Diacap alpha-polysulfone HI PS: a new dialysis membrane with optimum beta2-microglobulin elimination.

BACKGROUND: Plasma concentration of beta2-microglobulin (beta2-m) in the case of renal insufficiency is about 20 to 30 times higher than normal. Beta2-m is associated with secondary amyloidosis, a late complication of regular dialysis therapy. To prevent the complications of secondary amyloidosis beta2-m should therefore be eliminated as efficiently as possible during dialysis treatment. This can be accomplished with dialysis membranes which guarantee sufficient clearance for this molecule. It is a matter of discussion whether removal of beta2-m by dialysis may be able to prevent secondary amyloidosis. METHODS: The dialyzers Diacap HI PS 15 (B. Braun Melsungen) and F70 S (Fresenius Medical Care) were compared in five anuric dialysis patients. Arterial blood was taken at the start and at the end of dialysis. Dialysate samples were taken after 30 and 210 minutes and filtrate samples after 60 and 240 minutes from the start of dialysis. Beta2-m and total protein concentration were measured in plasma, filtrate and dialysate. SDS-PAGE of proteins in the filtrate was carried out and kinetics of beta2-m (Kt/V(beta2-m)) were calculated using the Stiller/Mann model. RESULTS: In both dialyzers beta2-m is detectable at any time in the dialysate leaving the dialyzer. In the filtrate beta2-m concentration is about 10 times higher than in the dialysate. Protein pattern in filtrate of both dialyzers is similar and corresponds to that of the glomerulum filtrate. Beta2-m reduction ratio is slightly lower than urea reduction ratio. Using both dialyzers Kt/V(beta2-m) was 0.80, removing about 60% of the generated beta2-m. CONCLUSIONS: In both dialyzers there is considerable removal of beta2-m. Examination of beta2-m kinetics showed an optimum of Kt/V(beta2) of 0.80 which can not be surpassed. Only 60% of generated beta2-m can be removed by three times per week hemodialysis therapy using high-flux dialyzers.

Filtration fluid for hemodialysis treatment.

Bacterial contamination of dialysis fluid has long been recognized as a problem in hemodialyis. Cytokines released as a consequence of contaminated dialysis fluid are believed to be responsible for many acute and chronic side effects in patients undergoing renal replacement therapy. For several years now, attempts have been made to eliminate pyrogenic substances and ensure a sterile and endotoxin-free dialysis fluid. A recent dialysis fluid filter known as DIASAFE, containing a membrane based on Polysulfone (Fresenius), was tested for a period of 1,000 hours (approx. 14 weeks). Dialysis fluid samples were collected once weekly before and behind the filter and cultivated for detection of microorganisms and endotoxins. Additionally, starting after the fourth week of the study, serum samples were collected weekly and the beta2-microglobulin concentration was determined. The filter reduced microorganisms at a rate of at least 10(5) and in the majority of cases (86% of samples) by more than 106. Under clinical conditions the stability and microbiological functionality of the filters could be demonstrated for more than 1,000 hours and 150 disinfecting cycles. In four cases of endotoxin burden (> 0.5 IU/ml) in the dialysis fluid in front of the filter the concentration behind the filter was lower than 0.1 IU/ml, indicating effective reduction of endotoxins. A tendency to a reduction of beta2-microglobulin in serum from 32.5+/-3.9 mg/L to 21.5+/-5.3 mg/L was observed. These results indicate that the dialysis fluid filter used was effective, dramatically reducing the bacterial contaminants in dialysis fluid, thus protecting patients from the potentially harmful acute and long-term life-threatening consequences of contaminated dialysis fluid.

Testing protein permeability of dialysis membranes using SDS-PAGE.

BACKGROUND: Permeability of dialysis membranes for high molecular weight compounds should be similar to that of the glomerular membrane in order to remove uremic toxins like the human kidney does. In order to evaluate permeability of high-flux dialysis membranes SDS-PAGE is applied for examination of filtrate of dialysers during routine dialysis with different membranes. METHOD: SDS-PAGE analysis is performed with silver staining method according to the modification of Melzer (5) and consecutive laser densitometry. RESULTS: The protein pattern of filtrate from dialysis membranes is similar to that of the glomerular membrane containing IgG, transferrin, albumin, alpha-1-microglobulin, retinol binding protein and beta-2-microglobulin. Comparing different membranes there are considerable differences depending on cut-off, charge and adsorption capacity of the particular membrane. In all membranes tested permeability of proteins decreases during one treatment session. CONCLUSION: Protein permeability of high-flux dialysis membranes is similar to the gloemerular membrane but modified according to pore-size, surface charge, adsorption and time on dialysis. In contrast to the glomerular membrane in each of the investigated membranes protein permeability decreases during function.

Influences of the site of diluting fluid substitution on hemodiafiltration processing.

In hemodiafiltration, the diluting fluid can be substituted before or after the ultrafilter. The advantages and disadvantages of each method are discussed below. To avoid hemoconcentration when passing through the ultrafilter, we prefer substitution of the diluting fluid to blood before the ultrafilter and accept the greater composition of diluting fluid.

The Donnan effect in artificial kidney therapy.

The calculation of the effective sodium gradient in dialysis has to consider a membrane potential difference which is generally derived from the Donnan effect. Strictly this is allowed only under equilibrium conditions. This paper considered the effect of the deviation from equilibrium in haemodialysis and haemofiltration. The mathematical analysis is based on the integration of the local transport rate over the membrane area. The local transport rate is calculated from the Nernst-Planck equation using the constant field assumption. Deviation from equilibrium results in a diffusion potential across the membrane. Experimental evidence was presented for part of the theoretical results. The diffusion potential, both in haemodialysis and in haemofiltration, is too small to have any clinical significance. From the theory it follows that better tolerance of haemofiltration in comparison with haemodialysis cannot be explained by a difference in sodium transport. Calculation of the sodium transport in dialysis therapy based on the equilibrium Donnan effect is sufficiently accurate for kinetic considerations in the dialysis routine.

Characteristic profiles of circulating blood volume during dialysis therapy.

From continuous measurements of the hemoglobin concentration in the arterial blood line during 50 hemodialysis sessions in 20 stable dialysis patients, the influence of the amount of ultrafiltered fluid, the ultrafiltration rate, and overhydration of the patient upon the circulating blood volume was derived. If ultrafiltration is stopped, blood volume increases until equilibrium is obtained. The amount of refilling is proportional to the ultrafiltration rate [2.5%/(L/hr)]. The decrease of blood volume after re-equilibration depends upon the ultrafiltered amount and the degree of overhydration. The mean decrease of blood volume per liter of ultrafiltrate was found to be 5.5% for an average overhydration of 3 L.

Vasoactive hormones during hemodialysis with intermittent ultrafiltration.

The correlations between actual blood volume (BV), blood pressure (BP), heart rate, and plasma levels of renin activity (PRA), serum aldosterone (ALD), antidiuretic hormone (ADH), epinephrine (E), norepinephrine (NE), atrial natriuretic factor (ANF), cGMP, and cAMP were investigated in 10 stable patients during HD. HD consisted of four periods of about 60 min each. One half with an UF rate greater than 1,000 ml/h, followed by a time interval of 30 min without UF resulting in a "saw tooth" profile of BV. Decrease in BV was measured by continuous hemoglobinometry. Average total decrease in BV was 25%, while BP and HR did not change significantly. E, NE, ANF and ADH levels were directly related to actual changes in BV, suggesting that BP regulation in this special mode of HD is mainly supported by endogenous catecholamine and ADH secretion. The second messenger cGMP did not follow actual BV changes, but showed a significant decrease correlated with diminished BV. A significant change in PRA and ALD was missing. It is concluded that vascular stability in these patients is maintained by the response of catecholamins and ADH to decrease in blood volume, and not by the renin-aldosterone system.

Venous stenosis and occlusion in hemodialysis shunts: follow-up results of stent placement in 65 patients.

PURPOSE: To provide follow-up data on the use of self-expanding stents in hemodialysis fistulas to improve the technical success of balloon angioplasty. MATERIALS AND METHODS: Ninety-two self-expanding vascular stents were placed in 65 patients (29 men and 36 women 25-79 years of age; mean, 57.6 years) with failing hemodialysis fistulas or shunts. RESULTS: Stent placement was successful in all patients, but rethrombosis of the shunt occurred in six patients (10%) within 1 week. There were 96 episodes of reobstruction. In 87 cases, percutaneous or combined surgical and percutaneous repeat intervention was performed. The cumulative shunt function rate was 88% after 6 months, 86% after 1 year, and 77% after 2 years. CONCLUSION: Stent placement in hemodialysis fistulas helps treat lesions that cannot be adequately treated with percutaneous transluminal angioplasty (PTA) alone but has a follow-up patency rate similar to that of PTA. Standard central venous stents have a better patency rate than after PTA.

Venous stenoses in dialysis shunts: treatment with self-expanding metallic stents.

A flexible, self-expanding metallic endoprosthesis was employed for the treatment of venous outflow stenoses in four patients with a polytetrafluoroethylene shunt and two patients with a Brescia-Cimino shunt. The stenoses had led to shunt occlusion in five patients and to flow impairment in one. In the occluded shunts, thrombectomy and subsequent balloon angioplasty were performed in four patients, and percutaneous recanalization with angioplasty was performed in one. One shunt with decreasing flow was percutaneously dilated. Since the underlying stenoses recurred in four patients after 24 hours and did not respond sufficiently to angioplasty in two patients, up to four stents were placed in the venous segments. Thrombosis of the stents occurred in two patients after 24 hours and in one after 6 weeks and was successfully recanalized with thrombectomy in two. At 2-6 months follow-up, the stents and the shunts were patent in five patients. In three of these patients, intima hyperplasia, associated with narrowing of the stent lumen in two, was noted within 4 months after stent placement.