REXEEDTM系列高通量透析器疗效和安全性的临床随机对照试验

目的 评价REXEEDTM系列高通量透析器的疗效和安全性。 方法 研究对象为上海两家医院规律性血液透析（血透）患者72例。采用随机化交叉设计,采用REXEEDTM不同膜面积（1.5 m2和2.1 m2）15AC、15UC、21AC、21UC透析器（试验组）以及APS-15U、BIO-HX100透析器（对照组）,分别按2个3×3拉丁方进行透析治疗。检测透析器尿素、肌酐、磷、β2微球蛋白清除率,尿素、肌酐下降比率及治疗前后安全性指标。观察及记录不良反应。 结果 试验组15AC、15UC透析器的尿素、肌酐清除率均显著大于对照组APS-15U[分别为（222.07±18.74） ml/min、（220.23±26.26） ml/min比（199.56±14.21） ml/min;（176.73±16.41） ml/min、（175.22±25.94） ml/min比 （165.42±14.68） ml/min,均P < 0.05]。两组间磷和β2微球蛋白清除率差异均无统计学意义。21AC、21UC透析器尿素、肌酐、β2微球蛋白清除率均显著大于对照组BIO-HX100[分别为（230.59±15.24） ml/min、（233.96±7.06） ml/min比（203.43±36.66） ml/min;（183.50±25.90） ml/min、（181.05±23.94） ml/min比（166.25±29.82） ml/min;（111.77±53.42） ml/min、（125.54±51.99） ml/min比（42.39±4.81） ml/min,均P < 0.05]。两组间磷清除率差异无统计学意义。试验组4种透析器尿素下降比率均大于89%,治疗前后安全性监测指标均无明显变化。不良反应和不良事件少而程度轻,无严重不良反应。 结论 REXEEDTM-AC、UC系列高通量透析器临床使用安全有效。     

Impact of bleach cleaning on the performance of dialyzers with polysulfone membranes processed for reuse using peracetic Acid

Dialyzer performance may change with reuse depending on whether or not the dialyzer is cleaned with bleach. Bleach is usually used in conjunction with formaldehyde as the germicide. Because few data are available for dialyzers cleaned with bleach and disinfected with peracetic acid, we examined dialyzer performance in a cross-over study of dialyzers containing polysulfone membranes reprocessed using bleach and peracetic acid or peracetic acid alone. Each dialyzer was used for a total of 16 treatments, or until it failed standard criteria for continued use. Urea, beta2-microglobulin, and albumin removal were determined during the first, second, seventh, and 16th use of each dialyzer. Urea removal did not differ between the two reprocessing methods and did not change with reuse. Overall, beta2-microglobulin removal remained unchanged in dialyzers reprocessed with peracetic acid alone, but tended to increase after the seventh use in dialyzers reprocessed with bleach and peracetic acid. Approximately 60% of beta2-microglobulin removal resulted from trapping of beta2-microglobulin at the dialyzer membrane. Albumin loss into the dialysate was clinically insignificant throughout the study with both reprocessing methods. These data show that the clearance of both small and large molecules by dialyzers containing polysulfone membranes is well maintained by reprocessing with peracetic acid and that additional cleaning with bleach has limited impact on performance.     

Severe dialyzer dysfunction undetectable by standard reprocessing validation tests

It is generally accepted that careful monitoring of total cell volume and ultrafiltration rates will ensure adequate function of reprocessed dialyzers. During routine urea kinetic measurements we noted that the percent of patients with clearances less than 200 ml/min increased from 5% to 48% despite adherence to these validation tests. As these patients did not have evidence of recirculation in the vascular access, possible causes of dialyzer dysfunction were investigated. Injection of methylene blue into the dialysate port revealed non-uniform flow of dialysate in dialyzers from patients with markedly reduced clearances. In vitro studies of dialyzers subjected to sequential daily reprocessing, without patient exposure, demonstrated that in vitro clearances declined in one lot but not another. The initial clearances of 218 +/- 4 ml/min fell progressively to 112 +/- 18 (P less than 0.001) after 15 reuses. No effects of reprocessing were found in a different lot (230 +/- 2 vs. 226 +/- 4 ml/min). Soaking the dialyzers from the affected lot in either the disinfectant or dialysate solution caused a decline in the clearances which was less than that of serial reuse. Although the magnitude of the problem of dialyzer malfunction with reuse is unknown, careful attention to dialyzer function is warranted in patients treated with reprocessed dialyzers.     

血液透析中应用低分子量肝素的交叉对照、随机、开放、多中心临床研究

目的比较低分子量肝素（Fragmin）与普通肝素（UFH）在血液透析中的抗凝疗效。方法100例慢性维持性血透患者（CHD）通过自身对照，按不同顺序给予Fragmin和UFH各4次作为血液透析抗凝剂，观察透析器凝血，透析器对尿素氮、肌酐清除效力，监测抗Xa活性及白陶土部份凝血活酶时间（KPTT），人工压迫止血时间。结果与UFH相比，Fragmin抗Xa活性明显高于UFH，而对KPTT影响不明显；两种肝素均应用常规剂量时，用Fragmin的透析器对尿素氮、肌酐的清除效力明显优于UFH，压迫止血时间缩短。结论Fragmin的抗凝效果与UFH相似，在血液透析中应用能保证透析效果而不增加出血危险。     

Evaluation with micro‐CT of different anticoagulation strategies during hemodialysis in patients with thrombocytopenia: A randomized crossover study

In patients with enhanced risk for bleeding, heparin‐free hemodialysis (HD) with conventional dialyzers is routinely used. To explore the potential benefit of using heparin‐coated dialyzers, we used a reference CT‐scanning technique and registered different clotting parameters to quantify coagulation with heparin‐coated versus non‐coated dialyzers. Six HD patients with thrombocytopenia were dialyzed 240 min in a randomized crossover study with Evodial 1.3 or FX600 Cordiax, each without anticoagulation. Blood samples were taken from the vascular access predialysis, and from the dialyzer inlet and outlet at 5 and 240 min after dialysis start. Predialysis blood samples were analyzed for hemoglobin, hematocrit, thrombocytes, fibrinogen, and activated partial thromboplastin time. On dialyzer inlet and outlet blood samples, a viscoelastic measurement of blood coagulation was performed using a Sonoclot analyzer. After dialysis, dialyzers were visually scored, subsequently dried for 24 h, weighed, and scanned with micro‐CT at a resolution of 25 µm. After image reconstruction, the open, non‐coagulated fibers were counted in a representative cross‐section at the dialyzer outlet. No sessions were terminated prematurely for circuit clotting. Heparin‐coated dialyzers had more patent fibers on micro‐CT versus non‐coated dialyzers and also had a better score of subjective visual assessment of fiber clotting. There was no difference in subjective assessment of clotting at the venous drip chamber. With both dialyzers, all ACT values remained in the normal range, and were lower at the dialyzer outlet versus inlet. In conclusion, dialysis with a heparin‐coated versus non heparin‐coated membrane results in substantially less coagulated fibers during 4 h hemodialysis without systemic anticoagulation. Eventual leaching of heparin, immobilized on the fiber membrane, does not result in measurable systemic anticoagulation.     

Outbreak of gram-negative bacteremia and pyrogenic reactions in a hemodialysis center

During the period from April 4, 1988, to April 20, 1988, nine pyrogenic reactions and five gram-negative bacteremias occurred in 11 patients undergoing dialysis. All pyrogenic reactions and gram-negative bacteremias occurred among patients in whom a reprocessed dialyzer was used. The rate of pyrogenic reactions or bacteremias per 100 sessions using a reprocessed dialyzer was higher than in sessions during which a new dialyzer was used (4.5 vs. 0; p = 0.03). Dialyzers were manually reprocessed with 2.5% Renalin germicide. The Renalin concentrations varied widely in 12 dialyzers stored after manual reprocessing during the epidemic period (0.9-4.2%); the median endotoxin concentrations varied from 0 to 246 ng/ml and were higher in dialyzers with Renalin concentrations less than or equal to 1.0% than in dialyzers with higher concentrations (p = 0.01). Experiments using a dilution technique described by a technician resulted in Renalin concentrations ranging from 1.4% at the surface to 3.5% at the bottom of the preparation container. These findings suggest that failure to adequately admix Renalin during dilution may be associated with low levels of disinfectant, high levels of bacteria and endotoxins in dialyzers, and outbreaks of pyrogenic reactions and gram-negative bacteremias in dialysis patients.     

A low molecular weight heparin ("fragmin") for routine hemodialysis: a crossover trial comparing three dose regimens with a standard regimen of commercial unfractionated heparin

In 20 hemodialysis patients using mainly flat plate dialyzers, we have conducted a controlled randomized crossover trial of three dose regimens of a low molecular weight heparin (LMWH), "Fragmin" (Kabi 2165), in comparison with a standard dose regimen of commercial unfractionated heparin (UFH) that had previously been shown to provide effective anticoagulation. The aim of the present study was to find the lowest dosage regimen of the LMWH which would be as effective as the standard UFH regimen. The UFH regimen comprised a prime with heparinized saline, an initial intravenous bolus of 5,000 international units (IU) and an infusion of 1,500 IU/h. The three LMWH regimens comprised a LMWH-saline prime, an infusion of 750 anti-factor Xa (aXa) U/h and three different bolus doses: 1) LMWH-low: 3,000 aXa U. 2) LMWH-medium: 4,000 aXa U. 3) LMWH-high: 5,000 aXa U. With the UFH regimen, plasma heparin levels of around 1.0 IU/ml were maintained during the heparin infusion, declining to 0.71 IU/ml an hour after the infusion was terminated. The LMWH-medium regimen produced very similar plasma aXa levels. The LMWH-high regimen also produced similar plasma aXa levels: therefore, it had no advantage over the LMWH-medium regimen. The LMWH-low regimen produced significantly lower levels than the other regimens during the heparin infusion (0.81-0.85 aXa U/ml, p less than 0.025). Dialysis proceeded uneventfully at all times and plasma levels of fibrinopeptide A (FPA) were suppressed well with all 4 regimens (2.77-5.74 pmol/ml) but tended to rise after the infusion was switched off (5.52-8.45 pmol/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dialyzer-dependent changes in solute and water permeability with bleach reprocessing

The effects of bleach reprocessing on the performance of high-flux dialyzers have not been comprehensively characterized. We compared the effects of automated bleach/formaldehyde reprocessing on solute and hydraulic permeability for cellulose triacetate (CT190) and polysulfone (F80B) dialyzers using an in vitro model. Dialyzers were studied after initial blood exposure (R0) and after 1 (R1), 5 (R5), 10 (R10), and 15 (R15) reuse cycles. Ultrafiltration coefficient (K(uf)), serial clearances, and/or sieving coefficients (SCs) of urea, creatinine, vancomycin, inulin, myoglobin, and albumin were determined. Urea, creatinine, and vancomycin clearances and SCs did not significantly differ from R0 to R15 with either dialyzer. Inulin clearances and SC also did not significantly change from R0 to R15 for the CT190. However, these same values for the F80B significantly increased (P < 0.05). The inulin clearance and SC values for the CT190 dialyzer were significantly higher than those for the F80B at all stages except R15. Myoglobin clearances significantly increased over 15 reuses for both dialyzers (P < 0.01). However, CT190 myoglobin clearances were significantly higher at all stages (R0 = 37.7 +/- 9.7; R15 = 52.5 +/- 8.8 mL/min) than the F80B (R0 = negligible; R15 = 41.3 +/- 16.5 mL/min; P < 0.01). Albumin pre- and postdialysis SCs significantly increased for both dialyzers (P < 0.01). K(uf) for R0 and R15 were 52.3 +/- 3.3 and 52.6 +/- 7.6 mL/h/mm Hg for CT190 (P = not significant) and 48.8 +/- 4.4 and 87.3 +/- 7.0 mL/h/mm Hg for F80B (P < 0.0001). We conclude that bleach reprocessing significantly increases larger solute and hydraulic permeability of high-flux cellulosic and polysulfone dialyzers. This effect is more pronounced for the polysulfone membrane. Until 10 reuses or greater, the removal of solutes greater than 1,500 d is significantly compromised with the polysulfone dialyzer used in this study.     

Mass Transfer Characteristics of Hollow-Fiber Dialyzers and Hemoperfusion Devices

Clearance versus time tests were carried out on three charcoal-based hemoperfusion devices (Sandev, Becton-Dickinson and Gambro) using solutions of 1 gm/L sodium salicylate in a pH 7.4 buffer and in bovine blood at flow rates of 200 ml/min. Similar tests were performed on a Cordis Dow 2.5 m2 hollow-fiber dialyzer at a tube side flow rate (QB) of 200 ml/min. Buffer was pumped through the dialysate side at a flow rate (QD) of 400 ml/min. Two dialyzers were run in series at QB = 200 ml/min and QD = 500 or 1000 ml/min. Mass transfer resistances were computed from the test results. These values are useful in that they constitute an index of the intrinsic initial kinetics of solute transfer in each device. However, the clearance versus time curves indicate that these initial kinetics decrease at different rates for each hemoperfusion unit as sorption capacity begins to be depleted. In contrast, the initial clearances for the dialyzers remain at their initial values. These data reveal much about the relative mass transfer characteristics of these devices.     

Effect of Dialyzer Reprocessing Methods on Complement Activation and Hemodialyzer-Related Symptoms

The effects of different dialyzer processing methods and of reuse on complement activation and dialyzer-related symptoms were studied in 96 maintenance hemodialysis patients. New dialyzers were either unprocessed (Group 1) or machine-washed with bleach and stored in formaldehyde (Group 2). Reused dialyzers were manually cleansed using the combination of bleach and formaldehyde (Group 3), or machine-washed in formaldehyde (Group 4) or peracetic acid (Group 5). Prewashed new dialyzers (Group 2) were associated with greater complement activation during dialysis when compared with unprocessed, new dialyzers (Group 1) (p less than 0.05). Reused, unbleached but formaldehyde-treated or peracetic acid-treated dialyzers (Groups 4 and 5) were associated with reduced complement activation (p less than 0.05). Complement activation was not reduced when bleach was used for reprocessing (Group 3). The percentage of patients without symptoms during dialysis was significantly greater with reused dialyzers than with new dialyzers (Groups 3 through 5 versus Groups 1 and 2; 39 versus 25%; p = 0.035). The severity of total symptoms correlated significantly (p = 0.0004) with complement activation. Our results suggest that total symptoms during dialysis are correlated with the degree of complement activation. However, trends in the data pertaining to chest pain suggest that factors other than complement activation may be important in the pathogenesis of some dialyzer-related symptoms.     

Association of dialyzer reuse and hospitalization rates among hemodialysis patients in the US

OBJECTIVES: To determine if reuse of hemodialyzers is associated with higher rates of hospitalization and their resulting costs among end-stage renal disease (ESRD) patients. METHODS: Noncurrent cohort study of hospitalization rates among 27,264 ESRD patients beginning hemodialysis in the United States in 1986 and 1987. RESULTS: Dialysis in free-standing facilities reprocessing dialyzers was associated with a greater rate of hospitalization than in facilities not reprocessing (relative rate (RR) = 1.08, 95% confidence interval (CI), 1.02-1.14). This higher rate of hospitalization was observed with dialyzer reuse using peracetic/acetic acids (RR = 1.11, CI 1. 04-1.18) and formaldehyde (RR = 1.07, CI 1.00-1.14), but not glutaraldehyde (p = 0.97). There was no difference among hospitalization rates in hospital-based facilities reprocessing dialyzers with any sterilant and those not reprocessing. Hospitalization for causes other than vascular access morbidity in free-standing facilities reusing dialyzers with formaldehyde was not different from hospitalization in facilities not reusing. However, reuse with peracetic/acetic acids was associated with higher rates of hospitalization than formaldehyde (RR = 1.08, CI 1.03-1.15). CONCLUSIONS: Dialysis in free-standing facilities reprocessing dialyzers with peracetic/acetic acids or formaldehyde was associated with greater hospitalization than dialysis without dialyzer reprocessing. This greater hospitalization accounts for a large increment in inpatient stays in the USA. These findings raise important concerns about potentially avoidable morbidity among hemodialysis patients. Copyright Copyright 1999 S. Karger AG, Basel     

Usefulness of Thrombelastography for Dosage Monitoring of Low Molecular Weight Heparin and Unfractionated Heparin During Hemodialysis

Low molecular weight heparin (LMH) acts as an anticoagulation agent mainly through its anti-activated coagulation factor X (Xa) activity. Thrombelastography (TEG) is expected to be useful to monitor the dosage of LMH during hemodialysis because reaction time on TEG (TEG-r) is considered to reflect blood thromboplastin formation time, which depends on the formation of Xa. To test this possibility, we compared the usefulness of TEG, activated coagulation time (ACT), activated partial thromboplastin time (APTT), and anti-Xa activity in 28 hemodialysis patients using both conventional unfractionated heparin (UFH) and LMH on separate dialysis procedures. Anti-Xa activity of LMH was comparable to that of UFH when it was measured using both LMH and UFH as standards. Anti-Xa activity, which theoretically depended on the heparin concentration in blood samples, did not correlate with the degree of dialyzer clotting. The APTT correlated well with anti-Xa activity in patients using LMH (r = 0.686, p less than 0.01) and UFH (r = 0.906, p less than 0.01), but not with the degree of dialyzer clotting. The TEG-r correlated well with the degree of dialyzer clotting both in patients using LMH and those using UFH (measurements of samples obtained from the venous side of the extracorporeal circuit) and weakly correlated with anti-Xa activity in patients using LMH (r = 0.402, p less than 0.05). The ACT did not correlate with the degree of dialyzer clotting or anti-Xa activity. These results suggest that TEG-r reflects the efficacy of heparin in the extra-corporeal blood circuit, whereas APTT mainly reflects heparin concentration of the blood samples.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anaphylactoid reactions associated with reuse of hollow-fiber hemodialyzers and ACE inhibitors.

From July 18 through November 27, 1989, 12 anaphylactoid reactions (ARs) occurred in 10 patients at a hemodialysis center in Virginia. One patient required hospitalization; no patients died. ARs occurred within minutes of initiating dialysis and were characterized by peripheral numbness and tingling, laryngeal edema or angioedema, facial or generalized sensation of warmth, and/or nausea or vomiting. All 12 ARs occurred with dialyzers that had been reprocessed with an automated reprocessing system. A cohort study, including all patients undergoing dialysis sessions on the six days when an AR occurred, showed that the patients who experienced ARs were significantly more likely than patients who did not to be treated with angiotensin-converting enzyme (ACE) inhibitors (7/10 vs. 3/33; relative risk = 7.9; 95% confidence interval = 2.5 to 25.2) and to have been exposed to reused dialyzers rather than to new dialyzers (12/70 sessions vs. 0/31; P = 0.016). In those sessions using a reused dialyzer, the mean number of dialyzer uses in case-sessions was significantly higher than for noncase-sessions (10.3 vs. 6.2; P = 0.016). After reuse of dialyzers was discontinued at the center, no further ARs occurred, despite the continued administration of ACE inhibitors. This is the first report of an outbreak of ARs associated exclusively with reused dialyzers. We hypothesize that interactions between a dialyzer that has been repeatedly reprocessed and reused, blood, and additional factors, such as ACE inhibitors, increased the risk of developing ARs.     

Influence of Blood Flow on Adsorption of β2-Microglobulin onto AN69 Membrane

Abstract: Adsorption onto the dialyzer membrane is a contributing factor to the elimination of β₂-microglobulin (β₂M) from the sera of uremic patients. The purpose of this prospective study was to ascertain the influence of the blood flow rate on adsorption of β₂M onto the polyacrylonitrile (AN69) hollow-fiber dialyzer membrane in 8 pa tients during regular hemodialysis (HD). Blood first passed through a low-flux polysulfone dialyzer and then through an AN69 dialyzer, which was not in contact with the dialysis fluid. During the investigation period (first hour of the HD session), the blood flow rate was 100 ml/min (first part of the study), 200 mumin (second part of the study), and 300 ml/min (third part of the study). Ultrafiltration was not performed during the investigation period. At the start of the HD sessions, the serum concentration of β₂M in the afferent blood line did not differ significantly among the 3 parts of the study. Serum β₂M was measured in samples taken from the afferent and efferent blood lines of the AN69 dialyzer at 5,10, 15, 30, 45, and 60 min. The serum β₂M concentration decreased significantly in blood that had passed through the AN69 dialyzer. This decrease, indicating membrane adsorption, was maximal during the first part and minimal during the third part of study. The decrease in the contact time between the blood and the AN69 could be the underlying cause. The calculated quantities of β₂M adsorbed onto the AN69 membrane (44.2 ± 10.2, 43.2 ± 12.1, and 42.6 ± 17.3 mg) did not differ significantly among the 3 parts of the study. These results suggest that an increase in blood flow rate from 100 to 300 ml/min did not significantly affect the quantity of β₂M adsorbed onto the AN69 membrane.     

Evaluation of Three Dry-Sterilized Hollow Fiber Artificial Kidneys

We investigated three new dry sterilized hollow fiber artificial kidneys (HFAK) (Cordis Dow CDAK 1.3, Travenol CF 1200, Extracorporeal Tri-Ex 1). Dry sterilization makes these dialyzers more economical by shortening set-up time. Dry sterilization also eliminates iatrogenic administration of residual sterilant. Water of imbibition can significantly increase the blood compartment volume of the dialyzer during dialysis. Consequently, a corrected blood volume for each dialyzer was established; these corrected volumes varied from 13-36% greater than the volume determined before dialysate flow. With low dose heparinization of these dialyzers there was between an 18 and 45% decrease in the post dialysis volume, presumably due to fiber clotting during dialysis. This volume added to the residual blood loss measured by a colori-metric technique accounted for a possible blood loss ranging between 26.9 and 53.9 ml per dialysis for these three dialyzers. Our results suggest that a relationship between dialyzer clotting and decreased dialyzer efficiency may exist. These three capillary flow dialyzers had a much lower platelet drop (0-9% pre to post) when compared to 30-40% drop of flat plate dialyzers. These dialyzers were found to be safe and easy to use but the high fiber clotting warrants further investigation in chronic dialysis patients on high dose heparin.     

Removal of plasma porphyrins with high-flux hemodialysis in porphyria cutanea tarda associated with end-stage renal disease.

Plasma porphyrin levels are markedly increased in patients with porphyria cutanea tarda (PCT) associated with end-stage renal disease. Conventional hemodialysis (CHD) with lower blood flow rates (less than 250 mL/min) and cuprophan or cellulose acetate membranes is ineffective in removing significant amounts of porphyrins in this condition. Changes in plasma porphyrin levels and porphyrin clearances during hemodialysis with higher blood flow rates and more-permeable, high-efficiency cellulose acetate and high-flux polysulfone dialyzers were evaluated in a chronic hemodialysis patient with PCT and markedly elevated plasma porphyrins. The polysulfone membrane achieved significantly better fractional porphyrin removal (P = 0.02) and porphyrin clearances (P less than 0.01) than did the high-efficiency cellulose acetate membrane. After conversion from maintenance CHD with a standard cellulose acetate dialyzer to a 4-wk period of high-flux hemodialysis (HFHD) with a polysulfone dialyzer, predialysis plasma porphyrins fell by 37%. After returning to CHD, plasma porphyrins returned to the higher prestudy levels. These observations suggest that HFHD with more permeable membranes and higher blood flow rates removes porphyrins more effectively than does CHD. HFHD may be a useful adjunct to other measures used in treating dialysis patients with PCT.     

Ethylene Oxide in Dialyzer Rinsing Fluid: Effect of Rinsing Technique, Dialyzer Storage Time, and Potting Compound

Ethylene oxide (ETO) is recognized as one of the main causes of dialyzer-associated hypersensitivity reactions. We studied the amount of ETO in the rinsing fluid of ETO-sterilized hollow-fiber dialyzers as a function of rinsing technique, dialyzer storage time, and the amount of potting compound (known to be an ETO reservoir) in the dialyzer. The results suggested that the initial 500 ml of rinsing fluid removes much of the residual ETO in the dialyzer. Ethylene oxide extraction was enhanced substantially by rinsing at 37 degrees C versus 5 degrees C. However, considerable amounts of ETO remained in the dialyzer after an initial 500 ml rinse, some of which could be removed by rinsing with an additional 1,500 ml. High concentrations of ETO were measured in fluid that had been recirculated through the dialyzer for 10 min or longer and in fluid that had been allowed to remain in the dialyzer for 10 min under zero-flow conditions. The amount of ETO in the rinsing fluid decreased markedly as the dialyzer storage time was increased from 4 to 8 weeks and in dialyzers in which a portion of the potting compound had been replaced with a polycarbonate ring. Our results suggest that the dose of ETO administered to the patient at the outset of dialysis can be minimized by rinsing the dialyzer with 2 L of fluid at 37 degrees C and by avoiding administration of rinsing fluid that has been allowed to remain in contact with the dialyzer for more than several minutes. Use of a long storage interval and use of dialyzers containing reduced amounts of potting material will also reduce the ETO load.     

Accelerated removal of deferoxamine mesylate-chelated aluminum by charcoal hemoperfusion in hemodialysis patients

Although deferoxamine mesylate (DFO) is effective in removing aluminum (Al) in hemodialysis patients, treatment with this drug is associated with a number of adverse effects. In order to limit the exposure of patients to DFO-Al complexes, the efficacy of colloidin-coated microencapsulated charcoal cartridges added in series to conventional dialyzers was investigated. The clearances of Al by the sorbent system were initially 116 +/- 4.7 mL/min, but decreased to 42.5 +/- 6.6 mL/min after 120 minutes of treatment. Thereafter, the Al clearances remained constant. In contrast, the Al clearances of the dialyzer were 29.5 +/- 1.8 mL/min initially and did not change during the treatment period. Both the percent and absolute decrease in Al levels after four hours of dialysis were greater with the dialyzers plus carbon cartridges than with the dialyzers alone. This resulted in an increase in the minimum net Al removal from 1,862 +/- 174 micrograms/treatment to 3,007 +/- 43 micrograms/treatment (P less than 0.05). Treatment with sorbent hemoperfusion should be considered in selected hemodialysis patients being treated with DFO for Al overload.     

Dialysis membrane-dependent removal of middle molecules during hemodiafiltration: the beta2-microglobulin/albumin relationship

AIM: Current hemodialysis therapy modalities such as online hemodiafiltration (HDF) attempt to enhance solute removal over a wide molecular weight range through a combination of diffusion and convection. While the effects of variations of treatment modalities and conditions have been studied reasonably well, few studies have examined the efficacy of HDF to remove middle molecules in relation to the dialyzer and membrane characteristics. In this investigation, diverse high-flux dialyzers, covering a wide range of membrane permeabilities, were compared under identical in vivo conditions to assess their ability to eliminate larger uremic retention solutes (using beta2-microglobulin as a surrogate of middle molecules) without simultaneously causing excessive leakage of useful proteins such as albumin. PATIENTS AND METHODS: In a prospective, crossover study, 3 ESRD patients were treated with 8 different brands of high-flux dialyzers at 4 different ultrafiltration (UF)/substitution flow rates (QS: 0, 30, 60, 90 ml/min) in post-dilution HDF mode. Thus, each patient underwent 32 treatment sessions, with a total of 96 treatment sessions conducted during the entire clinical study. Albumin and beta2-microglobulin levels were measured in both, dialysate and blood. Both, albumin and beta2-microglobulin elimination was dependent upon the permeability of the dialysis membrane as well as on the ultrafiltration/substitution flow rates applied. RESULTS: At the maximum UF rate of 90 ml/min, the total albumin loss (measured in the dialysate) ranged from 300 mg/4 h (for the FLX-15 GWS dialyzers) to 7,000 mg/4 h (for the BS-1.3U dialyzers). Up to 50% reduction of albumin occurred within the first 30 minutes of the dialysis treatment, and the leakage of albumin increased exponentially with increasing UF rates as well as increasing transmembrane pressure (TMP). The various dialyzers could be classified according to their UFR-dependent beta2-m reduction rates (RR), into low (< 50%; FLX-15 GWS, CT 150G), medium (50-70%; Polyflux 14 S, BLS 814SD, H4) and high (> 70%; BS-1.3U, APS 650, FX 60) removers of middle molecules. One dialyzer type (CT 150G) showed extremely low beta2-m RR and relatively high albumin losses. Most membranes, however, showed either low albumin leakage coupled with low beta2-m removal, or high beta2-m RR but at the expense of considerable albumin leakage. Only 2 membrane types approached the desired balance between high to medium beta2-m RR while simultaneously restricting the albumin leakage especially at higher filtration/substitution rates. CONCLUSION: Our investigations demonstrate that not all dialysis membranes classified as "high-flux" are comparable in their ability to specifically and efficiently remove middle molecules, or curtail the unwanted excessive leakage of essential proteins from the patient's blood. Thus, the selection of appropriate high-flux dialyzers for specific patient requirements should be based more upon clinical evaluations and analyses rather than on product specifications alone.     

Cardiac biomarkers are influenced by dialysis characteristics

INTRODUCTION: The cardiac biomarkers cardiac Troponin T (cTNT) and NT-proBNP tend to be elevated in nearly all hemodialysis patients. The high percentage and magnitude of these increased molecules is associated with cardiovascular morbidity and mortality in hemodialysis patients. This study investigates the impact of the dialysis procedure itself on cardiac biomarkers. METHODS: Standard chronic hemodialysis lasting 4-5 hs 3 times weekly and using polysulfone dialyzers (high-flux and low-flux) was performed. Blood flow rates varied between 250-350 ml/min. The cTNT levels of 49 chronic hemodialysis patients were measured twice (interval of 6 weeks) before and after a hemodialysis session by a third-generation assay (Elecsys Analyzer, Roche Diagnostics, Mannheim, Germany). NT-proBNP levels were measured with polyclonal antibodies capable of recognizing the N-terminal fragment of BNP. In a follow-up period of 42 months, cardiovascular events and death were assessed. RESULTS: The median concentration of cTNT prior to hemodialysis was 0.024 ng/ml (< 0.001-0.703). All dialysis patients presented high plasma levels of NT-proBNP (median 4,885 pg/ml). Oligoanuric patients had significantly higher cTNT and NT-proBNP levels prior to dialysis compared to patients with normal diuresis (p < 0.0001). cTNT and NT-proBNP levels increased significantly during the hemodialysis sessions in which a low-flux dialyzer was used (p < 0.0001) but remained unchanged when a high-flux dialyzer was utilized. Neither the predialytic nor the interdialytic changes in cTNT and NT-proBNP levels were influenced by blood flow. NT-proBNP levels increased markedly during hemodialysis sessions (p < 0.005) utilizing the low-flux dialyzer. Patients with a non-native fistula had significantly higher predialysis cTNT and NT-proBNP levels (p < 0.05). Patients with cardiovascular events had a significantly higher cTNT and NT-proBNP at the beginning of the study. CONCLUSION: Asymptomatic chronic hemodialysis patients have significantly higher levels of the cardiac biomarkers cTNT and NT-proBNP relative to the general population. The levels are associated with the time of measurement (before and after a hemodialysis session). Dialysis modalities like high-flux dialyzers influence cTNT and NT-proBNP levels and should be taken into account, particularly in patients with acute onset of cardiac ischemia. The elevation of cTNT and NT-proBNP levels after hemodialysis using a low-flux dialyzer are partly due to hemoconcentration. The significant association of cTNT and NT-proBNP with non-native fistulas (catheter or graft) may be due to the chronic inflammation commonly caused by these devices. Both cardiac biomarkers are of prognostic value determining cardiovascular events and death.