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Biomedical subjects

J Y Bosc

Publications and source records attributed to J Y Bosc.

26 records · Page 2Linked to original sources

Urea rebound and delivered Kt/V determination with a continuous urea sensor.

BACKGROUND: The recent introduction of urea sensors for dialysis monitoring has made possible new approaches to urea kinetic modelling. In this study we show how the equilibrated postdialysis urea concentration (Ceq) and Kt/V corrected for double-pool urea kinetics (Kt/Vdp) can be accurately determined using an on-line sensor providing a continuous measure of blood water urea. A modification of the Smye constant volume double-pool theory led to the following equations for Ceq and Kt/Vdp [formula: see text] where Cpre is the blood concentration measured at the start of dialysis, t is the length of the dialysis session (in min) and S(ex) is the constant slope of the blood urea logarithm concentration decline following development of the intercompartmental urea concentration gradient in the first 30-60 min of dialysis. METHODS: These equations were tested in 11 patients undergoing 165-240 min of paired filtration dialysis with continuous monitoring of blood urea concentration. Cpre was determined as the plateau concentration during a preliminary period of 15-20 min of slow isolated ultrafiltration. S(ex) was accurately determined from linear regression applied to the urea sensor data from the 80-min point to the end of dialysis. RESULTS: Ceq and Kt/Vdp determined from the above equations compared closely to values determined from 25-40 min of urea rebound monitoring with the urea sensor: 10.6 +/- 3.0 versus 10.8 +/- 2.7 mmol/l (mean +/- SD) for Ceq and 1.21 +/- 0.24 versus 1.18 +/- 0.20 for Kt/Vdp, compared to single-pool values of Kt/V = 1.34 +/- 0.23. CONCLUSION: This technique may be readily programmed into on-line urea monitors to provide current and extrapolated values of Ceq and Kt/Vdp from about the first hour of dialysis.

Adult↗

[Oxidative stress and chronic renal insufficiency: what can be a prophylactic approach?].

Cardiovascular diseases represent the first cause of mortality in chronic renal failure patients treated by hemodialysis. Alterations in lipid metabolism and oxidative stress are recognized as vascular risk factors. Their corrections could be of interest for atherosclerosis prevention. In order to evaluate interest of an therapeutic intervention, we have analyzed oxidative metabolism in hemodialysis patients by determining the production of oxygen reactive species (ROS), the level of defense mechanisms, and the balance between nitric oxide (NO) and ROS, responsible for anti- or proxidant effects of NO. During dialysis sessions performed with cellulosic membrane (Cuprophan) an increase in hydroperoxide production by platelets was noted (12 HETE) (5.62 +/- 0.94 pg); similarly, superoxide anion (O2(0)-) production by monocytes (fluorescence index: 115 +/- 24) and by polynuclear cells (fluorescence index: 115 +/- 24) was enhanced. On the other hand, anti-oxidant defenses were significantly reduced with a decrease in RBC SOC activity (0.92 +/- 0.06 U/mg Hg) and in RBC vitamin E (0.7 +/- 0.07 mg/l) concentration. We have demonstrated a profound alteration in the L-arginine/NO pathway consequently to an accumulation of NO synthases inhibitors or activators. The necessity to reduce the production of ROS during dialysis sessions justifies the use of more biocompatible membranes, such as modified cellulosic or synthetic membranes, decreasing leucocyte activation. In addition, NO synthetase inhibitors can be preferentially eliminated by convection. Finally, a supplementation with an exogenous anti-oxidant, such as oral vitamin E (500 mg/day for 6 months) normalizes RBC vitamin E levels and concomitantly allows a decrease in MDA concentrations In conclusion, oxidative metabolism alterations observed in hemodialysis are multifactorial: preventive measures include the use of a more biocompatible material, the reequilibrium of the NO/ROS balance, and supplementation with exogenous anti-oxidants.

Antioxidants↗

Removal of constitutive and inducible nitric oxide synthase-active compounds in a modified hemodiafiltration with on-line production of substitution fluid: the contribution of convection and diffusion.

Chronic renal failure and the uremic state lead to accumulation of various endogenous inhibitors of nitric oxide synthase. Previous studies on end-stage uremic patients nitric oxide synthase activity in murine vascular endothelium and cytokine-induced macrophage cell lines was shown to be modulated during treatment (Nephrol Dial Transplant 1995; 10: 1386-96). Paired filtration dialysis, a modified hemodiafiltration technique, physically separates convection from diffusion. Plasmas, ultrafiltrates and dialysates from seven uremic patients undergoing paired filtration dialysis performed using ultrapure apyrogen substitution fluid in the absence (first 120 min) or presence (last 120 min) of extracellular fluid reduction were tested for their inhibitory/stimulatory effect on ecNOS, constitutively expressed on t.End 1 cell line, a murine vascular endothelium, or for their inducing effect on iNOS, inducible on J774 cells, a macrophage cell line. On ecNOS, Group 1 (stimulatory, 3/7 patients) markedly enhanced the ecNOS activity as compared to control plasma, whereas group 2 plasma (inhibitory, 4/7 patients) inhibited ecNOS plasma. Post-dialysis plasma samples from all Group 1 and 2 patients showed a marked decrease of the predialysis stimulatory and inhibitory activity, respectively. On iNOS: all patient plasmas stimulated iNOS activity. The UF and particularly the dialysate had a remarkable iNOS inducing effect (Group 1). The substitution fluid obtained at 120 min during treatment in Group 1 and 2 had no effect on NOS activity. No correlation was found between predialysis ecNOS or iNOS activity values with mean systolic or diastolic pressures. These studies suggest a complex balance of ecNOS inhibitors/stimulators and iNOS inducers in uremia. Dialysis may remove ecNOS inhibitors and stimulators by convection and, in the latter case, by diffusion. iNOS inducers are removed during dialysis, suggesting the biocompatibility of the dialysis system with the on-line production of ultrapure substitution fluid.

Adult↗

Data acquisition system for dialysis machines. A model for membrane hydraulic permeability.

Membrane permeability is a key determinant of dialyzer performance; in vivo, membrane hydraulic permeability is affected by the formation of a protein cake on its surface, reducing ultrafiltration and convective fluxes. The purpose of this work was to evaluate the real hydraulic permeability of high flux polysulfone membrane under conditions of hemodiafiltration, and to consequently develop a mathematical model to estimate ultrafiltration Kuf and protein adsorption Kc coefficients. The DIB08 data acquisition system adapted to the Fresenius 2008E dialysis machine (Fresenius, Bad Homburg, Germany) allowed the recording of useful information for dialysis quantification, which was then processed by a bedside computer. The system was able to evaluate Kuf(t) profile, by calculation from the transmembrane pressure over time (TMP(t)) and ultrafiltration rate (Quf):Kuf (t) = Quf/TMP (t). Subsequent modeling of Kuf involved the determination of two key parameters: Kufhd (dialyzer permeability during diffusion only) (in mL/h/mmHg), and Kc (protein adsorption coefficient) (in mL/h/mmHg2). The model chosen was the following: Kuf (t) = Kuf0 x (1 - (Kc/Kuf0) x In(t + 1)) where Kuf0 represents the initial Kuf obtained at the beginning of the session. Thirty-one sessions were evaluated by real kinetic analysis, from which the mathematical model was derived. It included 27 postdilutional on-line hemodiafiltration and four hemodialysis sessions performed in four patients with nonreused HF80s dialyzers. For the analysis, three subgroups were defined: Group 1, first session of the week (Monday or Tuesday); Group 2, second session of the week (Wednesday or Thursday); and Group 3, third session of the week (Friday or Saturday). Results of Kuf and Kc obtained by real kinetic analysis are presented. The midweek session was associated with a higher membrane hydraulic permeability, most likely relative to lesser ultrafiltration rates and an associated relative decrease in membrane protein coating, represented by Kc. The described data acquisition system allowed the assessment of real time membrane hydraulic permeability and the subsequent development of a mathematical model to estimate this fundamental parameter as it functions to hemodialyzer performance.

Adult↗

On-line dialysis quantification in acutely ill patients: preliminary clinical experience with a multipurpose urea sensor monitoring device.

Direct dialysis quantification offers several advantages compared with conventional blood urea kinetic modeling, and monitoring urea concentration in the effluent dialysate with an on-line urea sensor is a practical approach. Such a monitoring device seems desirable in the short-term dialysis setting to optimize and personalize both renal replacement therapy and nutritional support of acutely ill patients. We designed a urea monitoring device consisting of a urea sensor, a multichannel hydraulic circuit, and a PC microcomputer. The sensor determines urea from catalysis of its hydrolysis by urease in liquid solution during neutral conditions. Hydrolysis of urea produces NH4+, and creates an electrical potential difference between two electrodes. Each concentration determination of urea is the average value of 10 measurements; samples are diverted and measured every 7 min. Laboratory calibration of the urea sensor has demonstrated linearity over the range 2-35 mmol/L. Urea monitoring was performed throughout the treatment course, either on the effluent dialysate or ultrafiltrate in seven acutely ill patients treated by either hemofiltration (n=5) or hemodiafiltration (n=2). The slope of the concentration of urea in the effluent over time was used to calculate an index of the dialysis dose delivered (Kt/V), urea mass removal, and protein catabolic rate. In addition, samples of the effluent were drawn every 21 min, and sent to the central laboratory for measurement of urea concentrations using an autoanalyzer. Kt/V values also were calculated with Garred's equation using pre and post session concentrations of urea in blood. Concentrations of urea in the effluent determined by the urea sensor were found to be very close to those obtained from the central laboratory over a wide range of values (3 to 42 mmol/L). In addition, Kt/V values for both hemofiltration and hemodiafiltration, when calculated with concentrations of urea in the effluent obtained by the urea sensor, did not significantly differ from Kt/V values obtained from the laboratory concentrations of urea in the effluent. On-line urea sensor monitoring of the effluent suppresses the cumbersome task of total effluent collection, and the complexity of urea kinetic analysis. The multipurpose prototype described here represents a new, simple, and direct assessment of dialysis dose and protein nutritional status of acutely ill patients, and is suitable for various modalities.

Acute Kidney Injury↗

The role of mineral metabolism and inflammation on dialysis vascular access failure.

Thrombosis of arteriovenous fistula (AVF) is the leading cause of vascular access (VA) loss usually due to silent stenosis. Therefore, assessment of relevant risk factors of VA monitoring may provide insight into potential therapeutic targets for stenosis and thrombosis. The aim of this study was to evaluate the influence of cardiovascular risk factors (including inflammation and mineral metabolism dysfunctions) on the failure of internal AVF in HD patients. 128 HD patients with internal AVF were included in the study and followed up for two years. At baseline, VA morphology and function were followed by Doppler ultrasonography and serum albumin, prealbumine, C-reactive protein, orosomucoid, calcium, phosphorus, parathyroid hormone, bone-type alkaline phosphatase, osteoprotegerin and receptor activator of nuclear factor ê ê B ligand were measured. At baseline, 50 stenoses were detected but none of them required any intervention. Age and biological parameters did not significantly differ between patients with or without VA stenosis. Over the two year- follow up, VA thrombosis occurred in 19 patients. Preexisting stenosis of VA was present in 9/19 patients (47.3% of cases) (chi-square = 3.708, p = 0.0538). Despite the low rate of events, phosphorus [1.75 (0.95-2.77) vs 1.42 (0.47-3.22) mmol/L, p = 0.0416], Calcium x Phosphorus product [4.00 (2.00-5.90) vs 3.40 (1.10-6.80) mmol(2)/L(2), p = 0.0676] and parathyroid hormone [165.00 (1.00-944.00) vs 79.50 (1.00-846.60) ng/L, p = 0.0814) levels were higher in the 19 thrombotic patients whereas all other biological parameters did not significantly differ. These results, which confirm that VA thrombosis occurs more frequently upon preexisting stenosis, also demonstrate that mineral metabolism disorders, compared to inflammation, may contribute to VA dysfunction leading to thrombosis.

Adult↗

Direct determination of blood recirculation rate in hemodialysis by a conductivity method.

Blood recirculation is one of the key factors of decreasing dialysis efficiency. Determination of recirculation rate (R) is necessary to optimize effective dialysis delivery and to monitor vascular access function. R can be directly measured by a conductivity method in paired filtration dialysis (PFD), a double-compartment hemodiafiltration system that permits direct access to plasma water via the ultrafiltration stream. Measurement of R, in this system, involves the first of two conductivity sensors integrated in a urea monitor (UMS, BelIco-Sorin, Mirandola, Italy), and two saline injections. The rise in conductivity (deltaC1) induced by a 2.7 ml bolus of hypertonic saline 20% (mg/dl) in the arterial line serves for calibration, and is followed by an equivalent injection into the venous line, giving rise to deltaC2. The ratio deltaC2/deltaC1 equals R. A comparison between R values obtained with this method and with the low-flow technique in 31 chronic dialysis patients during 138 PFD sessions is reported. Mean R+/-SD by the conductivity method was 5.1+/-2.0 and 5.7+/-2.0% after 65 and 155 minutes of PFD (correlation coefficient, r = 0.75), whereas it was 6.4+/-4.9% and 5.5+/-4.6% after 30 sec of low blood pump flow for urea and creatinine markers, respectively (r = 0.35). After 120 sec of low flow, mean R increased to 9.0+/-5.1 and 8.8+/-4.6% for urea and creatinine, respectively (r = 0.45). Considerable discrepancies were found in R values measured simultaneously with the two blood markers. Statistically significant differences were found between the two measurement modalities (blood-side and conductivity); the correlation coefficients (r) varied between 0.28 and 0.41. The observed differences in mean R results do not seem considerable from a clinical perspective. The best agreement between blood-side and conductivity R measurements was obtained with Rcreat after 30 sec of low flow. Overall, a wider distribution was found in R values from blood-side determinations, most likely consequent to variability in the dosing method. The conductivity method appears more accurate and simple in assessing total R, and can be readily automated and integrated into the dialysis machine. The authors, therefore, recommend evaluation of R using methods not based on chemical blood concentration values.

Adult↗