The cardiovascular burden of end-stage renal disease patients.

Patients with end-stage renal disease are 10 to 20 times more at risk of cardiovascular death than the general population. Traditional cardiovascular risk factors are not able to explain the increase in the onset of cardiovascular diseases in dialysis patients. Some of the most important non traditional risk factors in uremic patients are: the inflammatory state of the patients, cytokines and growth factors, hyperhomocysteinemia, the presence of alterations of the calcium phosphorous product which can already be in progress when the glomerular filtration rate decreases to less than 60 mL/min. Clinically, these alterations cause vascular calcifications, calcifications of the heart valves and calcific uremic arteriolopathy or calciphylaxis. The pathogenesis of vascular calcification is complex and cannot be assigned to a simple, passive process: in fact, it includes factors which promote or inhibit calcification. In turn, these pathologic conditions have been found to be highly predictive of general and cardiovascular death. Given the serious clinical consequences that vascular calcifications can cause, it is necessary to carry out an early mapping of the traditional and non traditional risk factors of uremic patients as it seems that therapeutic interventions aimed at reducing or inverting the calcification process can improve the outcome of patients, above all when they are started quickly.

[When native arteriovenous fistula is not possible: the permanent catheter is better]. / Quando la fistola artero-venosa con vasi nativi non è possibile: è preferibile un catetere tunnellizzato.

Native arteriovenous fistula is still the vascular access of choice in hemodialysis. Other options are arteriovenous graft or, in patients in whom it is not possible to create a surgical vascular access, a permanent venous catheter. International guidelines on vascular access for hemodialysis recommend an increase in the percentage of arteriovenous fistulas compared to other types of vascular access. An analysis of the data relative to the distribution of the types of vascular access in different countries highlights the difficulty in following this recommendation: the only country to have increased the number of arteriovenous fistulas in recent years is the US, where the percentage of grafts has decreased while the use of permanent catheters has increased. In Italy and the rest of Europe, the number of fistulas has remained stable, there has been a constant reduction in the number of grafts and an increase in the percentage of permanent catheters. The reasons for this distribution of the types of vascular access are multifactorial and include the increased average age of patients, frequent late referrals, and increased incidence of diabetes mellitus, cardiovascular disease, obesity, etc. These factors have brought about technical difficulties for the creation of fistulas and grafts, leading to an increase in the number of catheters used. In relation to the evolution of the clinical characteristics of dialysis patients, the permanent catheter should no longer be considered a last-choice vascular access: in selected patients, it can be a better choice than a surgical fistula or graft.

Mars and Prometheus: our clinical experience in acute chronic liver failure.

INTRODUCTION: In our clinical context, there are two groups that practice blood purification treatments on acute or chronic liver failure (AoCLF) patients: one group used MARS (molecular adsorbent recirculating system) and the other Prometheus. MATERIALS AND METHODS: The MARS group used the lack of response to standard medical treatment after 72 hours of observation as the access criterion. The Prometheus group used the access criteria of the multicenter Helios protocol for patients in AoCLF, as well as those with primary nonfunction (PNF) and secondary liver insufficiency. Both groups performed treatment sessions of at least 6 hours, which were repeated at least every 24 to 36 hours. RESULTS: The 56 treated AoCLF patients underwent 278 treatment sessions; 41 out of 191 procedures with MARS and 16 out of 87 procedures with prometheus, which was also applied in two cases in PNF and four in secondary liver insufficiency. The results showed that both systems accomplished a good purification efficiency and that application to patients enabled reinstatement on the transplant list and grafts in 70% of the cases with either method. CONCLUSION: Treatment led to recovery in dysfunction among patients not destined for transplantation, achieved with a 48.5% 3-month survival in the MARS group and 33.5% in the Prometheus groups. The treatment results were inversely proportional to the MELD at the time of entry; The treatment appeared to be pointless. Among PNF and secondary liver insufficiency cases.

Is beta2-microglobulin-related amyloidosis of hemodialysis patients a multifactorial disease? A new pathogenetic approach.

PURPOSE: Beta2-microglobulin amyloidosis (Abeta(2)M) is one of the main long-term complications of dialysis treatment. The incidence and the onset of Abeta(2)M has been related to membrane composition and/or dialysis technique, with non-homogeneous results. This study was carried out to detect: i) the incidence of bone cysts and CTS from Abeta(2)M; ii) the difference in Abeta(2)M onset between cellulosic and synthetic membranes; iii) other risk factors besides the membrane. METHODS: 480 HD patients were selected between 1986 to 2005 and grouped according to the 4 types of membranes used (cellulose, synthetically modified cellulose, synthetic low-flux, synthetic high-flux). The patients were analyzed before and after 1995, when the reverse osmosis treatment for dialysis water was started at our center, and the incidence of Abeta(2)M was compared between the two periods. Routine plain radiography, computer tomography (CT) and nuclear magnetic resonance imaging (MRI) as well as electromyography were used to investigate the clinical symptoms. RESULTS: Bone cysts occurred in 29.2% of patients before 1995 vs. 12.2% after 1995 (p<0.0001). CTS occurred in 24% of patients before 1995 vs. 7.1% after 1995 (p<0.0001). Bone cysts and CTS occurred in older patients, who began dialysis at a late age, with high CRP, low albumin, low residual GFR, and low Hb. Cox regression analysis showed that the risk factor for bone cysts was high CRP (RR 1.3, p<0.01), while albumin (RR 0.14, p<0.0001) and residual GFR (RR 0.81, p<0.0001) were revealed to be protective factors. Cox analysis for CTS confirmed CRP as a risk factor (RR 1.2, p<0.01), and albumin (RR 0.59, p<0.0001) and residual GFR (RR 0.75, p<0.0001) as protective factors. The comparison obtained between membranes did not suggest any protective effect on Abeta(2)M. CONCLUSIONS: The findings that the inflammatory status as well as low albumin and the residual GFR of the uremic patient are predictive of Abeta(2)M lesions suggests that Abeta(2)M has a multifactorial origin rather than being solely a membrane- or technique-related side effect.

Acute systemic, splanchnic and renal haemodynamic changes induced by molecular adsorbent recirculating system (MARS) treatment in patients with end-stage cirrhosis.

AIM: To evaluate the acute effect of treatment with the molecular adsorbent recirculating system (MARS) on splanchnic, renal and systemic haemodynamics in patients with end-stage cirrhosis. METHODS: Twelve patients with end-stage cirrhosis, undergoing MARS treatment, were enrolled. The following haemodynamic parameters were measured by means of Doppler ultrasonography and thoracic electrical bioimpedance, before and after each session: portal velocity, renal and splenic resistance indices, cardiac output, cardiac stroke volume, heart rate, mean arterial pressure, systemic vascular resistance. RESULTS: Median portal velocity increased significantly after treatment (23.7 vs. 20.3 cm/s, P < 0.05) while renal resistance index (0.72 vs. 0.75, P < 0.05) and splenic resistance index (0.60 vs. 0.65, P < 0.05) decreased significantly. Mean arterial pressure (83 vs. 81 mmHg, P < 0.05) and vascular resistance (899 vs. 749 dyne. s/cm5, P < 0.05) increased significantly, while cardiac output and stroke volume showed no significant changes. CONCLUSIONS: Data emerging from this investigation suggest that MARS treatment improves significantly various haemodynamic alterations in cirrhotic patients in the short term. The observed decrease in renal vascular resistance and improvement in splenic resistance index, a parameter related to portal resistance, which leads us to hypothesize that these haemodynamic effects are probably mediated by clearance of vasoactive substances during MARS treatment.

Jugular vein-mammary artery fistula after catheterism for hemodialysis: case report.

The demographic characteristics of hemodialysis (HD) patients increase the need for the tunneled cuffed permanent catheter (TCC) as a definitive vascular access (VA) for HD. The internal jugular vein is increasingly being used as a route for TCC or temporary catheter placement and can be associated with serious complications. Among them other authors have described arteriovenous fistula (AVF) creation between the common carotid artery and the right jugular vein. We describe a case of an AVF between the right internal jugular vein and the right internal mammary artery. The fistula was detected during the TCC placement in a patient who underwent several jugular and subclavian catheterisms for HD in her clinical history.

A mathematical model for the prediction of solute kinetics, osmolarity and fluid volume changes during hemodiafiltration with on-line regeneration of ultrafiltrate (HFR).

Hemodiafiltration with on-line regeneration of ultrafiltrate (HFR) is a technique indicated for the treatment of dialysis patients affected by inflammatory syndrome and malnutrition. In the present work, a mathematical model, which describes intradialytic fluid and solute kinetics during standard diffusive dialysis, has been adapted to analyze solutes and fluid dynamics during HFR. The model is an improved version of our previous ones, and represents a good compromise between simplicity and reliability. It considers the intradialytic kinetics of sodium, potassium and urea, and two body fluid compartments: intracellular and extracellular. Moreover, the model includes simple equations to predict the intradialytic time pattern of osmolarity. The model has been experimentally validated by using 9 HFR sessions on 9 patients (one per each patient), comparing the time course of plasma solutes and osmolarity measured every 30 minutes during HFR, with those predicted by the model. Predictions are performed a priori, i.e., without any parameter adjustment, but just starting from knowledge of a few quantities (plasma sodium, potassium, urea, osmolarity and body weight) at the beginning of the session. The average deviations between model and real data (sodium: 1.9 mEq/L; potassium: 0.32 mEq/L; urea: 1.04 mmol/L; osmolarity: 5.02 mosm/L) are of the same order as measurement errors and similar to those obtained using our previous models in standard and profiled hemodialysis. Moreover, the prediction on sodium concentration only scarcely worsens (from 1.9 to 2.02 mEq/L) if default values are used for the initial value of other solutes in blood (i.e., if the algorithm uses only initial body weight and initial sodium concentration in plasma). The results confirm the good predictive capacity of the model in HFR, and suggest its possible innovative use to optimize sodium balance in HFR, from knowledge of only the sodium concentration in the ultrafiltrate.

Anticoagulation therapy for the prevention of hemodialysis tunneled cuffed catheters (TCC) thrombosis.

BACKGROUND: Chronic oral anticoagulation is currently used to avoid thrombosis and the malfunction of tunneled cuffed catheters (TCCs) for hemodialysis (HD). The aim of the study was to assess the efficacy of early warfarin administration, after TCC placement, in comparison to its administration after the first thrombosis or malfunction event of the TCC. PATIENTS AND METHODS: One hundred and forty-four chronic dialysis patients, who underwent TCC placement between June 2001 and June 2005, were randomized into two groups: 81 patients, group A, started oral anticoagulation 12 hr after the TCC placement (target international normalized ratio (INR) 1.8-2.5), in association with ticlopidine 250 mg/die; 63 patients, group B, started warfarin after the first thrombosis/malfunction episode (target INR 1.8-2.5) in association with ticlopidine 250 mg/die. The efficacy of oral anticoagulation therapy in preventing TCC thrombotic complications was evaluated in a 12-month follow-up period, after TCC placement, in terms of: a) the number of patients with thrombotic-malfunction events; b) the number of thrombotic-malfunction events with urokinase infusion (events/patient/year); c) intradialytic blood flow rate (BFR, ml/min); d) negative blood pressure (BP) from the arterial line of the TCC (AP, mmHg); e) positive BP, in the extracorporeal circuit from the venous line (VP, mmHg); and f) bleeding complications. RESULTS: Ten patients (12%) in group A showed TCC thrombosis/malfunction vs. 33 patients (52%) in group B (p < 0.01). In group A, 0.16 events of thrombosis/malfunction per patient/year vs. 1.65 in group B (p < 0.001) were ob-served. BFR was respectively 305 +/- 34 vs. 246 +/- 42 ml/min (p < 0.001). AP was -124 +/- 13 in group A vs. -174 +/- 21 mmHg in group B (p < 0.05). VP was 112 +/- 28 in group A vs. 168 +/- 41 mmHg in group B (p < 0.05). No patient showed any bleeding events. CONCLUSIONS: Early warfarin therapy allows a significant reduction in TCC thrombotic complications and an improvement in both arterial and venous fluxes in comparison with the same therapy administered after the first TCC thrombotic/malfunction event. This therapy did not induce any bleeding complications in the patients included in the study.

Molecular adsorbent recirculating system (MARS) application in liver failure: clinical and hemodepurative results in 22 patients.

PURPOSE: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) still show a poor prognosis. MARS was used in 22 patients with ALF or ACLF to prolong patient survival for liver function recovery or as a bridge to transplantation. DESIGN: Evaluation of depurative efficiency, biocompatibility, hemodynamics, encephalopathy (HE) and clinical outcome. PROCEDURES: During 71 five-hour sessions we evaluated (0', 60', 120', 180', 240', 300'): bilirubin, ammonia, cholic acid (CCA), chenodeoxycholic acid (CCDCA), leukocytes, platelets, hemoglobin and mean arterial pressure (MAP). Serum creatinine, electrolytes, cardiac output, cardiac index (bioimpedence) and HE (West Haven Criteria score) were evaluated at 0' and 300'. STATISTICAL METHODS AND OUTCOME MEASURES: Student's t-test for pre- vs. end-session values was used. For bilirubin and ammonia the correlation test was made between pre- and end-session values and between pre-session values and removal rates (RRS). MAIN FINDINGS: Survival was 90.9% at 7 days, 40.9% at 30 days. Pre- vs. end-session: bilirubin from 37.2 +/- 12.5 mg/dL to 24.9 +/- 8.9 mg/dL (p < 0.01), ammonia from 88.0 +/- 60.4 micromol/L to 43.6 +/- 32.9 micromol/L (p < 0.01), CCA from 42.8 +/- 21.0 micromol/L 18.2 +/- 9.8 micromol/L (p < 0.01), CCDCA from 26.3 +/- 6.3 micromol/L to 15.7+/-7.6 micromol/L (p<0.01). The correlation test between pre-session values of bilirubin and ammonia vs. RR S was respectively 0.32 (p = 0.01) and 0.30 (p = 0.04). Leukocytes, platelets and hemoglobin remained stable. MAP increased from 82.0 +/- 12.0 mmHg to 87.0 +/- 13.0 mmHg (p < 0.05), West Haven Criteria score decreased from 2.7 +/- 0.7 to 0.7 +/- 0.7 (p < 0.001). CONCLUSION: MARS treatment led in all patients to an improvement of clinical, hemodynamic and neurological conditions, with significant reduction in the hepatic toxins blood level. Treatment biocompatibility and tolerance were satisfactory.

[Long-term use of Profiler in patients with dialysis intolerance: 8 months follow-up]. / Impiego a lungo termine del Profiler nei pazienti con intolleranza dialitica: follow-up a 8 mesi.

PURPOSE: A new method of profiled dialysis has been set up for many years in the Department of Nephrology, Dialysis and Renal Transplantation at the University of Bologna. This profiled dialysis is based on the use of a new kinetic mathematical model, in collaboration with the Faculty of Engineering at the University of Bologna, for the elaboration of individual sodium and ultrafiltration profiles. OBJECTIVE: The profiled dialysis aims are: 1) to stabilize the intradialytic blood volume, boosting the refilling of plasma water from the intracellular and the extravascular to the extracellular/intravascular compartments, to balance the ultrafiltration; 2) to counteract the disequilibrium syndrome reducing the shift of water from the extra to the intracellular compartment. The pre-dialysis elaboration of profiles is completely automatic and supported by a computerized programme, Profiler, which has been included in the software of the dialysis machine Bellco Formula 2000 Plus. METHODS: In this prospective and multicenter study, this profiled dialysis, performed according to the Profiler, was continuously applied, for an 8-month period, in a group of 13 hemodialysis (HD) patients with an intolerance to previous dialysis treatment. During the study, the following parameters were evaluated, comparatively, with the patient's basal treatment: a) sodium and water balance; b) percentage incidence of intradialytic complications such as hypotensive events, cramps, headache, and vomiting and; c) metabolic and nutritional status. RESULTS: Results evaluated in comparison with the patient's previous dialysis treatments, demonstrated: a) plasma sodium from 136.8 +/- 3 to 136.8 +/- 1.7 mEq/L (p=ns), dry body weight from 72.2 +/- 19.3 to 71.7 +/- 19.5 kg (p=ns), heart index from 3.7 +/- 0.7 to 3.1 +/- 0.5 L/min/m2 (p=ns), reactance from 5.3 +/- 15 to 4.9 +/- 11 ohm (p<0.05); b) incidence of intradialytic hypotensive events reduced from 64 to 4% (p<0.001), cramps reduced from 8 to 1% (p<0.01); c) plasma albumin from 3.5 +/- 0.2 to 3.7 +/- 0.3 g/dL (p=ns), Kt/Veq from 1.3 +/- 0.1 to 1.36 +/- 0.2 (p=ns). CONCLUSIONS: Patients treated with profiled dialysis had a higher stability of intradialytic blood pressure (BP) achieving a reduction in the incidence of disequilibrium syndrome symptoms, in comparison with previous treatment. These clinical intradialytic improvements were not correlated to clinical, instrumental or biochemical indexes of sodium-water overload nor to a worst dialysis adequacy and nutritional state.

Clinical application of sodium profiling in the treatment of intradialytic hypotension.

BACKGROUND: Intradialytic hypotension is mainly induced by the removal of extracellular sodium during dialysis, which impairs intravascular fluid refilling and reduces blood volume. To counter this complication we tested a new kind of profiled hemodialysis (PHD) consisting of the intradialytic modulation of dialysate sodium concentration according to individual profiles set up using a new mathematical model for intradialytic solutes and water kinetics. The clinical aim of this PHD is to stabilize blood pressure maintaining higher blood volume values than standard dialysis treatments. We clinically validated PHD in comparison with constant dialysate sodium dialysis (CHD). METHODS: Twenty hypotensive dialysis patients underwent one PHD and one CHD session maintaining the same dialysis length, sodium mass removal and body weight decrease. A new mathematical model was used to define both the dialysate sodium profiles for PHD and the constant dialysate sodium for CHD. Percent blood volume variation (Crit-line), mean blood pressure, heart rate, cardiac output (Doppler-echocardiography) were monitored intradialitically. RESULTS: Cardiovascular stability improved on PHD as compared with CHD sessions; blood volume and cardiac output during PHD showed a lower decrease than on CHD, the differences statistically significant (from 30' and 60' respectively). Mean blood pressure was, at all time intervals, more stable on PHD than on CHD and was accompanied, on PHD, by a lower heart rate increase (differences statistically significant). CONCLUSIONS: This study shows that PHD performed using dialysate sodium profiles elaborated by our mathematical model obtains, in hypotensive patients, a higher hemodynamic intradialytic stability than CHD, probably due to a higher stabilization of blood volume.

Artificial kidney: status of the art and new perspectives.

Extracorporeal dialysis was first performed in 1943 and has become a routine for End Stage Renal Patients from the early sixties. In the last 30 years researchers have focused on biocompatibility of artificial materials and optimisation of removal of uremic toxins by the membrane as in the long term treatment many complications like amylodosis heart and bone lesions, accelerated amyloidosis and immune system failure can occur. From this point of view high flux dialytic membranes are currently considered more biocompatible therefore being able to prevent such diseases.

Inflammatory response of a new synthetic dialyzer membrane. A randomised cross-over comparison between polysulfone and helixone.

Hemodialysis patients suffer from chronic inflammation due to intradialytic contact of blood with artificial materials. The FX 60 dialyzer which belongs to the new FX-class series of dialyzers is composed of the new membrane Helixone. This membrane is derived from the original Fresenius Polysulfone membrane. The FX-class design is based on modified geometry of fibres and housing and has resulted in a new dialyzer with improved efficiency, safety and ease of handling compared to the F series (F 60S) dialyzer. The aim of the study was to investigate whether the biocompatibility pattern in terms of inflammatory parameters of the new type of polysulfone dialyzer has changed compared to the standard. A clinical in vivo study was conducted to compare the intradialytic inflammatory response of the two dialyzers, FX 60 and F 60S. Eight chronic dialysis patients were selected for the study: mean age 65.5 +/- 15.5 years, mean time on dialysis 100 +/- 95 months. The randomized cross-over study involved a treatment period of 2 weeks (total 6 sessions), one week with each dialyzer, starting with one or the other according to the randomization scheme. Blood samples were taken at 0 (T0), 15, 60, and 240 minutes to evaluate white blood cell (WBC) count, complement factor C5a, leukocyte elastase, soluble intercellular adhesion molecule 1 (sICAM-1), platelet count, C-reactive protein (CRP). At 15 min, WBC count showed a comparably, low decrease for both dialyzers: -7.6% for FX 60 versus -6.6% for F 60S, p=not significant (ns). At the same time the C5a concentration decreased from 15.0 +/- 7.5 ng/ml to 13.5 +/- 6.7 ng/ml (p=ns) for FX 60, and from 15.1 +/- 12.5 ng/ml to 14.9 +/- 25.0 ng/ml for F 60S (p=ns). The elastase concentration progressively increased over time with no statistical difference between the two dialyzers. The levels of sICAM-1, CRP, and platelet count were similar at each time point for both dialyzers, varying around the baseline values (p=ns). No significant difference emerged in terms of inflammatory response between the two dialyzers, hemo demonstrating that the biocompatibility of the F-series was maintained in the FX-class series of dialyzers and is independent of design factors.

Fluidodynamic evaluation of arteriovenous fistulae for hemodialysis.

Arteriovenous fistulae (AVF) are commonly used in dialysis treatment of uremic patients. However, many AVF create problems and have to be re-examined. Problems arise in the cannulation site and must be treated with antibiotics, and stenosis, both in the arterial and in the venous side of the AVF. In the worst case, the AVF must be replaced for treatment to continue. However, this can only be repeated once before the AVF site is no longer viable. This increases the discomfort, the morbidity and the mortality of the dialysis patient. Several kinds of AVF were studied to determine whether flow disturbances give rise to these complications. Many studies have already demonstrated the importance of hemodynamic factors in vascular disease pathogenesis. These factors include: the pulsatility of flow, the elasticity of the vessel, the non-Newtonian blood, flow behavior and, very importantly for AVF, the vessel geometry. In model studies, intimal changes have been observed in bends and bifurcations, regions of vessel construction and vessel stenosis. In these regions, blood flow changes abruptly and this contributes to arterial disease. We prepared several one-to-one, true-to-scale elastic silicon rubber models of different AVF. The AVF models were based on angiographic studies of chronic dialysis patients and on AVF from the arms of cadavers. The models had a similar compliance to that of the human blood vessel. Flow was visualized using photoelasticity apparatus and a birefringent blood-like fluid. This method is suitable to analyze the spatial configuration of flow profiles, to differentiate laminar flow from disturbed flow, and to visualize flow separation, vortex formation and secondary flow. It was found that AVF create disturbances that are not found under normal physiological flow conditions. The X-formed AVF was very unsatisfactory, creating significant flow disturbances. The AVF had high velocity fluctuations. These could lead, for example, to aneurysm formation. A better configuration would be an end-to-end AVF. However, this formation creates other complications. For example, there is not enough blood to the hand and parts of the hand lose feeling. The recommended AVF would be an end-to-side anastomosis. In this case, attention is needed for placement geometry, to minimize additional flow disturbances. Several models as well as patient angiographic studies are discussed.

Platelet activation and PDGF-AB release during dialysis.

During hemodialysis the blood-membrane contact causes a release of platelet granule content, which contains Platelet Derived Growth Factor (PDGF-AB). In view of its possible role in accelerated atherosclerotic processes, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during hemodialysis sessions performed with Hemophan and Polysulfone membranes. PDGF-AB, PF4, betaTG and MPV levels were determined in the peripheral blood in 30 patients each of whom underwent 6 dialysis sessions: 3 with Hemophan (HE) membrane and 3 with Polysulfone (PS) membrane, interpolated by a wash out session with PS membrane. Blood samples were taken at times 0', 30', 120', 180', 240' during dialysis sessions and at 1, 4 and 20 hours after the end of the session. Statistical analysis was done using the ANOVA one way test and Student's t test PDGF-AB serum levels initially increased and, except for a sharp fall at 120', remained constantly high during HD with both membranes tested, not returning to basal values until 20 hours after the end of the session. PF4, betaTG and MPV all showed a similar trend to PDGF. No statistically significant difference was found between the two membranes tested. PDGF-AB, a powerful growth factor in cells of mesenchymal origin, is released during dialysis mainly as a result of the blood-membrane contact. This we found regardless of the type of dialyzer we tested, and, above all, proved to return very slowly to basal values. We speculate that the release of PDGF-AB could play a part like other atherosclerosis risk-factors in the appearance and worsening of atherosclerotic lesions in hemodialysis patients.

Intra- and post-dialytic platelet activation and PDGF-AB release: cellulose diacetate vs polysulfone membranes.

BACKGROUND: During haemodialysis the blood-membrane contact causes a release of platelet granule content, which contains platelet-derived growth factor AB (PDGF-AB). In view of the potential role of this in altering biocompatibility during haemodialysis, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during haemodialysis sessions performed with cellulose diacetate (CDA) and polysulfone (PS) membranes respectively. METHODS: PDGF-AB, platelet factor 4 (PF4), beta thromboglobulin (betaTG), and mean platelet volume (MPV) levels were determined in 30 patients, each of whom underwent six dialysis sessions: three with a CDA and three with a PS membrane. Blood samples were taken at times 0, 15, 30, 120, 180, and 240 min during dialysis and at 1, 4, and 20 h after the end of the session. Statistical analysis was performed using a one-way ANOVA and Student's t test. RESULTS: PDGF-AB at 15 min was increased to +41+/-9% with CDA vs +20+/-5% with PS (P<0.001) from the T0 values, and at 120 min it was +19+/-8% with CDA vs -25+/-9% with PS (P<0.001) from T0 levels. At 240 min it was +95+/-14% with CDA vs +49+/-15% with PS (P<0.001) from the T0 values, returning to basal only 20 h after the end of the session. betaTG at 15 min was +60+/-8% for CDA vs +24+/-7.5% for PS (P<0.001) from the T0 values. PF4 showed a similar trend to betaTG. MPV at 30 min from the start of dialysis was 7.4+/-0.3 fl with CDA and 8+/-0.3 fl with PS (P<0.001), and at 240 min MPV was 7.9+/-0.3 fl with CDA and 8.4+/-0.3 fl with PS (P<0.001). CONCLUSIONS: Platelet activation and platelet release reactions are lower with PS than with CDA membranes. PDGF-AB, released during and after dialysis, represents a clear biocompatibility marker. Its slow return to basal values and its action on vascular cells make it a potential risk factor for atherosclerosis in uraemic patients.

Kidney, patient and new millennium nephrology.

The way nephrology develops in the new millennium is bound to be affected by changes in the nephrologist's clinical environment, as well as by the progress made in basic research which will need to find a clinical application. The nephrologist can expect to be more and more involved in renal substitution therapy, not just providing the treatment, but also managing the cost of the service. In the field of nephropathology, the highest expectations surround molecular biology and its application to both acquired and hereditary renal disease; the goal is to find an outlet for gene therapy in clinical practice. Artificial substitution therapy will focus chiefly on the project of 'intelligent dialysis', whereby biological and diagnostic components are combined according the specific needs of the individual patient. The ideal scenario for renal transplantation in the coming millennium would be one where donor supply matches the demand (xenotransplant?), where immunomodulation is perfected, and where diagnoses are based on precise biomolecular events observed in real time.

Prediction of solute kinetics, acid-base status, and blood volume changes during profiled hemodialysis.

A mathematical model of solute kinetics oriented to the simulation of hemodialysis is presented. It includes a three-compartment model of body fluids (plasma, interstitial and intracellular), a two-compartment description of the main solutes (K+, Na+, Cl-, urea, HCO3-, H+), and acid-base equilibrium through two buffer systems (bicarbonate and noncarbonic buffers). Tentative values for the main model parameters can be given a priori, on the basis of body weight and plasma concentration values measured before beginning the session. The model allows computation of the amount of sodium removed during hemodialysis, and may enable the prediction of plasma volume and osmolarity changes induced by a given sodium concentration profile in the dialysate and by a given ultrafiltration profile. Model predictions are compared with clinical data obtained during 11 different profiled hemodialysis sessions, both with all parameters assigned a priori, and after individual estimation of dialysances and mass-transfer coefficients. In most cases, the agreement between the time pattern of model solute concentrations in plasma and clinical data was satisfactory. In two sessions, blood volume changes were directly measured in the patient, and in both cases the agreement with model predictions was acceptable. The present model can be used to improve the dialysis session taking some characteristics of individual patients into account, in order to minimize intradialytic unbalances (such as hypotension or disequilibrium syndrome).

Evaluation of intradialytic solute and fluid kinetics. Setting Up a predictive mathematical model.

A mathematical model of solute kinetics for the improvement of hemodialysis treatment is presented. It includes a two-compartment description of the main solutes and a three-compartment model of body fluids (plasma, interstitial and intracellular). The main model parameters can be individually assigned a priori, on the basis of body weight and plasma concentration values measured before beginning the session. Model predictions are compared with clinical data obtained in vivo during 11 different hemodialysis sessions performed on 6 patients with a profiled sodium concentration in the dialysate and a profiled ultrafiltration rate. In all cases, the agreement between the time pattern of model solute concentrations in plasma and the in vivo data proves fairly good as to urea, sodium, chloride, potassium and bicarbonate kinetics. Only in two sessions was blood volume directly measured in the patient, and in both cases the agreement with model predictions was good. In conclusion, the model allows a priori computation of the amount of sodium removed during hemodialysis, and makes it possible to predict the plasma volume changes and plasma osmolarity changes induced by a given sodium concentration profile in the dialysate and by a given ultrafiltration profile. Hence, it can be used to improve clinical tolerance to the dialysis session taking the characteristics of individual patients into account, in order to minimize intradialytic hypotension.

PDGF-AB release during and after haemodialysis procedure.

BACKGROUND: During haemodialysis blood membrane contact causes the release of the content of platelet alpha-granules, which contain platelet-derived growth factor (PDGF). In view of its possible role in accelerated atherosclerotic processes, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during haemodialysis sessions performed using a cellulosic membrane. METHODS: Using the ELISA method, PDGF-AB, platelet factor-4 (PF4) and beta-thromboglobulin (beta-TG) levels were determined in peripheral blood, as well as in arterial and venous haemodialyser lines, in 10 patients each of whom underwent five consecutive dialysis sessions with a CU membrane. Blood samples were taken at 0, 15, 30, 60, 120, 180 and 240 min during dialysis and at 1, 4 and 20 h after the end of the session. In the same group of patients the levels of the same molecules were also determined after a heparin bolus injection of 4500 IU, blood samples were taken at 0, 15 and 30 min after injection of the bolus. RESULTS: PDGF-AB serum levels increased, remained consistently high during the haemodialysis session (in particular +134+/-20% after 30 min, P<0.001, and +140+/-5% after 240 min, P<0.001) and returned to basal values only after 20 h following the end of the session. PF4 and beta-TG showed a similar trend to PDGF. The heparin bolus injection caused only a small increase (+15+/-5% at 30 min) in PDGF-AB serum levels. CONCLUSIONS: PDGF-AB is released during dialysis mainly as consequence of the blood-membrane contact and it returns only slowly to basal values.