Jean-Yves Bosc

Association between novel indices of malnutrition–inflammation complex syndrome and cardiovascular disease in hemodialysis patients

Background:  Inflammation and malnutrition are recognized as important risk factors for cardiovascular disease (CVD) in hemodialysis (HD) patients. Owing to substantial short‐term variability of serum C‐reactive protein (CRP), more reliable markers of malnutrition–inflammation complex syndrome should be sought with stronger associations with the risk of CVD in HD patients. We therefore explored the clinical relevance of a composite inflammatory index (prognostic inflammatory and nutritional index [PINI]) and of muscle protein mass indicators, derived from creatinine kinetics.

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, Bellco-Sorin, Mirandola, Italy), and two saline injections. The rise in conductivity (δC1) 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 δC2. The ratio δC2/δC1 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.

Vitamin E Supplementation Increases LDL Resistance to ex vivo Oxidation in Hemodialysis Patients

BACKGROUND Oxidative stress and alterations in lipid metabolism observed in hemodialysis patients potentiate the low-density lipoprotein (LDL) oxidability, recognized as a key event during early atherogenesis. OBJECTIVE To explore the effects of an oral vitamin E supplementation on oxidative stress markers and LDL oxidability in hemodialysis patients. METHODS Fourteen hemodialysis patients and six healthy volunteers were given oral vitamin E (500 mg/day) for six months. Oxidative stress was assessed using: plasma and lipoprotein vitamin E levels [high-performance liquid chromatography (HPLC) procedure]; thiobarbituric acid reactive substances (TBARS, Yaggi method); and copper-induced LDL oxidation. All parameters were evaluated before initiation of vitamin E supplementation, and at three and six months thereafter. RESULTS At baseline, a significantly higher TBARS concentration and a higher LDL oxidability were observed in hemodialysis patients when compared to controls. After six months of vitamin E supplementation, TBARS and LDL oxidability were normalized in hemodialysis patients. CONCLUSION Our data confirm that hemodialysis patients are exposed to oxidative stress and increased susceptibility to ex vivo LDL oxidation. Since oral vitamin E supplementation prevents oxidative stress and significantly increases LDL resistance to ex vivo oxidation, supplementation by natural antioxidants such as vitamin E may be beneficial in hemodialysis patients.

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 Garreds 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. ASAIO Journal 1998; 44:184–190.

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 χ (1 - (Kc/KuQ χ ln(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 nonre-used 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.

Does hemodiafiltration improve the removal of homocysteine

High prevalence of hyperhomocysteinemia is common in hemodialysis (HD) patients and could contribute to worsen the cardiovascular risk. Beyond vitamin B status, dialysis modality itself could influence homocysteine (Hcy) levels. The objective was compare the reduction rate (RR) of Hcy and cysteine in stable dialyzed patients treated by standard HD or hemodiafiltration (HDF). Seventy‐five patients undergoing stable dialysis through standard high‐flux HD (n = 35) or HDF (n = 40) were included. Biological parameters were determined before and after a midweek dialysis session. Urea percent reduction per session and Kt/V index (K, body urea clearance, T, time of dialysis, and V, urea distribution volume), defined as a marker of dialysis efficacy, were similar between HD and HDF groups. By contrast, higher RR of beta2 microglobulin (β2m) was observed in HDF compared with HD (78.6 vs. 72.0%, respectively; P < 0.001). Likewise, higher RR of Hcy was obtained with HDF compared to HD (46.0 vs. 41.5%, respectively; P < 0.05), whereas the RR of cysteine was similar in both groups. Interestingly, a positive correlation between Hcy RR and urea Kt/V index was observed (r = 0.29, P < 0.05) and between Hcy RR and β2m RR (r = 0.45, P < 0.001). Time‐averaged concentration (TAC) of Hcy was lower with HDF compared with HD (17.8 vs. 19.1 μmol/L, respectively), although not significant. There was no difference in median Hcy according to dialysis modality for neither pre‐ nor postdialysis levels. Significant higher removal of Hcy was observed with HDF compared with standard HD, although urea Kt/V index was similar. Enhanced removal of middle molecules, such as β2m, could be involved in Hcy RR improvement with HDF.

Biophysics of intermittent renal replacement therapy

This chapter on the technical and theoretical aspects of intermittent renal replacement therapy is divided into three parts. First we present the equations and theory relating to mass and fluid transfer for the principle forms of intermittent therapy: hemodialysis, hemodiafiltration and hemofiltration. This is followed by a discussion of urea kinetics, treatment quantification as Kt/V, and urea generation rate determination in acute renal failure. In the final section, we develop a quantitative framework to guide prescription of intermittent therapy for the acute renal failure patient.