Predilution haemofiltration--the Second Sardinian Multicentre Study: comparisons between haemofiltration and haemodialysis during identical Kt/V and session times in a long-term cross-over study.

BACKGROUND: The potential superiority of various renal replacement treatment modalities consisting largely of convective mass transfer as opposed to primarily diffusive mass transfer, is still a matter of debate. The objective of the present study was to evaluate acute and long-term clinical effects of varying degrees of convection and diffusion in a group of 24 clinically stable patients with end-stage renal disease. METHODS: The patients were prospectively assigned to three consecutive treatment schedules of 6 months each: phase I (HF1) (on-line predilution haemofiltration)-->phase II (HD) (high-flux haemodialysis)-->phase III (HF2; as phase I). We used the AK100/200 ULTRA monitor (Gambro), which prepares ultrapure dialysis fluid for HD and sterile, pyrogen-free substitution solution for HF. The membrane (polyamide), fluid composition, and treatment time were the same on HF and HD. The targeted equilibrated Kt/V was 1.2 for both treatment modes, creating a similar urea clearance. RESULTS: Fifteen patients, mean age 62.8+/-8.4 years, completed the study according to the above conditions. Urea kinetics, nutritional parameters, and dry weight were similar in the three periods. The frequency of intra-treatment episodes of hypotension/patient/month was significantly lower on HF1 (1.24) and HF2 (1.27) than on HD (1.80) (P<0.04). It decreased progressively on HF1, then increased on HD, and decreased again during HF2. Patients had fewer muscular cramps on HF than on HD (P<0.03) and required significantly less saline and plasma expander during HF than HD sessions. The prevalence of inter-treatment symptoms, including fatigue and hypotension, was lower on HF than on HD (score difference P=0.04). Quality of life, determined by the Laupacis method in all three periods, showed a tendency towards improvement during the study, reaching the best values during HF2. CONCLUSIONS: HF has a progressive stabilizing haemodynamic effect, producing a more physiological cardiovascular profile than HD. This long-term effect, observed in stable patients treated under strictly identical conditions, is probably due to the mechanism of convection, and is different from the acute effect observed mainly in unstable patients.

Does convective dialysis therapy applied daily approach renal blood purification?

Outcome studies in dialysis have generally failed to show an impact of changes in membrane flux or biocompatibility, and only dose increases up to a certain level have been shown to improve survival significantly. However, to see an effect of a potentially improved dialysis treatment, all available factors that make dialysis more physiological may need to be combined. A membrane that mimics the glomerular basement membrane in being hemocompatible, having a high hydraulic permeability and a generous sieving, yet not leading to albumin loss could be used. The dialysis fluid composition could be individualized, and the quality and volume appropriate for the selected application. The new system of online-prepared ultrapure dialysis fluid and sterile infusion solutions, as integral parts of the treatment, are cost effective and labor saving as well as biocompatible. Ideally, we should select a blood purification method that covers the same range of solutes as the kidney. Convection is equally effective for all solutes that can pass through the membrane, and the corresponding renal therapy is hemofiltration. For enhanced small solute removal, convection can be combined with diffusion as in hemodiafiltration, which has the potential to achieve the largest solute removal over a wide molecular weight spectrum among all forms of dialysis. Finally, the dialysis treatment should be applied as often as is practically possible-preferably daily-in order to reduce the peaks caused by uremic toxins, the exposure to acidosis and alkalosis, and the burden on the cardiovascular system by overhydration. While the designed therapy is already technically feasible today, a positive result from outcome studies will be needed to bring about the political and economic decisions required to change conventional dialysis into a treatment approaching true renal blood purification.

Acid-base correction and convective dialysis therapies.

Whichever dialysis therapy is used, there is a similar need for correcting the acid base balance. The most important tool for this is the buffer in the dialysis fluid and, when using convective therapies, also in the substitution solution. The buffer source in all modern versions of these therapies should be bicarbonate. The more efficient the dialysis treatment in terms of small solute transport, the more rapid the uptake of buffer. Thus, optimally applied haemodiafiltration has the potential for the largest buffer gain. The target for acid-base correction in dialysis is to maintain patients within or as close to the physiological plasma bicarbonate range as possible. However, cross-sectional studies of acid base status among patients treated with contemporary forms of dialysis often show moderate acidosis. As metabolic acidosis has been found to be an important stimulus for protein catabolism in experimental studies, an association with nutritional problems has been sought in dialysis patients. This has revealed a negative correlation between plasma bicarbonate and nutritional parameters. Acidotic patients were found to have better nutritional status than patients with normalized acid-base balance. However, caution should be exercised when interpreting plasma bicarbonate levels, since acidosis may be a cause as well as an effect of excessive protein catabolism. Although available clinical data suggest that the catabolic effect of mild acidosis can be compensated by adequate nutrition and adequate dialysis, it should be desirable to aim for a normalized acid-base balance in combination with adequate nutritional intake and delivery of dialysis.

On-line hemodiafiltration: technique and therapy.

On-line hemodiafiltration (HDF) provides the largest amount of blood purification over a wide molecular weight spectrum achievable with present renal replacement therapies. When used with state of the art dialysis membranes and treatment systems, the biocompatibility of on-line HDF is as high as can presently be defined. From an economic perspective, the added cost of the ultrafilters used to prepare the substitution solution is balanced by the therapeutic benefits of HDF. For optimal HDF, the ultrafiltration rate must be maximized with respect to the blood flow rate. In on-line HDF systems, the excess volume ultrafiltered, approximately 20 to 30 liters per treatment, is automatically replaced, preferably in postdilution mode, by a substitution solution that is continuously generated by stepwise ultrafiltration of dialysate. When properly prepared, this fluid fulfills the quality demands of commercially available infusion solutions; that is, it can be referred to as sterile and pyrogen-free. The most important factors in preparing substitution solution are the quality of the water, of the concentrates, of the ultrafilters, and the microbiological status of the entire flow path. The clinical safety of substitution solution prepared on-line has been documented by long-term users of on-line systems. Results from clinical studies with on-line HDF confirm the overall increased clearance of solutes in relation to high-flux dialysis using the same membrane.

Defining the microbiological quality of dialysis fluid.

With increasing awareness about the degree and the potential impact of microbiological contamination in dialysis fluids, there is a desire to improve their microbiological quality. To achieve this goal, the origin of the microbiological contamination has to be identified. The water, the bicarbonate concentrate, and the fluid distribution system can be major contributors. Regular disinfection of the entire fluid path is necessary to prevent the formation of biofilm. The bicarbonate concentrate should be handled with special attention because it constitutes an excellent growth medium for microflora that may not be detected with regular assays. With a well maintained reverse osmosis (RO) system, frequent disinfection of the entire flow path, and microbiological awareness, it is possible to produce dialysis fluid that meets the most stringent standard (<10(2) colony forming units (CFU)/ml and <0.25 IU/ml of endotoxin). Adding a step of ultrafiltration just before the dialyzer can make the dialysis fluid ultrapure (<10(-1) CFU/ ml and <0.03 IU/ml). One additional step of controlled ultrafiltration provides sterile and pyrogen-free fluids (<10(-6) CFU/ml and <0.03 IU/ml) that can be used for infusion.

Automated peritoneal dialysis with 'on-line'-prepared bicarbonate-buffered dialysate: technique and first clinical experiences.

BACKGROUND: Automated peritoneal dialysis (APD) has the possibility of increasing the dialysis efficacy by using higher fill volumes, frequent dialysate exchanges, and tidal techniques. It is then possible to treat patients adequately without residual renal function. The drawbacks of the required high amounts of dialysis solution of up to 30 litres per session are the high costs of lactate-based dialysate bags and difficulties for the patients in handling these bags. So far, bicarbonate-based peritoneal dialysate, which may be more biocompatible, is only available for CAPD in double-chamber bags. In APD this could be overcome by 'on-line' preparation of bicarbonate-buffered dialysate using advanced technologies originally designed for on-line preparation of substitution fluid for haemofiltration. METHODS: Four patients without residual renal function were treated with APD five times weekly in a crossover study design. Patients received standard lactate-based (35 mmol/l) treatment (25 litres per session each) in weeks 1 and 3. In week 2 on-line-produced bicarbonate-buffered (37 mmol/l) dialysate was used. This dialysate was prepared by an AK 100 Ultra haemodialysis machine. The machine was modified for adding glucose from a 50% concentrate to the desired concentration of 1.7%. Electrolytes, pH, pCO2, and dialysis efficacy parameters were measured. Microbiological testing was carefully performed. RESULTS: Creatinine clearances, Kt/V, and pCO2 did not vary between the different treatment phases, whereas the pH showed a distinct increase during the bicarbonate phase. Repeated determinations of endotoxins and culturing showed no contamination of the dialysate. The composition of the produced dialysate was reproducible with respect to pH, pCO2, sodium, calcium and bicarbonate, whereas the glucose concentration varied by +/- 20%. CONCLUSIONS: On-line preparation of PD fluid with the AK 100 Ultra is easy and safe to handle. APD with dialysate containing 37 mmol/l bicarbonate provides improved acid base balance and possibly improved biocompatibility, and may lead to a significant cost reduction. Further development in order to provide smaller machines and more precise ways of achieving a desired dialysate glucose concentration is necessary.

Principles and practice of hemofiltration and hemodiafiltration.

There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafiltration (HDF). Both require dialysis membranes which are highly permeable to solutes as well as fluid, and in both cases large volumes of ultrafiltration are the condition for convective transport. In HDF the convection is combined with diffusion, and as a consequence, maximum clearance over the entire molecular weight spectrum is achieved. Optimal forms of HDF provide urea clearance 10-15% higher than the corresponding diffusive mode. The larger the solute, the greater is the impact of convection, and beta2-microglobulin (beta2m) levels may be up to 70% reduced. Traditional postdilution HF provides high clearance of medium sized and large molecules. Satisfactory clearance of small solutes requires blood flows in excess of 500 ml/min. With access to practically unlimited volumes of substitution solution through on-line ultrafiltration, predilution HF can now be used. This increases the clearance of small solutes to an acceptable range. For HDF as well as HF, large patient populations consistently treated for longer periods of time are needed to make valid outcome comparisons with other therapies.

Predilution hemofiltration: a new technology applied to an old therapy.

Postdilution hemofiltration (HF) as practised during the 80's is today associated with limitations of a medical, practical and economical nature. High blood flow rates are required to generate sufficient ultrafiltrate in order to achieve a clearance of small solutes comparable to hemodialysis within a reasonable time. High hematocrit and large body weight lead to extended treatment times. IV-quality solution is required in large volumes. This makes the use of bicarbonate difficult and has placed HF among the most expensive renal replacement therapies. These limitations can be resolved by performing HF in a predilution mode using an on-line prepared infusion solution. Diluting the blood before filtration increases the filtration fraction and the clearance of all solutes which are sieved by the membrane. Comparing pre- to postdilution at similar blood flow rates, the clearance may increase by 50% but three times as much infusion solution is required. To make predilution economically viable, the on-line preparation of the infusion solution is necessary, and this facilitates the use of bicarbonate. Compared to other dialysis therapies this new form of HF offers unequalled solute removal over a large molecular range.

Divalent cations in the envelope of a psychrophilic Achromobacter.

The function of Ca2+ in a psychrophilic Achromobacter, previously found to bind large amounts of these ions to its envelope, has been studied. Bacteria suspended in media of low ionic content showed decreases in wet weight, dry weight and growth capacity, and increases in light scattering and in the release of u.v.-absorbing substances into the medium. The permeability barrier to Ca2+ was also damaged, and there was a release of radioactivity from bacteria labelled with 45Ca2+. These events occurred at the optimum growth temperature, and took place at increased rates at higher temperatures. Damage was prevented to about the same extent by 0.1 mM-CaC12, BaC12 or MgC12 and by 10 mM-NaC1, KC1 or LiC1. Ion competition experiments showed that Ca2+ was preferentially taken up and retained in comparison with Ba2+, Mg2+ and Na+, in that order. Isolated envelopes gave similar results. The dry weight of envelopes was reduced by 35% when they were suspended in water at 40 degrees C. It is clear that the function of certain envelope components in Achromobacter is highly dependent on divalent cations; and that both the integrity of the permeability barrier and the stability of the envelope are affected at low ion concentrations.