Evaluation of the impact of a new synthetic vitamin E-bonded membrane on anemia and rHuEPO requirement in ESRD patients with central venous catheters: a pilot study.

In the last years, the number of hemodialysis (HD) patients with erythropoietin (rHuEPO) resistance is increasing. Probably, central venous catheters (CVCs) contribute to this resistance by inducing inflammation and oxidative stress. This study was aimed to compare vitamin E-bonded dialyzer (PSVE) versus polyethersulfone membrane. Sixteen subjects with CVCs were included in a prospective two-arm crossover 12-month study. The primary endpoints were the rHuEPO requirement and the erythropoiesis-stimulating agents (ESA) index, which was defined by the ratio between weekly EPO dosage (IU/kg/week) and Hb levels (g/dl). The mean dosages of rHuEPO to maintain hemoglobin between 10.5 and 12 g/dl were 135 ± 59 and 101 ± 57 IU/kg/week with polysulfone and PSVE, respectively (P = 0.14). The ESA indexes were 12.1 ± 5.2 and 8.7 ± 5.2 (P < 0.0001) with polysulfone and PSVE, respectively. A trend towards consensual changes in protein glycoxidation, antioxidant, and inflammatory markers was observed. In conclusion, the study suggests a role for PSVE in the reduction of ESA index in HD patients with CVCs.

[Anti convection: convective therapies aren't the future of extracorporeal blood purification]. / Contro la convezione: le terapie convettive non rappresentano il futuro della depurazione extracorporea.

Despite technological advances in dialysis therapies and modalities, the mortality and morbidity among patients on hemodialysis (HD) are still high. Membrane permeability, convection techniques, and the number and duration of dialysis sessions have been considered as being potentially related to patient outcome. The available data from 2 randomized controlled clinical trials suggest that treatment with high-flux membranes does not significantly reduce all-cause mortality in kidney patients. However, subgroups of patients such as diabetics, malnourished patients and patients with >3.7 years of dialysis could have a greater survival advantage with high-flux membranes. Interest in alternative hemodialysis regimens has grown substantially during the past decade. Delivered as either daily (1.5 to 2.5 h, 6 d/wk) or nocturnal (6 to 8 h, 6 d/wk) treatment, alternative HD has shown promising results with better control of blood pressure, reduction of left ventricular hypertrophy, and easier control of phosphate metabolism. Elderly patients, patients with heart disease and those with vascular instability during HD could benefit from daily regimens. If well motivated, young patients may improve their dialysis efficiency, nutritional status and work capacity mainly with long nocturnal HD while waiting for a kidney transplant. However, before significant resources are invested in initiating alternative hemodialysis programs, further data on mortality and cardiovascular morbidity, preferably from randomized clinical trials, are required.

Catheter lock solutions: it's time for a change.

In recent years, the number of patients on hemodialysis (HD) with central vascular catheters (CVCs) has grown. However, CVC use is often associated with an important risk for catheter related bloodstream infections (CR-BI) and inadequate dialysis due to flow problems. In this study, we reviewed alternative solutions to heparin for locking HD CVCs. Several experiences have demonstrated that trisodium citrate (TSC) (30-47%), citrate (4%) and taurolidine (1.35%) solutions are effective and safe for the prevention of CRBI, while heparin stimulates biofilm formation. High citrate (47%) concentrations can also provide significant advantages in reducing catheter clotting, but controlled studies with larger populations are necessary to confirm and to extend the use of such solutions in clinical practice. Side effects with high sodium citrate concentrations have been reported only immediately after locking, the symptoms are probably caused by a temporary drop in ionized calcium and magnesium, but it is evident that these solutions should only be used by skilled and authorized personnel, with a rigorous protocol.

How to improve dialysis adequacy in patients with vascular access problems.

Blood flow rate is a critical factor in the achievement of an adequate dialysis dose. The aim of this review is to evaluate the possibility of optimizing dialysis dose in terms of Kt/V in patients with reduced vascular access (VA) flow rate, considering effective blood flow (Qb eff), recirculation, access flow and hemodialyzer. In patients where the achievement of adequate blood flow rates are difficult to obtain and no surgical revision is necessary, to avoid under dialysis the increase in the treatment time should be the first choice solution. If such a solution is difficult for various reasons, a forced partial blood flow recirculation, especially in central venous catheters (CVCs) with reversed lines can be useful, on condition that the dialysis session is prolonged. The possibility of increasing the efficiency of dialysis through an increase in filter clearance has to be considered. Monitoring arterial pre-pump pressure (P asp) and optimizing ratio P asp/Qb eff during hemodialysis (HD) is one possible solution to improve blood flow rates, but it is necessary to educate and involve the staff. Recent developments in a new class of highly effective hemodialyzer due to dialysate distribution, has opened up interesting opportunities in terms of dialysis adequacy in patients with reduced VA flow rate.

Evaluation of hygiene and safety controls for on-line paired hemodiafiltration (PHF).

BACKGROUND: On-line hemodiafiltration is gaining popularity due to increasing evidence of clinical benefits however it also requires strict attention to hygiene and safety as notable quantities of liquid are reinfused into the patient. Although most centers are improving their attention to water quality, a frequent concern is the inadvertent or accidental contamination of water and whether the redundant safety controls are sufficient to protect the patient. In the present study, in order to simulate a worst-case safety condition, we tested in vitro the reliability of paired hemodiafiltration - (PHF), under low, moderate and high bacterial contamination of the water supply. Tests were performed using various bacterial concentrations (range 85-2000 cfu/mL) of Pseudomonas Aeruginosa. Samples were analyzed from different sites throughout the entire on-line hemodiafiltration circuit for bacteria endotoxin, fungus and ability to stimulate whole blood production of TNFalfa. RESULTS: In the in vitro contamination study, with the three bacterial concentrations tested at various points of the circuit, bacteria were below the level of detection and endotoxins were < 0.01 UE/mL. Addition of dialysate samples taken after the first stage of microfiltration, as well as after the first and second stage of ultrafiltration and incubated with whole blood were not associated with stimulated production of TNFalfa . CONCLUSIONS: PHF appeared to be a safe and feasible method for on-line hemodiafiltration even in the unforeseen presence of bacterial contamination of the feed water or water distribution system.

Leptin and beta2-microglobulin kinetics with three different dialysis modalities.

BACKGROUND: Leptin is a protein produced by fat cells and involved in body weight regulation. In patients with normal kidney function, leptin has been considered an independent predictor of cardiovascular events. In uremic patients, leptin in plasma serum was assumed to be associated with malnutrition, inflammation and atherosclerosis. Because of its molecular weight and characteristics, leptin can be considered as a protein-bound uremic retention solute. Some authors have reported the possibility of decreasing the serum leptin concentration with high flux membranes, but limited data are available on the elimination with medium-flux membranes or alternative dialysis strategies such as hemodiafiltration. METHODS: We evaluated the kinetics of leptin and beta2m in a study of 18 chronic hemodialysis patients using low-flux, medium-flux and high-flux biocompatible membranes, the last one used in hemodiafiltration (HDF). Blood samples for leptin and beta2m were collected pre- and post-treatment and 30 minutes after the end of treatment, over a 1-week period that included 3 dialysis sessions. Clearances of leptin and beta2m across the dialyzer were also determined directly from the arterial and venous blood concentrations 60 and 210 minutes after starting dialysis. RESULTS: At baseline, all groups showed similar leptin (18.8+/-4.4 ng/mL) and beta2m concentrations (29.2+/-7.1 ng/mL). After a single dialysis session, a reduction of both solutes was observed with HDF (39.8+/-1.9%, 78.1+/-4.9) and medium flux membranes (18.2+/-0.9%, 52.2+/-1.7%), whereas the concentrations remained unchanged with the low-flux membranes. After one-week period, a trend of reduction of plasma pre dialysis leptin and beta2m were observed with HDF and medium flux membranes. At 60 minutes, HDF showed the best instantaneous clearance across the filter for leptin (56.2+/-10.1 ml/min) and beta2m (75.3+/-4.4 ml/min). The magnitude of post dialysis rebound of leptin at 30 min was variable and strongly correlated with the instantaneous clearance of the solute (r2= 0.88). CONCLUSIONS: Leptin serum concentration can be influenced by dialysis modalities and membrane permeability; data on rebound suggest a multicompartimental kinetic of leptin similar to beta2m. Leptin removal, as measured by the reduction rate, can be considered as an index of dialysis efficiency for protein-bound uremic retention solutes.

Von Willebrand factor and autoantibodies against oxidized LDL in hemodialysis patients treated with vitamin E-modified dialyzers.

Oxidant stress is a well known cause of damage in the atherosclerotic process. Vitamin E is one of the most promising natural antioxidants. In this study we investigated if a vitamin E-coated dialyzer was able to reduce the plasma levels of auto-antibodies against oxidized-LDL, von Willebrand factor (vWf) and thrombomodulin (TM) as markers of endothelial damage. In this controlled 6-month prospective study, we investigated these markers in two matched groups (n=16 each) of patients on regular hemodialysis not yet diagnosed for atherosclerosis cardiovascular disease (ACVD) (mean age=58.3+/-7.0 yrs, mean dialysis age=30.1+/-10.0 months), in which cellulosic (CLS) and vitamin E-modified dialyzers (CLE) were compared. At inclusion all the patients were treated with CLS. Then, the study group was shifted to CLE for 6 months. At baseline the patients showed normal levels of vitamin E and high levels of oxLDL-Ab, vWf and TM compared to healthy subjects. In the CLE group oxLDL-Ab and vWf, but not TM levels, decreased progressively (from 472+/-287 to 264+/-199 mU/mL, p<0.0001 and from 101.1+/-7.5% to 76.7+/-18.5%; p<0.001, respectively), and vitamin E increased from 4.40+/-0.81 to 7.81+/-1.16 microg/mg of cholesterol. At the end of the study, 8 of the patients treated with CLE were randomly selected and went back to the membrane without Vitamin E for six months. They showed an significant increase in OxLDL-Ab and vWf levels and a significant reduction in tocoferol levels. In conclusion, CLE compared to cellulosic dialyzers can lower some indices of damage to LDL and endothelial cells.

[Alterations of cardiac output during bicarbonate hemodialysis and its relationship with other hemodynamic parameters]. / Modificazioni della gittata cardiaca durante emodialisi con bicarbonato e sue relazioni con altre variabili di pertinenza cardiologica.

PURPOSE: Time course of cardiac output (CO) and other hemodynamic parameters were measured during hemodialysis (HD). Our aims were to identify a characteristic CO profile and investigate the relationship with other hemodynamic parameters. PATIENTS AND METHODS: CO was measured with ultrasound dilution method in 45 chronic hemodynamically stable HD patients. Diabetics and patients with heart diseases were excluded. Ultrafiltration rate (UFR) was fixed at 649 +/- 244 mL/min. Pre/post statistical comparisons were performed for CO, cardiac index (IC), central blood volume (CBV) and total peripheral resistance (TPR). RESULTS: CO was pre 5.7 +/- 1.8 and post 4.5 +/- 1.4 L/min (p=0.001); IC was pre 3.2 +/- 0.9 and post 2.6 +/- 0.7 L/m2 (p=0.001); CBV was pre 1.28 +/- 0.39 and post 1.09 +/- 0.32 L (p=0.001). TPR increased from 18.7 +/- 5.6 to 22.7 +/- 6.1 mmHg/L/min (p=0.001). Maximal CO reduction rate was found at 60 min, thereafter it reduced progressively. Log(CO1) increased in a non-linear way with body weight gain and similarly it decreased during UFR. A negative correlation was found between log(TPR1) and log(CO1-QA). CO reduction was associated with UFR and not with age, dialysis duration, left ventricular hypertrophy, sex and hemoglobin (Hb) in a multiple regression model (r2 =0.31, p=0.05). Qa/CO1 was 0.16 +/- 0.12. CBV/CO increased from 0.23 +/- 0.06 to 0.25 +/- 0.07%. CONCLUSIONS: Progressive CO reduction and TPR increase appear to be the typical hemodynamic features of bicarbonate HD with a UFR of moderate degree. Volume overload and CO increase were related in a non-linear way. TPR1 was strongly correlated with CO1-Qa, suggesting that a large arterovenous shunt was associated with increased resistance.

[Safety controls in a new hemodiafiltration on line technique (PHF)]. / Controlli di sicurezza in una nuova tecnica di emodiafiltrazione on-line (PHF).

PURPOSE: On-line hemodiafiltration (HDF) is gaining popularity due to increasing evidence of clinical benefits. The purpose of this study was to test a new on-line technique paired hemodiafiltration (PHF). In addition, we evaluated the PHF system during in vitro contamination. METHODS: Five patients used the PHF technique over a 6-month period. We performed a disinfection protocol and tested for bacteria, endotoxin, halogenated carbons and metals in the feed water, and we tested for bacteria, endotoxins and fungi in the dialysate after different ultrafiltration stages. In vitro tests were performed using three bacterial concentrations of pseudomonas aeruginosa. Samples were analyzed from different sites throughout the entire on-line HDF circuit for bacteria endotoxins, fungus and the ability to stimulate whole blood production of tumor necrosis factor-alpha (TNF-alpha). RESULTS: The bacteriological control from the feeding machine water and at the entrance to the monitors had a bacterial level of <100 CFU/mL. No bacteria were detected in the dialysate and endotoxin levels were <0.03 EU/mL. In the in vitro contamination study, with the three bacterial concentrations tested at various points in the circuit, bacterial and fungi were below the level of detection and endotoxins were <0.03 UE/mL. The addition of dialysate samples taken after the 1st microfiltration stage, as well as after the 1st and 2nd ultrafiltration stage and incubated with whole blood were not associated with stimulated TNF-alpha production. CONCLUSIONS: PHF appeared to be a safe and feasible method for on-line HDF even in the unforeseen presence of the bacterial contamination of the feed water or in the water distribution system.

Vitamin E-coated membrane dialyzer and beta2-microglobulin removal.

This study was designed to test the removal of beta2-microglobulin (beta2M) in a vitamin E-modified membrane. We investigated in vivo the dialyzer (Excebrane, series EE, 1.8 m2) with respect to hydraulic permeability (Kuf), maximum ultrafiltration rate (UF max), sieving coefficient (Sc), and solute clearances in hemodialysis (HD) and in soft hemodiafiltration (HDF). Kuf was 18.4 ml/h/mmHg, UF max was 75 ml/min, and Sc for beta2M was 0.45. Clearance values at 400 ml/min of Qb in HD were 258 ml/min for urea, 201 ml/min for creatinine, and 135 ml/min for phosphate. In soft HDF, clearances were slightly higher. beta2M clearance was 26 ml/min in HD and 43 ml/min in soft HDF. In conclusion, Excebrane (series EE) procures a soft HDF with an amount of substitution fluid in post dilution mode of over 60 ml/min. Remarkable small solute clearances were obtained when the blood flow was raised to 400 ml/min. A significant reduction of beta2M is demonstrated by HDF.

[Acute renal failure and thrombotic microangiopathy (TM)]. / Insufficienza renale acuta e microangiopatia trombotica.

BACKGROUND: Thrombotic microangiopathy (TM) is a disorder characterized by fibrin formation and platelet aggregation in the small arteries and capillaries. Two main clinical settings are reported in association with this disorder: hemolitic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Both conditions share common findings such as microangiopathic anemia and thrombocytopenia. HUS is more frequent in children and is mainly characterized by renal symptoms, whereas PTT is dominated by neurologic abnormalities. However, in many patients, the clinical distinction between HUS and PTT is not clear; therefore, some authors consider the two syndromes as manifestations of the same entity. In children, the most common cause of HUS is an enteric infection caused by cytotoxin-producing bacteria (mainly Escherichia coli with serotype O157:H7). This toxin--the Shiga toxin--can bind to glomerular endothelial cells and stimulate the production of cytokines and the secretion of von Willebrand factor (vWf). TM may be caused by drugs such as cyclosporin, tacrolimus, mytomicin C, ticlopidine, quinine, and oral contraceptives. It may be associated with disorders of pregnancy (severe pre-eclampsia and postpartum HUS) or with systemic disorders such as systemic lupus erythematosus (SLE), antiphospholipid syndrome, systemic sclerosis, and human immunodeficiency virus (HIV) infection. Abnormalities of the gene of complement factor H have been found in familial HUS and in some sporadic cases of HUS not associated with diarrhea. Factor H abnormalities induce an uncontrolled complement activation that can activate the coagulation cascade. In familial PTT, genetic abnormalities of the cleaving metalloproteinase of fWf ADAMTS 13 have been identified. In other patients with TTP, antibodies inhibiting this enzyme have been found. As a consequence of plasma ADAMTS 13 deficiency, unusually large vWf multimers are produced. This abnormality, in the presence of an increased shear stress, stimulates platelet adhesion and aggregation. CONCLUSIONS: Knowledge of the type of causative abnormality is relevant to a therapeutic approach. Children with diarrheal HUS usually do not benefit from plasma infusion or exchange, whereas in patients with factor H or ADAMTS 13 deficiency procedures that include the administration of the lacking product and removal of the inhibiting or toxic factors, such as ultralarge vWfs, are mandatory. Potentially renal transplantation candidates should be screened for genetic defects to avoid the recurrence of TM in the graft.

Impact of blood and dialysate flow and surface on performance of new polysulfone hemodialysis dialyzers.

Optimization of hemodialysis treatment parameters and the characteristics of the dialyzer are crucial for short- and long-term outcome of end stage renal disease patients. The new high-flux membrane Helixone in the dialyzer of the FX series (Fresenius Medical Care, Germany) has interesting features, such as the relationship of membrane thickness and capillary diameter which increases middle molecule elimination by convection, as well as higher capillary packing and microondulation to improve the dialysate flow and distribution. Blood flow, dialysate flow and surface area are the main determinants of the performance of a dialyzer, however the impact of each parameter on small and middle molecule clearance in high flux dialysis has not been well explored. In order to find the best treatment condition for the new dialyzer series, we evaluated urea, creatinine, phosphate clearances and reduction rate of beta2-microglobulin in ten stable patients treated with different blood flows (effective Qb 280 and 360 ml/min), dialysate flow (Qd 300 or 500 ml/min) and dialyzer surfaces (1.4 and 2.2 m2, FX60 or FX100). KoA and Kt/V were also calculated. Blood flow, dialysate flow and surface area demonstrated a significant and independent effect on clearance of urea, creatinine and phosphate, as well as on Kt/V. Small solute clearance was stable over the treatment. In contrast to small solutes, reduction rate of beta2-microglobulin was related to increasing dialyzer surface only. The new dialyzer design of the FX series proves highly effective due to improved dialysate distribution and reduced diffusive resistance as shown by the small solute clearance. A high reduction rate of beta2-microglobulin is favored by improved fiber geometry and pore size distribution. These findings have potential long-term benefits for the patient.

[New dialysis therapy modalities: what role do they play in the hemodialysis patient's outcome?]. / Nuovi schemi di terapia dialitica: quale ruolo nell'"outcome" del paziente in emodialisi?

Many studies have been devoted to investigating new techniques and new dialysis strategies aimed at achieving adequate removal of "uremic toxins". Conversely, few studies focus on the effect of different dialysis techniques on long-term outcome, including large series and with adequate follow-up. Dialysis dose, membrane biocompatibility and permeability, convective techniques, and the number and duration of dialysis sessions have all been considered as potentially related to patient outcome. The available data from the literature clearly show a significant relationship between the urea kinetic model based dialysis delivered and long-term patient outcome. A significant positive correlation between survival and Kt/V up to 1.3 per session in patients treated three times a week with standard low flux cellulosic dialyzers has been shown. Many studies have shown an effect of high flux membranes on the appearance of symptoms related to dialysis amyloidosis. It is likely that such an effect is further enhanced by convective or mixed techniques. The role of these techniques in patient survival is suggested by some studies, but should be confirmed in larger series. The use of techniques suitable for ultra-pure dialysis fluids are mandatory whenever high permeability membranes are used. Treatment schedules which include long dialysis sessions or an increased number of sessions such as daily dialysis, seem to be beneficial for the control of hypertension or hyperphosphatemia. However, their role on patient survival has not yet been clearly assessed. Together with the choice of the best strategy, great attention should be paid to other factors known to be related to patient outcome, such as early patient referral, and the type and efficiency of vascular access.

Central venous catheter and the hemodialysis patient: a difficult symbiosis.

In the last ten years, tunneled central venous catheters (pCVCs) have been increasingly utilized in chronic hemodialysis patients, sometimes in the place of fistulas. They have gained popularity for their unquestioned advantages, such as the possibility for immediate use. However, several problems have emerged following their diffusion. In this paper we review the main complications of pCVCs. Complications connected with insertion are generally due to an inaccurate approach to the vein. Ultrasonographic guidance has partially solved this problem and EC-ECG (endocavitary ECG) allows an accurate positioning of the tip. Infections, venous and/or pCVCs) thrombosis and dysfunctions are the most important catheter-related complications. Infections may occur with and without symptoms of systemic illness. Early diagnosis and appropriate antibiotic treatment are essential for saving the catheter. The pathogenesis of infections and strategies for prevention are discussed. Thrombosis and stenosis are well known complications of subclavian and jugular catheterization. In uremic patients, for temporary use, we suggest using the femoral position. Protocols for application of thrombolytic agents in pCVCs are considered. Dysfunction, defined as the failure to maintain a blood flow of at least 250 ml/min, remains the Achilles' heel of the system. Adequate look therapy and tip position are only two basic aspects. In conclusion, a pessimistic outlook on the matter could lead us to consider that the advantages of catheter use are far outweighed by the disadvantages. However, we cannot avoid using central venous catheters in our dialysis units and a great challenge awaits both physicians and manufactures in the coming years.

Factors influencing permanent catheter performance.

UNLABELLED: Permanent dual lumen catheters (PDLC) provide an alternative vascular access in patients considered unsuitable for arteriovenous fistula, graft or peritoneal dialysis. However, the use of PDLC is often complicated by inadequate blood flow. The aim of this study was to identify catheter dysfunctions. We studied prospec-tively 57 chronic hemodialyzed patients, 73+/-11 years of age, with PDLC for 18+/-14 (1-48) months. Catheters were tunneled in silicone (MedComp Tesio n= 40) or in polyurethane (Permcath Quinton n = 11, GamCath Gambro n = 6) in left or right internal jugular (n = 49), in left or right subclavian (n = 3) and in right femoral vein (n = 5). We studied the blood viscosity indices (hematocrit, total protein, cholesterol and triglycerides), catheter intra-dialytic parameters (pre-pump and venous pressure), localization of the catheter tip (superior vena cava = SVC, right atrium = RA, inferior vena cava = IVC), blood pressure before and after hemodialysis during the 3 last dialyses, use of anticoagulant (ACT) or antiaggregant therapy (AAT) and previous infectious episodes. The mean blood flow was 269+/-37 ml/min (median 280 ml/min). The patients were divided according to the median value into groups I (Qb < 280, n = 28) and group II (Qb > 280, n =29). RESULTS: Blood viscosity, patients' mean arterial pressure and venous catheter line pressure did not differ between the two groups. Pre-pump pressure, at the start and at the end of treatment, was higher in group I. ACT, AAT and previous infectious episodes could not explain the low-performance. Blood flows of catheters localized in RA, SVC, and in IVC were respectively 287+/-20, 268+/-39, 244+/-27 ml/min. In the first case the Qb was significantly higher than IVC (p = 0.03) and SVC (p = 0.04). In conclusion, the most important factor influencing blood flow rates seems to be the position of the catheter tip in the venous system. The best blood flows were found in catheters with the tip localized in the right cardiac cavities, while PLDC placed in inferior vena cava showed lower blood flow.

Blood flowrate and dialysis adequacy in patients with permanent central venous catheters.

Vascular access efficiency is a major determinant of an adequate dialytic treatment and reports from literature indicates a growing interest in the field of central venous catheterisation as permanent vascular access for hemodialysis. The main reasons are the continuous improvement in design and biomaterials along with the increased number of patients with failure of their vascular beds. In this paper it is presented and commented a series of negative crucial factors which can reduce the quality of the hemodialysis treatment: the problem of re-circulation and the catheter related (and the patient related) causes of inadequate flowrate. Finally the Authors conclude with a short presentation of their clinical experience in the field.

Dialysis prescription in elderly hemodialysis patients.

A growing number of elderly patients have started dialytic treatment in recent years. In spite of this fact, there is very little literature on dialysis prescription in these patients. In this paper, the authors examine the single variables of Kt/V index and report on their own experience when prescribing the dialytic dose in elderly patients. Regarding dialyzer clearance (Kd), it is known that in order to obtain a high Kd we need an adequate vascular access. In our experience, with a radiocephalic fistula elderly patients showed less (but not significantly so) Qac than younger patients (738 +/- 350 ml/min versus 892 +/- 491 ml/min). We can therefore consider this type of fistula as the first vascular access in elderly patients also. As far as Kr is concerned, its rate of decline (0.4+/-0.4 ml/min/month) in these patients, excluding those with diabetes or a history of heart failure, is not different from that of younger patients. Treatment time remains a crucial point for adequacy. In order to avoid hypotensive episodes, especially in the elderly, we suggest T = 180 minutes minimum, and ultrafiltration rates should not exceed 0.6-0.8 kg/h. As regards V, it can be stated that these patients have a reduced lean body mass and total body water, and could therefore require smaller dialysis doses. However, we think that the target of Kt/V in malnourished elderly patients requires further study. What our data on Kt/V delivered to a large group of patients shows is that the elderly received the same adequate dialytic dose (Kt/V > 1.3) as that of younger patients.

In vitro and in vivo biocompatibility of substituted cellulose and synthetic membranes.

Regenerated cellulosic membranes are held as bioincompatible due to their high complement - and leukopenia - inducing properties. Adherence of polymorphonuclear neutrophils and monocyte purified from normal human blood to the three membranes were evaluated in an in vitro recirculation circuit in the presence or absence of fresh, autologous plasma after recirculation in an in vitro circuit using minimodules with each of the three membranes. In in vivo studies, 9 patients were treated with conventional haemodialysis for 2 weeks with each membrane and 1 week for wash-out using haemodialysers with the following surface: 1.95 m2 for benzyl-cellulose, 1.8 m2 for acetate-cellulose and low-flux polysulfone. Measurement of leukopenia, plasma C3a des Arg and elastase-alpha1 proteinase inhibitor complex levels as well as urea, creatinine, phosphate and uric acid clearances was performed. Plasma-free neutrophils adhered maximally to acetate-cellulose (65% remaining in the circulation), while there was no significant difference between low-flux polysulfone and benzyl-cellulose (80% circulating neutrophils, at 15 min, p<0.001 vs acetate cellulose). In the presence of fresh plasma, as source of complement, the differences between acetate cellulose vs polysulfone and benzyl-cellulose were even more evident, suggesting the role of complement-activated products in neutrophil adherence. A similar trend was observed for monocyte adherence with the three membranes in the absence or presence of plasma. In vivo studies showed that the nadir of leukopenia was at 15 and 30 min with acetate-cellulose (79%) and benzyl-cellulose (50%) (p<0.05 acetate- vs benzyl-cellulose) and at 15 min with polysulfone (24%) (p<0.01 vs acetate- and benzyl-cellulose). Plasma C3a des Arg levels arose to 2037 +/- 120 ng/ml, 1216 + 434 ng/ml and 46 +/- 55 ng/ml with acetate-, benzyl-cellulose and polysulfone, respectively. No pre- vs post-dialysis increase in the intracellular content of TNF-alpha was detected with any of three membranes. Clearance values of urea, creatinine and uric acid were superimposable for all the three membranes. However, benzyl cellulose had a significantly higher clearance for phosphorus (normalized for surface area) (p<0.01 vs acetate-cellulose, 0.001 vs polysulfone). These results implicate that synthetic modification of the cellulose polymer as for the benzyl-cellulose significantly reduces the in vitro adherence, delays the in vivo activation of "classic" biocompatibility parameters and notably improves the removal of inorganic phosphorus.