Large-Surface Hemodialysis

A hemodialysis device with a surface of 5 m2, a blood flow (QB) of 500 ml/min, and a dialysate flow (QD) of 1,000 ml/min has enabled the authors to obtain in 6 h/week the same clearances for urea, creatinine, uric acid, phosphates, and vitamin B12 as has conventional hemodialysis (CH), which takes from 12 to 15 h/week. Twenty-five patients were hemodialyzed throughout 1 year with CH and another year with large-surface hemodialysis, 20 with a creatinine clearance (CCr) of 0.5 ml/min and 5 with a CCr between 0.5 and 4.5 ml/min. All followed a free diet and led a normal life. Hemodialysis time was 6 h/week, and the results obtained were equal to those of the previous year with a CH of 12 h/week. The use of a bicarbonate dialysate rich in glucose, with a relatively high level of potassium and sodium, can avoid the disequilibrium syndrome caused by quick hemodialysis and makes possible the removal of excess liquid in only 6 h/week, without disturbances for the patient.     

Validation of limulus tests for endotoxin evaluation in dialysate

Summary: To measure endotoxin (ET) levels in dialysate accurately, three commercial limulus tests (Endospecy, Seikagaku, Tokyo, Japan; Kinetic QCL, BioWhittacker, MD, USA; ET single test-ES, Wako, Osaka, Japan) were validated in order to determine whether or not they are enhanced or inhibited by bicarbonate dialysate. Two reference standard ET, one from US Pharmacopoeia (Escherichia coli reference standard endotoxin; RSE) and the other from European Pharmacopoeia (Salmonella RSE), were adjusted with dialysate at concentrations of 0.05, 0.10 and 0.15 EU/mL for measurement by each kit. A simple linear regression line forced to the origin was generated for each kit. the validation criteria, based upon accuracy and precision analysis, includes the fact that the range of slope of the regression line of 95% confidence must fall between 0.75 and 1.25, and the correlation coefficient must be no less than 0.99 with significance ( P < 0.05). No enhancement/inhibition was observed with Endospecy. Kinetic QCL showed enhancement with Salmonella RSE and no enhancement/inhibition with E. coli RSE. the ET single test-ES kit was inhibited with both RSE. Clinical dialysate samples were also measured for ET activity by each limulus kit which revealed that Endospecy and Kinetic QCL gave almost identical values; however, the ET single test-ES kit gave significantly lower values (41%) than the others ( P < 0.05). These results suggest that either the validation test using RSE or comparative analysis with an already validated kit (Endospecy) is necessary for measuring ET levels in dialysate.     

Assessing the utility of the stop dialysate flow method in patients receiving haemodiafiltration.

BACKGROUND: The stop dialysate flow (SDF) method of post-dialysis urea sampling is the most commonly used method in the UK. It can also be used with a published formula to predict 30 min equilibrated urea accurately. The method has not been validated in patients undergoing haemodiafiltration (HDF). Given the increased use of HDF across Europe, we felt it prudent to assess the utility of the SDF method and prediction equation in this modality. METHODS: Fourteen patients from two renal units were studied. Blood samples were taken at 1 min intervals from the arterial side of the dialysis circuit in the first 5 min after HDF had ceased whilst blood circulation continued. A peripheral sample was taken from the contralateral arm immediately after HDF had ceased and a 30 min sample was taken from the arterial needle. These samples were used to assess the utility of 5 min arterial blood urea and the 30 min prediction formula, respectively. RESULTS: Blood urea measured from the arterial circuit at 5 min correlated closely with the contralateral sample taken immediately post-HDF, with no significant difference (6.45+/-2.11 vs 6.52+/-2.19 mmol/l, P = 0.39). The use of 5 min arterial blood urea and prediction formula allowed an accurate prediction of 30 min urea (R2 = 0.96). CONCLUSIONS: The use of the SDF method with a 5 min post-HDF arterial sample is valid in patients receiving HDF. The previously published prediction formula for estimating 30 min urea is also valid using the 5 min post-HDF sample.     

人参总皂甙对乳酸盐腹膜透析液致人腹膜间皮细胞损伤的保护作用

目的 :观察人参总皂甙 (GS)对乳酸盐腹膜透析液 (L -PDS)在体外所致的人类腹膜间皮细胞 (HPMC)活力和增殖抑制的影响。方法 :采用胰蛋白酶消化法从人腹膜组织中分离间皮细胞 ,建立稳定的体外培养模型 ;用乳酸脱氢酶 (LDH)的释放和四甲基偶氮唑盐比色法 (MTT法 )评估细胞的活性及增殖能力。结果 :2 .5 %和 4.2 5 %葡萄糖L-PDS组与对照组相比HPMC的LDH释放增多 ,且两浓度差异无显著性 ;随L -PDS暴露时间的延长 ,HPMC的存活率逐渐降低 ;GS可以减少LDH的释放 ,提高细胞存活率 (P <0 .0 1) ,并能促进HPMC的增殖 (P <0 .0 5 )。结论 :GS对L-PDS体外所致HPMC活力和细胞增殖的抑制具有一定的保护作用。     

Changes in CD14 expression on monocytes and changes in serum soluble CD14 level during hemodialysis

Background. CD14 is a receptor of lipopolysaccharide (LPS) and LPS binding protein (LBP) complex expressed on monocytes, and changes in the cell surface CD14 expression are thought to be a marker of activation of these cells. CD14 is shed from the cell surface when monocytes are activated. In this study, we assessed the influence of dialyzer membrane material and dialysate purity on monocyte CD14 expression and serum soluble CD14 (sCD14) levels in chronic hemodialysis (HD) patients in vivo during HD. Methods. We measured LPS concentrations in dialysate at two institutions by limulus assay. From one institution where LPS was undetectable in dialysate over a 2-year period, we selected seven patients. In the first period of the study, they were treated with a regenerated cellulose (RC) dialyzer, and then they were treated with a polysulfone (PS) dialyzer. We named them the "RC group" and the "PS group", respectively. From the other institution, where dialysate was contaminated with LPS, we selected eight patients. They were treated with a PS dialyzer, and were named the "PS + LPS group". CD14 expression on monocytes and serum sCD14 concentrations were measured by flow cytometry analysis and enzyme-liked immunosorbent assay, respectively. Results. During HD, in the RC group, upregulation of CD14 expression across the dialyzer was greater than in the PS group. There was no significant variation in serum sCD14 levels during HD in the RC and PS groups, while in the PS + LPS group, serum sCD14 level on the venous side of the dialyzer was significantly increased at 30 and 180 min after the initiation of HD compared with the predialysis value, and at 30 and 180 min compared with the level on the arterial side of the dialyzer. These results suggest that the changes in CD14 expression reflected the effect of dialyzer membrane material, while the changes in serum sCD14 levels reflected the effect of LPS influx from the dialysate. Conclusion. Dialysate purity may be an important factor in preventing monocyte activation during HD. Received: April 13, 1999 / Accepted: July 16, 1999     

Ultrapure versus standard dialysate: A cost‐benefit analysis

Low‐level bacterial and endotoxin contamination of water used to generate dialysate propagates chronic inflammation in patients with a wide‐range of potential adverse consequences, including erythropoietin hyporesponsiveness. Advancements in hemodialysis systems now allow for the generation of ultrapure dialysate that has lower bacterial and endotoxin levels than the standard dialysate. The cost associated with ultrapure dialysate is thought to be a major barrier to its widespread adoption. In this report, we conduct a cost‐benefit analysis examining the excess cost of generating ultrapure dialysate and the potential cost saving from a lower erythropoietin dose requirement. Our analysis suggests a potential cost saving of approximately $371 to $425 million per year with full adoption of ultrapure dialysate in the United States.     

Nonlinear plasma protein binding and haemodialysis clearance of prednisolone

Summary The impact of nonlinear plasma protein binding of a drug on its removal by haemodialysis has been quantified. Prednisolone 10–100 mg was given i.v. to 10 renal transplant patients on haemodialysis for acute tubular necrosis. Dialysate and afferent and efferent blood samples were collected simultaneously in 67 instances. Total and unbound prednisolone in plasma and its total concentration in blood and dialysate were assessed by high performance liquid chromatography and equilibrium dialysis. The amount of prednisolone lost, as measured directly in the dialysate (21.8±4.4 µg/min, ± SE), was predictable from the afferent-efferent blood concentration differences (20.1±4.8 µg/min), but not from measurements of total afferent-efferent prednisolone concentrations in plasma (13.1±3.0 µg/min). The amount of prednisolone lost in the dialysate increased linearly with unbound (r ²=0.96) and hyperbolically with the total prednisolone concentration in plasma. The latter hyperbolic relationship is adequately described by the equation for nonlinear plasma protein binding, using the affinity and capacity constants of albumin and transcortin for prednisolone (r ²=0.98). Thus, the haemodialysis clearance of total prednisolone is concentration-dependent, while the clearance of unbound prednisolone is constant (76 ml/min). Free clearance values or measurements of afferent-efferent blood concentrations are mandatory for a drug showing nonlinear plasma protein binding in order to predict the amount lost in the dialysate.Abbreviations Used C_Ba Afferent blood concentration [ng/ml] - C_Be Efferent blood concentration [ng/ml] - C_D Dialysate concentration [ng/ml] - C_Pa Afferent plasma concentration [ng/ml] - C_PaFree Free concentration of prednisolone in afferent plasma [ng/ml] - C_Pe Efferent plasma concentration [ng/ml] - CAP_A Binding capacity of albumin [µg%] - CAP_T Binding capacity of transcortin [µg%] - Cl_B Blood clearance [ml/min] - Cl_Free Free plasma clearance [ml/min] - Cl_P Plasma clearance [ml/min] - H_a Haematocrit in afferent blood - H_e Haematocrit in efferent blood - K Partition coefficient between red blood cells and plasma - KD_A Dissociation constant of albumin (M/L) - KD_T Dissociation constant of transcortin (M/L) - Q_B Blood flow [ml/min] - Q_D Dialysate flow [ml/min] - Q_F Flow of ultrafiltrate [ml/min] - t₁ First sampling time point after haemodialysis started - t₂ Last sampling time point before haemodialysis was discontinued - Z_Ddi Loss of prednisolone in the dialysate by diffusion [µg/min] (Z indicates calculated for each sampling time point) - _Ddi Mean loss of prednisolone in the dialysate by diffusion [µg/min] ( indicates calculated for the entire haemodialysis period) - Z_Dtot Total amount of prednisolone recovered in the dialysate [µg/min] - _Dtot Mean total amount of prednisolone recovered in the dialysate [µg/min] - Z_Du Loss of prednisolone in the dialysate by ultrafiltration [µg/min] - _Du Mean loss of prednisolone in the dialysate by ultrafiltration [µg/min] - Z_cB Amount of prednisolone lost in the dialysate calculated from afferent-efferent blood concentrations [µg/min] - _cB Mean amount of prednisolone lost in the dialysate calculated from afferent-efferent blood concentrations [µg/min] - Z_cP Amount of prednisolone lost in the dialysate calculated from afferent-efferent plasma concentrations [µg/min] - _cP Mean amount of prednisolone lost in the dialysate calculated from afferent-efferent plasma concentrations [µg/min] - Z_cPK Amount of prednisolone lost in the dialysate calculated from afferent-efferent plasma concentrations corrected by the partition coefficient [µg/min] - _cPK Mean amount of prednisolone lost in the dialysate calculated from afferent-efferent plasma concentrations corrected for the partition coefficient [µg/min] Abstract presented to the American Society of Nephrology, Washington, 1981     

A New Method for Removal of Albumin‐Binding Uremic Toxins: Efficacy of an Albumin‐Dialysate

Abstract: It is difficult for conventional hemodialysis to remove albumin‐binding uremic toxins (ABUTs) even though they are low molecular weight substances. We investigated the efficiency of albumin‐dialysate (AD) for removal of ABUT. Phenols and indoxyl sulfate were selected as ABUT. In vitro dialysis was performed for 2 h in the closed circuit with ABUT containing plasma as a test solution using conventional dialysate (CD) or AD. By the use of CD, the ABUT concentration in the test solution only was reduced by 20 to 30%. On the other hand, AD caused a marked reduction and an increase in test solution and dialysate concentration of ABUT, respectively. ABUT in AD could be adsorbed effectively by activated‐charcoal column; accordingly, the ABUT concentration in the test solution continued to decrease throughout the study period. These results suggest that AD could remove ABUT more efficiently than CD, and AD may be useful for reducing accumulated ABUT levels.