The effect of high-flux hemodialysis on dialysis-associated amyloidosis

Amyloidosis is an important cause of mortality and morbidity in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). In this study, depending on the idea that the clearance of middle and high molecular weight toxins could be improved, we aimed to investigate the effect of high-flux dialyzer on clearance of beta-2 microglobulin (beta2-MG) and calcium (Ca) phosphorus (P) metabolism in patients under HD treatment. Forty-eight patients with ESRD under chronic HD treatment were included in the study. All patients were randomized into two groups, and HD was performed with low-flux or high-flux dialyzer for 6 months. In the high-flux group, the reduction of beta2-MG and P levels during dialysis was significantly higher when compared with the low-flux group (p<0.001). During the follow-up period, while beta2-MG levels decreased significantly in the high-flux group (p<0.05), there was an increase in the low-flux group (p<0.05). As a result, our findings suggest that use of high-flux dialyzer can be an efficient alternative in terms of controlling the clearance of beta2-MG and impaired Ca and P metabolism. These beneficial effects of high-flux dialyzers are probably mediated by the improved clearance of middle and high molecular weight toxins.     

Isolated Central Nervous System Posttransplant Lymphoproliferative Disorder Treated with High-Dose Intravenous Methotrexate

Posttransplant lymphoproliferative disorder (PTLD) is an uncommon neoplastic complication of kidney transplantation, affecting about 1% of recipients. It is generally associated with Epstein–Barr virus (EBV) infection of B-lineage lymphocytes. Central nervous system (CNS) involvement is rare. There is little clinical experience with treatment of CNS PTLD due to the relative rarity of the disease other than reduction or withdrawal of immunosuppression, but it is usually fatal. We describe six patients with renal allografts and histologically proven isolated CNS PTLD. Tissue analysis from the biopsy specimens was positive for EBV material in five of the six patients. All six patients were treated with high-dose intravenous methotrexate (HD IV MTX). Methotrexate was initiated at 8 g/m², with later adjustments for creatinine clearance. With MTX therapy, four patients have had a sustained complete response, and two had progressive disease and were referred for radiation therapy. This finding suggests a subgroup of patients may benefit from MTX but our case series is inadequate to describe overall efficacy. No unexpected toxicities were encountered in 37 courses of treatment. HD IV MTX chemotherapy should be considered as an alternative for treatment of CNS PTLD.     

The effect of high-flux hemodialysis on renal anemia

BACKGROUND: Anemia is an important predictor of mortality and morbidity in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Erythropoietin (EPO) is an expensive drug, which increases the cost of therapy. In addition, anemia persists in 20-30% of cases despite EPO treatment. In this study, which depended on the idea that the clearance of moderate and high molecular weight erythropoiesis inhibitors leads to an improvement in terms of anemia, we aimed to investigate the effect of high-flux dialysis on anemia and EPO requirement in patients undergoing HD. METHODS: The study included 48 patients with ESRD on chronic HD treatment who could not reach the target hemoglobin (Hb) level, despite treatment with at least 200 IU/kg/week subcutaneous EPO. Patients were randomized into two groups and HD was performed with polysulphone low-flux dialyzer (Fresenius F6 HPS) or polysulphone high-flux dialyzer (Fresenius F60) for 6 months. RESULTS: Although the EPO doses were significantly lower (p<0.001) in the high-flux dialysis group, Hb levels showed a significant increase (p<0.001). In the low-flux dialysis group, Hb levels showed no significant increase, despite the steady increase in EPO doses. In the high-flux group, the reduction of beta2-microglobulin (b2-MG) and phosphorus levels during dialysis was significantly higher when compared to the low-flux group (p<0.001). During the follow-up period, while b2-MG levels decreased significantly in the high-flux group (p<0.05), there was an increase in the low-flux group (p<0.05). Kt/V(urea) values showed no significant difference throughout the study. CONCLUSIONS: Our results suggest that high-flux dialysis use is effective and this can be an alternative method in terms of controlling renal anemia and reducing the cost of therapy. These beneficial effects of high-flux dialysis are probably mediated by the improved clearance of moderate and high molecular weight toxins.     

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.     

Comparison of Hemodialysis versus Hemoperfusion in the Clearance of High-Dose Methotrexate in Pigs

Abstract: To evaluate the different capabilities of hemoperfusion (HP) and hemodialysis (HD) treatment in resolving the side effects during high-dose methotrexate (MTX) therapy, an experimental comparative study was done. Under general anesthesia, 12 female Large-White pigs, 35 ± 5 kg body weight, underwent a bilateral renal vessel ligature to create an acute renal failure and avoid the physiologic elimination of MTX. An MTX i.v. infusion was performed using a dose of 12.5 g/m² and for a specific time according to its pharmacokinetics. The animals were divided into 2 groups of 6 animals each and connected to the extracorporeal circuit; the first group was submitted to a 1-h HP with an anion exchange resin (Dow 1X-2, Dow Chemical) and the second group to 1-h HD with capillary polysulfone fibers (F6, Fresenius). Blood samples were taken at established intervals for he-matological and biochemical evaluations. The results demonstrate a higher capability of HP treatment (p < 0.001) related to HD in MTX removal.     

Influence of hemodialysis membrane permeability on serum levels of advanced glycation end products (AGEs) and homocysteine metabolites

BACKROUND: Advanced glycation end products (AGEs), total homocysteine (tHcy) and the homocysteine metabolites cystathionine (Cysta) and dimethylglycine (DMG) are increased in serum of patients with end-stage renal disease. The aim of this prospective randomized study was to compare the efficacy of polysulfone high-flux vs. polysulfone low-flux hemodialysis (HD) treatment regarding removal of AGEs, tHcy, Cysta and DMG. PATIENTS AND METHODS: Twenty-nine patients on chronic HD treatment were randomly assigned to 2 groups in a 3-period 2-treatment design with low flux (A)--high flux (B)--low flux (A) for group I and B-A-B for group II, 6 weeks each period. The following parameters were measured in pre- and postdialytic serum samples at baseline and the end of each period: total serum fluorescence, Nepsilon-carboxymethyllysine (CML), free and protein-bound pentosidine, tHcy, Cysta and DMG. RESULTS: There was increased removal of free pentosidine during high-flux HD treatment compared to low-flux HD treatment, attaining significance between the second and third treatment periods (group 1: 86.0 +/- 4.7% vs. 79.2 +/- 8.8%, p = 0.007; group II: 84.0 +/- 6.3% vs. 79.8 +/- 9.8%, p = 0.049 for high vs. low flux). The intradialytic reduction rates for total serum fluorescence, tHcy, Cysta, DMG did not differ between high- and low-flux HD treatment. Protein-bound pentosidine and CML did not decrease during the dialysis sessions, neither with high-flux nor with low-flux HD membrane. Despite a strong decrease during single HD session, the predialytic levels of free pentosidine, tHcy, Cysta and DMG remained unchanged during the study period both for high- and low-flux HD treatment. CONCLUSION: The more pronounced effect of high-flux dialysis on the removal rate of free pentosidine, found in this randomized crossover study, could not translate into a significant difference in predialysis levels after a 6-week treatment period. We could not find any differences between polysulfone high- and low-flux membranes for lowering predialytic serum concentrations of the measured AGEs, which are mainly bound on albumin.     

Characterization of insulin adsorption behavior of dialyzer membranes used in hemodialysis

Although it has been reported that plasma insulin is removed by hemodialysis (HD), the mechanism for this has not been elucidated. We investigated the mechanism of insulin removal during HD treatment and the characteristics of insulin removal with three high-flux membranes. In our in vivo study, 20 stable diabetic patients on HD were randomly selected for three HD sessions with three different membranes: polysulfone (PS), cellulose triacetate (CTA), and polyester polymer alloy (PEPA). Blood samples were obtained from the blood tubing at the arterial (A) site at the beginning and end of the sixth HD session to investigate insulin reduction in patients. At 1 h after the initiation of dialysis, blood samples were obtained from both the A and venous sites of the dialyzer to investigate the insulin clearance with the different membranes. There was a significant reduction in patients' plasma insulin at each time point with each of the three membranes. The insulin clearance with the PS membrane was significantly higher than that with the CTA and PEPA membranes. Although no difference was observed in the plasma insulin reduction rate between the three membranes in the total subject group, there was a significantly higher reduction rate with the PS membrane in insulin-dependent diabetes mellitus subjects. The clearance of insulin in in vitro tests was significantly higher with the PS and PEPA membranes than with the CTA membrane in both new and clinically used dialyzers. Insulin was not detected in the dialysate or ultrafiltration fluids in either the in vivo or in vitro studies. The mechanism of plasma insulin clearance by HD is mainly by adsorption, and the amount of insulin adsorbed differed depending on the dialyzer membrane used.     

Identical decline of residual renal function in high-flux biocompatible hemodialysis and CAPD.

BACKGROUND: Patients on conventional hemodialysis lose residual renal function more rapidly than patients on continuous ambulatory peritoneal dialysis (CAPD). The effect of dialysis using synthetic membranes and ultrapure water is less clear. METHODS: The decline of urea clearance was compared in a cohort of 475 incident end-stage renal failure patients who received treatment with CAPD (N=175) or hemodialysis (HD) utilizing high-flux polysulphone membranes, ultrapure water, and bicarbonate as the buffer (N=300). RESULTS: CAPD patients were significantly younger, fitter (lower comorbidity severity score), less dependent (higher Karnofsky performance score) and less likely to have presented late than HD patients. There was no difference in the mean urea clearance in each group at dialysis initiation, or at any 6-month time point during the ensuing 48 months. This was true even after exclusion of patients who had died in the first year after initiation, those transferred to another dialysis modality, or those who had been transplanted. Only age and chronic interstitial disease predicted retention of urea clearance at one year. The rate of decline of urea clearance was similar in pre- and post-dialysis initiation phases, though there may have been a step-decline of about 2 mL/min at initiation, which requires further investigation. CONCLUSIONS: In hemodialysis using high-flux biocompatible membranes and ultrapure water, residual renal function declines at a rate indistinguishable from that in CAPD. This may have important implications, since preservation of residual renal function has major benefits and is a valid therapeutic goal.     

Improved lipid profiles in patients undergoing high-flux hemodialysis.

Hyperlipidemia is one of many atherogenic risk factors encountered by patients undergoing chronic hemodialysis (HD). We have studied lipid profiles in these patients and have found less hypertriglyceridemia in those undergoing high-flux HD than those receiving traditional HD. Mean +/- SEM triglyceride level was 1.62 +/- 0.15 mmol/L (143.3 +/- 13.6 mg/dL) in high-flux dialysis patients, 2.39 +/- 0.27 mmol/L (211.6 +/- 24.1 mg/dL) in conventional dialysis patients, and 1.55 +/- 0.13 mmol/L (137.1 +/- 11.5 mg/dL) in normal age- and sex-matched controls. In addition, we found that in patients undergoing high-flux HD, females had higher high-density lipoprotein2 (HDL2) levels (0.62 +/- 0.03 mmol/L [23.8 +/- 1.3 mg/dL]) than males (0.33 +/- 0.04 mmol/L [12.9 +/- 1.7 mg/dL]) (P < 0.01). The mechanism(s) responsible for divergent lipid profiles in subsets of HD patients deserves further investigation. Whether reductions of hypertriglyceridemia and/or increases of HDL2 will diminish the incidence of cardiovascular disease in dialysis patients is unknown.     

High-flux dialysis lowers plasma leptin concentration in chronic dialysis patients

Leptin is a protein produced by fat cells and involved in body weight regulation. Plasma leptin is significantly higher in some hemodialysis (HD) patients than in normal controls. We examined the influence of dialyzer membrane biocompatibility and flux on elevated plasma leptin concentrations in hemodialysis patients. Employing a crossover design, leptin and tumor necrosis factor-alpha (TNF-alpha) levels were serially determined in eight chronic dialysis patients. Patients were dialyzed sequentially on low-flux cellulosic (TAF) dialyzers, low-flux (F8) polysulfone, high-flux (F80B) polysulfone, then low-flux polysulfone and cellulosic dialyzers again. Mean leptin concentrations were similar when low-flux polysulfone or cellulosic dialyzers were employed (141.9+/-24.2 microg/L versus 137.8+/-18.4 microg/L, respectively (P=NS). In contrast, leptin fell significantly on the high-flux polysulfone dialyzer (99.4+/-16.2 microg/L) compared with cellulosic (P < 0.005), and low-flux polysulfone dialyzers (P < 0.02). Leptin clearance by the high-flux polysulfone dialyzer was significantly higher than the low-flux dialyzers (50.4+/-21.5 v -9.6+/-10.3 mL/min; P=0.043), but did not account fully for the 30% decline in plasma leptin during the high-flux arm of the study. Concentrations of TNF-alpha were lower when high-flux polysulfone dialyzers were employed, but there was no correlation of individual TNF-alpha levels with leptin concentrations. High-flux dialysis lowers plasma leptin concentrations an average of 30%, but biocompatibility does not influence leptin levels. The decrease in plasma leptin on high-flux dialysis cannot be explained solely by enhanced clearance.     

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.     

Plasma adrenomedullin levels in patients on hemodialysis

Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 +/- 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 +/- 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.     

Influence of hemodialysis membrane type on pentosidine plasma level, a marker of "carbonyl stress".

Influence of hemodialysis membrane type on pentosidine plasma level, a marker of "carbonyl stress." BACKGROUND: The accumulation of advanced glycation end products (AGEs) in uremia has been ascribed to the retention of carbonyl precursors of AGEs. Pentosidine plasma level has been identified as a surrogate marker of carbonyl precursors ("carbonyl stress"). The influence of hemodialysis (HD) membrane type and residual diuresis on carbonyl stress has not been studied. METHODS: We measured protein-linked and free plasma pentosidine (a surrogate marker of carbonyl stress) by high-performance liquid chromatography in patients on HD with low-flux cellulose (N = 29), high-flux polysulfone (PS; N = 57), polymethylmethacrylate (PMMA) (N = 25), and AN69 (N = 15). RESULTS: Both protein-linked and free pentosidine were similar on low-flux cellulose, high-flux PMMA, and AN69, but were lower (P < 0.01) on high-flux PS. Pentosidine levels were virtually identical on Fresenius and Asahi PS in Japanese and Belgian patients. By multivariate analysis, only the type of HD membrane and residual diuresis proved to be independent determinants (P < 0.001) of pentosidine levels. During a single HD session, the clearance of free pentosidine was similar with all membranes. In three patients who were switched from AN69 to PS, the protein-linked pentosidine level dropped to the control level after resumption of the AN69 membrane. CONCLUSIONS: Both HD membrane type and residual diuresis are independent determinants of pentosidine plasma level, which is a marker of carbonyl stress.     

The effect of two different high-flux dialysis membranes on insulin resistance in non-diabetic end-stage renal disease patients

Abstract

Objective: The aim of this study was to investigate the effect of two different types of high-flux dialysis membranes on insulin resistance among patients who are receiving hemodialysis (HD) due to end-stage renal failure (ESRF). Materials and methods: Forty-six (21 female, 25 male) patients were included in the study, who were on HD treatment due to stage-5 chronic renal failure. Prior to the study, fasting insulin resistance via Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) and fractioned urea clearance (Kt/V) values were calculated using the urokinetic model. The polysulfone (PS) dialysis membrane of all patients included in the study was replaced with “polyarylethersulfone, polyvinylpyrrolidone, polyamide (PPP)” high-flux membrane that has the same surface area over 12 weeks. At the end of the 12-week period, HOMA and Kt/V values were recalculated. Results: At the end of the 12-week period, Kt/V values rose statistically significant from 1.575 to 1.752 (p?=?0.002). HOMA-IR values declined, though not statistically significant, from 3.268 to 2.926 (p?=?0.085). PPP high-flux membrane increased the Kt/V values significantly compared to the PS membrane, while it decreased the insulin resistance and increased insulin sensitivity. Conclusion: The two different types of high-flux dialysis membranes used for HD have different effects on insulin sensitivity. Compared to the PS membrane, PPP high-flux membrane decreased insulin resistance by increasing insulin sensitivity among non-diabetic ESRF patients.     

Estimation of residual renal function using beta-trace protein: Impact of dialysis procedures

Beta-trace protein (BTP), a low molecular weight protein of 23-29 kDa, has been proposed as a promising biomarker to estimate residual renal function (RRF) in patients on maintenance hemodialysis (HD). Indeed, BTP is cleared by native kidney but not during conventional HD session. By contrast, the removal rate of BTP using convective processes (mainly hemodiafiltration [HDF]) and peritoneal dialysis (PD) has been little or not investigated. Therefore, an aim of this study was to evaluate the impact of dialysis procedures (high-flux HD, on-line post-dilution HDF and PD) on BTP removal in comparison with beta-2 microglobulin (B2M) and cystatin C (CYSC) removals after a single session. In addition, the ability of BTP to predict RRF in PD was assessed. This observational cross-sectional study included a total of 82 stable chronic kidney disease patients, 53 patients were on maintenance dialysis (with n = 26 in HD and n = 27 in HDF) and 29 were on PD. Serum concentrations of BTP, B2M, and CYSC were measured (a) before and after a single dialysis session in HD and HDF anuric patients to calculate reduction percentages, (b) in serum, 24-hour-dialysate and 24-hour-urine in PD patients to compute total, peritoneal, and urinary clearance. RRF was estimated using four equations developed for dialysis patients without urine collection and compared to the mean of the urea and creatinine clearances in PD. The concentrations of the three studied molecules were significantly reduced (P < .001) after dialysis session with significantly higher reduction ratio using HDF compared to HD modality (P < .001): BTP 49.3% vs 17.5%; B2M 82.3% vs 69.7%; CYSC 77.4% vs 66% in HDF and HD, respectively. In non-anuric PD patients, B2M and CYSC were partly removed by peritoneal clearance (72.3% and 57.6% for B2M and CYSC, respectively). By contrast, BTP removal by the peritoneum was negligible and a low bias for the BTP-based equation to estimate RRF (−1.4 mL/min/1.73 m²) was calculated. BTP is significantly removed by high-flux HD or HDF, thereby compromising its use to estimate RRF. By contrast, BTP appears as a promising biomarker to estimate RRF in PD patients since it is not affected by peritoneal clearance, unlike B2M and CYSC, and it is well correlated to RRF.     

Warning of high-flux hemodialysis.

In order to estimate the influence of flux on plasma refilling during hemodialysis (HD), prospective crossover studies were performed in 10 HD patients with low-flux and high-flux dialyzers. Hematocrit was continuously monitored to assess changes in blood volume. In addition, plasma osmolarity and total protein concentration were measured. Intradialytic reductions in body weight (-5 +/- 1 vs -5 +/- 1%) and plasma osmolarity (-5 +/- 1 vs -5 +/- 1%) were similar in both conditions. Although mean blood pressure remained unchanged in either state, the decrease in blood volume was larger in high-flux HD (-13 +/- 2 vs -10 +/- 2%, p<0.05). In spite of greater contraction in blood volume during high-flux HD, total proteins were increased equally between low-flux and high-flux HD (11 +/- 4 vs 11 +/- 4%). Our data that although high-flux HD failed to induce significant drops in blood pressure, it elicited greater magnitude of decreases in blood volume, implicate the judicious application of high-flux HD.     

The influence of hemodialysis membrane permeability on serum paraoxonase-1 activity and oxidative status parameters

We aimed to measure oxidative stress parameters and paraoxonase-1 (PON-1) enzyme activities in chronic hemodialysis (HD) patients and to investigate whether HD membrane permeability has any influence on those measures. Forty-seven HD patients and 24 controls were enrolled. At the first step of the study, all HD patients had undergone HD treatment via "low-flux" membranes for 4 weeks. At the second step of the study, the membranes were switched to "high-flux" membranes and HD treatments were also performed via "high-flux" membranes for 4 weeks. Blood samples were withdrawn after completion of 4 weeks treatment for each membrane. Total oxidant status (TOS), total antioxidant status (TAS), and paraoxonase and arylesterase activities were measured in blood samples of the patients and the controls. TOS and oxidative stress index (OSI) of both membranes were higher than controls (all, P < 0.05), while TAS and paraoxonase and arylesterase activities were lower (all P < 0.05). Paraoxonase (P < 0.05, r = -0.437 and P < 0.05, r = -0.453, respectively) and arylesterase (P < 0.05, r = -0.333 and P < 0.05, r = -0.371, respectively) activities of "low-flux" and "high-flux" membranes were inversely correlated with OSI. There were no significant differences between "low-flux" and "high-flux" membranes in regard to oxidative stress parameters or PON-1 enzyme activities (all, P > 0.05). HD patients have increased oxidative stress and decreased serum PON-1 activities inversely correlated with oxidative stress. Membrane permeability seems to have no influence on oxidative stress parameters and PON-1 enzyme activities.     

Pulmonary hypertension in hemodialysis patients without arteriovenous fistula: the effect of dialyzer composition

Pulmonary hypertension (PHT) increases mortality rate in hemodialysis (HD) patients. Numerous clinical, hemodynamic, and metabolic abnormalities have been suggested to be associated with the development of PHT in HD patients. We aimed to investigate the acute effects of two different dialyzer membranes on pulmonary arterial pressure (PAP) throughout a HD session in maintenance HD patients. Seventy-four HD patients dialyzed through permanent tunneled jugular central venous catheter were enrolled. A first-use cellulose acetate and high-flux polysulfone dialysis membrane were tested using a crossover design. For each membrane, pre- and post-dialysis pulmonary artery pressures were measured echocardiographically. Elevated pulmonary artery pressure was observed in 68.8% of patients (n = 51), whereas mild PHT was observed in 28.3% of patients (n = 21) and moderate PHT in 40.5% (n = 30). Decrease in pulmonary artery pressure following HD procedure performed using high-flux polysulfone membrane was significantly higher than the decrease observed following HD procedure performed using cellulose acetate membrane (p < 0.05). Significant decrease in pulmonary artery pressures was observed only after HD procedures performed using high-flux polysulfone membrane (p < 0.05). Ultrafiltered volume was only significantly correlated with the decrease in pulmonary artery pressure observed after HD procedure performed through high-flux polysulfone membrane (β = 0.411, p < 0.05). PHT seems to be prevalent among HD patients even in the absence of AV fistula and abnormal cardiac functions. Membrane composition seems to be important, which may overwhelm the improving effects of ultrafiltration.     

Hemodiafiltration--a new treatment option for hyperphosphatemia in hemodialysis patients.

BACKGROUND: Hemodiafiltration is used to increase the convective transport and thereby the elimination of small and middle molecules, mainly beta2-microglobulin (beta2-M) across the dialysis membranes. There is little information concerning urea, creatinine, beta2-M and principally phosphate kinetics during hemodiafiltration in vivo. In this prospective study, we evaluated the transmembrane solute mass removal (TSR) and clearance (Kd) of urea, creatinine and phosphate as well as serum beta2-M reduction rate (beta2-MRR) and collected beta2-M in dialysate plus ultrafiltrate during high-flux hemodialysis (HD) and post-dilutional hemodiafiltration (HDF). PATIENTS AND METHODS: 16 patients were studied using a polysulfone capillary filter (1.6 m2 surface area, 40 microm fiber internal diameter and 200 microm, wall thickness) during 2 one-week periods: first week HD 1.6 m2 and second week HDF 1.6 m2. Treatment time was 4 hours, blood flow rate 300 ml/min with constant dialysate and ultrafiltration rates for HD and HDF periods. TSR, Kd, beta2-MRR and beta2-M collection were assessed during the mid-week treatment. In a second part of the study, we repeated the same protocol using a second high-flux polysulfone capillary filter (2.4 m2 surface area, 30 microm fiber diameter and 150 microm wall thickness). RESULTS: TSR and Kd of urea and creatinine were not improved by HDF, however, HDF increased TSR and Kd of phosphate. Phosphate clearance rose from 120 (HD 1.6 m2) to 159 (HDF 1.6 m2) (p < 0.005) and from 146 (HD 2.4 m2) to 206 (HDF 2.4 m2) (p < 0.005) ml/min. Beta2-MRR increased from 64.1 +/- 8.6 to 77.7 +/- 8.2% (p < 0.005) and from 75.0 +/- 5.1 to 82.9 +/- 8.5% (p < 0.005) during HDF 1.6 m2 and HDF 2.4 m2, respectively. Collected beta2-M remained unchanged. This discrepancy seems to be due to an enhanced beta2-M adsorption to the polysulfone membrane during HDF. CONCLUSION: Our results provide a strong evidence that HDF has no advantage over HD with respect to urea and creatinine removal in vivo. However, HDF did improve the elimination of phosphate and should be considered as an additional treatment option for hyperphosphatemia in dialysis patients. HDF improves significantly the elimination of beta2-M.     

Procalcitonin serum levels in children undergoing chronic haemodialysis

Infections account for considerable morbidity and mortality in patients requiring haemodialysis (HD). Procalcitonin (PCT)—a low molecular weight protein of 13 kDa—helps one to distinguish viral from bacterial infections and to evaluate the severity of bacterial infections. We investigated (1) PCT baseline levels in eight children undergoing chronic HD with high-flux membranes and (2) changes in the serum levels of PCT, C-reactive protein (CRP) and beta-2-microglobulin (β2-MG)—a peptide with biochemical characteristics similar to those of PCT—before and after haemodialysis sessions. Blood sampling was performed three times in the mid-week session. Serum PCT of the seven uninfected children before HD sessions was increased (0.75±0.07 ng/ml), whereas CRP levels were normal. PCT after dialysis decreased significantly by 40% (P<0.0001) compared with initial values, whereas CRP levels before and after HD were not different. β2-MG decreased by 70%, probably due to different biochemical proprieties of both proteins. PCT serum levels 15 min and 60 min after the HD session remained unchanged in comparison with those at the end of the HD session, suggesting accumulation of PCT between HD sessions rather than HD-induced production to be responsible for the increased baseline PCT serum levels. We concluded that CRP serum levels were not affected by HD in our group. Moderately elevated baseline PCT serum levels that are presumably due to reduced renal clearance and uraemia and dialysability of PCT should be taken into consideration. However, increase of serum PCT in patients with severe bacterial infections is generally massive (10-fold to 1,000-fold), suggesting a low risk for false negative results in such cases.