Effect of RenNew-D as a sterilant on the performance of reused dialyzers

RenNew-D (Alcide), a novel demand-release sporocidal agent, was employed instead of formaldehyde in the reprocessing for reuse of cuprophan hollow fiber dialyzers (Gambro) and the performance of these dialyzers was evaluated over 40 consecutive dialyses in six patients on maintenance hemodialysis. When RenNew-D was part of automated reprocessing performed with 4.3% bleach as specified by the manufacturer (Lixivitron), dialyzer survival was prolonged (16.7 +/- 7.2 uses) and hemodialysis neutropenia was unchanged with reuse. When RenNew-D was part of manual reprocessing conducted in the absence of bleach, marked improvement in dialyzer biocompatibility was observed but with a decreased survival (4.8 +/- 3.0). The majority of dialyzer failures were due to a fall in fiber bundle volume below a 85% set limit. Small solute clearances were maintained with both types of reprocessing. Dialyses were well tolerated throughout. Our data suggest that RenNew-D is a safe and efficacious product which can serve as a valuable alternative to formaldehyde for the purpose of dialyzer reuse.     

Effect of hemodialysis on serum concentrations of HPLC-analyzed accumulating solutes in uremia

The concentration changes, during hemodialysis treatment, of 18 characteristic uremia compounds, analyzed by high-pressure liquid chromatography in sera of renal patients were studied. Pre- to postdialysis concentration ratios (dialysis ratio, D) varied from 0.83 to 3.04 for the different solutes. A division into three solute groups, on the basis of their D values, could be rationalized qualitatively from data on protein binding and dialyzer clearance. One group showed low dialysis ratios which could be explained from plasma protein binding. The second group had intermediate D values, comparable to those of creatinine. For some of the members of the third group, high D values might indicate a compartmentalization and resistance to mass transfer across biological membranes. Among the latter are the tubularly secreted hippuric acid and p-hydroxyhippuric acid. For most of the (protein-bound) solutes, protein binding was shown to decrease during hemodialysis. Protein binding levels were higher after dialysis only for hippuric acid and the as yet unidentified fluorescent solute designated UFK8. In conclusion, the change of serum concentrations and of protein binding resulting from hemodialysis treatment are presented and are compared for 18 accumulating solutes in sera of patients with end-stage renal failure.     

Removal of plasma porphyrins with high-flux hemodialysis in porphyria cutanea tarda associated with end-stage renal disease.

Plasma porphyrin levels are markedly increased in patients with porphyria cutanea tarda (PCT) associated with end-stage renal disease. Conventional hemodialysis (CHD) with lower blood flow rates (less than 250 mL/min) and cuprophan or cellulose acetate membranes is ineffective in removing significant amounts of porphyrins in this condition. Changes in plasma porphyrin levels and porphyrin clearances during hemodialysis with higher blood flow rates and more-permeable, high-efficiency cellulose acetate and high-flux polysulfone dialyzers were evaluated in a chronic hemodialysis patient with PCT and markedly elevated plasma porphyrins. The polysulfone membrane achieved significantly better fractional porphyrin removal (P = 0.02) and porphyrin clearances (P less than 0.01) than did the high-efficiency cellulose acetate membrane. After conversion from maintenance CHD with a standard cellulose acetate dialyzer to a 4-wk period of high-flux hemodialysis (HFHD) with a polysulfone dialyzer, predialysis plasma porphyrins fell by 37%. After returning to CHD, plasma porphyrins returned to the higher prestudy levels. These observations suggest that HFHD with more permeable membranes and higher blood flow rates removes porphyrins more effectively than does CHD. HFHD may be a useful adjunct to other measures used in treating dialysis patients with PCT.     

Microvascular and clinical effects of altered peritoneal dialysis solutions.

Blood flow in the peritoneum is one of the more important factors governing the efficiency of peritoneal dialysis. Yet there have been no previous studies which relate alterations and control of the peritoneal microcirculation to dialysis efficiency. Thus, we used closed-circuit television microscopy to quantitative the in vivo response (changes in diameter) to dialysis solutions of the small arteries on the mesothelial surface of the rat cecum and arterioles of the rat cremaster muscle. These responses were correlated wiht solute clearances from multiple peritoneal dialysis performed in humans. In the cremaster, a transient constriction was followed by a prolonged dilation. pH adjustments of the dialysis solution from 5.6 to 7.4 had no effect on the microvascular response and no effect on solute clearances during human peritoneal dialysis. In the cecum, dialysis solution caused a prolonged dilation which reached a maximum in about 10 min. Since dilation appears to be an important determinant of solute clearances during human peritoneal dialysis, the effects of a vasodilator, sodium nitroprusside, were determined. Sodium nitroprusside decreased the time to maximal dilation, which correlated clinically with an increased solute clearance during exchanges with this drug. Since nitroprusside increased clearances of the larger molecular weight solutes proportionally more than the smaller molecular weight solutes did, we hypothesize that nitroprusside increases solute clearances by both a vasodilatory effect and by an effect on vascular membrane permeability and area for solute exchange.     

Adequacy of dialysis in children: does small solute clearance really matter?

Measurement of dialysis adequacy relies on an assessment of small molecule clearance during the dialysis procedure. However, recent adult studies (HEMO and ADEMEX) that pushed clearance to maximally achievable levels within practical constraints of thrice-weekly hemodialysis or four times daily continuous ambulatory peritoneal dialysis failed to demonstrate improvements in patient outcome above current guidelines. The relatively low incidence of pediatric compared with adult end-stage renal disease limits large-scale study of pediatric dialysis. Several single-center pediatric studies demonstrate a lack of association between small solute clearance alone and patient growth. The aim of the current article is to review the relevant pediatric and adult studies of small solute clearance and put them in the context of optimal dialysis provision. While small solute clearances do indeed matter, clearance is not all that matters. Our quest to provide optimal dialysis requires that we also focus our attention on patient nutritional status, increased dialysis delivery (daily/nocturnal hemodialysis), and adjunctive dialysis modalities (hemofiltration and renal tubular replacement therapy).     

Septicemia in dialysis patients: incidence, risk factors, and prognosis

BACKGROUND: Infection is second to cardiovascular disease as a cause of death in patients with end-stage renal disease (ESRD), and septicemia causes a majority of these infectious deaths. To identify patients at high risk and to characterize modifiable risk factors for septicemia, we examined the incidence, risk factors, and prognosis for septicemia in a large, representative group of U.S. dialysis patients. METHODS: We conducted a longitudinal cohort study of incident ESRD patients in the case-mix study of the U.S. Renal Data System with seven years of follow-up from hospitalization and death records. Poisson regression was used to examine independent risk factors for hospital-managed septicemia. Cox proportional hazards analysis was used to assess the independent effect of septicemia on all-cause mortality and on death from septicemia. Separate analyses were performed for patients on peritoneal dialysis (PD) and hemodialysis (HD). RESULTS: Over seven years of follow-up, 11.7% of 4005 HD patients and 9.4% of 913 PD patients had at least one episode of septicemia. Older age and diabetes were independent risk factors for septicemia in all patients. Among HD patients, low serum albumin, temporary vascular access, and dialyzer reuse were also associated with increased risk. Among PD patients, white race and having no health insurance at dialysis initiation were also risk factors. Patients with septicemia had twice the risk of death from any cause and a fivefold to ninefold increased risk of death from septicemia. CONCLUSIONS: Septicemia, which carries a marked increased risk of death, occurs frequently in patients on PD as well as HD. Early referral to a nephrologist, improving nutrition, and avoiding temporary vascular access may decrease the incidence of septicemia. Further study of how race, insurance status, and dialyzer reuse can contribute to the risk of septicemia among ESRD patients is indicated.     

Superior dialytic clearance of beta(2)-microglobulin and p-cresol by high-flux hemodialysis as compared to peritoneal dialysis

Both residual renal and dialytic clearance confer to the total solute clearance in dialysis patients. Dialytic clearances of the middle molecule beta-microglobulin (beta(2)M) and the protein-bound solute p-cresol (pcr) are generally believed to be higher with peritoneal dialysis (PD) as compared to hemodialysis (HD). Supportive data, however, are lacking. We performed a single-center cross-sectional observational study including 70 unselected patients treated with either high-flux HD (n=20) or PD (n=50). Mid-day serum levels (PD) and time-averaged concentrations (HD) of the water-soluble solutes urea nitrogen, creatinine and phosphate, the middle molecule beta(2)M, and the protein-bound solute pcr were determined. Dialytic solute clearances (l/week/1.73 m(2)) were calculated from total dialysate collection during the mid-week session in HD and 24 h dialysate collection in PD. Renal clearances were calculated for each of the respective solutes from a timed urine collection. Total clearances were obtained by summation. HD delivered significantly higher clearances of all retention solutes studied. This superiority was especially pronounced for pcr (30.9+/-62.7 vs 4.4+/-2.3, HD vs PD, P<0.0001) and beta(2)M (28.6+/-6.6 vs 5.8+/-3.1, HD vs PD, P<0.0001). Renal clearances, conversely, were significantly higher in patients on PD. Serum levels of all solutes but pcr were significantly lower in HD than in PD. Both a higher residual renal function and a lower generation rate contribute to the lower pcr levels in PD. In conclusion, superior dialytic clearance of both water-soluble solutes, beta(2)M, and pcr is achieved by high-flux HD as compared to PD.     

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.     

Impact of hemodialysis duration on the removal of uremic retention solutes

Several studies have stressed the importance of dialysis time in the removal of uremic retention solutes. To further investigate this, nine stable chronic hemodialysis patients were dialyzed for 4, 6, or 8 h processing the same total blood and dialysate volume by the Genius system and high-flux FX80 dialyzers. Inlet blood and outlet dialysate were analyzed for urea, creatinine, phosphorus, and beta2-microglobulin at various times. Total solute removal, dialyzer extraction ratios, and total cleared volumes were significantly larger during prolonged dialysis for urea, creatinine, phosphorus, and beta2-microglobulin. Reduction ratios increased progressively, except for phosphate and beta2-microglobulin, where the ratios remained constant after 2 h. In contrast, no significant difference was found for the reduction ratios of all solutes and Kt/V(urea) between the three different sessions. With longer dialyses, solutes are efficiently removed from the deeper compartments of the patient's body. Our study shows that care must be taken when using Kt/Vurea or reduction ratios as the only parameters to quantify dialysis adequacy.     

Relationship between dialyzer reuse and the presence of anti-N-like antibodies in chronic hemodialysis patients.

One hundred eleven chronic hemodialysis patients from five dialysis units were tested for the presence of antibodies reactive with red blood cell N substance; 77 patients were available for follow-up study after 18 to 24 months. Initially, 18 patients (16%) had serum anti-N-like antibodies. Thirteen of these patients were in a home dialysis program and were reusing hollow fiber dialyzers. The other five had practiced hollow fiber dialyzer reuse in the past. None of 37 patients using coil dialyzers had anti-N-like antibody. On follow-up testing, anti-N-like antibody persisted in all patients restudied except for one who had a successful renal transplant. Anti-N-like antibodies developed in four additional patients: three were reusing hollow fiber dialyzers at the time, but one had not reused dialyzers for 24 months. Statistical analyses indicated that dialyzer reuse, hollow fiber dialyzers, and home dialysis were significantly related to the presence of anti-N-like antibodies. We interpret the clinical and statistical data to indicate that dialyzer reuse is the major clinical factor in the development of anti-N-like antibody. The likely mechanism involves the prolonged exposure of red cells trapped in the dialyzer to formaldehyde used in preparing dialyzers for reuse. No adverse clinical effects of anti-N-like antibodies were evident in our patients, but hemolysis and acute transplant failure have been reported by others.     

An update on uremic toxins

In the last decade, uremic toxicity as a potential cause for the excess of cardiovascular disease and mortality observed in chronic kidney disease gained more and more interest. This review focuses on uremic toxins with known cardiovascular effects and their removal. For protein-bound solutes, for example, indoxylsulfate and the conjugates of p-cresol, and for small water-soluble solutes, for example, guanidines, such as ADMA and SDMA, there is a growing evidence for a role in cardiovascular toxicity in vitro (e.g., affecting leukocyte, endothelial, vascular smooth muscle cell function) and/or in vivo. Several middle molecules (e.g., beta-2-microglobulin, interleukin-6, TNF-alpha and FGF-23) were shown to be predictors for cardiovascular disease and/or mortality. Most of these solutes, however, are difficult to remove during dialysis, which is traditionally assessed by studying the removal of urea, which can be considered as a relatively inert uremic retention solute. However, even the effective removal of other small water-soluble toxins than urea can be hampered by their larger distribution volumes. Middle molecules (beta-2-microglobulin as prototype, but not necessarily representative for others) are cleared more efficiently when the pore size of the dialyzer membrane increases, convection is applied and dialysis time is prolonged. Only adding convection to diffusion improves the removal of protein-bound toxins. Therefore, alternative removal strategies, such as intestinal adsorption, drugs interfering with toxic biochemical pathways or decreasing toxin concentration, and extracorporeal plasma adsorption, as well as kinetic behavior during dialysis need further investigation. Even more importantly, randomized clinical studies are required to demonstrate a survival advantage through these strategies.     

Solute transport in continuous hemodialysis: a new treatment for acute renal failure

A pumpless dialysis technique which combines continuous convection and diffusion was studied in 15 critically ill acute renal failure patients. Fluid identical in composition and purity to that used in peritoneal dialysis was continuously circulated (single-pass) at 16.6 cc/min through the dialysis compartment of a 0.43 m2 flat plate PAN membrane dialyzer. Whole blood clearances for urea, creatinine and phosphate averaged 25.3 +/- 4.4 cc/min, 24.1 +/- 5.5 cc/min and 21.3 +/- 5.6 cc/min, respectively. Over the range of blood flows studied (50 to 190 cc/min) clearances of these solutes were independent of blood flow rate but rather were determined by both dialysate flow rate and ultrafiltration rate. In contrast net fluxes of calcium and sodium were correlated only with ultrafiltration rate. Bicarbonate loss was 0.52 +/- 0.11 mEq/min; K+ balance varied with dialysate K+; glucose uptake from dialysate was 107 +/- 24.0 mg/min. In fresh non-clotting dialyzers, mean ultrafiltration rate was 8.1 cc/min. At QBi of 70 to 190 cc/min, dialysate and blood solute equilibrate yielding a total clearance equal to the dialysate outflow, or 25 cc/min, that is, the sum of dialysate flow rate plus ultrafiltration rate. In comparison to currently used continuous arteriovenous hemofiltration (CAVH), the exceptionally-high solute clearances obtained with continuous hemodialysis constitute a significant improvement in continuous renal replacement therapy.     

Dialyzer reuse--part II: advantages and disadvantages

Although single dialyzer use and reuse by chemical reprocessing are both associated with some complications, there is no definitive advantage to either in this respect. Some complications occur mainly at the first use of a dialyzer: a new cellophane or cuprophane membrane may activate the complement system, or a noxious agent may be introduced to the dialyzer during production or generated during storage. These agents may not be completely removed during the routine rinsing procedure. The reuse of dialyzers is associated with environmental contamination, allergic reactions, residual chemical infusion (rebound release), inadequate concentration of disinfectants, and pyrogen reactions. Bleach used during reprocessing causes a progressive increase in dialyzer permeability to larger molecules, including albumin. Reprocessing methods without the use of bleach are associated with progressive decreases in membrane permeability, particularly to larger molecules. Most comparative studies have not shown differences in mortality between centers reusing and those not reusing dialyzers, however, the largest cluster of dialysis-related deaths occurred with single-use dialyzers due to the presence of perfluorohydrocarbon introduced during the manufacturing process and not completely removed during preparation of the dialyzers before the dialysis procedure. The cost savings associated with reuse is substantial, especially with more expensive, high-flux synthetic membrane dialyzers. With reuse, some dialysis centers can afford to utilize more efficient dialyzers that are more expensive; consequently they provide a higher dose of dialysis and reduce mortality. Some studies have shown minimally higher morbidity with chemical reuse, depending on the method. Waste disposal is definitely decreased with the reuse of dialyzers, thus environmental impacts are lessened, particularly if reprocessing is done by heat disinfection. It is safe to predict that dialyzer reuse in dialysis centers will continue because it also saves money for the providers. Saving both time for the patient and money for the provider were the main motivations to design a new machine for daily home hemodialysis. The machine, developed in the 1990s, cleans and heat disinfects the dialyzer and lines in situ so they do not need to be changed for a month. In contrast, reuse of dialyzers in home hemodialysis patients treated with other hemodialysis machines is becoming less popular and is almost extinct.     

Thrombosis in end-stage renal disease

Although renal failure has classically been associated with a bleeding tendency, thrombotic events are common among patients with end-stage renal disease (ESRD). A variety of thrombosis-favoring hematologic alterations have been demonstrated in these patients. In addition, "nontraditional" risk factors for thrombosis, such as hyperhomocysteinemia, endothelial dysfunction, inflammation, and malnutrition, are present in a significant proportion of chronic dialysis patients. Hemodialysis (HD) vascular access thrombosis, ischemic heart disease, and renal allograft thrombosis are well-recognized complications in these patients. Deep venous thrombosis and pulmonary embolism are viewed as rare in chronic dialysis patients, but recent studies suggest that this perception should be reconsidered. Several ESRD treatment factors such as recombinant erythropoietin (EPO) administration, dialyzer bioincompatibility, and calcineurin inhibitor administration may have prothrombotic effects. In this article we review the pathogenesis and clinical manifestations of thrombosis in ESRD and evaluate the evidence that chronic renal failure or its management predisposes to thrombotic events.     

Severe dialyzer dysfunction undetectable by standard reprocessing validation tests

It is generally accepted that careful monitoring of total cell volume and ultrafiltration rates will ensure adequate function of reprocessed dialyzers. During routine urea kinetic measurements we noted that the percent of patients with clearances less than 200 ml/min increased from 5% to 48% despite adherence to these validation tests. As these patients did not have evidence of recirculation in the vascular access, possible causes of dialyzer dysfunction were investigated. Injection of methylene blue into the dialysate port revealed non-uniform flow of dialysate in dialyzers from patients with markedly reduced clearances. In vitro studies of dialyzers subjected to sequential daily reprocessing, without patient exposure, demonstrated that in vitro clearances declined in one lot but not another. The initial clearances of 218 +/- 4 ml/min fell progressively to 112 +/- 18 (P less than 0.001) after 15 reuses. No effects of reprocessing were found in a different lot (230 +/- 2 vs. 226 +/- 4 ml/min). Soaking the dialyzers from the affected lot in either the disinfectant or dialysate solution caused a decline in the clearances which was less than that of serial reuse. Although the magnitude of the problem of dialyzer malfunction with reuse is unknown, careful attention to dialyzer function is warranted in patients treated with reprocessed dialyzers.     

Removal of middle molecules and protein-bound solutes by peritoneal dialysis and relation with uremic symptoms

BACKGROUND: Current guidelines for peritoneal dialysis adequacy are based on kinetics of small water-soluble molecules and do not consider the role of other compounds such as middle molecules and protein-bound solutes. Information on the elimination characteristics of the latter solutes by peritoneal dialysis is limited. Moreover, their relation with uremic symptoms remains unclear. The aim of the present study was (1) to investigate the relative contribution of residual renal function to the overall clearances of beta2-microglobulin (beta2m), a middle molecule, and p-cresol, a protein-bound solute, in adults on peritoneal dialysis as compared to small water-soluble molecules and (2) to evaluate relations between serum levels and uremic symptoms. METHODS: We performed a cross-sectional observational study, including 30 nonanuric peritoneal dialysis patients. Total, peritoneal, and renal clearances were calculated for urea nitrogen (60 D), creatinine (113 D), phosphate (96 D), beta2m (11.8 kD), and p-cresol (108 D). All patients were asked to complete a uremic symptom questionnaire. RESULTS: Declining total clearances (L/week/1.73 m2) were measured for urea nitrogen, creatinine, phosphate, beta2m, and p-cresol, respectively: 97.3 +/- 4.6, 98.9 +/- 6.1, 64.0 +/- 3.4, 23.1 +/- 2.6, and 17.5 +/- 2.3 (Friedman test P < 0.001). Conversely, the contribution of residual renal function (%) to the respective solute clearances increased significantly: 31.6 +/- 3.2, 51.0 +/- 4.0, 42.4 +/- 4.0, 68.0 +/- 5.4, 61.9 +/- 4.6 (Friedman test P < 0.001). The serum level of p-cresol, but of none of the other solutes examined, correlated significantly with the symptom score (Pearson r= 0.48, P= 0.008). CONCLUSION: During peritoneal dialysis p-cresol behaves like beta2m, probably due to its protein binding. The total clearance of both molecules is significantly lower as compared to water-soluble solutes and mainly depends on residual renal function. Our data further suggest that protein-bound solutes are involved in the pathophysiology of uremic symptoms.     

Effects of a reduced inner diameter of hollow fibers in hemodialyzers

BACKGROUND: The clearance of middle molecules in high-flux hemodialyzers is due to the higher contribution of convection in the overall solute transport. Although net filtration can be maintained low by the machine control, internal filtration in the proximal part of the dialyzer remains high. The final fluid balance is achieved by significant amounts of backfiltration in the distal part of the dialyzer. To increase further middle molecule clearance (MMK), hemodiafiltration has been used. This technique, however, requires complex machines and large amounts of substitution fluid. We present a novel solution to increase the convective transport of middle molecules in high flux dialyzers without the need for substitution fluids. In particular, high-flux dialyzers with a reduced hollow fiber diameter are compared with standard dialyzers in terms of internal filtration and solute clearances. METHODS: Hemodialyzers with 175 micro inner diameter polysulfone fibers were compared with standard 200 micro polysulfone hollow fiber dialyzers. The study was carried out in vitro using a previously published method to measure internal filtration and backfiltration rates. The method is based on the detection by a gamma camera of segmental variations in concentration along the length of the dialyzer of a nondiffusable Tc99-labeled marker molecule injected in the blood in vitro circuit. At the same time, pressures were detected in the blood and dialysate compartment. The system was operated at zero net filtration maintaining volumetrically constant both dialysate and blood circuits. In vivo clearances were also measured for solutes with different molecular weight. RESULTS: The pressure drop in the blood compartment at 300 mL/min of blood flow passed from 112 to 159 mm Hg. At the same blood flow, the internal filtration-backfiltration rates increased from 23. 1 to 48.2 mL/min. This resulted in a significant increase of in vivo in clearances of vitamin B12 and inulin of more than 30%. Urea, creatinine, and phosphate clearance did not display any change. CONCLUSIONS: A reduction of the inner diameter of the hollow fibers in high-flux dialyzers may result in a significant increase of the blood compartment resistance. In turn, this results in increased rates of internal filtration and backfiltration. The practical effect in clinical dialysis is demonstrated on middle molecules. While, in fact, the clearances for small solutes such as urea and creatinine are not affected, the clearances of larger solutes such as vitamin B12 or inulin increase significantly (P < 0.01).     

Effects of long and short hemodialysis on endothelial function: a short-term study

BACKGROUND: Endothelial dysfunction is common in end-stage renal disease and may contribute to the development of both hypertension and atherosclerosis. Long-slow hemodialysis (HD) has been associated with superior blood pressure control and fewer cardiovascular complications. We hypothesized that long dialysis times would improve endothelial function compared with shorter dialysis times. METHOD: Eight long-term hemodialysis patients, not on antihypertensive drugs and with no evidence of vascular disease, were studied in a three-way randomized crossover-controlled trial. Each received, for one week and in randomized sequence, four hours of HD (SD), eight hours of HD, and eight hours of HD using a smaller dialyzer and slower blood pump. The same post-dialysis target weights were used with each treatment. On the third day of each treatment endothelium-dependent (flow mediated) and independent glyceryl trinitrate (GTN) induced vasodilation were measured by forearm strain-gauge plethysmography, and von Willebrand (vW) antigen, plasma homocysteine (tHcy) and neurohormones were measured pre- and post-dialysis. RESULTS: Despite achieving target post-dialysis weights with all treatments, pre-dialysis weight tended higher on SD. Endothelial dependent vasodilation increased after all HD treatments but did not differ between them. Adrenomedullin, N-terminal brain natriuretic peptide and vW antigen increased similarly across all HD whereas atrial and C-type natriuretic peptide, and endothelin-1 decreased across dialysis and were higher with SD. Pre-dialysis plasma tHcy concentrations were 13% higher during SD treatment. CONCLUSION: Hemodialysis improved endothelial-dependent vasodilation but the effect was similar with all three HD treatments. Improved endothelial function might result in part from altered local hormone production (endothelin-1 and adrenomedullin). These data suggest that increasing dialysis time is unlikely, in the short-term, to significantly improve endothelial function in patients with end-stage renal disease, but longer term studies are needed.     

Ofloxacin clearance during hemodialysis: a comparison of polysulfone and cellulose acetate hemodialyzers

The pharmacokinetics of ofloxacin were studied in 13 patients with end-stage renal disease during hemodialysis using two different dialyzers: a polysulfone membrane (Fresenius F6) and a cellulose acetate dialyzer (Nissho Nipro FB-150T). All patients received 100 mg ofloxacin orally per day before dialysis. The hemodialysis clearance per square meter surface area was significantly different, with 5.0+/-0.7 L/h and 3.7+/-1.6 L/h, respectively. The serum concentration was reduced by a 3-hour hemodialysis by 49.6%+/-5.8% per square meter surface area and 45.5%+/-4.8% per square meter surface area. The half-life was 4.2+/-1.8 hours and 4.8+/-1.6 hours during the hemodialysis period and 22.8+/-2.2 hours and 23.3+/-1.7 hours between the dialysis sessions, respectively. Comparing polysulfone and cellulose acetate dialyzers, the material of the membrane influences the half-life, the dialysis clearance, and the percentage of drug extracted during hemodialysis. We conclude that the type of dialyzer used has to be taken into account in dosage recommendations for antimicrobial therapy in hemodialysis patients.     

Vitamin E-coated dialyzer and antioxidant defense parameters: three-month study

Atherosclerotic cardiovascular disease is the most frequent cause of death in patients with end-stage renal disease who have undergone dialysis treatment. Oxidative stress, increased lipid peroxidation, and impaired function of antioxidant systems may contribute to the accelerated development of atherosclerosis in chronic renal failure patients during renal replacement therapy. The aim of this study was to investigate the influence of a vitamin E-coated dialyzer on antioxidant defense parameters in hemodialysis (HD) patients. In 14 HD patients, hemodialysis was performed using a vitamin E-coated dialyzer (Terumo CL-E15NL; Terumo Corporation, Tokyo, Japan) during a 3-month study. In these patients, erythrocyte (ER) antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT), plasma total antioxidant capacity (TAC), RBC glutathione (GSH), plasma malondialdehyde (MDA), plasma, and RBC vitamin E were investigated. Each parameter was measured at the beginning of the study, after the 1st, 2nd, and 3rd month of the study, and 10 weeks after the interruption of the use of vitamin E-coated dialyzer. All HD patients were treated by erythropoietin (EPO) and received vitamin C 50 mg/d, pyridoxine 20 mg/d, and folic acid 5 mg/wk during the entire study. The 3-month treatment with the vitamin E-coated dialyzer led to a significant decrease of plasma MDA level (from 2.85 +/- 0.44 to 2.25 +/- 0.37 micromol/L) and to an increase of plasma TAC, RBC, GSH, and the vitamin E levels both in plasma (from 25.9 +/- 2.8 to 33.6 +/- 3.8 micromol/L) and in the RBCs (from 6.7 +/- 0.8 to 7.4 +/- 0.7 micromol/L) by 30% and 10.5%, respectively. Ten-week interruption of the use of the vitamin E-coated dialyzer led to near initial values of MDA (2.90 +/- 0.28 micromol/L), plasma (28.6 +/- 3.5 micromol/L), and RBC (6.9 +/- 0.7 micromol/L) vitamin E and of other investigated parameters. Statistical analysis of results was performed by conventional methods and analysis of variance. The findings of the current study confirm the beneficial effect of the vitamin E-coated dialyzer against oxidative stress in HD patients.