be included in Tx waiting list again. Anemia improved, decreasing index resistance of ESF. In relation with this, the time necessary to improve the response to ESF was different, showing a decrease in the first month higher than 40% in two cases dialyzing with a membrane high‐flux with pore size 100 A, appearing high Hb levels also in a polycystic patient always without ESF. We observed by analyzing the results in 12 stable patients; the patients with high‐flux dialyzers showed better response to ESF. Perhaps it could offer a better clearance of large molecules (inhibitor erythropoiesis factor and high molecular weight toxins) that participate to respond to ESF.Conclusion: Our experience shows new indications for SDHD with very good results. Anemia was improved in relation with SDHD, when synthetic high‐flux membranes and high pore size were used.

Short Daily Dialysis (SDHD) Efficacy : Pilot Multicentric Study with Nine Patients from Madrid

Interest in quotidian (daily) hemodialysis (HD) seems to be growing. Clinical data consistently showed improved quality of life, better control of blood pressure, less need for medications including erythropoietin (EPO) and better nutrition. We evaluate the SDHD efficacy in 9 patients in conventional HD (3 weekly sesions/4 hours), mean age 57,78 years range (33–75), 6 males and 3 females who needed increased dialysis efficiency by different medical indications: 5 cases with hypertensive miocardiopathy and severe LVH, 2 of them with EFLV 26% and 27%. 2 cases with ischemic cardiopathy symptoms, one of them with anger and restless dysnea with a non resvascularizable coronary lesion, and other with cardiac insufficiency episodes requiring hospitalization once a month. 1 patient with big body surface area and elevated phosphorus levels although without control, with conventional three times/week HD. 1 patient indication was made by 12 years on HD with multiple vascular accesses failed needing a Tessio cathéter being into infradialysis regimen for his malnutrition status.The schedule in all of them was 6 days per week sessions between 2.15 hrs till 3 hours depending of body surface area to obtain a weekly kt/v nearest to 4. HD session were realized in the Hospital (4 pts) or in satellite unit (5 pts) due to the characteristics of the patients. The time remaining in this schedule was between 5 months to 2 years and 9 months. All the patients showed clinical improvement, subjective and objective, since the first weeks of starting SDHD. Sleep symptoms were the first to improve. All patients showing good coping with this HD alternative. Blood pressure levels were controlled without need for antihypertensive drugs, although the dry weight increased significantly in all cases. Albumin serum levels increased as nutrition parameter, controlling also the osteodystrophy and phosphorus. In a patient the EFLV was normalized from 6 months (26%–50%) improving in other. Two patients could be included in Tx waiting list. Again, anemia improved and decreasing EPO was required. No vascular access (autologous AVF) malfunction was detected in relation to daily procedure. Conclusion: Our pilot experience shows a clinical and biochemical improvement in the patients and quality of life as well. Prospective studies to demonstrate the financial benefits of these modalities are needed.

Long-Term On-Line Hemodiafiltration Reduces Predialysis Beta-2-Microglobulin Levels in Chronic Hemodialysis Patients

Background: Hemodiafiltration (HDF) is effective in delaying the surgical need for carpal tunnel syndrome in chronic hemodialysis patients, however, predialysis β₂-microglobulin levels were not reduced in most short-term studies. The aim of this study was to assess the effect of long-term and differing frequencies of on-line HDF on serum β₂-microglobulin levels in comparison to high-flux hemodialysis (HD). Methods: One hundred and twelve patients in the Chang Gung Memorial Hospital Dialysis Unit were divided into three groups to receive different frequencies of on-line HDF alternating with high-flux HD. Group 1 was treated once with HDF and twice with high-flux HD per week (n = 21). Group 2 was treated twice with HDF and once with high-flux HD per week (n = 33). Group 3 was treated with HDF three times per week (n = 58). Analysis was performed to compare the serum β₂-microglobulin levels in these groups and to high-flux HD. Results: After receiving HDF for a mean of 7.9 months, group 3 patients had a reduced predialysis β₂-microglobulin level (22.2 ±5.3 vs. 34.8 ±6.3 mg/l, p < 0.001), postdialysis β₂-microglobulin level (6.3 ± 2.0 vs. 13.8 ± 6.8 mg/l, p < 0.001) and an increased β₂-microglobulin reduction rate (76.1 ± 5.6 vs. 61.1 ± 13.3%, p = 0.03) when compared to high-flux HD. A significant improvement in URR (p = 0.0004), Kt/V (p = 0.0002) and TAC urea levels (p = 0.006) but not nPCR (p = 0.122) was found after patients had been treated with on-line HDF. The β₂-microglobulin reduction rate was positively correlated with the overall volume of the replacement solution per session (p < 0.0001). Patients in group 3 had lower predialysis β₂-microglobulin levels than those in group 1 and group 2 (22.2 ± 5.3 vs. 25.2 ± 7.2 vs. 26.0 ± 4.2 mg/l, p = 0.02). Furthermore, an inverse correlation was found between the predialysis β₂-microglobulin level and the duration of HDF, if patients were treated for more than 12 months (p = 0.031). Conclusion: On-line HDF has an increased dialysis efficiency compared to high-flux dialysis. Long-term HDF further reduced predialysis β₂-microglobulin levels, thus, it may provide an improved modality for renal replacement therapy.

Urea Reduction Ratio Considering Urea Rebound

An American National Study shows that survival benefits from higher dialysis doses appear to be present up to a Kt/V level of 1.3 or a urea reduction ratio (URR) of 70%. The effect of increasing dialysis efficiency magnified urea rebound and the error in URR determinations. Several formulas have been developed to calculate URR considering the urea rebound (URRr). Smye and coworkers have proposed a method whereby the equilibrated blood urea nitrogen is predicted by additional intradialytic urea sample. Maduell and colleagues, based on analysis of postdialysis urea rebound, have proposed a method whereby the urea rebound is predicted. To compare measured URRr to estimated by Smye and Maduell formulas, 384 patients were studied, 211 males and 173 females, who received a dialysis session with their habitual parameters. Measurements of plasma urea concentration were obtained at the beginning, 90–100 min following the start of dialysis, at the end, and 45 min after dialysis. The postdialysis urea rebound was 22.4 ± 9.7%. The urea kinetic model Kt/V was 1.365 ± 0.26, and Kt/Vr was 1.14 ± 0.23. URR was 68.7 ± 6.6%, and when it was calculated with urea rebound, it decreased to 61.9 ± 7.4%. The URRr correlated with calculations by Smye and Maduell formulas: 60.7 ± 8.4 (r = 0.722, p < 0.001) and 61.8 ± 6.6 (r = 0.933, p < 0.001), respectively. The precision of estimated limits of agreement and percentage of error by Bland and Altman analysis show that URRr estimated Maduell formula could be used in place of the URRr. Otherwise, the degree of agreement of the Smye method was not clinically acceptable. In conclusion, our results led us to suggest that in actual dialysis, the use of URR is not adequate for delivered hemodialysis dose, and URRr should be used. URRr estimated by Maduell formula could be a simple and accurate method for use in clinical practice. The recommended dialysis dose by the American National Study of URR of 70% could correspond, considering urea rebound, to Kt/Vr 1.18 or URRr of 64%.

Ｌａｒｇｅ‐ｄｏｓｅ Ｃｙｃｌｉｃ Ｔｉｄａｌ Ｐｅｒｉｔｏｎｅａｌ Ｄｉａｌｙｓｉｓの有用性について

我々は中間排液併用の大量の透析液 (およそ20～40l) を使用したTPD (large-dose cyclic TPD) について，(1) 尿素窒素除去に対する有効性についての検討，(2) 総透析液量と治療時間を一定にしたlarge-dose cyclic TPDにおいて最大尿素窒素除去が得られるタイダール量が何%かの検討，(3) large-dose cyclic TPDの溶質除去の限界 (総透析液量はどこまで増やすべきか) についての検討を行った。 (1) 総透析液量は主に20l使用 (およそNPDの3から7倍)，NPDの1.2～2.3倍のKT/Vが得られた。(2) 最大尿素窒素除去が得られるタイダール量は50%であった。(3) 総注液量1,200ml/kgでKT/Vはおよそ3前後を得ることができ，これ以上増やしてもKT/Vの増加はあまり期待できないと思われた。

Simulating the effect of exercise on urea clearance in hemodialysis.

A two-compartment model of urea kinetics during hemodialysis is used to predict the effect of exercise on hemodialysis dose. It is assumed that the two compartments represent tissues that are perfused by low and high blood flows (initially 1.1 L/min and 3.8 L/min). The effect of changing the distribution of flows between the compartments, emulating the effect of exercise, is simulated using the model equations for a range of dialyzer clearances. Compartmental volumes are assumed constant (33.4 L and 8.6 L for low- and high-flow compartments, respectively). The analysis identifies muscle perfusion as a rate-limiting factor during the later stages of hemodialysis and illustrates the benefit of exercise during this phase in increasing dialysis efficiency. The model suggests that the postdialysis rebound in the blood urea concentration is eliminated by increasing flow to the low-flow compartment from 1.1 L/min to 7.1 L/min and sustaining this for at least 30 min of a 150-min dialysis session, independent of the dialyzer clearance. Additional exercise will not increase the dialysis dose. Experimental studies are required to confirm the analysis.

Validation of different methods to calculate Kt/V considering postdialysis rebound.

The effect of increasing dialysis efficiency magnifies rebound urea and the error in Kt/V determinations from single pool urea kinetics. Several formulae have been developed to calculate Kt/V taking into account the rebound urea (Kt/Vr). Smye et al. proposed a method whereby the equilibrated BUN is predicted by an additional intradialytic urea sample (Kt/VrSmye). Daugirdas et al. proposed a method where a single pool Kt/V is modified according to the speed of dialysis to obtain a double pool Kt/V (Kt/VrDaug). Maduell et al. developed a method based on analysis of post-dialysis urea rebound whereby the Kt/Vr is predicted according to the single pool Kt/V and K/V (Kt/VrMad). We compared Kt/Vr estimated by these three formulae (Smye, Daugirdas, and Maduell) in 384 patients consisting of 211 males and 173 females, who received dialysis according to their regular protocols. Plasma urea was measured at the beginning, 90-100 min following the start of dialysis, the end, and 45 min post-dialysis. Post-dialysis rebound urea was 22.4 +/- 9.7%. Kt/V and Kt/Vr obtained with rea kinetic model Kt/V 1.184 +/- 0.22 and 0.984 +/- 0.20, respectively. These was a good correlation between Kt/Vr and the Smye formula (Kt/VrSmye = 0.956 +/- 0.21, r = 0.729, P < 0.001), and a better one for Daugirdas (Kt/VrDaug = 0.984 +/- 0.18, r = 0.931, P < 0.001), and Maduell formulae (Kt/VrMad = 0.980 +/- 0.18, r = 0.946, P < 0.001). Limits of agreement and percentage of error estimated according to Bland and Altman show that Kt/Vr estimated by Daugirdas and Maduell formulae could be used in place of the Kt/Vr. The degree of agreement with the Smye method is not clinically acceptable. Our results suggest that the use of a single pool Kt/V is not adequate to estimate the haemodialysis dose delivered and Kt/V taking rebound urea in consideration. Kt/Vr estimated by Daugirdas or Maduell formulae are a simple and accurate method for use in clinical practice.

Hemodialysis urea rebound: The effect of increasing dialysis efficiency

Urea rebound has been documented to occur after hemodialysis, but the magnitude and causes are not clearly defined. In this study we evaluated the effect of high-flux hemodialysis on urea rebound and Kt/V. Blood urea nitrogen samples were obtained before, immediately after, and 30 minutes after hemodialysis in 49 patients. Rebound was evaluated with respect to dialysis efficiency, dialysis treatment time, the occurrence of hypotension, and hematocrit. Urea rebound was significant and resulted in an overall decrease in Kt/V from 1.2 ± 0.3 to 1.0 ± 0.2 (P < 0.001). Of the 45 patients with a measured Kt/V of greater than 1.0, 40% had an actual delivered Kt/V of less than 1.0 once rebound was taken into account. Urea rebound correlated strongly with dialysis efficiency but not with hypotension, suggesting that rebound resulted primarily from delayed urea mass transfer across cell membranes. We conclude that increasing dialysis efficiency increases urea rebound and increases the error in Kt/V determinations from single pool urea kinetics.