On-line urea kinetics in haemodiafiltration.

BACKGROUND: Calculation of Kt/V and assessment of nutrition have so far been dependent upon off-line urea measurements of blood or dialysate samples. Here we describe a biosensor for on-line urea measurement during haemodiafiltration. Methods. The biosensor consisted of a cartridge containing covalently linked urease placed between two conductivity cells. The biosensor was placed on the outlet line of a haemofilter in series with a dialyser in order to obtain an aliquot of plasma ultrafiltrate for on-line measurement of urea. RESULTS: Urea nitrogen concentrations were highly correlated to the difference (Delta) in conductivity measured by the two conductivity cells both in aqueous solutions (in-vitro studies, y=-6. 676+32.12x, R2=0.998, P<0.0001) and in ultrafiltrates (ex-vivo studies, y=-637+32.01x, R2=0.98, P<0.00001). Delta conductivity was highly reproducible (% variation: ).8-5.3%) and stable (maximal % variation at 150 mg/dl after 100 min. 0.9+/-0.3 vs initial values). The intradialytic plasma water urea profile was obtained in 10 haemodialysis patients. To study recirculation, the plasma water urea profile was analysed before and 3 min after stopping the dialysate flow. The pre- and post-stopped flow ratio (1.21+/-0.1, mean+/-1 SD) was superimposable to conventional blood sampling data (opposite arm venous arterial: 1.22+/-0.11) and allowed correction for recirculation. A novel approach to urea kinetic modelling was described and used to reliably project end-dialysis and post-dialysis rebound urea concentration as early as 90 min. Projected (29.2+/-10.4 g) or measured (29.8+/-10.5 g) net urea removal was highly correlated with the amount of urea collected in the total spent dialysate (29.7+/-10.6 g) (R2=0.99, R2=0.97 respectively). CONCLUSIONS: These results indicate that on-line, real-time analysis of urea kinetics may provide information on delivery of adequate dialysis in high-efficiency techniques.

Effects of automatic blood volume control over intradialytic hemodynamic stability.

Due to the crucial role of hypovolemia in the genesis of dialysis-induced hypotension, we have evaluated whether the automatic control of the intradialytic blood volume (BV) decrease along a preset trajectory might be beneficial to the hemodynamic stability during treatment. Five frequently hypotensive HD patients were studied and a 3-period-protocol (A1-B-A2) was adopted, each period lasting 6 sessions per patient. During the B periods the patient BV decrease was kept along a predefined profile, thanks to an automatic system with a retroactive control of both the ultrafiltration rate (UFR) and dialysate conductivity (DC); instead, during the A periods, conventional HD was performed, with linear UFR and constant DC, inducing a spontaneous decrease in BV. The intradialytic BV behaviour was much more stable during the B-periods (-10.2 +/- 1.4% by the end of the treatment) than during the A1 (-11.2 +/- 3%) and A2 periods (-11.5 +/- 2.5%). Only one dialysis-hypotension episode was observed during the B periods, compared to 8 and 5 during the A1 and A2 periods, respectively (p < 0.05). The automatic control of the BV changes during dialysis could improve the intra-treatment cardiovascular stability in critically-ill patients.

Biochemical aspects and clinical perspectives of continuous urea monitoring in plasma ultrafiltrate. Preliminary results of a multicenter study.

We tested a new biosensor for urea monitoring in the ultrafiltrate during PFD in a group of 5 hemodialyzed stable patients. The inspection of the UF-urea profile reflects the dynamical changes of the plasma urea concentration during diffusive dialysis and allows the fitting of the main mathematical models of urea kinetics. The biosensor efficiency was 98.4% on average (SD: 1.5%) at Uf fluxes varying from 45 to 55 ml/min (mean: 51 ml/min; SD: 3.2) and at Uf-urea concentrations varying from 23 to 165 mg/dl. The mean difference between Uf-urea determined by the laboratory method and Uf-urea assayed by the biosensor was -1.07 mg/dl and the 95% confidence interval ranged from -2.01 to 0.13 mg/dl. The mean difference between laboratory plasma urea and Uf-urea from the biosensor was on average -1.9 mg/dl and the estimated limits of agreement with a confidence of 95% were -3.16 and 0.64 mg/dl. Comparison between kinetic models and experimental profiles of plasma urea decrease, evaluations of recirculation and post-dialytic rebound, the role of Kt/V on-line during dialysis were the preliminary clinical applications of this biosensor.

Automatic control of blood volume trends during hemodialysis.

Dialysis induced hypovolemia plays an important role in triggering intradialytic hypotension. The authors developed an automatic system (BVAC) with feedback changes in the ultrafiltration rate (UFR) and dialysate conductivity (DC) to match blood volume (BV) intradialytic profiles with the desired trajectories. The system consists of three subunits: (1) an optical probe to continuously detect the BV changes derived from hemoglobin changes, and (2) a dialysis machine interfaced with (3), a personal computer in which a time-dependent model is implemented. The model is based on a dynamic regulator that can set the actual BV changes against the corresponding desired values. Any discrepancy is offset by changes in UFR and DC. To verify the efficacy of the BVAC system in reducing intradialytic cardiovascular instability, five hypotension-prone patients were studied during a three period protocol (A1-B-A2) that lasted six sessions per period per patient. During periods A1 and A2, the dialysis procedure was conventional hemodialysis (HD) with linear UFR and constant DC. During period B, both UFR and DC were automatically regulated by the BVAC system. Mean BV reduction and its variability were lower during period B than during periods A1 and A2 (-10.2%, -11.3%, and -11.5, respectively). Episodes of hypotension were significantly (P < 0.05) fewer during period B (n = 1) than during periods A1 (n = 8) and A2 (n = 5). The therapeutic interventions defined as infused milliliters of isotonic and hypertonic solution were fewer during period B compared with periods A1 and A2. Total UF and end-dialysis plasma sodium concentrations did not differ in the three study periods. BVAC was effective in improving cardiovascular tolerance to treatment.

Regulation of base balance in bicarbonate hemofiltration.

The purpose of this study was to investigate the feasibility of bicarbonate as a substitute for acetate or lactate in hemofiltration solutions using a new bag for the bicarbonate substitution fluid. We analysed 24 hemofiltration sessions with different HCO3- concentrations (30, 35 and 40 mEq/L) in the substitution fluid. The increase in the HCO3- concentration in the substitution fluid resulted in a more positive HCO3- balance. The Net Base Gains (NBG) were, respectively, 73.7 +/- 92 with 30, 138.2 +/- 97 with 35 (p < 0.05 vs 30) and finally 201 +/- 65.9 with 40 mEq/L (p < 0.001 vs 30). The physical separation between the base losses and gains could facilitate the modelling approach in hemofiltration. By means of a stepwise regression analysis, we studied a series of variables that could influence end-treatment HCO3-, which was significantly and directly dependent (F = 6.003, r = 0.747, p = 0.0027) on the HCO3- concentration in the substitution fluid and the apparent HCO3- space. HCO3- values predicted by the statistical model correlated well with those actually measured (r = 0.757; p < 0.001). This mathematical modelling approach allowed us to predict the quantities and concentrations of HCO3- to be infused in order to obtain an ideal acidosis correction, tailored to individual patient needs.

Continuous on-line optical absorbance recording of blood volume changes during hemodialysis.

Conventional techniques that measure blood volume changes during hemodialysis are invasive, hard to reproduce, and provide only intermittent evaluations. To overcome these drawbacks, we have developed an optoelectronic instrument that estimates intradialytic blood volume percentage changes by the optical absorbance of blood. This device is based on the absorption of light transmitted through blood, which is directly related to the hemoglobin concentration. A personal computer interfaced to the device provides a continuous on-line graphic display of the hemoglobin levels and the percentage changes in blood volume. The noninvasive measurement of dialysis blood volume changes by an optical method may be helpful in detecting the appearance of severe hypovolemia that can be dangerous in critically ill patients.

Analysis of the factors influencing bicarbonate balance during acetate-free biofiltration.

In acetate-free biofiltration (AFB), the physical separation between the base losses and the gains could facilitate the modeling of intradialytic bicarbonate (HCO3) balance. In order to verify this hypothesis, we analyzed in a multicenter study, 126 AFB sessions in which differing parameters were evaluated (dialysis time, blood flow, ultrafiltration, infused HCO3, pre- and post-dialytic HCO3, hematocrit and body wt). Statistical analysis performed with multiple linear regression showed that the post-dialysis HCO3 was significantly dependent (F = 21.68, d.f. 5.95, P < 0.001) directly on the amount of infused HCO3, the level of pre-dialysis HCO3 and the final body weight, and inversely on the dialysis time and the blood flow. HCO3 values predicted by the statistical model correlated well with the observed ones (r = 0.788, P < 0.0001) with a mean absolute difference of 2.138 mEq/liter. This modeling approach allowed us to predict, with a computer-aided procedure, the quantities of HCO3 to be infused to obtain a desired and personalized acidosis correction.

Paired filtration dialysis: optimizing depurative efficiency with separate convection and diffusion processes.

To overcome reciprocal interaction between convection and diffusion occurring in hemodiafiltration, we separated the two processes in a new dialysis technique called paired filtration dialysis (PFD). In this technique, convection and diffusion take place separately on two capillary membranes: a polysulfone hemofilter and a hemophan dialyzer. The depurative effectiveness of PFD with respect to small (blood urea nitrogen, creatinine, uric acid, phosphate) and large (beta 2-microglobulin) molecules was acutely assessed in 6 patients on maintenance acetate hemodialysis. Despite a 3-hour treatment time, a high mass removal of small and large solutes was found in PFD without high ultrafiltration rates or blood flows in excess of 300 ml/min. There was no significant difference in solute removal between the two different depurative sequences adopted in PFD, i.e., convection followed by diffusion or vice versa. A significant reduction in beta 2-microglobulin serum levels was observed in both PFD modes. Twenty patients, on a 12-month period of 3-hour PFD treatment, maintained an unaltered metabolic, clinical, and acid-base status, and cardiovascular stability was not affected. PFD thus provides excellent depurative results, along with simple technical features that are particularly useful in treating patients with high depurative needs and yet are unable to tolerate high-flux techniques.

Acetate-free biofiltration: hemodiafiltration with base-free dialysate.

Bicarbonate dialysis has several clinical advantages compared to conventional acetate hemodialysis. However, the use of bicarbonate in the dialysate requires complicated hardware with considerable maintenance and servicing. We have developed a new dialysis technique, a modification of hemodiafiltration, called acetate-free biofiltration (AFBF), with no base replacement agents in the dialysate and with the infusion of bicarbonate solution in postdilution fluid. This study consisted of two parts, an acute phase (8 dialysis patients) and a chronic phase (4 patients) lasting up to 12 months. In the first phase we evaluated the effects of different amounts of infused bicarbonate (from 751 to 1,002 mEq per session) on acid-base balance. The best correction of uremic acidosis was obtained with the infusion of 900-1,000 HCO3 mEq during a 3-hour AFBF. There was a significant (p less than 0.0001) positive correlation between infused and gained bicarbonate. In the chronic part, 880-910 HCO3 mEq was infused per session and there was an increase in mean pretreatment plasma bicarbonate from 18.1 +/- 2.2 upon starting to 22.8 +/- 0.4 mEq/l by the end of the 12-month period. A very low incidence of intradialytic hypotension and stable serum chemistries were achieved with this technique as compared with standard hemodialysis despite a reduction of 3 h in weekly treatment time. AFBF is an easy-to-use, safe alternative to bicarbonate dialysis thanks to the absence of pyrogen reactions and comparatively low-cost maintenance.

A haemodynamic study of hypotension during haemodialysis using electrical bioimpedance cardiography.

Continuous recording of beat-to-beat changes in haemodynamic parameters such as arterial pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance, was done in 52 uraemic patients. The study was performed during the haemodialysis session, using a system combining a personal computer, an arterial pressure recorder, and an electrical bioimpedance cardiography monitor. Forty-six episodes of dialysis-induced hypotension occurred in 26 patients. Systolic arterial pressure and total peripheral resistance decreased by -39.3 +/- 2% and -36.3 +/- 4% respectively during acute hypotension; in contrast, there was an increase in cardiac output (+13.9 +/- 6.7%), while heart rate and stroke volume did not change significantly. It was possible to distinguish two types of collapse on the basis of heart rate behaviour: the classic 'tachycardiac' collapse with heart rate increase and stroke volume decrease, and the so-called 'bradycardiac' collapse with a paradoxical reduction in heart rate and an increase in stroke volume. 'Bradycardiac' collapses were observed in 54% of the cases. The administration of atropine in one patient resulted in an immediate increase in heart rate. The development of bradycardia and hypotension during haemodialysis seems to be related to a sudden parasympathetic vagal overactivity and could be attributed to the Bezold-Jarish reflex.

[Carpal cysts in hemodialysis patients]. / Le cisti carpali nei pazienti in emodialisi.

A new type of amyloidosis due to beta 2-microglobulin depositions has been recently described in long-term hemodialysis patients. This systemic complication mainly affects the osteoarticular system, with diffuse articular symptoms; among them carpal tunnel syndrome is the most frequent. The syndrome etiopathology is unknown, even though many causal factors have been identified, among which the repeated use of non-biocompatible dialytic membranes. The authors conducted a retrospective study of 138 hemodialysis patients, with mean dialytic age of 79.3 months, to evaluate both incidence and evolution of bone cysts involving the carpal bones. Bone cysts were detected in the hands of 18.8% of the patients at the beginning of dialytic treatment; their incidence was over 50% after 10 years of treatment. Their size and number showed a rapid progression after the 6th year of hemodialysis, and their features were not related to osteodystrophic bone lesions. The carpal tunnel syndrome appeared after several years and its incidence was 7.9%; a direct correlation was demonstrated with the size of carpal bone cysts. The influence of hemodialysis membrane type on the occurrence of hemodialysis-related amyloidosis was strong, but not exclusive.

Acetate-free biofiltration: a viable alternative to bicarbonate dialysis.

Eight patients were studied during four sessions of acetate-free biofiltration (AFBF). AFBF is a new dialysis technique with no base replacement agents in the dialysate and with the addition in postdilution mode of bicarbonate (HCO3) solution directly into the extracorporeal blood circuit. In this study the effects on acid-base balance of different infusions of sodium bicarbonate (NaHCO3) ranging from 751 to 1,002 mEq per session was evaluated. There were significant positive correlations between the HCO3 infused and net HCO3 gained (r = 0.776, p less than 0.0001) and between HCO3 infused and plasma intratreatment HCO3 changes (n = 0.562, p less than 0.001). Stepwise multiple linear regression analysis demonstrated that HCO3 infused and plasma predialysis HCO3 values played the major role in HCO3 balance in AFBF. The best correction of metabolic acidosis was obtained with the infusion of 900-1,000 mEq of HCO3. The use of substitution fluid with 145 mEq/L of Na concentration avoids the risk of a positive intratreatment Na balance.

[Course of acquired renal cystic disease. An ultrasonic follow-up study]. / Evoluzione della malattia cistica renale acquisita (MCRA). Studio mediante follow-up ecografico.

The authors evaluated the evolution of acquired renal cystic disease with a 40-month US follow-up. Eighty-one patients were examined by US: 66 of them were hemodialysis patients, and 15 transplant recipients. Cystic kidney disease had progressed in 52/66 hemodialysis patients, whereas the picture was unmodified in 14/15 transplant recipients. As an explanation to the different evolution possibilities, the authors hypothesize that disease etiopathogenesis is to be sought in uremic toxic elements together with constitutional factors. Hemodialysis, prolonging the life of these patients, appears to facilitate the onset and/or evolution of the disease. On the contrary, kidney transplantation stops disease evolution, because it removes biologically active substances associated to uremia. In no cases new kidney tumors were found.

Continuous computerized monitoring of hemodynamic parameters during acetate dialysis, bicarbonate dialysis, and acetate-free biofiltration.

The effects of continuous, computerized, non-invasive hemodynamic monitoring on the appearance of intradialytic symptoms, aided by preventive therapeutic maneuvers, were evaluated in 30 critically ill patients undergoing regular acetate dialysis. The hemodynamic behavior was assessed by a system that interfaces a personal computer with a blood pressure monitor and to a transthoracic electrical impedance-measuring instrument. Monitoring allowed us to reduce significantly the frequency of some important intradialytic symptoms such as nausea, vomiting, and hypotension. The same monitoring system was used acutely to characterize differing hemodynamic behaviors during acetate dialysis (AD), bicarbonate dialysis (BD), and acetate-free biofiltration (AFBF). AD showed a prevalent vasodilation effect with a compensatory increase in heart rate and higher cardiac output values, which were not sufficient to maintain blood pressure stability. BD and AFBF were characterized by a more efficient vasoconstrictor effect and good hemodynamic stability. AFBF, despite a 1 h reduction in session length compared to BD, did not present significant differences in hemodynamic response resulting from session shortness or other technical changes.

A digital computer model for optimal programming of hemodialytic treatment.

A mathematical model of hydroelectrolyte exchanges and arterial pressure regulation in the human body during dialysis has been set up. It is conceived as a tool for a new dialysis unit which will be able to "interpret" the signals supplied by suitable instruments connected to the patient and modify the machine set-points in real time in order to obtain clinical results defined by the physician. The main aim is the prevention of hypotensive episodes during treatment. An experimental protocol has been developed for parameter estimation of each patient during a single dialysis. Clinical tests illustrated the model's ability to fit the patient's state during dialysis. This is the first step in the more general task of validation of the model, necessary for the achievement of a closed-loop dialysis unit.

[Angiographic study of the complications of vascular access in patients under hemodialysis]. / Studio angiografico delle complicanze degli accessi vascolari nei pazienti in emodialisi.

Periodic hemodialysis requires the vascular access to be capable of functioning perfectly for a long time; therefore early diagnosis of the most common complications is very important. Fifty-four patients in dialysis treatment for end-stage renal failure (ESRF) were examined over a six-year period for vascular access (VA) complications. Eighty vascular accesses were studied: 68 arteriovenous fistulas and 12 arteriovenous grafts. The most frequent radiological investigation was phlebography, followed by arteriography by direct puncture of the humeral artery, and, in few cases only, by arteriography through femoral approach; the total number of radiographic examinations performed was 101. The most frequent complications were thromboses (50%) and stenoses (21%); aneurysms, pseudoaneurysms and radial artery steals were observed in 11% of the cases. Findings prove complications to depend neither on the type of VA (fistula, prosthesis) nor on its site (proximal, distal). In 50% of the cases angiography allowed a therapy to be adopted for VA recovery. Percutaneous transluminal angioplasty (PTA), performed on 3 patients, failed. Thus, in the authors' opinion, angiography is the method of choice for the evaluation of VA pathology, and surgery is the most efficient treatment for complications. Despite failures, PTA represents a valid alternative in the treatment of stenoses in larger vessels and prostheses.

Long-term effects of parathyroidectomy on cardiac and autonomic nervous system functions in haemodialysis patients.

Ten patients receiving regular haemodialysis therapy who underwent parathyroidectomy for secondary hyperparathyroidism were investigated to evaluate the effects of parathyroid hormone on left ventricular and autonomic nervous system functions. The study which included M-mode echocardiography and autonomic nervous system tests (hormonal and cardiovascular response to the postural test, cold pressor test, handgrip test, diving reflex test and Valsalva manoeuvre) were performed prior to parathyroidectomy, and 5-8 months after, on a nondialysis day. The cardiovascular response and plasma noradrenaline changes to postural test remained unchanged following parathyroidectomy. The resting heart rate decreased from 73.1 +/- 2.4 to 66.4 +/- 2.3 beats/min (P less than 0.05) but mean blood pressure did not change post-parathyroidectomy. Mean blood pressure and heart rate changes during the cold pressor test, handgrip test, diving test and Valsalva manoeuvre were unaffected by parathyroidectomy. End-diastolic and end-systolic dimensions, fractional fibre shortening, mean velocity of fibre shortening and the ratio of the pre-ejection period to the left ventricular ejection time were normal prior to parathyroidectomy and remained unchanged following it. This study suggests that the reduction in parathyroid hormone concentrations obtained by parathyroidectomy does not significantly modify heart function and autonomic nervous system activity in the long term.