[Acute and chronic effects of standard hemodialysis and soft hemodiafiltration on interdialytic serum phosphate levels]. Removal of the protein-bound solute p-cresol by convective transport: a randomized crossover study. Pre-dilution on-line haemofiltration vs low-flux haemodialysis: a randomized prospective study. Comparison between hemofiltration and hemodiafiltration in a long-term prospective cross-over study. Removal of beta 2-microglobulin by hemodialysis and hemofiltration: a four year follow up. A prospective comparison of bicarbonate dialysis, hemodiafiltration, and acetate-free biofiltration in the elderly. Effect of acetate-free biofiltration and bicarbonate hemodialysis on neutrophil activation. Acetate-free biofiltration versus bicarbonate haemodialysis in the treatment of patients with diabetic nephropathy: a cross-over multicentric study. On-line haemodiafiltration. Remarkable removal of beta2-microglobulin. Long-term clinical observations. Online hemodiafiltration versus acetate-free biofiltration: a prospective crossover study. Clinical improvement by increased frequency of on-line hemodialfiltration. The effect of hemodialysis and acetate-free biofiltration on anemia. Effect of acetate, bicarbonate dialysis, and acetate-free biofiltration on nitric oxide synthesis: implications for dialysis hypotension. Comparison of hemodialysis and hypertonic hemodiafiltration on cardiac function [corrected]. Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group. Effect of acetate-free biofiltration on the anaemia of haemodialysis patients: a prospective cross-over study. A comparison of on-line hemodiafiltration and high-flux hemodialysis: a prospective clinical study. On-line haemodiafiltration versus low-flux haemodialysis. A prospective randomized study. Cardiovascular response during hemodialysis and hemofiltration: thermal, membrane, and catecholamine influences. Improved cardiovascular variables during acetate free biofiltration.
The dialytic management of hyper-phosphoremia, which is inadequate because of insufficient intra-dialytic removal of phosphate (P), is further limited by PDR-P, i.e. the significant increase in serum P levels during the early postdialytic period. Patients and methods. To investigate the effects of enhanced P removal by haemodiafiltration on the inter-dialytic phosphoremia, we studied 12 uremic patients that were switched, with cross-over randomised modality, to a single session of standard hemodialysis (HD) and hemodiafiltration (HDF) (Acute Study). Blood samples were obtained before the treatment, at the end (T0), after 30, 60, 90 and 120 minutes, and at 24, 48 and 68 hours. During both dialytic treatments the whole effluent dialysate was collected to evaluate the intradialytic removal of P. Thereafter, patients were randomised to receive either HD or HDF for three months, in the presence of constantly similar Kt/V, food intake and dose of phosphate binder (Chronic Study).
                Acute Study. Compared to HD, P removal in HDF was about 44% greater in the presence of identical predialytic P levels (6.0+/-0.2 and 5.9+/-0.4 mg/dl) and Kt/V (1.35+/-0.06 and 1.34+/-0.05); however, the inter-dialytic decline of serum P levels did not differ (-50+/-3% versus -42+/-3%, p=0.098). In HDF, PDR-P was faster (30 min versus 90 min) and better (at T120: +69+/-6% versus +31+/-4%, p<0.001). The higher P levels were maintained throughout the inter-dialytic period whereas Ca x P changed in parallel. Chronic Study. During the three months, pre-dialytic serum P diminished in HDF (from 5.8+/-0.2 to 4.4+/-0.3 mg/dl, p<0.05), while it remained unchanged in HD. A similar pattern of changes was detected in Ca x P.
                Enhancement of P removal, acutely amplifies the extent of PDR-P, but allows better control of Ca-P homeostasis in the medium term. This effect is likely to be dependent on the enhanced mobilisation of phosphate from a deep compartment. Middle molecules (MMs) and protein-bound solutes are poorly removed by conventional hemodialysis (HD). Hemodiafiltration (HDF) combines convection and diffusion in a single therapy and has been shown to be superior for the elimination of several small and larger retention molecules. Information on the elimination of protein-bound solutes during convective strategies is scarce. The primary aim of this randomized crossover study is to evaluate the influence of internal filtration, postdilution HDF, and predilution HDF on removal of the protein-bound solute p-cresol.
                Fourteen stable patients on regular thrice-weekly medium-flux HD therapy were assigned to 5 treatment periods of 2 weeks each for: HD with HF80(S); HD with FX80; postdilution HDF, 20 L, with FX80; predilution HDF, 20 L, with FX80; and predilution HDF, 60 L, with FX80 (all dialyzers from Fresenius Medical Care, Bad Homburg, Germany).
                As for the water-soluble solutes, elimination of p-cresol was better during HDF and increased with greater filtration volumes. Removal of beta2-microglobulin (beta2m) also was enhanced during HDF. However, the positive effect of convection was offset when high predilution substitution volumes were applied, probably as a result of dilution. Within each dialytic approach, removal of the MM beta2m and the protein-bound solute p-cresol was significantly less than that of the water-soluble molecules urea nitrogen and creatinine.
                Our data indicate that convection can provide superior protein-bound solute removal compared with high-flux HD. Our findings also suggest that better elimination of the unbound fraction is the most plausible underlying mechanism. Accumulation of larger molecular weight uraemic toxins molecules may have a negative effect on the cardiovascular and nutritional state of dialysis patients and influence uraemic symptomatology. Their clearance can be enhanced by the use of haemofiltration (HF).
                The effects of low-flux haemodialysis (HD) (ultrapure dialysate; polyamide membranes) and pre-dilution on-line HF (1:1 blood/substitution ratio; target filtration volume: 1.2 times body weight) on cardiovascular and nutritional parameters, interdialytic levels of uraemic toxins and quality of life (QOL; Laupacis questionnaire) were assessed during 1 year follow-up. Forty patients were randomized.
                After 1 year, 27 patients were eligible for analysis (HF: 13 patients; HD: 14 patients). Left ventricular mass index did not change in the HF patients (127+/-33 --> 131+/-36 g/m(2) after 12 months) or in the HD group (135+/-34 --> 138+/-32 g/m(2)). Also, there were no changes in pulse wave velocity, and 48 h systolic and diastolic blood pressures. Lean body mass, assessed by dual-energy X-ray absorptiometry, increased in the HF group (44.8+/-8.9 --> 46.2+/-9.6 kg; P<0.05), but not in the HD group (49.4+/-9.2 --> 50.6+/-8.8 kg), although differences between groups were not significant. Insulin-like growth factor-1 levels remained stable in the HF patients, but decreased in the HD group (P<0.05 between groups). QOL for physical symptoms improved in the HF group (4.2+/-1.2 --> 5.0+/-1.1; P<0.05 within the HF group and P = 0.06 between groups), but not in the HD group (4.0+/-1.0 --> 4.4+/-1.4). beta2-microglobulin, complement factor D and homocysteine decreased significantly in the HF but not in the HD group, whereas l-ADMA, leptin and advanced glycation end-products-related fluorescence did not change.
                No changes in cardiovascular parameters were observed during pre-dilution on-line HF compared with low-flux HD. Treatment with on-line HF resulted in marked changes in the uraemic toxicity profile, an improvement in physical well-being and a small improvement in nutritional state. The objective of the study was to compare the convective treatment modes, on-line hemofiltration (HF) and on-line hemodiafiltration (HDF), regarding cardiovascular tolerance and effects on blood pressure, when applied under similar conditions in stable dialysis patients.
                39 clinically stable dialysis patients were treated with HD for 6 months (run-in period), followed by HF and HDF in random order for 2x6 months. Similar biocompatibility (same membrane and fluid quality), similar treatment time and urea Kt/V were achieved using AK100/200 ULTRA machines, polyamide membranes in low-flux and high-flux versions and appropriate adjustment of blood flow rate (Qb) and dilution ratio (Qb/Qinf). Predilution was used for HDF (target dilution ratio = 2/1 ) as well as for HF (target dilution ratio = 1/1).
                30 patients completed the study; 5 dropped out for non-study related reasons and 4 for non-compliance. Treatment with HF in comparison to HDF showed fewer hypotension episodes during the sessions per patient and month (HF: 0.5, HDF 1.1; p = 0.017), less plasma expander administration per patient and month (HF: 35.9 ml, HDF: 103.1 ml; p = 0.035), fewer episodes of intra-session headache (HF: 0.1, HDF: 0.4; p = 0.06), and higher pre-session MAP (HF: 98.4 mmHg, HDF: 93.8 mmHg; p = 0.037). No significant difference was found in inter-treatment weight gain, post-session MAP, or pre-session plasma sodium.
                HF and HDF provide good control of intra-session symptoms and blood pressure in stable patients. Treatment with HF resulted in a significant reduction in intra-session hypotension and a slight but significant increase in pre-session MAP, caused by an increase in systolic BP without any effect on the prevalence of hypertension or the dose of antihypertensive drugs, all compared to HDF. Efficient removal of total body burden beta 2-Microglobulin (beta 2-M) in uremia is a continuing challenge, as dialysis-related amyloidosis represents a major complication of chronic renal replacement therapy. To investigate long-term beta 2-M removal we studied 3 groups of stable end-staged renal failure patients over a period of 4 years; we compared low flux (cuprophane) hemodialysis (n = 12), high flux (polysulfone) hemodialysis (n = 12) and hemofiltration using high flux polysulfone (n = 8). In contrast to the cuprophane membrane, the polysulfone membrane eliminated considerable amounts of beta 2-M. This was associated with a sustained reduction of predialysis serum beta 2-M-levels (by 20%). Compared with high flux hemodialysis, hemofiltration provided a 50% higher elimination of beta 2-M. Thus, our long-term evaluation of beta 2-M removal suggests that hemofiltration rather than hemodialysis may be the treatment of choice for delaying the incidence of dialysis-related amyloidosis. Hemodiafiltration (HDF) and more recently acetate-free biofiltration (AFB) have shown good blood purification and cardiovascular stability in young and middle-aged hemodialysis patients. It is not clear if this is also valid for elderly patients. Twelve patients aged more than 70 years (mean age +/- SD, 76 +/- 4 years) on regular dialysis for at least 5 months were treated with bicarbonate dialysis (BD), HDF, or AFB in a randomized sequence and prospectively followed for 6 months (72 dialysis sessions/patient) for each procedure. The dialysis solution (containing bicarbonate), blood flow rate, and dialysate flow rate were the same with all the methods. During HDF and AFB solutions containing bicarbonate at a concentration of 27 to 30 mEq/L and 145 mEq/L, respectively, were infused postdilution at a rate of 66 +/- 7 mL/min and 2.81 +/- 0.12 L/hr, respectively. During the period of observation we evaluated the number of intradialytic hypotensions, the episodes of nausea, vomiting, headache (dialysis intolerance), body weight, the interdialysis weight gain, the duration of the dialysis session, the number of hospitalizations/patient, and the length of hospitalization/patient. At the end of each observation period we determined: Kt/V, protein catabolic rate, acid base balance, serum creatinine, serum calcium, serum phosphorus, alkaline phosphatases, and serum intact parathyroid hormone. After the switch from BD to either HDF or AFB, the results have shown a significant reduction of dialysis hypotension episodes (18 percent on BD, 14 percent on HDF, and 13 percent on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.0001; and HDF v AFB, P = NS) and of dialysis intolerance (3.3 percent on BD, 1.3 percent on HDF, and 1.1 percent on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.019; and HDF v AFB, P = NS). Kt/V improved significantly after the switch from BD to either HDF or AFB (1.17 +/- 0.06 on BD, 1.32 +/- 0.12 on HDF, and 1.32 +/- 0.13 on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.003; HDF v AFB, P = NS). Protein catabolic rate also improved in HDF and AFB compared with BD (0.90 +/- 0.12 on BD, 1.03 +/- 0.15 on HDF, and 1.04 +/- 0.14 on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.009; and HDF v AFB, P = NS). AFB showed a better correction of acidosis compared either with BD or HDF (serum bicarbonate, 20.3 +/- 1.1 mEq/L on BD, 20.8 +/- 2.2 mEqL on HDF, and 22.2 +/- 2.4 mEq/L on AFB; BD v HDF, P = NS; BD v AFB, P = 0.01; and HDF v AFB, P = 0.030). The other parameters observed did not differ. In conclusion HDF and AFB show a better dialysis efficiency and a better hemodynamic tolerance compared with BD. This fact is associated with an improvement in protein intake as assessed by kinetic criteria. Acetate-free biofiltration has the further advantage of a better control of the acid-base balance compared with BD and HDF. HDF and AFB are useful dialytic options to traditional BD hemodialysis even in patients older than 70 years. Activation of polymorphonuclear neutrophils (PMNs) and monocytes has been described during hemodialysis (HD), which results in the release of reactive oxygen species and cytokines. Acetate-free biofiltration (AFB) has been shown to cause less monocyte activation and cytokine release than bicarbonate HD (BHD). No data are available to date on the effect of AFB on PMN activation.
                We studied ex vivo superoxide anion release by PMNs isolated from nine patients treated in random order with AFB or BHD (three sessions each). Plasma interleukin-1beta (IL-1beta) levels and the nitric oxide (NO) synthetic pathway also were evaluated. A polyacrylonitrile (AN69; Hospal, Bologna, Italy) dialyzer was used for both treatments. Fourteen healthy volunteers were used as controls. Blood samples were drawn predialysis and 5 and 15 minutes after starting dialysis to obtain plasma and PMNs.
                Neither ex vivo superoxide anion release nor blood PMN count was affected by AFB. Conversely, a peak in superoxide anion production associated with a decrease in PMN count was observed at 5 minutes during BHD. Results of superoxide anion production by control PMNs exposed in vitro to AFB or bicarbonate dialysis bath or Hank's balanced salt solution supplemented with bicarbonate or acetate indicated that BHD-induced PMN activation could be attributed to the amount of bicarbonate present in the dialysis bath. IL-1beta plasma levels did not change during dialysis with AFB and were numerically higher at 5 and 15 minutes with respect to predialysis values during BHD. Uremic plasma obtained during either AFB or BHD induced greater NO synthesis by human umbilical vein endothelial cells than control plasma.
                AFB, unlike BHD, does not cause PMN and monocyte activation, which could have a positive impact on dialysis-associated cardiovascular disease of dialyzed patients.
                Copyright 2002 by the National Kidney Foundation, Inc. Morbidity and mortality rates in diabetic patients on regular dialysis treatment (RDT) are higher than in non-diabetic-subjects on RDT. Moreover, diabetic patients experience an intradialitic morbidity unacceptably higher than in patients with other causes of terminal renal failure. The aim of the present investigation was to compare standard bicarbonate haemodialysis (BHD) with acetate-free biofiltration (AFB) in a group of 41 diabetic patients stable on dialysis treatment for 25 +/- 22 months.
                Twenty-four type II and 17 type I diabetic patients, all requiring insulin therapy, were included and were followed for 1 year in a 6-month cross-over randomized study for both methods. The analysis was carried out on dialysis symptoms, interdialysis symptoms, and nutritional status, and the multivariate analysis of variance for repeated measures on the same subjects in the two techniques was used.
                AFB significantly reduced dialytic and extradialytic symptoms (P=0.003 and 0.001 respectively). Cardiovascular collapses decreased by 43%, and other dialysis symptoms showed a similar trend (-35%). The interdialysis symptoms decreased by 28% and were accompanied by an increase in subjective wellbeing (39%) when patients were switched from traditional haemodialysis to AFB. Acid base control was better with AFB (P=0.01), both at the beginning and during the session. Slightly significant differences were also obtained for Kt/V (AFB 1.48 +/- 0.29 vs BHD 1.38 +/- 0.30), while no significant difference was noted with respect to sodium mass balance, nutritional status, calorie-protein intake, nPCR, blood glucose profile, and insulin requirements. The number of hospital admissions and the mortality rate, which were much lower during the AFB than the BHD period, were not analysed statistically.
                AFB allows better control of some metabolic aspects, reduces intra- and extradialysis symptoms, and improves patient quality of life. Whether the long-term prognosis can be improved by AFB remains to be established with further studies. The accumulation of beta2-microglobulin (beta2-M) in long-term dialysis patients may lead to dialysis amyloidosis. In this respect, the removal with different modes of on-line haemodiafiltration (HDF) of beta2-M was studied. Long-term clinical observations in patients with more than 10 years of dialysis, treated mainly with biocompatible and highly permeable membranes and in the last years with on-line HDF are also reported.
                In the first part of this report, the reduction ratios and clearances of beta2-M, blood urea nitrogen, creatinine and phosphorus (P) of on-line HDF with 40 to 120 ml/min replacement fluid are compared with bicarbonate haemodialysis (HD). In the second part, we investigated 16 patients with more than 10 years of dialysis treatment. The prevalence of dialysis amyloidosis and the mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol and parathyroid hormone are reported, as well as the mean dose of erythropoietin.
                In the first part with on-line HDF, starting from HDF 60 ml/min a significantly higher beta2-M reduction ratio and clearance vs HD is noted. In HDF100 (i.e. with 241 replacement volume per 4-h treatment) vs HD, a beta2-M reduction ratio of 72.7% vs 49.7% (P= 0.0000) and a beta2-M clearance of 116.8 vs 63.8 ml/min (P=0.0000) was obtained. Comparing HDF120 with HDF100, there is a significantly higher beta2-M clearance with the former (P<0.005), although the beta2-M reduction ratio was not significantly better. In the HDF120 session the amount of beta2-M in the total dialysate was 292 mg per session. If one adds the known 17% adsorption on the polysulfone membrane, a total of 341.6 mg beta2-M per session is removed, which adds up to 1024.8 mg a week. Concerning the small molecules, our results with HDF100 also show a higher creatinine and especially P clearance vs HD. In the second part with 16 patients with more than 10 years of dialysis treatment (mean 14 years 1 month), the mean time on HDF amounted to 39.5% of the total treatment time. In four patients only biocompatible and highly permeable membranes were used, AN69 and mainly polysulfone, and in four other patients these membranes were used for more than 95% of the treatment time. Therefore, it is not surprising that the prevalence of carpal tunnel syndrome was only 12.5% in the patients after 10 years of dialysis. Twenty-five percent of these patients met the criteria for diagnosis of beta2-M bone-amyloidosis, proposed by van Ypersele de Strihou et al., but without a retrospective X-ray analysis. The mean predialysis beta2-M value was 29.6 mg/l. The mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol were within normal limits. For the parathyroid hormone a mean of 287.5 pg/ml was found. Subtotal parathyroidectomy was performed in five patients. The mean dose of 43 U erythropoietin/kg per session is comparable with those reported in the literature. Conclusions. Like Canaud, in our renal unit, treatment with on-line HDF with a highly permeable and biocompatible membrane has proven to be an efficient, well-tolerated and safe technique. Furthermore it leads to a low prevalence of dialysis amyloidosis and a superior P clearance. However, continuous attention must be paid to an on-line sterile and apyrogenic dialysate. Although on-line HDF is undoubtedly a more optimal approach of chronic dialytic treatment, it also carries a higher cost, which is currently evaluated to be nearly US$11 per session. Online hemodiafiltration (online HDF) and acetate-free biofiltration (AFB) are 2 innovative renal replacement therapies. Convincing evidence has shown that both techniques are superior to conventional hemodialysis in many aspects. The aim of the present investigation was to compare online HDF and AFB in 12 stable maintenance hemodialysis patients in a prospective, randomized crossover trial. Twelve stable dialysis patients, age 49.7 +/- 11.3 years and on dialysis for 83.5 +/- 76.7 months, were treated prospectively and randomly by either AFB, predilution HDF (pre-HDF), or postdilution HDF (post-HDF) for a total of 36 weeks using exclusively F60S high-flux dialyzers. Routine blood biochemical tests, bone metabolism parameters, and clearance for both small and larger molecular weight substances were measured at defined intervals. During the trial period inter- and intradialysis symptoms, e.g., hypotensive episodes and intradialysis arterial blood gas analyses, were recorded. Both online HDF and AFB were well accepted by the overwhelming majority of patients and also by the dialysis staff. Pretreatment sodium, total and ionized calcium, chloride, bicarbonate, and urea did not differ within or between the 3 treatment groups. Potassium increased slightly in HDF patients while phosphate and beta2-microglobulin (beta2-M) decreased in all groups. After dialysis, AFB patients exhibited a significantly higher bicarbonate concentration and lower potassium level when identical potassium concentrations in dialysate were used. Patients receiving AFB manifested less intradialysis partial pressure of oxygen drop and partial pressure of carbon dioxide rise than those on HDF treatments. HDF treatments could afford higher single-pool and double-pool Kt/V, higher effective urea and beta2M clearance, and lower total interdialysis symptom scores than the AFB treatment method. While bone metabolism parameters did not differ between the 3 dialysis modalities, some parameters such as deoxypyridinoline in HDF and osteocalcin, pyridinoline, and deoxypyridinoline in AFB deteriorated at the end of the crossover study. Aluminum concentration decreased progressively to about one-third of prestudy values at the end of the study with all 3 treatments. AFB was associated with a lower predialysis mean arterial pressure (MAP), a smaller drop in MAP during treatment, and similar hypotension episodes compared with the 2 HDF treatments. Albumin concentration showed a trend to decrease during the first 2 months of the trial period followed by a slight increase thereafter but still significantly lower than initial value at the end of crossover. Both online HDF and AFB share most of the features of optimal renal replacement therapy. Online HDF is superior to AFB in such aspects as increased delivered dialysis dose both for small and larger molecular weight toxins and less interdialysis symptoms. On the other hand, AFB is associated with a smaller effect on arterial blood gas values and improved intradialysis hemodynamic tolerance. Some dialysis-related symptoms and complications in the case of our AFB practice could be attributable, at least in part, to low dialysate calcium level. In spite of the better efficiency of on-line hemodiafiltration (HDF) compared with conventional hemodialysis (HD), it is relatively expensive. The aim of this study was to assess the advantages in the biochemical, hemodynamic and clinical effects in uremic patients treated with on-line HDF and with different frequencies of combination high-flux HD.
                One hundred eleven patients were divided into four groups receiving different frequencies of on-line HDF (thrice, twice, once per week) and high-flux HD.
                Hemodynamic parameters including maximum drop of systolic blood pressure, episodes of symptomatic hypotension and mean saline infusion volumes during dialysis were reduced when frequencies of on-line HDF were increased. Significant improvements in urea kinetic were observed when frequencies of on-line HDF were increased. On-line HDF significantly reduced the amount of erythropoietin needed and improved intra- and inter-dialysis symptoms, physical well-being, menstruation and skin pigmentation when frequency of HDF is increased to three time per week.
                On-line HDF offers a better cardiovascular stability and clinical improvement. Thrice weekly on-line HDF offers a significant benefit when compared with lower frequencies of HDF per week and high-flux HD. The authors monitored, for a period of 12 months, anemia-, nutrition-, and free radical-related parameters and the rHuEPO dose required to maintain target hemoglobin (Hb) in 20 patients with chronic renal failure. Ten patients each were randomized for treatment by either acetate-free biofiltration (AFB) or low-flux hemodialysis (HD). At baseline, Hb levels were 102+/-2 (AFB) vs. 98+/-2 g/L (HD) (not significant difference, NS), the rHuEPO dose was 4050+/-976 vs. 5100+/-1538 lU/week (NS). Compared with baseline and with HD, lower rHuEPO doses were required during AFB at months 8, 9, 10 and 11, and 12 when they were 2100+/-510 (AFB) vs. 6000+/-1153 (HD), p=0.008. Prealbumin, transferrin and cholinesterase levels rose in the AFB group. Kt/V, albumin, transferrin saturation, aluminium, bicarbonate in serum, superoxide dismutase and glutathione peroxidase in erythrocytes, and malondialdehyde and antioxidant capacity in plasma did not differ between the AFB and HD groups. In terms of anemia control, AFB using an AN69 membrane was found to be more advantageous than low-flux HD, AFB improves some nutritional parameters. The compared methods do not differ in their effect on lipid peroxidation and the antioxidant system. The effect of acetate dialysis (AD), bicarbonate dialysis (BD), and acetate-free biofiltration (AFB) on nitric oxide (NO) synthesis and the implications for dialysis hypotension was studied. The finding that uremic plasma is a potent inducer of NO synthesis by endothelial cells in vitro suggested that the cardiovascular instability of dialysis patients might result from excessive NO formation. Cardiovascular instability is more frequent in patients undergoing AD than BD. To see whether these differences were attributable to NO, we studied the NO synthetic pathway ex vivo in patients undergoing different dialysis procedures. Five patients were treated, in a random order, with AD, BD, and AFB, a technique using a buffer-free dialysate and postdilution of a sterile bicarbonate solution. Each type of dialysis was used for 1 week, comprising three dialysis sessions. A polyacrylonitrile dialyzer was used for all three methods. Before and after the third dialysis, plasma was collected, added to [3H]L-arginine, and incubated with human umbilical vein endothelial cells (HUVECs) for 24 hours. NO synthesis was evaluated as [3H]L-citrulline formation. Plasma concentrations of interleukin-1beta (IL-1beta), a potent inducer of inducible NO synthase (iNOS) in endothelial cells, were also measured. Plasma collected from patients after AD stimulated endothelial NO synthesis more than plasma from the same patients before the dialysis session (pre-AD, 0.173+/-0.028 nmol/10(5) cells v post-AD, 0.280+/-0.093 nmol/10(5) cells; P < 0.05). A slight, although not significant, increase was also observed when HUVECs were incubated with plasma drawn after BD (pre-BD, 0.151+/-0.014 nmol/10(5) cells; post-BD, 0.230+/-0.055 nmol/10(5) cells). AFB did not aggravate the stimulatory effect of uremic plasma on endothelial NO synthesis (pre-AFB, 0.184+/-0.038 nmol/10(5) cells; post-AFB, 0.189+/-0.040 nmol/10(5) cells). Plasma IL-1beta was greater (P < 0.01) after AD than after BD and AFB (post-AD, 0.234+/-0.028 pg/mL; post-BD, 0.124+/-0.019 pg/mL; post-AFB, 0.120+/-0.013 pg/mL). With AD, there was a greater intradialytic decrease in systolic blood pressure than with BD or AFB. Weight and blood volume loss and sodium balance were similar in AD, BD, and AFB. These data were consistent with the possibility that NO and cytokines, released in excessive amounts during AD, may contribute to hemodynamic instability. This study compared the acute and chronic effects on cardiac function of treatment with hypertonic hemodiafiltration (H HDF) and hemodialysis (HD). Cardiac function was assessed before, during and after a run of H HDF and HD using echocardiography and impedance cardiography in 10 patients in a randomized cross-over sequence, two months after stabilization on each treatment. Blood biochemistry was performed before and after each run. Ejection fraction and fractional shortening were significantly higher before the H HDF run, compared to the HD run, and this difference persisted during and after the treatment runs (both P less than 0.05). There was a corresponding significant difference in the increase of the velocity of circumferential fiber shortening and in the reduction of end systolic diameter during and after H HDF (P less than 0.05). Heart rate, stroke volume, cardiac output, systemic vascular resistance and mean arterial pressure did not differ significantly between the two treatments. Plasma calcium and bicarbonate were significantly higher (P less than 0.03) at the start of H HDF and this difference was enhanced at the end of the run. In conclusion, H HDF compared with HD, is associated with a better myocardial function in both the short and long term treatments. The evidence suggests that this may be due to improved levels of plasma calcium, bicarbonate, and/or the removal of an as yet unidentified myocardial toxin. There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage (in terms of treatment tolerance, nutritional parameters and pre-treatment beta-microglobulin levels) over a traditional membrane (Cuprophan). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan hemodialysis (Cu-HD), low-flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 +/- 10.46 mg/liter (23%) and in hemodiafiltration of 6.35 +/- 12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes (P = 0.032). The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications. The discussion about the pathogenesis of renal anaemia, whether it is primarily due to relative erythropoietin (Epo) deficiency or to uraemic inhibition of erythropoiesis, is still open. Although it has so far not been possible to identify or isolate a substance retained in uraemia with a suppressive action directed specifically against red-cell production, dialysis therapy can improve the effect of both residual endogenous Epo and exogenous rHuEpo. To what extent the mode and/or the dose of dialysis influence Epo efficacy is as yet poorly understood.
                This study was performed as a single-centre trial. The protocol included a run-in period of 4 months followed by a prospective cross-over study including 6 months each of acetate-free biofiltration (AFB) with a high-flux biocompatible membrane and standard bicarbonate dialysis (BD) with a low-flux cellulosic membrane in a random sequence. AFB is a haemodiafiltration technique based on a continuous post-dilution infusion of a sterile isotonic bicarbonate solution. At the start of the run-in period (and for the entire length of the study), rHuEpo administration was withdrawn; patients whose haemoglobin (Hb) levels dropped at a level <8.0 g/dl at one single monthly check, had to be withdrawn from the study. A blood sample was collected every month for the blood gas analysis and for the determination of blood urea nitrogen, serum creatinine, sodium, potassium, calcium, phosphorus, Hb, erythrocyte, reticulocyte, leukocyte and thrombocyte cell counts, mean globular volume and haematocrit. An equilibrated single pool Kt/V(urea)>1.2 was mandatory in both treatment modalities. Serum iron, total iron-binding capacity, and ferritin were checked every 3 months.
                Twenty-three of 137 haemodialysis patients were considered eligible for the trial on the basis of the entry criteria. Of these, 15 volunteered and only 10 completed the study. No significant differences in the haematological indices, in the biochemical parameters assessing body iron stores, or in i.v. iron dosage was observed when comparing AFB with BD treatments. The equilibrated single pool Kt/V(urea) was always >1.2 and in no case was a significant difference observed when comparing AFB with BD treatments. Treatment time was significantly different between the two treatments (262+/-2 min in BD and 249+/-1 in AFB, P<0.0001). Neither pre- nor post-dialysis systolic and diastolic blood pressures, pre-dialysis serum bicarbonate and pH, pre-dialysis serum sodium, potassium, calcium, or phosphorus were significantly different when comparing the two treatment modalities. All 10 patients completed the 1-year follow-up without any major side-effects.
                Our study did not show any improvement of anaemia when treating a highly selected patient group, in the absence of any Epo therapy, with AFB compared with standard BD. Even though these conclusions cannot be extended in toto to the entire dialysis population, in which there is a large proportion of Epo-treated patients with Hb levels around 11 g/dl, we may nevertheless conclude that when patients are well selected, adequately dialysed, and not iron- and/or vitamin-depleted, the effect of a haemodiafiltration technique with a high-flux biocompatible membrane is less than might be expected from the results of uncontrolled studies. Some of the morbidity associated with chronic hemodialysis is thought to result from retention of large molecular weight solutes that are poorly removed by diffusion in conventional hemodialysis. Hemodiafiltration combines convective and diffusive solute removal in a single therapy. The hypothesis that hemodiafiltration provides better solute removal than high-flux hemodialysis was tested in a prospective, randomized clinical trial. Patients were randomized to either on-line postdilution hemodiafiltration or high-flux hemodialysis. The groups did not differ in body size, treatment time, blood flow rate, or net fluid removal. The filtration volume in hemodiafiltration was 21 +/-1 L. Therapy prescriptions were unchanged for a 12-mo study period. Removal of both small (urea and creatinine) and large (ss(2)-microglobulin and complement factor D) solutes was significantly greater for hemodiafiltration than for high-flux hemodialysis. The increased urea and creatinine removal did not result in lower pretreatment serum concentrations in the hemodiafiltration group. Pretreatment plasma beta(2)-microglobulin concentrations decreased with time (P< 0.001); however, the decrease was similar for both therapies (P = 0.317). Pretreatment plasma complement factor D concentrations also decreased with time (P<0.001), and the decrease was significantly greater with hemodiafiltration than with high-flux hemodialysis (P = 0.010). The conclusion is that on-line hemodiafiltration provides superior solute removal to high-flux hemodialysis over a wide molecular weight range. The improved removal may not result in lower pretreatment plasma concentrations, however, possibly because of limitations in mass transfer rates within the body. Current methods of renal replacement therapy lead only to an insignificant removal of larger, potentially toxic, substances, which are excreted by healthy kidneys. On-line preparation of substituate from dialysate and the use of high-flux membranes allow substantial convective removal of such substances. A modified on-line haemodiafiltration method with the use of a large membrane surface and a high convective part was chosen to test whether the elimination of larger substances, such as low-molecular-mass proteins, has a clinical impact.
                In a prospective, controlled study over 24 months, 44 unselected chronic dialysis patients were randomized to undergo either low-flux haemodialysis (HD; n = 21) or haemodiafiltration (HDF; n = 23). To eliminate confounding factors, low-molecular efficacy was matched (Kt/V 1.8), and the same membrane material (polysulfone), ultrapure dialysate and the same treatment duration (4.5 h) were applied to each group.
                Morbidity, mortality, blood pressure, dialysis-associated hypotensive episodes, haematocrit and erythropoietin dose did not differ between the groups. The same was true for body weight and, accordingly, bioimpedance values, clinical hydration score, skinfold thickness, plasma albumin, prealbumin and transferrin. beta2-Microglobulin in the plasma did not change in the HD group and varied between 32 and 43 mg/l throughout the 2 years. In HDF, beta2 microglobulin decreased from similar values to 18 mg/l predialysis (P<0.01) in the first 6 months of HDF treatment and then remained constant during the remaining 18 months.
                In the absence of any clinical marker of uraemic toxicity the removal of larger molecules over the time-span of 2 years during HDF had no clinical implication compared with extremely (and for routine practice unrealistically) well-dialysed patients with low-flux HD. In the absence of any side-effects of on-line HDF and supposing that plasma beta2-microglobulin is a marker of morbidity, on-line HDF ensures an excellent dialysis quality which apparently takes time to translate into measurable clinical sequelae. Nine patients on regular dialysis were studied, in a cross-over format comparing hemodialysis (HD) and hemofiltration (HF), to identify potential mechanisms of the disparate hemodynamic responses. Dialysis and substitution fluid composition (high sodium, acetate), treatment time, fluid loss rate, and membrane type (AN 69) were matched. Cardiac output was determined by changes in thoracic electrical bioimpedance. Cardiac output remained stable during HF but increased during HD (p < 0.001, HD vs. HF), despite a parallel reduction in stroke volume. The heart rate response was significantly greater during HD relative to HF (p < 0.01). Systemic vascular resistance remained stable during HF but decreased significantly during HD (p < 0.05). Although there was a modest fall during HD, the difference in blood pressure at the end of treatment between HD and HF was not significant. Comparable increases in body temperature were observed during both treatments. Plasma catecholamines increased in parallel during HD and HF and following orthostatic stimulation at the end of treatment, and extracorporeal catecholamine clearances were similar. The values for serum sodium, total CO2, anion gap, potassium, and hematocrit at the end of treatment were similar, whereas total serum calcium was significantly greater following HD. There were no significant differences in indices of myocardial contractility or central blood volume. These results suggest that the disparate hemodynamic responses to fluid and solute removal during HD and HF can be dissociated from changes in osmolality or venous tone, membrane bioincompatibility, thermal stress, or differences in acetate delivery or catecholamine release. The explanation for the disparate hemodynamic responses between these two treatment modalities remains unclear. A role for an as yet unidentified vasodilatory substance generated during dialysate exposure, or convectively removed during hemofiltration, remain intriguing possibilities. Acetate free biofiltration (AFB) provides a well-tolerated and efficient renal replacement therapy. Replacement of most of the acetate by bicarbonate in standard hemodialysis has resulted in a decrease in intradialytic hypotensive episodes. This has been attributed to a decrease in the acetate-induced impairment of myocardial contractility. The aim of the present study was to investigate whether the total absence of acetate in AFB would further enhance dialysis stability and improve cardiovascular status.
                In a long-term, randomized trial we included 11 patients on AFB and 9 patients on bicarbonate hemodialysis (HD) for one year. Patients were matched for age, sex and urea reduction rate, but not for the presence of hypertension or cardiovascular history. During each dialysis session blood pressure was measured automatically and the presence of significant hypotension was recorded. Antihypertensive medication was registered every three months. Before and at the end of the study M-mode echocardiography was performed and left ventricular mass index (LVMi) was calculated. Every six months serum lipids were measured.
                At baseline, mean arterial pressure (MAP) before and after dialysis, the percentage of hypotensive dialyses, LVMi and serum lipids did not differ between AFB and HD. Pre-dialysis MAP decreased in AFB (from 112.5 to 107 mmHg) and increased in HD (from 101.7 to 105.3 mmHg; p = 0.01, HD versus AFB). Postdialysis MAP remained stable in both groups (AFB 91.6 mmHg at 0 months and 90.6 mmHg at 12 months, for HD respectively 83.9 and 86.5 mmHg, NS). The percentage of hypotensive dialyses did not differ significantly between the groups during the study. LVMi decreased in AFB from 195.4 to 162.1 gr/m2 and increased in HD patients from 153.8 to 182.5 gr/m2 (p = 0.03 HD versus AFB). The number of antihypertensive medications per patient did not differ between groups. Serum lipids remained unchanged during the trial.
                In conclusion, AFB provided better control of pre-dialysis MAP compared to HD, and stable postdialysis MAP. The percentage of dialysis sessions with hypotension did not differ. LVMi decreased significantly in AFB, but rose in HD.
We were unable to demonstrate whether convective modalities (either HF, HDF or AFB) have significant advantages over HD with regard to clinically important outcomes of mortality, dialysis-related hypotension and hospitalisation. More adequately-powered good quality RCTs assessing clinically important outcomes (mortality, hospitalisation, quality of life) are needed.