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.

Evaluation of high-flux hemodiafiltration efficiency using an on-line urea monitor.

On-line urea monitoring of the effluent dialysate offers a real-time assessment of dialysis efficiency and metabolic/nutritional characteristics of hemodialysis patients. Quantitative parameters were evaluated by dialysate urea kinetic modeling (DUKM) with an on-line urea sensor in 23 patients treated by high-flux hemodiafiltration (HDF) (215 sessions of 210 to 240 minutes with a mean blood flow rate of 367 +/- 44 mL/min). Overall, the mean effective Kt/V was 1.52 +/- 0.29, the urea mass removed (22.8 +/- 5.5 g/session or 814 +/- 198 mmol/session), the solute removal index (SRI) 73% +/- 6.1%, and the mean normalized protein catabolic rate (nPCR), 1.15 +/- 0.31 g/kg/day. Blood urea kinetic modeling (BUKM), based on pre- and postsession urea concentrations, using equations from Daugirdas and Garred to calculate equilibrated Kt/V and nPCR, respectively, were in good agreement with DUKM, the differences observed appearing not clinically relevant. The variability of evaluated parameters was verified over consecutive sessions for a mean period of 3 weeks in the entire group. Mean variation in Kt/V was 8%; in urea mass removal, 18%; and in nPCR, 18%. When assessed over 1 week in a subgroup of 13 patients, Kt/V and PCR remained relatively stable, and urea mass removal per- and postsession declined from 23.5 +/- 8.0 g (840 +/- 285 mmol) to 18.7 +/- 6.3 g (667 +/- 225 mmol) from the first to the third session of the week, most likely as a consequence of interdialytic intervals. Predialysis urea concentrations followed the same trend. In the current study, DUKM with on-line urea sensor has confirmed that HDF is a highly efficient renal replacement modality; the variability observed in quantitative parameters supports a need for frequent adequacy monitoring. On-line urea monitoring of effluent dialysate is a simple device that provides the opportunity to tailor treatment to patient needs.

Effective blood flow and recirculation rates in internal jugular vein twin catheters: measurement by ultrasound velocity dilution.

The ultrasound dilution technology (Transonic Systems, Ithaca, NY) is a reliable method to assess blood flow (Qb) and recirculation rates (R) in vascular access during hemodialysis. However, the information available on these parameters for central venous dialysis catheters remains scarce at this point. Real Qb and R were evaluated in 33 well-functioning TwinCath (Medcomp, Harleysville, PA) inserted as mid- or long-term hemodialysis vascular access (mean duration since insertion, 270 +/- 253 days); all were implanted into the right internal jugular vein with their multiperforated distal tips located in the superior vena cava or right atrium. Several types of dialysis machines were used (Monitral and AK100, Hospal-Gambro, Lyon, France; 2008E and 4008E, Fresenius, Bad Homburg, Germany). Real Qb was measured with the ultrasound dilution method and compared with the set Qb (indicated by the dialysis machine); R, also evaluated by ultrasound dilution, was evaluated at various Qb with nonreversed lines; therefore, a total of 121 measures were performed. Arterial and venous pressures (PA and PV) were recorded simultaneously. The 33 measures at a set Qb of 200 mL/min showed a mean effective Qb of 210 +/- 18 mL/min and a mean R of 5.3 +/- 5.3%. At a Qb of 300 mL/min, 33 repeated measures resulted in mean effective Qb of 303 +/- 21 mL/min and R of 8.5 +/- 7.0%; 28 measures performed at a set Qb of 350 mL/min showed that the effective Qb was 336 +/- 24 mL/min and that R was 7.8% +/- 6.7%. Finally, an effective Qb of 372 +/- 26 mL/min and an R of 10.9 +/- 8.6% were found for the 27 measures performed at an indicated Qb of 400 mL/min. The difference between indicated and effective Qb was particularly significant for set Qb equal to or above 350 mL/min (P < 0.001). Variable correlations were observed between obtained parameters: Qb eff and R (r = 0.34), PV and R (r = 0.36), Qb eff and PV (r = 0.78), Qb eff and PA (r = 0.71), and PV and PA (r = 0.53). In conclusion, TwinCath delivers an effective Qb of nearly 375 mL/min when Qb is set at 400 mL/min on most dialysis machines. Mean R in TwinCath varies between 5% and 11% for Qb within the range of 200 to 400 mL/min. In well-functioning TwinCath, the ratio between PV and Qb remains usually below 0.5.

Urea as a marker of adequacy in hemodialysis: lesson from in vivo urea dynamics monitoring.

BACKGROUND: "Dialysis dose," a concept developed by Sargent and Gotch based on urea kinetic modeling, is a useful and recognized tool that is used to quantitate and optimize a dialysis-efficacy program. However, it has been shown that oversimplification of the "dialysis adequacy" concept to the Kt/V index might lead to dramatic underdialysis and subsequent deleterious consequences on morbidity and mortality of dialysis patients. With this perspective, the determination of Kt/V must be very cautious and rely on accurate measurement of postdialysis urea concentration and its use integrated as a tool in a quality-assurance process. METHODS: In this study, we analyzed urea dynamics by means of a blood side (ultrafiltrate) continuous online urea monitoring system interfaced with a two-pool model hosted in a microcomputer. The study was designed to provide instantaneous dialysis performances (body and dialyzer clearances, dialyzer mass transfer coefficient) and to determine the in vivo functional permeability characteristics of the patient [intercompartment urea mass transfer coefficient (Kc)]. Thirteen end-stage renal disease patients (age 54 +/- 16 years; 12 male and 1 female) were studied during nine consecutive dialysis sessions (3 weeks). RESULTS: Urea kinetics obtained from the urea monitoring system fitted closely the urea kinetic modeling prediction, confirming the validity of the double-pool model structure. Effective in vivo urea mass transfer coefficient averaged 912 +/- 235 mL/min/1.73 m2, a value close to those reported with more invasive methods. Large variations ranging from 363 to 1249 mL/min were observed among patients, confirming very large interindividual patient permeability differences. Interestingly, the urea mass transfer coefficient was inversely correlated with the postdialysis rebound values. Intraindividual variations were also noted as a function of time denoting functional changes in urea mass transfer coefficient values. The urea distribution volume was 38.1 +/- 7, 8 L (53 +/- 8% body weight). V1 referring to the extracellular volume and V2 to the intracellular volume were 9 +/- 2 L (13 +/- 2% body weight) and 29.2 +/- 6.6 L (41 +/- 1.3% body wt), respectively. The extracellular/intracellular volume ratio was 0.31 (approximately one third) and was not as usually defined by the paradigm 1/2 ratio. CONCLUSION: Online double-pool urea kinetic modeling gave a new insight in urea kinetic modeling approach. Urea dynamics fit perfectly a double-compartment model structure. Accessible extracellular volume to hemodialysis is smaller than expected. The in vivo urea mass transfer coefficient must be considered as an individual and variable characteristic of ESRD patients that should be taken into consideration when prescribing the hemodialysis schedule.

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.

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.

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.

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.

Microbiological purity of dialysate for on-line substitution fluid preparation.

Dialysate purity has become a major concern in recent years since it was shown that low levels of endotoxin in dialysate were able to induce the production of proinflammatory cytokines, which were putatively implicated in the development of dialysis-related pathology. On-line haemodiafiltration (HDF; or haemofiltration) using the dialysate as the source of substitution fluid magnifies this risk and reinforces the critical role of the dialysate quality to be used. In order to virtually abolish the risk related to dialysate contaminants, it is mandatory to ensure the highest purity of the dialysate used in order that the substitution fluid produced satisfies the quality demands of a sterile and pyrogen-free infusion solution. Ultrapure dialysate production is therefore a common need for all on-line systems where substitution fluid is prepared continuously by sterilizing filtration of the dialysate. However, since dialysate purity plays a role in the complex haemocompatibility interaction which occurs during the haemodialysis session, the use of ultrapure dialysate must be considered as a suitable option for all haemodialysis modalities. To achieve this goal, one must keep in mind that ultrapure dialysate and infusate result from a complex chain of production where ultrapurity and/or sterility of the final solution relies on the weakest or worst component of the chain. Reliable production of ultrapure dialysate and infusate relies on several prerequisites: use of ultrapure water, use of clean electrolytic concentrates, implementation of ultrafilters on specifically designed HDF machines, microbiological monitoring of the chain with adequate and sensitive methods, and hygienic handling of the chain including frequent disinfection to reduce the level of contamination and to prevent biofilm formation. When properly done, the safety and reliability of on-line systems have been confirmed in large clinical studies. It is now time to validate the on-line process in large controlled clinical trials.

Analysis of the influence of the infusion site on dialyser clearances measured in an in vitro system mimicking haemodialysis and haemodiafiltration.

BACKGROUND: Blood flow (QB), dialysate flow (QD), and dialyser characteristics are the three major factors driving dialysis efficacy. Haemodiafiltration has added an increased convective volume to increase efficacy. We aimed to assess the influence of the infusion site of the replacement fluid in an in vitro system emulating haemodiafiltration. METHODS: An in vitro system allowing us to control the dialysate temperature, concentration gradient, the flow of both dialyser sides over a range wider than that compatible with clinic, was set to evaluate the influence of the different parameters on dialysis efficacy. The total ion clearance was used as an accepted method for small molecule clearance assessment. Cellulose triacetate (CT190C, Baxter; FB170U, Nipro) and polysulfone (HF80, Fresenius) dialysers were included in the study. Dialysis as well as on-line diafiltration both with pre- and postdilutional infusion were assessed. The experimental conditions presented in this study included QD 620 and 970 ml/min. The convective flows ranged from 50 to 200 ml/min. RESULTS: For a QD = 620 ml/min and a QB = 350 ml/min the total ion clearance ranged from 269 to 274 for HF80, from 291 to 294 for FB170 and from 294 to 302 for CT190. The variability of the measurements was very low (SD < 1%). Total ion clearance increased by 17-21% when QB was raised from 300 to 400 ml/min. Increasing QD from 420 to 970 ml/min (for QB = 350 ml/min), resulted in an increase in total ion clearance which was more marked at lower QD (from 420 to 620 ml/min) and plateaued thereafter (from 620 to 970 ml/min). Postdilutional on-line diafiltration with 100 ml/min of infusate resulted in an additional increase in total ion clearance of 5.4-8.6%. This increase was proportional to the infused volume. On the contrary, predilutional on-line diafiltration resulted in a decrease in total ion clearance which was also proportional to the infused volume (between -5.1 and -6.9% at 100 ml/min infusion volume and -9.7 to -12.9% at 200 ml/min). CONCLUSIONS: The present in vitro system provided accurate and reproducible results on dialyser clearances. Our experiments confirmed previous studies on the influence of QB and QD on dialyser efficacy. Further, they show that the proportional increase in postdilutional on-line diafiltration is lesser than that previously reported. More importantly, they also show that pre-dilution infusion in high efficiency systems results in a drop in dialyser clearance compared to dialysis alone, again proportional to the infusion rate. Thus, increasing the convective flow may increase dialysis efficacy even more than increasing QD alone. However, the choice of infusion site is crucial to obtaining this benefit in small molecule clearances.

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.

Microbiologic purity of dialysate: rationale and technical aspects.

Dialysate purity has become a major concern in hemodialysis since it has been shown that microbial-derived products were stimulating the production and the release of proinflammatory cytokines in hemodialysis patients. This chronic microinflammatory state induced by hemodialysis has been putatively implicated in the development of dialysis-related pathology. In order to prevent risk related to these offenders and to reduce patient/dialysis interaction, it appears highly desirable to use ultrapure dialysis fluid aiming at sterility and apyrogenicity on a regular basis. Ultrapure dialysate results from a complex chain of production where purity grade relies on the weaker link of this chain. Technical aspects and pitfalls in the production of ultrapure dialysate are summarized in this paper. Production of ultrapure dialysate may be achieved on a routine basis, provided adequate components are used, and hygienic handling is regularly ensured. It includes the use of ultrapure water, clean and or sterile electrolytic concentrates (liquid or powder), implementation of ultrafilters on hemodialysis machines, microbiologic monitoring and hygienic handling of the chain with frequent disinfection. Safety and reliability of ultrapure dialysate production relies on a continuous quality assurance process, where results are coupled to corrective action in a feedback loop process.

Protein catabolic rate over lean body mass ratio: a more rational approach to normalize the protein catabolic rate in dialysis patients.

Protein catabolic rate (PCR), equivalent to dietary protein intake in "stable" dialysis patients, is widely accepted as a marker of their protein nutritional status. PCR is usually established from urea generation rate using urea kinetic modeling (UKM), but the normalizing factor is still a matter of controversy. By convention, PCR is expressed in grams of protein degraded daily divided by the dry body weight (BW) (nPCRBW). To be valid, this implies that dry BW is close to ideal BW and that body composition is preserved with a lean body mass (LBM) over BW ratio near 0.73. Such conditions being infrequently found in dialysis patients, it has been proposed to normalize PCR to ideal BW or to total body water, but these correction factors are not really appropriate. A more rational approach would be to express PCR as the ratio of protein degraded to the kilograms of LBM (nPCRLBM), thus offering the main advantage of directly coupling PCR to changes in protein or nitrogen reserve. In this study, we developed a combined kinetic model of urea and creatinine applied to the midweek dialysis cycle in 66 end-stage renal disease (ESRD) patients. UKM provided Kt/V and PCR, whereas creatinine kinetic modeling (CKM) was used to calculate LBM. Thirty-four patients with a preserved LBM (LBM/dry BW ratio equal to or greater than 0.70; mean ratio, 0.81 +/- 0.11) and with a dry/ideal BW ratio of 1.01 +/- 0.16 had a mean PCR of 1.14 +/- 0.30 g/kg/24 h when normalized to BW (nPCRBW) and of 1.40 +/- 0.30 g/kg/24 h when normalized to LBM (nPCRLBM). In the 32 patients with a reduced LBM (LBM/dry BW ratio, below 0.70; mean ratio, 0.60 +/- 0.09) and dry/ideal BW ratio of 1.11 +/- 0.23, the mean nPCRBW was 0.99 +/- 0.31 g/kg/24 h, whereas nPCRLBM was 1.62 +/- 0.32 g/kg/24 h. For both subgroups, Kt/V was similar, with mean values of 1.76 +/- 0.34 and 1.69 +/- 0.27. Normalizing PCR to LBM offers a double benefit: it compensates for the error induced by abnormal body composition (eg, obese patients) and permits PCR to be adjusted for the decrease in LBM that occurs with age. We propose nPCRLBM as a more rational index to express PCR in dialysis patients.

Central venous dialysis catheter dysfunction.

Central venous catheter dysfunction is a limiting factor in regard to renal replacement therapy efficiency and can thus influence patient morbidity. Early catheter dysfunction is frequently due to mechanical problems such as inadequate positioning, kinking, or constriction, but early fibrin deposition can develop soon after insertion. Delayed dysfunction usually results from thrombus formation, either within the lumen, around the catheter ("fibrin sleeve"), or in the host vein. Catheter dysfunction is suspected clinically or documented by simple imaging studies. It is usually evident and manifested by failure to aspirate blood from the lumen(s), inadequate blood flow and/or high resistance pressures during hemodialysis. However, a more subtle dysfunction may lead to a high recirculation of dialyzed blood and be overlooked if dialysis adequacy is not monitored regularly. Local instillation of a fibrinolytic agent is usually successful in restoring catheter patency. Central venous dialysis catheters present intrinsic limitations consequent to their composition and design, whereas extrinsic limitations result from site of insertion, blood properties and anatomic particularities of a given individual. These characteristics largely determine overall catheter performances. Performance parameters to consider include maximal consistently achievable blood flow rate, resistance to blood flow indicated by arterial and venous pressures during hemodialysis, and blood recirculation rate. Catheter longevity is an important consideration for cuffed catheters implanted for long-term use. The tolerated blood recirculation within central venous dialysis catheters should be below 10% to 15%, and is ideally between 3% to 7% in most clinical settings. Several recent studies confirm that short femoral catheters recirculate significantly more than is desirable. Well functioning and nonreversed internal jugular and subclavian venous catheters have, in general, recirculation rates less than 5%. With regard to various performance criteria, the TwinCath (Medcomp, Harleysville, PA) appears particularly advantageous. In any case, a good catheter maintenance program is of critical importance for the prevention and the early detection of catheter dysfunction.

[Surveillance of permanent central venous access for hemodialysis]. / Surveillance et suivi des accès veineux centraux permanents pour hémodialyse.

Central venous catheters have emerged as a valuable alternative for permanent access in hemodialysis. Thanks to steady improvements of materials and design they have been successfully used as bridging solution until another vascular access became available or even long term solution for patients with limited or insuffisant vascular resources. Since the use of central venous catheters is affiliated with a higher dysfunction rate and morbidity, special attention is indicated. This should include regular surveillance, clinical examination and intervention using specific methods, bacteriological exams and regular dialysis quantification. Such a constant quality control followed by strict and adapted rules for catheter handling are essential necessities to reduce catheter-related complications and assure an adequate dialysis.

Intradialytic glucose infusion increases polysulphone membrane permeability and post-dilutional haemodiafiltration performances.

INTRODUCTION: During real-time monitoring of the ultrafiltration coefficient (Kuf) in haemodiafiltration (HDF), it was noticed that the ultrafiltration performance of polysulphone membrane dialysers increased when hypertonic glucose (D50%) was administered through the venous blood return. METHODS: This observation was explored in six non-diabetic chronic dialysis patients during 48 HDF sessions using 1.8 m(2) polysulphone membrane dialysers. In all six patients, 24 sessions were performed with glucose supplementation (as a continuous D50% (500 g/l) infusion at 40 ml/h) and 24 sessions without supplementation. RESULTS: Glucose supplementation led to a marked increase in Kuf from 22.8+/-2.2 (without D50%, n=24) to 32. 1+/-3.9 ml/h/mmHg (with D50%, n=24) (P<0.0001). An increase in percentage reduction ratios for urea and creatinine were also consistently observed during the sessions with glucose administration (from respective mean values of 75+/-5 and 68+/-4% to 79+/-4 and 74+/-10%). Mean double-pool Kt/V, calculated from serum urea concentrations, rose from 1.65+/-0.24 (n=24) to 1.86+/-0.24 (n=24) (P<0.005). Similar results were observed in a subgroup of 18 HDF sessions (nine with glucose and nine without) monitored with an on-line urea sensor of spent dialysate. No detrimental effects were induced at any time. CONCLUSIONS: We conclude that intravenous glucose administration during high-flux HDF using polysulphone membranes increases significantly both ultrafiltration capacity and dialysis dose delivery.

Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation.

Oxidative stress can produce profound alterations to cellular membrane lipids, impairing cell metabolism and viability. This phenomenon, previously observed in haemodialysis patients, has been proposed as a significant factor in regard to haemodialysis-related shortened red blood cells (RBC) survival. In the present study, several parameters associated with oxidative stress were evaluated in a group of haemodialysis patients either receiving erythropoietin therapy (n = 12, mean erythropoietin dose 88 +/- 24 U/kg/week) or not receiving such therapy (n = 30), and in 38 controls. Malonyldialdehyde (MDA, nmol/ml), an end-product of lipid peroxidation, and RBC antioxidant systems were measured, including RBC alpha-tocopherol (RBC vitamin E, mg/l), RBC glutathione (GSH, nmol/mgHb), and RBC superoxide dismutase activity (SOD, U/mgHb). Plasma vitamin E concentrations were also evaluated. Finally, oral vitamin E supplementation (500 mg daily), an exogenous antioxidant, was administered for 6 months to seven patients from the dialysis group receiving erythropoietin while oxidative parameters were repeatedly evaluated and erythropoietin requirements monitored, in order to appreciate the therapeutic relevance of an antioxidant supplementation. An elevation of serum MDA was observed in all haemodialysis patients and a significant decrease in RBC vitamin E, despite normal serum vitamin E levels. Furthermore, the reduction in RBC vitamin E was more important in patients treated with erythropoietin. Vitamin E supplementation resulted in a significant increase in RBC vitamin E (from 0.3 +/- 0.1 to 1.2 +/- 0.2 mg/l of pellet) and a reduction in erythropoietin dose (from 93 +/- 24 to 74 +/- 26 U/kg/week) while maintaining stable haemoglobin concentrations. These results suggest that the oxidative stress could be one of the resistance factors to erythropoietin response in haemodialysis and that vitamin E supplementation could have a sparing effect on erythropoietin dosage requirement.

On-line haemodiafiltration: state of the art.

Faced with the shortcomings of conventional dialysis on a long-term basis, as illustrated by the dialysis-related pathology, a need for a new strategy exists to improve the overall quality of treatment in end-stage renal failure (ESRF) patients. On-line haemodiafiltration (HDF) seems to be the best therapeutic option to achieve this goal at the present time. By enhancing convective clearances through highly permeable membranes, HDF offers the greatest solute fluxes both for low and higher molecular weight uraemic toxins. As for example, in our routinely performed HDF programme based on 3 weekly sessions lasting 3-4 h each, double-pool urea Kt/V achieved was 1.55+/-0.20 and beta2-microglobulin Kt/V was 0.91. By producing substitution fluid from fresh dialysate, the technique of HDF is simplified and becomes economically affordable. By improving the haemodynamic tolerance, HDF allows more elderly and high risk cardiovascular patients to be treated more safely. By using bicarbonate-buffered infusate, HDF facilitates the correction of acidosis. Both by using ultrapure bicarbonate dialysate and down-regulating the membrane reactivity via a 'protein cake', HDF introduces the first step for a full haemocompatibility concept. Finally, by giving access to virtually unlimited amounts of sterile and non-pyrogenic fluid, HDF should introduce new therapeutic options such as a totally automated and feed-back-controlled machine. Today's on-line HDF is already a step forward to enhance the overall efficacy of renal replacement therapy and to improve the global care of ESRF patients.

Monitoring the microbial purity of the treated water and dialysate.

Dialysate purity has become a major concern in recent years since it has been proven that contamination of dialysate is able to induce the production of proinflammatory cytokines, putatively implicated in the development of dialysis related pathology. In order to reduce this risk, it is advised to use ultrapure dialysate as a new standard of dialysate purity. Ultrapure dialysate preparation may be easily achieved with modern water treatment technologies. The reliable production of ultrapure dialysate requires several prerequisites: use of ultrapure water, use of clean electrolytic concentrates, implementation of ultrafilters in the dialysate pathway to ensure cold sterilization of the fresh dialysate. The regular supply with such high-grade purity dialysate relies on predefined microbiological monitoring of the chain using adequate and sensitive methods, and hygienic handling including frequent disinfection to reduce the level of contamination and to prevent biofilm formation. Reliability of this process requires compliance with a very strict quality assurance process. In this paper, we summarized the principles of the dialysate purity monitoring and the criteria used for surveillance in order to establish good antimicrobial practices in dialysis.