'Clean dialysate' requires not only lower levels of endotoxin but also sterility of dilution water

Clean dialysate should be used in dialysis with a high-flux dialysis membrane to avoid contamination of endotoxin into blood circuits. For this purpose, we should not only clean up the end stream dialysate by endotoxin-cut filters, but also prevent bacterial growth in dilution water lines. Delivery lines of the prepared dialysate from a central dialysate-supplying machine are sterilized in all dialysis facilities, but those of the dilution water in cases of using personal dialysis machines are not sterilized in most facilities in Japan. In our dialysis department, the endotoxin level in the dilution water lines decreased to <50 EU/l in 3 weeks by sterilization with a low concentration of sodium hypochlorite (30-100 ppm) once a week from the peak level of >1,000 EU/l just after the start of sterilization.     

Microbiological survey of dialysate: vantage of use of sterile bag concentrate

Haemodialysed patients are exposed to nearly 400 litres of dialysis water weekly. The bacterial contamination of treated dialysate and water induces acute pyrogenic reactions or chronic damage and cytokine activation. The aim of this study was to value the microbiological parameters of dialysis water and dialysate of our monitors by bacterial culture (measured as colony forming units [CFU]) of water samples at 37 degrees C after 48 hours, at 22 degrees C after 72 hours and after seven days, and by measuring endotoxin levels (endotoxin units [EU]). In our centre, there are 16 monitors (6 monitors use sterile dialysate fluid and 10 monitors use non sterile dialysate fluid). The chemicals used for disinfection are chlorine and paracetic acid. Water samples were taken under sterile procedures every three months for a year. No bacteria were found in the samples of water of the dialysis ring; EU were lower than the limit value of 0.25 EU/ml fixed by the European Pharmacopoeia. The concentration of CFU and EU of the dialysate, taken from monitors with a sterile bag, were lower than those of other monitors (p < 0.05 t Student test). However, the levels of CFU/ml and EU/ml of dialysate samples, taken from monitors with a non-sterile bag, were lower than the guideline value of the European Pharmacopoeia (v.n. CFU < 50 CFU/ml and EU < 0.05 EU/ml). Frequent examination of CFU and EU is essential to reduce the damage caused by the use of contaminated water, therefore the goal of future dialytic techniques will be the use of "sterile dialysate".     

Reduced cytokine induction and removal of complement products with synthetic hemodialysis membranes

The increasing use of high-flux membranes for hemodialysis (HD) has raised concerns that these membranes may confer a higher risk of exposure to cytokine-inducing, bacterial substances (CIS) in the dialysate. Several studies, however, reported higher transfer of CIS through low-flux cellulosic than high-flux synthetic membranes. This surprising paradox was explained by adsorption of CIS to certain high-flux membranes. In order to investigate flux and membrane type independently, we studied two synthetic Polyflux (PF) membranes of the same type but with different flux properties and compared them to a cellulosic membrane (Cuprophan). Three different approaches were employed: (1) cytokine induction in whole blood during in vitro HD contaminated with bacterial filtrates, (2) removal of recombinant C5a, and (3) transfer of purified lipopolysaccharide (LPS). After 90 min recirculation of whole blood, the appearance of IL-6-inducing substances on the blood side was lowest with high-flux PF (1.1 +/- 0.2 ng/ml), slightly higher with low-flux PF (1.9 +/- 0.7 ng/ml) and highest with Cuprophan (4.1 +/- 1 ng/ml). Recombinant C5a added to plasma on the blood side was markedly removed by high-flux PF (by 83%), to a lesser degree and only in the presence of ultrafiltration with low-flux PF (by 54%) and not significantly with Cuprophan (by 11%). Significant transfer of purified LPS from the dialysate onto the blood side was only observed with the cellulosic membrane. We conclude that in contrast to cellulosic membranes, certain synthetic membranes do not permit transfer of LPS. Cytokine induction on the blood side is further reduced by the use of high-flux membranes due to removal of activated complement factors.     

Implementing On-Line Hemodiafiltration as a Renal Replacement Therapy for ICU Acute Renal Failure: A Single-Center Report of Feasibility, Safety and Hemodynamic Tolerance over a Seven-Year Period

Background/Aims: On-line hemodiafiltration (HDF) is not yet routinely used in ICUs given the potential risk of microbial contamination of dialysis fluids. We evaluated the safety and the tolerance of its use in our ICU. Methods: A weekly measurement of bacterial growth (CFU/ml) and endotoxin level (endotoxin units/ml) was performed in dialysis fluids over a 7-year period. Intradialytic hypotensive events and pyrogenic reactions were collected during 466 on-line HDF sessions. Results: A bacterial count <0.1 CFU/ml was achieved in 977/978, 288/290, and 278/280, and an endotoxin level <0.03 endotoxin units/ml in 564/576, 330/337 and 318/323 ultrapure water, dialysate, and infusate samples, respectively. Seventy-six intradialytic hypotensive events but no pyrogenic reaction occurred. Conclusion: The great majority of dialysis fluid samples were considered suitable with a 99% compliance rate. Use of on-line HDF, at a large scale of dialysate and infusate flows, is well tolerated and may be safely performed in critically ill.     

When good water goes bad: how it happens, clinical consequences and possible solutions

Dialysis fluid produced by state-of-the-art water preparation and distribution is contaminated with gram-negative bacteria and cytokine-inducing substances (CIS) derived from these microorganisms. The presence of a biofilm increases the risk of continuous contamination of dialysis fluid. Depending on the type of dialyzer membrane (cellulosic vs. synthetic) and the mode of dialysis (low flux vs. high flux with backfiltration), CIS may penetrate intact dialyzer membranes, induce cytokine production in the patient's blood and contribute to chronic inflammation associated with long-term hemodialysis therapy. Measures to improve the microbiological quality of dialysis fluid are: (1) the awareness of the problem and regular testing of dialysate samples using adequate methods; (2) disinfection of the entire water preparation and distribution system on a regular basis, replacement of biofilm-containing tubings, and (3) installation of ultrafilters in the dialysate circuit in particular when high-flux hemodialysis modalities are performed.     

Effects of Dialysis Purity on Uremic Dyslipidemia

Dyslipidemia, a prominent feature of end-stage renal disease, is considered a risk factor for premature atherosclerosis in hemodialysis (HD) patients. Dyslipidemia is related to loss of kidney function as well as use of low-flux cellulosic dialyzer membranes, but the effects of dialysate purity are unknown. Forty-eight incident HD patients started high-flux polysulfone maintenance HD, either with conventional (potentially contaminated) or with on-line produced ultrapure dialysate. The quality of the dialysis fluid (CFU/mL, endotoxin concentration), markers of inflammation (C-reactive protein, Il-6), and parameters of the lipid profile and oxidative stress (oxidized low-density lipoprotein) were measured before initiation of HD, and after 6, 12 and 24 months on HD. Compared to baseline, treatment with conventional (mildly contaminated) dialysate significantly increased the uremic low-grade systemic inflammatory response syndrome (SIRS), augmented uremic dyslipidemia (triglycerides by +21%, and high-density lipoprotein (HDL) cholesterol by −10%) and enhanced oxidative stress. In contrast, the use of ultrapure dialysate significantly decreased uremia-associated SIRS, dyslipidemia (triglycerides −7% and HDL cholesterol +11%) and oxidative stress. Ultrapure dialysis fluid improves potential parameters of cardiovascular risk by decreasing inflammatory reactions, improving uremic dyslipidemia and lowering oxidative stress.     

Measurement of backfiltration rates during hemodialysis with highly permeable membranes.

A method for determining local transmembrane fluid movement in a commercial hemodialyzer at low dialysate flow rates by measuring changes along the dialyzer length in the local concentration of a marker macromolecule added to the dialysis solution has been developed. The method was evaluated in vitro at zero net ultrafiltration using dialyzers containing polysulfone (n = 4) and cuprophane (n = 3) membranes. The local concentration of the marker macromolecule along the dialyzer length was higher than the input dialysate concentration only during experiments with dialyzers containing polysulfone membranes. These observations provide direct empirical evidence that fluid movement in the dialysate to blood direction, i.e., backfiltration, occurs during hemodialysis with this highly permeable membrane. Net rates of backfiltration for the dialyzer containing polysulfone membrane were also calculated from changes in the local concentration of the marker macromolecule and mass balance considerations. The calculated backfiltration rates increased with increasing blood flow rate and trended upward with increasing dialysate flow rate. The described methodology provides a novel approach for the further characterization of fluid and solute transport during hemodialysis with highly permeable membranes.     

Reprocessed (high-flux) Polyflux dialyzers resist trans-membrane endotoxin passage and attenuate inflammatory markers

BACKGROUND: Bacterial contamination of dialysis water can contribute to the chronic microinflammatory state observed in dialysis patients. This study characterized the selective permeability of new and peroxyacetic acid/acetic acid/hydrogen peroxide (Renalin) reprocessed high-flux, polyarylethersulfone-polyvinylpyrrolidone (Polyflux-17R) dialyzers after exposure to endotoxin-contaminated dialysate during in vitro dialysis. Clinical correlation with pre-dialysis levels of systemic markers of inflammation, and clearance of middle molecules was also assessed in vivo. METHODS: Six hemodialysis (HD) patients were enrolled in the study. After reuses 0, 1, 5, 10, and 15, the dialyzers were reclaimed and submitted to an in vitro dialysis circuit using standard dialysate and blood from healthy volunteers. New and reprocessed dialyzers were sequentially exposed to escalating doses of Pseudomonas aeruginosa endotoxin in the dialysate compartment, and whole blood tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production was used as an index of reverse passage of endotoxin. In vivo, IL-6, C-reactive protein (CRP) and serum amyloid A (SAA) levels were measured to assess the impact of reprocessing on the systemic inflammatory response. Finally, pre- and post-dialysis samples were collected to measure urea and beta(2)-microglobulin (beta(2)-M) clearances. RESULTS: During in vitro dialysis, blood-side endotoxin levels were undetectable following dialysate contamination. TNF-alpha production remained unchanged (p = NS), and IL-6 production fell significantly on reuses 0, 1, 10, and 15 (p = 0.03) suggesting membrane adsorption, as a result of reuse-dependent surface binding. In vivo, whereas IL-6 and SAA levels did not significantly differ (p = 0.90 and 0.59, respectively), CRP levels fell near significantly, over the course of 15 reuses (p = 0.06). In vivo, beta(2)-M clearance was not affected by the reuse technique (p = 0.28). CONCLUSIONS: This study provides in vitro and in vivo evidence arguing that high-flux Polyflux dialyzers provide more than adequate dialysis, while preventing the in vitro back-diffusion of bacterial endotoxin despite 15 reuses with Renalin. Clinically, this may translate into an attenuation of the microinflammatory milieu.     

Membrane flux not biocompatibility determines beta-2-microglobulin levels in hemodialysis patients

BACKGROUND: Serum beta(2)-microglobulin (beta(2)M) levels are important in dialysis-related amyloid deposition but can be influenced by dialysis technique. METHODS: We measured beta(2)M levels in 3 centres using different dialysis regimes. Centre 1 (73 patients) used high-flux biocompatible, centre 2 (72 patients) low-flux biocompatible and centre 3 (142 patients) cuprophane dialysers. RESULTS: beta(2)M levels were lower with high-flux biocompatible than with low-flux biocompatible or cuprophane dialysis (22.3 +/- 5.4 vs. 43.4 +/-13.7 and 37.6 +/-13.1 mg/l, respectively; p < 0.001). Levels were higher with low-flux biocompatible than with cuprophane dialysis (p < 0.001), but not if patients dialysed over 10 years were excluded. With low-flux biocompatible (47.4 +/- 9.8 vs. 38.7 +/- 15.2 mg/l; p < 0.01) and cuprophane dialysis (43.4 +/- 8.2 vs. 36.7 +/- 13.0 mg/l; p < 0.02), beta(2)M levels were higher in patients dialysed over 5 years than in those dialysed less. Despite beta(2)M levels increasing as residual renal function declined, there was no similar rise with high-flux biocompatible dialysis. CONCLUSIONS: Techniques allowing significant convection maintain lower beta(2)M levels over many years. Membrane flux, not biocompatibility, is the main determinant of beta(2)M levels in routine practice.     

Characterization of the DialGuard device for endotoxin removal in hemodialysis

Bacterial pyrogens, capable of penetrating dialyzer membranes, are responsible for a systemic inflammatory reaction in hemodialysis patients. Dialyzer reuse, involving rinsing of the dialyzer with pyrogen-containing water, may exacerbate this situation. Studies of the mechanism of action of endotoxin suggest that it irreversibly damages the vascular endothelium. The novel endotoxin removal method described here, is based on affinity-binding of endotoxin by the adsorbent ClarEtox, a USP Class VI-certified resin that is the active component of the medical device DialGuard. Under standard hemodialysis operating conditions, challenge of DialGuard with Pseudomonas maltophilia supernatant-spiked dialysate, containing 35-193 EU/ml endotoxin, resulted in endotoxin levels below 0.05 EU/ml in the treated dialysate. DialGuard was able to decrease endotoxin concentrations in the dialysate from a range of 2.39-8.49 to <0.005 EU/ml. DialGuard supports high fluid velocities at low back pressures and can be sanitized using the heat sanitization cycle of hemodialysis machines. DialGuard offers a simple, user-friendly way to reduce the concentration of endotoxin in dialysate and water for dialysis at a low cost.     

Intradialytic body weight changes and dialyzer pore size as main contributing factors to the evolution of beta-2-microglobulin in dialysis

Cuprophane hemodialysis is associated with an early fall of leukocyte counts and an intradialytic rise in serum beta 2-microglobulin (beta 2M), in contrast to dialysis with more compatible dialyzers. It has been suggested that these two phenomena may be related. This study sets out to verify this hypothesis by comparing the evolution of leukocyte counts with that of beta 2M: (1) during dialysis with 5 dialyzer types with different pore size and/or leukocyte biocompatibility; (2) during first use and reuse of 3 dialyzer types, and (3) during sequential ultrafiltration and dialysis with cuprophane. In first-use dialyses, no relation could be found between changes in leukocyte counts and the evolution of beta 2M levels. Reuse of cuprophane and saponified cellulose ester resulted in a marked attenuation of the intradialytic fall in leukocyte counts after 15 min (change in white blood cell count: -72 and -17% for first-use and third-reuse cuprophane, -72 and -23% for saponified cellulose, respectively), but had no influence on the increase in beta 2M. Correlation studies of these data revealed that the intradialytic evolution of beta 2M was related to membrane pore size and, for membranes with a small pore size, to the intradialytic fluid losses: first-use cuprophane (p less than 0.05), saponified cellulose ester (p less than 0.001) and hemophane (p less than 0.01), and pooled first-use and reuse cuprophane and saponified cellulose ester (p less than 0.001). Cuprophane dialysis without ultrafiltration (dialysate Na+: 138 and 132 mEq/l) caused a fall in leukocytes, but induced no rise in beta 2M. Ultrafiltration with cuprophane either preceding or following dialysis consistently caused a rise in serum beta 2M, although a fall in leukocyte counts only occurred in the first case. Our data point away from a relationship between membrane biocompatibility, expressed as changes in leukocyte counts, and beta 2M concentration during hemodialysis. The major contributing factors appear to be dialytic fluid losses and membrane pore size.     

Should dialysis machines be disinfected between patients' shifts?

The disinfection of dialysis machines is performed after each session in some units but only at the end of the day in other ones. In a multicentre study, in 15 units (five with and ten without disinfection after each session), the incidence of sero-conversion for HCV was reduced to zero, after reinforcement of general hygiene precautions only, without changing the above-mentioned machine disinfection policies. Recently reported episodes of blood contamination of dialysis machines beyond pressure transducers demonstrate that pressure isolator inspection and care should be added to the general hygiene precautions. In a second investigation, no difference was found in dialysate bacterial and endotoxin characteristics between dialysis machines, disinfected after each dialysis (n = 2) and those disinfected at the end of the day only (n = 2). In conclusion, the systematic disinfection of all dialysis machines after each session does not appear to help prevent HCV infection nor to have a detectable impact on optimal dialysate bacterial and endotoxin characteristics.     

SHOULD DIALYSIS MACHINES BE DISINFECTED BETWEEN PATIENTS' SHIFTS?

The disinfection of dialysis machines is performed after each session in some units but only at the end of the day in other ones. In a multicentre study, in 15 units (five with and ten without disinfection after each session), the incidence of sero‐conversion for HCV was reduced to zero, after reinforcement of general hygiene precautions only, without changing the above‐mentioned machine disinfection policies. Recently reported episodes of blood contamination of dialysis machines beyond pressure transducers demonstrate that pressure isolator inspection and care should be added to the general hygiene precautions. In a second investigation, no difference was found in dialysate bacterial and endotoxin characteristics between dialysis machines, disinfected after each dialysis (n = 2) and those disinfected at the end of the day only (n = 2). In conclusion, the systematic disinfection of all dialysis machines after each session does not appear to help prevent HCV infection nor to have a detectable impact on optimal dialysate bacterial and endotoxin characteristics.     

Preparation of ultrapure dialysate in Japan--clinical usefulness and short-term future

In 1994, the water quality standard of dialysate and substitution fluid for on-line HDF was established by the Kyushu Society for HDF. On the other hand, with the widespread use of high-flux membrane, reverse filtration and reverse diffusion became evident, and purification of the dialysate has become essential even for usual hemodialysis. By using ultrapure dialysate, new blood purification methods can be performed, such as internal filtration-enhanced hemodialysis, on-line HDF, and on-line HF. As a result, various clinical effects have been reported, such as improvement in anemia and in chronic inflammatory reactions. Suppression of complications involving long-term dialysis is expected, and even the prolongation of life expectancy. By using ultrapure dialysate as substitution fluid for saline solution, a fully automated dialysis machine has been developed. Furthermore, if fully automated consoles can be made smaller in size, they will contribute to the widespread use of home hemodialysis.     

Continuous venous-venous hemofiltration for the treatment of fluid overload in continuous ambulatory peritoneal dialysis patients

Fluid overload is not infrequent in continuous ambulatory peritoneal dialysis (CAPD) patients. In our experience, extemporaneous continuous venous-venous hemofiltration (CVVHF) was able to correct fluid imbalances refractory to high dose diuretics and hypertonic solutions. We treated 8 of 52 patients (5 females, 3 males, mean age 52 years) on CAPD from 4 to 36 months and with fluid overloads of up to 10 kg. A Biospal SCU/CAVH flat-sheet high-flux hemodialyzer employed for 10 h produced an ultrafiltration rate (QB:150 ml/min) of 11.12 +/- 4.97 ml/min. With an isotonic replacement solution, the filter provided sufficient extraction of small molecules so that CAPD could be interrupted during CVVHF. The procedure appeared well tolerated. This approach reduced the use of hypertonic dialysate, which is not devoid of side effects on ultrafiltration capacity of the peritoneal membrane.     

透析用水及透析液中内毒素污染状况的分析

目的　研究透析用水、透析液内毒素及细菌污染状况。方法　对北京１８ 家医院透析室反渗水、透析液用改良鲎试验检测内毒素,用血琼脂培养基做细菌培养,用ＥＬＩＳＡ法测定患者血浆白介素（ＩＬ）１、ＩＬ６ 及肿瘤坏死因子（ＴＮＦ）α。结果　反渗水内毒素为（０．１１６±０ ．０６３） ＥＵ／ｍｌ;细菌培养有两家医院阳性,均为１００ ＣＦＵ／ｍｌ。Ｂ浓缩透析液内毒素为（０．４６ ±０．３５） ＥＵ／ｍｌ,而Ａ浓缩透析液内毒素仅（０．０９１±０ ．０８４） ＥＵ／ｍｌ（Ｐ＜０ ．００１） ;Ｂ浓缩透析液细菌培养１１ 家阳性,其中８ 家≥２ ０００ ＣＦＵ／ｍｌ,Ａ浓缩透析液细菌培养阳性仅３ 家,均＜ ２ ０００ ＣＦＵ／ｍｌ。１６ 例患者中有５ 例透析器入口透析液内毒素＞０．５ ＥＵ／ｍｌ,且透后血ＩＬ６ 及ＴＮＦα显著增高。结论　目前透析用水及透析液存在内毒素及细菌的污染,定期检测反渗水、透析液的内毒素水平及进行细菌培养,定期消毒反渗水装置及透析液容器,对减少热源反应至关重要。     

Ultrapure dialysate reduces plasma levels of beta2-microglobulin and pentosidine in hemodialysis patients

BACKGROUND: beta2-Microglobulin (beta2MG) and carbonyl stress are reported to contribute to the development of dialysis-related amyloidosis. The aim of this study was to determine whether the purity of dialysate affects plasma levels of beta2MG and pentosidine (a surrogate marker of carbonyl stress) in hemodialysis patients. METHODS: Sixteen patients on hemodialysis with a polysulfone membrane participated in this study. We switched the dialysate from conventional dialysate (endotoxin level 0.055-0.066 endotoxin units (EU)/ml) to ultrapure dialysate (endotoxin level <0.001 EU/ml), followed patients for 6 months, and then switched back to conventional dialysate once again. Plasma levels of beta2MG, pentosidine, CRP and interleukin-6 (IL-6) were determined before the switch to ultrapure dialysate, 1 and 6 months after the switch to ultrapure dialysate, and 1 month after the switch back to conventional dialysate. RESULTS: The switch from conventional to ultrapure dialysate significantly decreased plasma levels of beta2MG, from 30.1 +/- 1.4 to 27.1 +/- 1.4 mg/dl (p < 0.05) and pentosidine, from 1,535.8 +/- 107.5 to 1,267.6 +/- 102.9 nmol/l (p < 0.01) after 1 month of use. The change of dialysate also significantly decreased plasma levels of CRP, from 0.28 +/- 0.09 to 0.14 +/- 0.05 mg/dl (p < 0.05) and IL-6, from 9.4 +/- 2.7 to 3.5 +/- 0.8 pg/ml (p < 0.01) over the 1-month period. These changes in plasma levels of beta2MG, pentosidine, CRP and IL-6 were maintained over 6 months after switching to ultrapure dialysate and returned to basal levels by switching back to a conventional dialysate. CONCLUSIONS: Ultrapure dialysate decreases plasma levels of beta2MG, pentosidine and inflammatory markers in hemodialysis patients. The use of ultrapure dialysate might be useful in preventing and/or treating complications of dialysis, such as dialysis-related amyloidosis, atherosclerosis and malnutrition.     

N-Acetylglucosamine- an osmotic slute for peritoneal dialysis without inducing hyperinsulinemia

METHODS: N-Acetylglucosamine (NAG) was compared to glucose as an osmotic solute during peritoneal dialysis in rats. The effect of the tested solutes on blood glucose and insulin levels during dialysis was evaluated. RESULTS: During 6-hour exchange with NAG (220 mmol/l) solution, the dialysate volume was higher than in rats dialyzed with fluid containing glucose (220 mmol/l; GLU: 34.5 +/- 1.7 vs. 32.8 +/- 1.1 ml, respectively; p < 0.05). The peritoneal permeability to protein (D/S x 1,000) was lower in the NAG group (9.7 +/- 2.5 vs. 16.3 +/- 5.6 in GLU; p < 0.02). Dialysis with GLU-based solution resulted in hyperglycemia up to 180 +/- 39 mg/dl; in the NAG group the increase in the blood glucose level was moderate (up to 91 +/- 9 mg/dl; p < 0.001). Dialysis with GLU fluid caused an increase in blood insulin level by 53.2 +/- 62.4 pmol/l, whereas the insulin blood concentration in NAG-treated animals was increased by 5.0 +/- 5.4 pmol/l (p < 0.001). CONCLUSIONS: NAG is more effective than GLU osmotic solute during peritoneal dialysis and it reduces peritoneal permeability to protein. Dialysis with NAG results in lower hyperglycemia and hyperinsulinemia, both effects are favorable in diabetic peritoneal dialysis patients.     

Outbreak of pyrogenic reactions at a dialysis center. Association with infusion of heparinized saline solution

Twenty-three pyrogenic reactions occurred in 16 patients undergoing hemodialysis at a private dialysis center in the south central United States between November 23 and December 2, 1978. No deaths were attributed to reactions; however, 10 patients were hospitalized for observation after experiencing a reaction. Cultures of all blood specimens obtained from the patients gave negative results. Chills (75 percent), nausea and/or vomiting (30 percent), and fever (90 percent) were the most common signs and symptoms, with mean times of onset after starting dialysis of 1.1, 1.6, and 3.6 hours, respectively. An epidemiologic and laboratory investigation documented that reactions occurred only in patients who had anticoagulation with a dilute solution of heparin. Analyses of heparinized saline solution used during the outbreak revealed a bacterial count of 7.4 X 10(5)/ml and a bacterial endotoxin level of 1,300 ng/ml. Acinetobacter calcoaceticus var. Iwoffi was isolated from the solution. Diluted heparin solution was prepared at the dialysis center by adding commercially supplied sodium heparin to 0.9 percent sodium chloride infusion fluid. Bacteria and endotoxin were not detected in vials of stock heparin and bags of unopened 0.9 percent sodium chloride infusion fluid. We concluded that contamination of the solution occurred at the dialysis center. After changes in the preparation and use of heparin were instituted on December 4, 1978, no pyrogenic reactions occurred in more than 400 subsequent dialyses.     

Paired filtration dialysis: studies on efficiency, flow dynamics and hydraulic properties of the system

Several strategies have been proposed to increase dialysis efficiency in order to reduce dialysis treatment time. Paired filtration dialysis (two-chamber technique) is a new technique combining the advantages of highly permeable membranes and convective transport with the high depurative efficacy of diffusion. The system operates with two units in series (hemofilter + dialyzer) with membranes of polysulfone and hemophan, respectively. A detailed analysis of the hydraulic properties of the system and its possible optimization in terms of depurative efficiency is reported in this paper. In vitro and in vivo tests provided data sufficient to draw some hypotheses on a new utilization of the system. The system appears to be adequate for operating under conditions of high blood flows, however, some limitations were evidenced during our evaluation: the convective component may be insufficient and further increases are impossible because of the limiting effect of the low surface area of the hemofilter; the configuration in which the weight loss is achieved in the hemofilter exposes to the risk of backfiltration in the dialyzer, reducing the benefits of a highly biocompatible system, and the use of acetate in the dialysate and/or lactate in the substitution fluid may interfere with a satisfactory correction of metabolic acidosis. On the basis of our evaluations, some changes can be proposed such as: (1) increased surface area of the hemofilter; (2) use of blood flows higher than 300 ml/min; (3) use of bicarbonate in the dialysate and in the replacement solution; (4) increased convective component with ultrafiltration rates of 50-60 ml/min and full replacement with substitution fluid in between the two filters, and (5) weight loss achieved in the dialyzer with a constantly positive transmembrane pressure. With such a modification of the operative conditions, paired filtration dialysis can be probably applied as a highly efficient dialysis technique in a large number of patients with a significant reduction of dialysis treatment time.