Requirements and Pitfalls of Dialyzer Sieving Coefficients Comparisons.

Sieving coefficients reported in dialyzer data sheets and instructions for use (IFUs) indicate the potential of different solutes to pass across a particular membrane. Despite being measured in vitro, sieving coefficient data are often used as a predictor of the clinical performance of dialyzers. Although standards for the measurement of sieving coefficients exist, the stated methodologies do not offer sufficient guidance to ensure comparability of test results between different dialyzers. The aim of this work was to investigate the relationship between sieving coefficients and published clinical performance indicators for two solutes, albumin loss and beta-2 microglobulin (ß2 M) reduction ratio (RR), and to assess the impact of different in vitro test parameters on sieving coefficient values for albumin, ß2 M, and myoglobin. Clinical albumin loss and ß2 M RR for commercially available dialyzers used in hemodialysis (HD) and post-dilution hemodiafiltration (HDF) were extracted from the literature and plotted against sieving coefficients reported in data sheets and IFUs. Albumin, ß2 M, and myoglobin sieving coefficients of a selection of dialyzers were measured per the ISO 8637 standard. The impact of in vitro testing conditions was assessed by changing blood flow rate, ultrafiltration (UF) rate, sampling time, and origin of test plasma. Results showed variation in albumin loss and ß2 M RR for the same sieving coefficient across different dialyzers in HD and HDF. Changes in blood flow rates, UF rates, sampling time, and test plasma (bovine vs. human) caused marked differences in sieving coefficient values for all investigated solutes. When identical testing conditions were used, sieving coefficient values for the same dialyzer were reproducible. Testing conditions have a marked impact on the measurement of sieving coefficients, and values should not be compared unless identical conditions are used. Further, variability in observed clinical data in part reflects the lack of definition of test conditions.

Hemodialyzer Reuse and Gram-Negative Bloodstream Infections.

BACKGROUND: Clusters of bloodstream infections caused by Burkholderia cepacia and Stenotrophomonas maltophilia are uncommon, but have been previously identified in hemodialysis centers that reprocessed dialyzers for reuse on patients. We investigated an outbreak of bloodstream infections caused by B cepacia and S maltophilia among hemodialysis patients in clinics of a dialysis organization. STUDY DESIGN: Outbreak investigation, including matched case-control study. SETTING & PARTICIPANTS: Hemodialysis patients treated in multiple outpatient clinics owned by a dialysis organization. PREDICTORS: Main predictors were dialyzer reuse, dialyzer model, and dialyzer reprocessing practice. OUTCOMES: Case patients had a bloodstream infection caused by B cepacia or S maltophilia; controls were patients without infection dialyzed at the same clinic on the same day as a case; results of environmental cultures and organism typing. RESULTS: 17 cases (9 B cepacia and 8 S maltophilia bloodstream infections) occurred in 5 clinics owned by the same dialysis organization. Case patients were more likely to have received hemodialysis with a dialyzer that had been used more than 6 times (matched OR, 7.03; 95% CI, 1.38-69.76) and to have been dialyzed with a specific reusable dialyzer (Model R) with sealed ends (OR, 22.87; 95% CI, 4.49-∞). No major lapses during dialyzer reprocessing were identified that could explain the outbreak. B cepacia was isolated from samples collected from a dialyzer header-cleaning machine from a clinic with cases and was indistinguishable from a patient isolate collected from the same clinic, by pulsed-field gel electrophoresis. Gram-negative bacteria were isolated from 2 reused Model R dialyzers that had undergone the facility's reprocessing procedure. LIMITATIONS: Limited statistical power and overmatching; few patient isolates and dialyzers available for testing. CONCLUSIONS: This outbreak was likely caused by contamination during reprocessing of reused dialyzers. Results of this and previous investigations demonstrate that exposing patients to reused dialyzers increases the risk for bloodstream infections. To reduce infection risk, providers should consider implementing single dialyzer use whenever possible.

Reuse and Biocompatibility of Hemodialysis Membranes: Clinically Relevant?

The practice of reprocessing dialyzers for reuse, once predominant in the United States, has been steadily declining over the last 20 years. The professed roles of reuse in improving dialyzer membrane biocompatibility and lowering the risk of first-use syndrome have lost relevance with the advent of biocompatible dialyzer membranes and favorable sterilization techniques. The potential for cost-savings from reuse is also called into question by the easy availability of comparatively cheaper dialyzers and rising regulatory demands and operational cost of reprocessing systems. While the environmental concerns from additional dialyzer-related solid waste from rising single-use practice remains pertinent and requires development of safer dialyzer disposable system technologies, there is no meaningful medical rationale for the continued practice of dialyzer reuse in the twenty-first century.

Public health benefits of water purification using recycled hemodialyzers in developing countries.

In rural regions with limited resources, the provision of clean water remains challenging. The resulting high incidence of diarrhea can lead to acute kidney injury and death, particularly in the young and the old. Membrane filtration using recycled hemodialyzers allows water purification. This study quantifies the public health effects. Between 02/2018 and 12/2018, 4 villages in rural Ghana were provided with a high-volume membrane filtration device (NuFiltration). Household surveys were collected monthly with approval from Ghana Health Services. Incidence rates of diarrhea for 5-month periods before and after implementation of the device were collected and compared to corresponding rates in 4 neighboring villages not yet equipped. Data of 1,130 villagers over 10 months from the studied communities were studied. Incidence rates showed a decline following the implementation of the device from 0.18 to 0.05 cases per person-month (ppm) compared to the control villages (0.11 to 0.08 ppm). The rate ratio of 0.27 for the study villages is revised to 0.38 when considering the non-significant rate reduction in the control villages. Provision of a repurposed hemodialyzer membrane filtration device markedly improves health outcomes as measured by diarrhea incidence within rural communities.

The current and future landscape of dialysis.

The development of dialysis by early pioneers such as Willem Kolff and Belding Scribner set in motion several dramatic changes in the epidemiology, economics and ethical frameworks for the treatment of kidney failure. However, despite a rapid expansion in the provision of dialysis - particularly haemodialysis and most notably in high-income countries (HICs) - the rate of true patient-centred innovation has slowed. Current trends are particularly concerning from a global perspective: current costs are not sustainable, even for HICs, and globally, most people who develop kidney failure forego treatment, resulting in millions of deaths every year. Thus, there is an urgent need to develop new approaches and dialysis modalities that are cost-effective, accessible and offer improved patient outcomes. Nephrology researchers are increasingly engaging with patients to determine their priorities for meaningful outcomes that should be used to measure progress. The overarching message from this engagement is that while patients value longevity, reducing symptom burden and achieving maximal functional and social rehabilitation are prioritized more highly. In response, patients, payors, regulators and health-care systems are increasingly demanding improved value, which can only come about through true patient-centred innovation that supports high-quality, high-value care. Substantial efforts are now underway to support requisite transformative changes. These efforts need to be catalysed, promoted and fostered through international collaboration and harmonization.

A comparison of methods for determining urea distribution volume for routine use in on-line monitoring of haemodialysis adequacy.

BACKGROUND: The availability of haemodialysis machines equipped with on-line clearance monitoring (OCM) allows frequent assessment of dialysis efficiency and adequacy without the need for blood samples. Accurate estimation of the urea distribution volume 'V' is required for Kt/V calculated from OCM to be consistent with conventional blood sample-based methods. METHODS: Ten stable HD patients were monitored monthly for 6 months. Time-averaged OCM clearance (K(OCM)) and pre- and post-dialysis blood samples were collected at each monitored session. The second generation Daugirdas formula was used to calculate the single-pool variable volume Kt/V, (Kt/V)(D). Values of V to allow comparison between OCM and blood-based Kt/V were determined from Watson's formula (V(Watson)), bioimpedance spectroscopy (V(BIS)), classical urea kinetic modelling (V(UKM_C)) and a simple computation of V (V(UKM_S)) from the blood-based Kt/V and K(OCM)t. RESULTS: Comparison of K(OCM)t/V with (Kt/V)(D) shows that using V(Watson) leads to significant systematic underestimation of dialysis dose. K(OCM)t/V(BIS) agrees with (Kt/V)(D) to within +/- 10%. K(OCM)t/V(UKM_S) is, by definition, identical to (Kt/V)(D) when initially calculated. However, if a historical value of V is used, agreement between K(OCM)t/V and (Kt/V)(D) over 6 months varies by 5% for V(BIS) and 10% for V(UKM_S). CONCLUSIONS: When investigating the effect of different treatment strategies on dialysis efficiency, any estimate of V can be used provided it is constant, as K is the relevant parameter. When frequent supervision of actual dialysis dose is required, the greatest consistency between K(OCM)t/V and the reference, Kt/V(D), over time is achieved with V(BIS).

The Effect of Dialysis Modality and Membrane Performance on Native Immunity in Dialysis Patients.

Chronic Kidney Disease (CKD) is characterized by immune activation with development of chronic inflammation. However, immune deficiency also exists in CKD patients. The number and the activity of Natural Killer cells (NK-cells) are influenced by the biocompatibility of various dialysis membranes. In this study we investigated the effect of dialysis modality and membrane type on NK-cell number and on phagocytic activity of neutrophils in patients on different dialysis methods. Sixty patients were included in the study and divided in three groups of 20 patients each. Patients on conventional hemodialysis using Low Flux membrane (cHD-LF) were included in Group I, patients on conventional dialysis using High Flux membrane (cHD-HF) were included in Group II and patients treated by on-line hemodiafiltration with High Flux polysulphone membrane (on-line HDF) were included in Group III. Native immunity was investigated using the number of NK-cells and the phagocytic activity of neutrophils. NK-cells count was significantly lower (p<0.001) in the three groups of dialyzed patients in comparison to healthy subjects. However, no significant difference was observed in the NK-cells count among patients treated by conventional dialysis using Low or High Flux membrane and patients treated by on-line hemodiafiltration. Similarly, although the phagocytic activity of neutrophils was significantly decreased in all patients on dialysis (p<0.001), no difference related to the dialysis modality or membrane performance was observed. A strong positive correlation was recognized between parathormone blood levels and number of NK-cells (r=0.305, p<0.01). In conclusion, an impairment of the native immunity represented by NK cell number and phagocytic activity of neutrophils is observed in patients on dialysis. Dialysis modality and membrane performance do not influence the native immunity of dialyzed patients. However, parathormone blood levels are possibly involved in the development of immune system disturbances in such patients.

Data acquisition system for dialysis machines. A model for membrane hydraulic permeability.

Membrane permeability is a key determinant of dialyzer performance; in vivo, membrane hydraulic permeability is affected by the formation of a protein cake on its surface, reducing ultrafiltration and convective fluxes. The purpose of this work was to evaluate the real hydraulic permeability of high flux polysulfone membrane under conditions of hemodiafiltration, and to consequently develop a mathematical model to estimate ultrafiltration Kuf and protein adsorption Kc coefficients. The DIB08 data acquisition system adapted to the Fresenius 2008E dialysis machine (Fresenius, Bad Homburg, Germany) allowed the recording of useful information for dialysis quantification, which was then processed by a bedside computer. The system was able to evaluate Kuf(t) profile, by calculation from the transmembrane pressure over time (TMP(t)) and ultrafiltration rate (Quf):Kuf (t) = Quf/TMP (t). Subsequent modeling of Kuf involved the determination of two key parameters: Kufhd (dialyzer permeability during diffusion only) (in mL/h/mmHg), and Kc (protein adsorption coefficient) (in mL/h/mmHg2). The model chosen was the following: Kuf (t) = Kuf0 x (1 - (Kc/Kuf0) x In(t + 1)) where Kuf0 represents the initial Kuf obtained at the beginning of the session. Thirty-one sessions were evaluated by real kinetic analysis, from which the mathematical model was derived. It included 27 postdilutional on-line hemodiafiltration and four hemodialysis sessions performed in four patients with nonreused HF80s dialyzers. For the analysis, three subgroups were defined: Group 1, first session of the week (Monday or Tuesday); Group 2, second session of the week (Wednesday or Thursday); and Group 3, third session of the week (Friday or Saturday). Results of Kuf and Kc obtained by real kinetic analysis are presented. The midweek session was associated with a higher membrane hydraulic permeability, most likely relative to lesser ultrafiltration rates and an associated relative decrease in membrane protein coating, represented by Kc. The described data acquisition system allowed the assessment of real time membrane hydraulic permeability and the subsequent development of a mathematical model to estimate this fundamental parameter as it functions to hemodialyzer performance.

Dialyzer reprocessing: improved treatment quality and increased dialyzer reuse using a team approach.

Use of the performance improvement process can yield unexpected positive results. Through the implementation of performance improvement concepts, the Dialysis Centers of Dayton LLC East was able to increase the average dialyzer reuse number and achieve economical benefits while improving the quality of patient care delivered. Employment of the team approach, staff education, and communication was vital to the success of this Over the last 10 years, the use of dialyzer reprocessing has steadily increased in dialysis units across the country. If the reuse average was down in a unit, it was not uncommon to look to the reuse staff for an explanation, since it is "their" job to keep the numbers up. After consultation with a Minntech representative, the Dialysis Centers of Dayton LLC East staff discovered that the most effective methods to increase the average reuse number were those implemented on the dialyzer before it ever reached the reprocessing area. Several technical changes were initiated, including the use of standardized heparin protocols, all of which contributed to the improvement in the reuse average. Although some of these changes had been done previously, they were not implemented and reviewed according to the formal performance improvement model. Two methods for calculating the reuse average were employed. Over a 12-month time frame, reuse numbers increased from 7.1 and 7.5 to 36.6 and 18.1, respectively (utilizing the Hartline [1996] and conventional method of reuse calculation). Review of patient adequacy showed no detrimental effects and a slight improvement in the percentage of patients with a Kt/V of more than 1.2. Focusing on performance improvement in the reprocessing area has yielded many benefits to both patients and staff.

[Electron-microscopy studies of capillaries of the dialyser C-DAK 4 with reference to multiple use]. / Elektronenmikroskopische Untersuchungen von Kapillaren des Dialysators C-DAK 4 unter dem Aspekt der mehrfachen Wiederverwendung.

The results of the examinations show that the integrity of the wall of the capillary is not impaired by the process of purification, but, on the other hand, functional changes by thrombotic occlusion as well as disseminated deposits of protein may be expected. The temporary regime of dialysis mus consider this fact in order to achieve a constant effect. But on principle from the clinical experience and on the basis of these results of examinations a manifold use of the dialysator of the capillary in carrying out the purification measures mentioned may be recommended.

Influence of reuse and of reuse sterilants on the first-use syndrome.

Over a 4 year period, five of 98 patients at our dialysis unit developed signs and symptoms consistent with first-use syndrome (FUS). Marked improvement was noted after subjecting new dialyzers to automated processing using either formaldehyde or peracetic acid. No episodes of FUS occurred in patients being treated with reused dialyzers. Use of formaldehyde sterilization was associated with development of anti-N-like antibodies in the blood of four (8%) of 50 patients over a follow-up period of 14 months. In two patients on the reuse program, itching during dialysis resolved after changing from formaldehyde-sterilization to a method using peracetic acid. Our results confirm the beneficial effects of reuse with regard to first-use syndrome. However, our data also suggest that use of formaldehyde, the most common reuse sterilant, continues to be associated with undesirable clinical and laboratory side effects.

Dialyzer reuse following manual reprocessing with a new sterilant, RenNew-D.

Dialysis patients are at risk for toxicity from formaldehyde used in the reprocessing of dialyzers for reuse; therefore, replacing formaldehyde as a dialyzer sterilant would be advantageous. The potential for RenNew-D as a sterilizing agent was investigated in seven stable in-center hemodialysis patients over 20 consecutive dialyses with cuprammonium cellulose hollow-fiber dialyzers. Treatment with RenNew-D showed no toxicity to patients or dialyzers except for two blood leaks occurring in one patient. The mean number of dialyzer uses was 4.9. In all the dialyzers that passed functional testing small solute clearances were maintained with reuse. The ability of RenNew-D to improve the biocompatibility of reused dialyzers was documented with mean neutrophil counts falling to only 78% of initial values during first reuse of dialyzers processed with RenNew-D compared with a decrease in neutrophil count to 2% of initial values during first use of the same dialyzers. Our results suggest that RenNew-D may be a useful alternative to formaldehyde for the purpose of dialyzer reuse. A reuse procedure that includes processing with RenNew-D is associated with improved biocompatibility, possibly because of maintenance of the blood-derived membrane coating established during prior dialysis.

Multiple use of dialyzers: safety and efficacy.

The practice of multiple use of dialyzers was examined over a 15-month period on all 104 patients in a chronic maintenance hemodialysis facility. A computerized medical information system permitted analysis of the incidence of events in over 10,000 successive hemodialyses. It also allowed analysis of the events in 27 patients dialyzed for a total of 655 months successively in two units practicing single and multiple dialyzer use. The incidence of complications during dialysis, of complications that might be related to infection, and the rate of hospitalization was not greater when the 27 patients were dialyzed in the unit practicing multiple use as compared with the rates in the unit practicing single use. Events possibly associated with infection did not occur more frequently during dialyses in which the dialyzer had been used between 2 and 20 times than they did with the initial use of the dialyzer. With successive dialyzer use, there was no significant change in the ability to remove fluid or in the dialysance of urea and creatinine. The neutropenia that characteristically occurs early in dialysis was substantially less with reused dialyzers than with their initial use. Under the operating conditions described, we conclude that multiple dialyzer use over a 15-month period is safe, efficacious, and is not associated with an increased rate of infection, of morbidity from any cause, or of mortality.

Multiple use of dialysers: an Australian view.

Multiple uses of dialyzers has been studied in a single hospital and by survey of all Australian dialysis units. An annual saving of $84,000 was achieved in a 46-patient unit. No significant patient morbidity or mortality occurred. In Australia 43% of all haemodialysis patients are on a multiple use regime. The 1-year patient cumulative survival for units with a reuse policy is 92.8% and for those with a single use of policy is 87.1%. Anti-N-like antibodies are being found in low but increasing frequency as the reuse program continues.

Reuse of a disposable dialyser for home dialysis.

A disposable parallel flow plate dialyser (Gambro Lundia) has been evaluated. It is comparable in surface area and efficiency to the standard Kiil dialyser and can be regularly reused six times, combining the reliability and convenience of a prefabricated, factory-tested unit with the low cost of the Kiil dialyser.