Computational assessment of the effects of a pulsatile pump on toxin removal in blood purification

<p>Abstract</p> <p>Background</p> <p>For blood purification systems using a semipermeable membrane, the convective mass transfer by ultrafiltration plays an important role in toxin removal. The increase in the ultrafiltration rate can improve the toxin removal efficiency of the device, ultimately reducing treatment time and cost. In this study, we assessed the effects of pulsatile flow on the efficiency of the convective toxin removal in blood purification systems using theoretical methods.</p> <p>Methods</p> <p>We devised a new mathematical lumped model to assess the toxin removal efficiency of blood purification systems in patients, integrating the mass transfer model for a human body with a dialyser. The human body model consists of a three-compartment model of body fluid dynamics and a two-compartment model of body solute kinetics. We simulated three types of blood purification therapy with the model, hemofiltration, hemodiafiltration, and high-flux dialysis, and compared the simulation results in terms of toxin (urea and beta-2 microglobulin) clearance and the treatment dose delivered under conditions of pulsatile and non-pulsatile pumping. <it>In vivo </it>experiments were also performed to verify the model results.</p> <p>Results</p> <p>Simulation results revealed that pulsatile flow improved the convective clearance of the dialyser and delivered treatment dose for all three types of therapy. Compared with the non-pulsatile pumping method, the increases in the clearance of urea and beta-2 microglobulin with pulsatile pumping were highest with hemofiltration treatment (122.7% and 122.7%, respectively), followed by hemodiafiltration (3.6% and 8.3%, respectively), and high-flux dialysis (1.9% and 4.7%, respectively). EKRc and std Kt/V averaged 28% and 23% higher, respectively, in the pulsatile group than in the non-pulsatile group with hemofiltration treatment.</p> <p>Conclusions</p> <p>The pulsatile effect was highly advantageous for all of the toxins in the hemofiltration treatment and for β₂-microglobulin in the hemodiafiltration and high-flux dialysis treatments.</p

Progress in Hemodialysis

Hemodialysis (HD) represents the first successful long-term substitutive therapy with an artificial organ for severe failure of a vital organ. Because HD was started many decades ago, a book on HD may not appear to be up-to-date. Indeed, HD covers many basic and clinical aspects and this book reflects the rapid expansion of new and controversial aspects either in the biotechnological or in the clinical field. This book revises new technologies and therapeutic options to improve dialysis treatment of uremic patients. This book consists of three parts: modeling, methods and technique, prognosis and complications

Body composition analysis with bioelectric impedance in adult Indians with ESRD: Comparison with healthy population

Evaluation of body composition provides clinically useful information in several diseases including chronic kidney disease. Bioimpedance analysis (BIA) is a simple, cheap, and noninvasive tool for monitoring body composition. We performed BIA in 451 healthy adults and 162 end-stage renal disease (ESRD) patients. Resistance (R) and reactance (Xc) values were obtained at 50-kHz frequency using a tetrapolar impedance meter. Body compartments were derived using population-specific regression equations. Phase angles (arctan Xc/R) were calculated and impedance vector distribution was determined using the RXc graph method. Compared to healthy population, ESRD patients had similar post-dialysis resistance with lower reactance and phase angle, indicating decreased soft tissue mass and inadequate ultrafiltration. BIA equations estimated decreased fat mass index and intracellular water, whereas the total body and extracellular water percentages were increased. Sex-specific reference RXc plots with 95, 75, and 50% tolerance ellipses were drawn for the healthy population. A significant difference was noted in the vector positions and 95% confidence ellipses of the two sexes and body mass indices of ≤25 and >25. In conclusion, we present the reference BIA parameters for Indian population. ESRD patients show significant body compartment alterations. The RXc score graph can differentiate ESRD patient from normal controls and can be used to monitor nutrition and hydration status

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study. The ongoing HEMO Study, a National Institutes of Health (NIH) sponsored multicenter trial to test the effects of dialysis dosage and membrane flux on morbidity and mortality, was preceded by a Pilot Study (called the MMHD Pilot Study) designed to test the reliability of methods for quantifying hemodialysis. Dialysis dose was defined by the fractional urea clearance per dialysis determined by the predialysis BUN and the equilibrated postdialysis BUN after urea rebound is completed (eKt/V). In the Pilot Study the blood side standard for eKt/V was calculated from the predialysis, postdialysis, and 30-minute postdialysis BUN. Four techniques of approximating eKt/V that eliminated the requirement for the 30-minute postdialysis sample were also evaluated. The first adjusted the single compartment Kt/V using a linear equation with slope based on the relative rate of solute removal (K/V) to predict eKt/V (rate method). The second and third techniques used equations or mathematical curve fitting algorithms to fit data that included one or more samples drawn during dialysis (intradialysis methods). The fourth technique (dialysate-side) predicted eKt/V from an analysis of the time-dependent profile of dialysate urea nitrogen concentrations (BioStat method; Baxter Healthcare, Inc., Round Lake, IL, USA). The Pilot Study demonstrated the feasibility of conventional and high dose targets of about 1.0 and 1.4 for eKt/V. Based on the blood side standard method, the mean ± SD eKt/V for patients randomized to these targets was 1.14 ± 0.11 and 1.52 ± 0.15 (N = 19 and 16 patients, respectively). Single-pool Kt/Vs were about 0.2 Kt/V units higher. Results were similar when eKt/V was based on dialysate side measurements: 1.10 ± 0.11 and 1.50 ± 0.11. The approximations of eKt/V by the three blood side methods that eliminated the delayed 30-minute post-dialysis sample correlated well with eKt/V from the standard blood side method: r = 0.78 and 0.76 for the single-sample (Smye) and multiple-sample intradialysis methods (N = 295 and 229 sessions, respectively) and 0.85 for the rate method (N = 295). The median absolute difference between eKt/V computed using the standard blood side method and eKt/V from the four other methods ranged from 0.064 to 0.097, with the smallest difference (and hence best accuracy) for the rate method. The results suggest that, in a dialysis patient population selected for ability to achieve an equilibrated Kt/V of about 1.45 in less than a 4.5 hour period, use of the pre and postdialysis samples and a kinetically derived rate equation gives reasonably good prediction of equilibrated Kt/V. Addition of one or more intradialytic samples does not appear to increase accuracy of predicting the equilibrated Kt/V in the majority of patients. A method based on dialysate urea analysis and curve-fitting yields results for equilibrated Kt/V that are similar to those obtained using exclusively blood-based techniques of kinetic modeling

Which Analysis Approach Is Adequate to Leverage Clinical Microdialysis Data? A Quantitative Comparison to Investigate Exposure and Reponse Exemplified by Levofloxacin

Purpose Systematic comparison of analysis methods of clinical microdialysis data for impact on target-site drug exposure and response. Methods 39 individuals received a 500 mg levofloxacin short-term infusion followed by 24-h dense sampling in plasma and microdialysate collection in interstitial space fluid (ISF). ISF concentrations were leveraged using non-compartmental (NCA) and compartmental analysis (CA) via (ii) relative recovery correction at midpoint of the collection interval (midpoint-NCA, midpoint-CA) and (ii) dialysate-based integrals of time (integral-CA). Exposure and adequacy of community-acquired pneumonia (CAP) therapy via pharmacokinetic/pharmacodynamic target-attainment (PTA) analysis were compared between approaches. Results Individual AUCISF estimates strongly varied for midpoint-NCA and midpoint-CA (≥52.3%CV) versus integral-CA (≤32.9%CV) owing to separation of variability in PK parameters (midpoint-CA = 46.5%–143%CVPK, integral-CA = 26.4%–72.6%CVPK) from recovery-related variability only in integral-CA (41.0%–50.3%CVrecovery). This also led to increased variability of AUCplasma for midpoint-CA (56.0%CV) versus midpoint-NCA and integral-CA (≤33.0%CV), and inaccuracy of predictive model performance of midpoint-CA in plasma (visual predictive check). PTA analysis translated into 33% of evaluated patient cases being at risk of incorrectly rejecting recommended dosing regimens at CAP-related epidemiological cut-off values. Conclusions Integral-CA proved most appropriate to characterise clinical pharmacokinetics- and microdialysis-related variability. Employing this knowledge will improve the understanding of drug target-site PK for therapeutic decision-making

Peritoneal dialysis in older adults: evaluation of clinical, nutritional, metabolic outcomes, and quality of life

The number of older adults requiring dialysis is increasing worldwide, whereas the use of peritoneal dialysis (PD) in this population is lower respect to younger patients, despite the theoretical advantages of PD respect to hemodialysis. This is most likely due to the concern that older patients may not be able to correctly and safely manage PD. We aimed to prospectively compare clinical, nutritional and metabolic outcomes and measures of quality of life between younger (&lt;65years old) and older (≥65years old) patients on PD. PD patients were enrolled and divided into 2 groups according to age (Group A &lt; 65 years, Group B ≥ 65 years). Clinical and instrumental parameters, and quality of life were evaluated at baseline (start of PD) (T0) and at 24 months (T1). Technique survival, mortality, total number of hospitalizations, and the index of peritonitis (episodes of peritonitis/month) were also evaluated. Fifty-one patients starting PD were enrolled. Group A included 22 patients (48.7±8.3 years), and Group B consisted of 29 patients (74.1 ± 6.4 years). At baseline, the 2 groups showed no differences in cognitive status, whereas Group A showed higher total cholesterol (p=0.03), LDL (p=0.03), and triglycerides (p=0.03) levels and lower body mass index (p=0.02) and carotid intima media thickness (p&lt;0.0001) with respect to Group B. At T1 Group B showed, compared to baseline, a significant reduction in albumin (p&lt;0.0001) and phosphorus (p=0.045) levels, while no significant differences on body composition, technique survival, total number of hospitalizations, index of peritonitis and quality of life indices were observed. Our data do not show clinically relevant barriers to use PD in older adult patients, supporting its use in this population. Nutritional and metabolic parameters should be carefully monitored in older PD patients

An assessment of solute kinetics and the application of mathematical modelling in the haemodialysis process

AIM: The aim of this thesis is to enhance knowledge about solute clearance during haemodialysis and to provide insight into factors that may influence dialysis efficiency. By improving the understanding of the kinetics of solute removal the limitations of current dialysis therapy will be better understood, and suggestions can be made for future improvements in the delivery of dialysis.METHODS: The history of dialysis technique and adequacy measurement is detailed. The origin and potential problems with urea kinetic modelling, including the effect of high haematocrit on adequacy, are explored.Mathematical modelling is utilised to provide potential explanations for the clearance characteristics of phosphate and beta2-microglobulin during chronic dialysis. The phosphate model is explored further with studies in acute renal failure and the effect of dialysis on intra-erythrocytic phosphate concentrations is assessed. Diurnal variation in phosphate concentration is explored.The effect of different dialysis modalities on beta2-microgloblin levels and symptoms of dialysis related amyloid is studied. Dialysis related amyloid deposition is investigated by a scintigraphic imaging technique.RESULTS: Haematocrit. High haematocrit is not found to have a significant effect on the clearance of solutes across a wide range of molecular size.Phosphate. A four-pool model that can be applied in both acute and chronic renal failure is proposed to explain the observed kinetic behaviour of phosphate. Studies of intracellular phosphate concentrations fail to demonstrate release of phosphate from erythrocytic stores during dialysis. Diurnal variation in phosphate concentration is demonstrated in subjects with normal renal function and also in advanced chronic kidney disease.Beta2-microglobulin. A multi-pool model explains the kinetic behaviour of beta2- microglobulin during dialysis. Beta-2-microglobulin deposition is assumed to be a staged process with some deposits easily accessible during dialysis and some more resistant to depuration. Patients receiving high-flux dialysis or haemodiafiltration are shown to have lower circulating beta2-microglobulin levels and less symptomatic dialysis related amyloid, but evidence of amyloid deposition is still found when assessed by a scintigraphic imaging technique. Age and duration of dialysis are shown to be the best predictors of symptomatic amyloid deposition.CONCLUSIONS: The results of the studies in this thesis indicate that, for solutes such as phosphate and beta2-microglobulin which have complex intra-dialytic kinetics, current dialysis techniques are insufficient to achieve adequate solute removal. It will be necessary to deliver longer or perhaps more frequent dialysis therapy in order to achieve this goal. Mathematical modelling facilitates understanding of the pathophysiology of the dialysis process and provides a platform for the development and monitoring of improved dialysis strategies