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PubMed1981

The role of mRNA competition in regulating translation. IV. Kinetic model.

A kinetic model of protein synthesis is presented, primarily designed to analyze the accompanying data (Brendler, T., Godefroy-Colburn, T., Carlill, R. D., and Thach, R. E. (1981) J. Biol. Chem. 256, 11747-11754; Walden, W. E., Godefroy-Colburn, T., and Thach, R. E. (1981) J. Biol. Chem. 256, 11739-11746). Our model treats initiation as a multistep process in which mRNA must bind to a "discriminatory factor" prior to its recognition by the native 40 S subunit. Interaction with the latter is followed by an irreversible rearrangement which yields the functional 40 S initiation complex capable of binding the 60 S ribosome with release of all the factors. Elongation is simply treated as a series of irreversible steps with a single rate constant. The model takes into account the recycling of ribosomal subunits, initiation factors, discriminatory factor, and message initiation site. We can thus mimic the simultaneous translation of several messages, each with its own concentration, size, binding constants, and rate constants. The only limit to the number of messages is the capacity of the computer (3 kilobytes of accessible memory is sufficient for 5 messages). Thus, we are able to evaluate quantitatively the effect of each parameter on the rate of synthesis of individual polypeptides, on polysome size, and on the repartition of message species between the untranslated and the polysomal pools. Several applications are considered: (i) competitive translation of alpha- and beta-globin in vitro (Kabat, D., and Chappel, M. R. (1977) J. Biol. Chem. 252, 2684-2690); (ii) determination of the relative affinities of reoviral messages for the discriminatory factor in vitro (Brendler, T., Godefroy-Colburn, T., Carlill, R. D., and Thach, R. E. (1981) J. Biol. Chem. 256, 11747-11754); (iii) effect of elongation inhibitors on the translation of reoviral and cellular messages in SC-1 fibroblasts (Walden, W. E., Godefroy-Colburn, T., and Thach, R. E. (1981) J. Biol. Chem. 256, 11739-11746); and (iv) effect of the growth state on the initiation efficiency of Vero cell messages (Lee, G. T.-Y., and Engelhardt, D. L. (1979) J. Mol. biol. 129, 221-233). In each case we find that the experimental data are consistent with the notion that mRNAs compete for a discriminatory factor independent of the ribosome. This factor has a high enough affinity for mRNAs to ensure nearly quantitative binding. When present in a limiting amount (with respect to the message pool but not necessarily with respect to the rest of the translation apparatus), the discriminatory factor selects against those messages for which its affinity is lowest, thereby modulating their initiation efficiency. When the factor is present in excess, on the other hand, all the messages are translated at maximum efficiency. This form of translational control could be remarkably efficient as an on-off switch for the synthesis of a few key proteins.

Animals↗
PubMed1991

An approach to optimal dialysis using urea kinetic modeling.

Urea kinetic modeling (UKM) was carried out to evaluate the water control in patients undergoing long-term hemodialysis. In 21 patients on chronic dialysis, the results of two different determinations of the total body water, i.e. by the deuterium oxide (D2O) method and by UKM, were compared. A correlation was observed with Y = 0.98X + 5.9 (P less than 0.01, r = 0.91) for males and Y = 0.97X + 6.2 (P less than 0.01, r = 0.90) for females, indicating that UKM is useful for determining the total body water. In addition, the 21 patients were classified into two groups based on their ECG findings, and UKM was performed in the two groups for comparison. The values of the total body water were 68.5 +/- 4.0% and 68.6 +/- 6.2% of body weight, respectively, with no significant difference between them. However, the CTR was 50.2 +/- 2.8% and 46.2 +/- 4.4%, respectively. Thus, not only X-ray examinations but also UKM should be carried out to determine the standard weight (SW-DW) in the presence of cardiac dysfunction. Instructions for water control were given when the total body water exceeded 73% during the UKM measurements over 5 years, which allowed an optimal total body water to be maintained thereafter. The possible influence of erythropoietin (EPO) was also examined by performing UKM in 8 cases receiving EPO and 7 cases without EPO. No noticeable difference was observed between the two groups. 17 patients using a polyacrylonitrile (PAN) membrane were further divided into those with and those without EPO to evaluate the possible influence of the PAN membrane-EPO combination. As a result, no significant difference was demonstrated, suggesting that UKM can be satisfactorily performed under such conditions. In 11 patients on chronic dialysis, the levels of alpha-human atrial natriuretic peptide (alpha-hANP) were measured pre- and post-dialysis to examine the relationship between the change in alpha-hANP and rate of weight loss (%). A significant correlation was observed with Y = 12.8X + 5.1 (P less than 0.05, r = 0.68). In conclusion, UKM was found to be useful for evaluating the water control and for assessing the optimal dialysis in patients receiving long-term hemodialysis.

Acrylic Resins↗
PubMed2002

Monte Carlo model of nonlinear chromatography: correspondence between the microscopic stochastic model and the macroscopic Thomas kinetic model.

The Monte Carlo model of chromatography is a description of the chromatographic process from a molecular (microscopic) point of view and it is intrinsically based on the stochastic theory of chromatography originally proposed by Giddings and Eyring. The program was previously validated at infinite dilution (i.e., in linear conditions) by some of the authors of the present paper. In this work, it has been further validated under nonlinear conditions. The correspondence between the Monte Carlo model and the well-known Thomas kinetic model (macroscopic model), for which closed-form solutions are available, is demonstrated by comparing Monte Carlo simulations, performed at different loading factors, with the numerical solutions of the Thomas model calculated under the same conditions. In all the cases investigated, the agreement between Monte Carlo simulations and Thomas model results is very satisfactory. Additionally, the exact correspondence between the Thomas kinetic model and Giddings model, when near-infinite dilution conditions are approached, has been demonstrated by calculating the limit of the Thomas model when the loading factor goes to zero. The model was also validated under limit conditions, corresponding to cases of very slow adsorption-desorption kinetics or very short columns. Different hypotheses about the statistical distributions of the random variables "residence time spent by the molecule in mobile and stationary phase' are investigated with the aim to explain their effect on the peak shape and on the efficiency of the separation.

Journal Article↗
PubMed2002

Positron emission tomography compartmental models: a basis pursuit strategy for kinetic modeling.

A kinetic modeling approach for the quantification of in vivo tracer studies with dynamic positron emission tomography (PET) is presented. The approach is based on a general compartmental description of the tracer's fate in vivo and determines a parsimonious model consistent with the measured data. The technique involves the determination of a sparse selection of kinetic basis functions from an overcomplete dictionary using the method of basis pursuit denoising. This enables the characterization of the systems impulse response function from which values of the systems macro parameters can be estimated. These parameter estimates can be obtained from a region of interest analysis or as parametric images from a voxel-based analysis. In addition, model order estimates are returned that correspond to the number of compartments in the estimated compartmental model. Validation studies evaluate the methods performance against two preexisting data led techniques, namely, graphical analysis and spectral analysis. Application of this technique to measured PET data is demonstrated using [11C]diprenorphine (opiate receptor) and [11C]WAY-100635 (5-HT1A receptor). Although the method is presented in the context of PET neuroreceptor binding studies, it has general applicability to the quantification of PET/SPECT radiotracer studies in neurology, oncology, and cardiology.

Artifacts↗
PubMed1998

Kinetic modeling of omega-transamination for enzymatic kinetic resolution of alpha-methylbenzylamine.

A kinetic model for omega-transaminase from Bacillus thuringiensis JS64 was developed by using the King-Altman method to simulate the kinetic resolution of alpha-methylbenzylamine (alpha-MBA). Starting from a ping-pong bi-bi mechanism, a complete kinetic model including substrate inhibition only in the reverse reaction (i.e., transamination between acetophenone and L-alanine) was developed. The asymmetric synthesis of (S)-alpha-MBA proved to be difficult due to a much lower maximum reverse reaction rate than the maximum forward reaction rate, thermodynamically exergonic forward reaction (i.e., transamination between (S)-alpha-MBA and pyruvate), and the severe product and substrate inhibition of the reverse reaction. Experimental values for kinetic parameters show that the product inhibition constant of (S)-alpha-MBA is the most important parameter on determining the resolution reaction rate, suggesting that the resolution reaction rate will be very low unless (S)-alpha-MBA strongly inhibits the reverse reaction. Using the kinetic model, the kinetic resolution of alpha-MBA in aqueous buffer was simulated, and the simulation results showed a high degree of consistency with experimental data over a range of reaction conditions. Various simulation results suggest that the crucial bottleneck in the kinetic resolution of alpha-MBA lies mainly in the accumulation of acetophenone in reaction media as the reaction proceeds, whereas L-alanine exerts a little inhibitory effect on the reaction. The model predicts that removing acetophenone produced during the reaction can enhance the reaction rate dramatically. Indeed, the biphasic reaction system is capable of extracting acetophenone from the aqueous phase, showing a much higher reaction rate compared to a monophasic reaction system. The kinetic model was also useful in predicting the properties of other, better enzymes as well as the optimal concentrations of amino acceptor and enzyme in the resolution reaction.

Acetophenones↗
PubMed1997

Requirements and implementation of a flexible kinetic modeling tool.

UNLABELLED: Kinetic (or compartment) modeling is a highly versatile tool for the analysis of experiments within living systems. In PET, it is essential for developing tracers, for assessing tracer behavior and for extracting quantitative information about the target process. However, tools to support the modeling tasks involved are not easily available. METHODS: This article presents a requirements analysis for kinetic modeling in PET. The interactive kinetic modeling tool KMZ implements many of these features. It facilitates model development by a set of predefined models and by the ease of introducing new models. Monte Carlo studies allow assessing parameter identifiability. The responses in the different compartments as well as the expected time-activity curve can be simulated for specific model configurations. For measured time-activity curves, model optimization can be performed by the Powell or the Marquardt algorithm. Both support weighted nonlinear least-squares fitting and allow optional constraints of parameter ranges. To further improve parameter estimation, the fitting of several regional time-activity curves can be coupled, resulting in lower standard errors for parameters common among regions. It is possible to highly automate the evaluation of study series and to forward the results into statistical analysis tools. RESULTS: The KMZ tool has proven highly suitable in evaluating data from different types of studies, and the intuitive user interface enables medical doctors to successfully perform routine evaluations after a short training period. CONCLUSION: A portable kinetic modeling tool with the described features would provide easy access to model development and may help consolidate kinetic modeling in clinical settings for well-defined applications.

Algorithms↗
PubMed1983

CELLSIM and CELLGROW: tools for cell kinetic modeling.

Cell kinetics relates to the movement and proliferation of cells through their generative cycle and to how this cycle is affected by drugs, radiation, and other types of treatment. Two stochastic simulation systems have been developed to model this behavior.

Antineoplastic Agents↗
PubMed1999

Modeling cellobiose hydrolysis with integrated kinetic models.

The enzyme cellobiase Novozym 188, which is used for improving hydrolysis of bagasse with cellulase, was characterized in its commercial available form and integrated kinetic models were applied to the hydrolysis of cellobiose. The specific activity of this enzyme was determined for pH values from 3.0-7.0, and temperatures from 40-75 degrees C, with cellobiose at 2 g/L. Thermal stability was measured at pH 4.8 and temperatures from 40-70 degrees C. Substrate inhibition was studied at the same pH, 50 degrees C, and cellobiose concentrations from 0.4-20 g/L. Product inhibition was determined at 50 degrees C, pH 4.8, cellobiose concentrations of 2 and 20 g/L, and initial glucose concentration nearly zero or 1.8 g/L. The enzyme has shown the greatest specific activity, 17.8 U/mg, at pH 4.5 and 65 degrees C. Thermal activation of the enzyme followed Arrhenius equation with the Energy of Activation being equal to 11 kcal/mol for pH values 4 and 5. Thermal deactivation was adequately modeled by the exponential decay model with Energy of Deactivation giving 81.6 kcal/mol. Kinetics parameters for substrate uncompetitive inhibition were: Km = 2.42 mM, Vmax = 16.31 U/mg, Ks = 54.2 mM. Substrate inhibition was clearly observed above 10 mM cellobiose. Product inhibition at the concentration studied has usually doubled the time necessary to reach the same conversion at the lower temperature tested.

Journal Article↗
PubMed1995

Creatinine kinetic modelling: a simple and reliable tool for the assessment of protein nutritional status in haemodialysis patients.

While the mathematical modelling of urea kinetics is in wide use for evaluating treatment adequacy and protein nutrition in dialysis patients, the kinetics of creatinine generation in dialysis patients has been relatively unexplored. In this study creatinine kinetic modelling as a clinical tool was investigated in a group of 90 patients treated by haemodialysis (n = 20), haemodiafiltration (60), haemofiltration (7), or biofiltration (3) over a 6-36-month period. A single pool model of creatinine kinetics was employed to obtain monthly values of creatinine distribution space and creatinine appearance rate. Extrarenal creatinine degradation rate, estimated using a clearance of 0.038 l/kg/24 h as suggested by Mitch and co-workers, was added to creatinine appearance rate in urine and dialysate to calculate a corrected creatinine index (CI). Extrarenal degradation accounted for 12 +/- 2% of CI. CI was higher in males (22.4 +/- 4.5 mg/kg/24 h) than females (19.8 +/- 4.8) and decreased with age, falling off more sharply for the female group (CI = 29.9-0.185.age, R = 0.72) than the males (CI = 24.1-0.030.age, R = 0.31). CI was found to correlate strongly with protein catabolic rate determined by urea kinetic modelling (CI = 8.84 +/- 10.91.PCR). Low or reduced CI was associated in this study group with severe malnutrition status and high mortality rate. CI is suggested as a strong predictor of patient morbidity and mortality.

Creatinine↗
PubMed1980

Distribution of subcutaneous thyroxine, triiodothyronine, and albumin in man: comparison with intravenous administration using a kinetic model.

Distributional kinetics of radioiodinated T4 (T4), T3 (T3), and albumin (RISA), after simultaneous administration by the sc and iv routes of 125I- and 131I-labeled compounds, were measured in normal subjects. Data were analyzed by fitting them, using the SAAM technique, to models with three compartments for the iv administered compounds and a fourth compartment for the site of the sc injection. The radiopharmaceuticals administered sc transfered by first order kinetics from the injection site to plasma with half-lives of 20.4, 5.6, and 63.0 h for T4, T3, and RISA, respectively. Percentages of 3.3, 1.2, and 2.1 of the sc dose appeared directly in the vascular compartment. In some, but not all, studies with sc T4 and RISA, a portion of the disappearance from the sc site appeared to be due to in situ deiodination, rather than to transfer of the parent compound into the circulation. After T3 administration, both iv and sc, a product with kinetics similar to RISA appeared, accounting for 3% of the T3 decay for the averaged data and ranging from 0.9--19.4% in individual cases. Comparing T3 kinetic analysis by this technique (in which the iodoprotein byproduct is accounted for by modeling instead of chemical separation), the resulting parameters are similar to those reported by others after chemical separation of T3. Judging by compartment size and distributional kinetics, the model compartments derived for iv administration of these compounds appear to represent the vascular pool (central compartment), the hepatic and renal distribution sites (fast peripheral compartment), and other peripheral tissues (slow peripheral compartment). The latter, which presumably includes the site of sc injection, transfers into the central compartment at approximately the same rate as does the compartment representing the sc injection site itself.

Adult↗
PubMed1996

Radical-initiated lipid peroxidation in low density lipoproteins: insights obtained from kinetic modeling.

We present kinetic models of various complexity for radical-initiated lipid peroxidation in low density lipoproteins (LDL). The models, comprised of simultaneous differential equations programmed in Mathematica, were used to evaluate the concentration profiles of the reactants of interest. Single-phase reaction schemes describing lipid peroxidation and antioxidation according to the "conventional" and tocopherol-mediated peroxidation (TMP) model were simulated for conditions of low and high radical fluxes produced by thermolabile azo initiators. The results show that the particular dependencies of the rates of lipid peroxidation (Rp) on the rates of initiation (Ri) for the two reaction schemes were accurately predicted by the simulations. Both models qualitatively predicted inhibition of lipid peroxidation in the presence of alpha-tocopherol (alpha-TOH) under high radical flux conditions, suggesting that both can describe inhibited lipid peroxidation in solution under these conditions. TMP, but not the conventional model, could also predict the experimentally observed complex behavior of LDL lipid peroxidation induced with different concentrations of azo initiators. Specifically, TMP faithfully reproduced the observed kinetic chain length of lipid peroxidation of > > 1 at low and < < 1 at high concentration of the initiator (i.e., 0.2 and 10 mM, respectively for LDL at 1 mumol apoB-100/L) during the alpha-TOH-containing period of oxidation. It also demonstrated the experimentally observed nondependence of RpTMP on Ri. Kinetic analysis of radical generation and initiation of lipid peroxidation in an extended, two-compartment model of TMP showed that phase separation of bimolecular reactions in a suspension of LDL particles can lead to a approximately 400-fold increase in the rate of lipid hydroperoxide formation. The experimentally observed co-antioxidant action of water-soluble ascorbate and lipid-soluble ubiquinol-10 were verified using this model. A simple biophysical model constituting the reactions of TMP and incorporating the compartmental nature of an LDL suspension is proposed. Together, the results demonstrate that TMP is the only model that fits the experimental data describing the early stages of LDL lipid peroxidation under various oxidizing conditions. The implications of our findings are discussed in relation to atherogenesis and a recently proposed alternative model of LDL lipid peroxidation (Abuja and Esterbauer (1995) Chem. Res. Toxicol. 8, 753).

Antioxidants↗
PubMed2006

Further investigation of the mechanism of Doxorubicin release from P105 micelles using kinetic models.

The kinetics of the release of Doxorubicin from Pluronic P105 micelles during ultrasonication and its subsequent re-encapsulation upon cessation of insonation were investigated. Four mechanisms are proposed to explain the acoustically-triggered Doxorubicin (Dox) release and re-encapsulation from Pluronic P105 micelles. The four mechanisms are: micelle destruction; destruction of cavitating nuclei; reassembly of micelles, and the re-encapsulation of Dox. The first mechanism, the destruction of micelles during insonation, causes the release of Dox into solution. The micelles are destroyed because of cavitation events produced by collapsing nuclei, or bubbles in the insonated solution. The second mechanism, the slow destruction of cavitating nuclei, results in a slow partial recovery phase, when a small amount of Dox is re-encapsulated. The third and fourth mechanisms, the reassembly of micelles and the re-encapsulatin of Dox, are independent of ultrasound. These two mechanism are responsible for maintaining the drug release at a partial level, and for recovery after insonation ceases. A normal distribution was used to describe micellar size. Parameters for the model were determined based upon the best observed fit to experimental data. The resulting model provides a good approximation to experimental data for the release of Dox from Pluronic P105 micelles.

Doxorubicin↗
PubMed1991

Quantitating hemodialysis: a comparison of three kinetic models.

Three urea kinetic analyses were applied to hemodialysis and their conformity assessed. Sixteen patients underwent 50 measurements of dialyzer clearance (K), protein catabolic rate (PCR), and dialysis quantification (Kt/V) using the urea kinetic model (UKM) of Gotch and Sargent, Malchesky's direct dialysis quantification (DDQ), and the graphic technique of urea reduction analysis (URA) devised by Keshaviah. Additionally, the equations proposed by Jindal (percent urea reduction), and Daugirdas were used to calculate Kt/V values for each study. Dialyzer performance determined by whole blood urea clearance consistently exceeded simultaneous dialysate urea removal and was 55% greater than the clearance calculated by DDQ. Despite these variations, dialysis adequacy (Kt/V) and normalized protein catabolic rate (nPCR) were remarkably constant when derived by fixed-volume single-pool analyses (ie, UKM, DDQ, and URA). Application of variable-volume corrections increased Kt/V and nPCR, but caused DDQ values to diverge from those of UKM and URA. During rapid high-efficiency dialysis (RHED), the UKM predicted urea removal in excess of that documented by DDQ. During this trial (low-level RHED with K = 2.98 mL.kg-1 per min), urea dysequilibrium across blood-cell interfaces was sufficient to cause UKM to overestimate protein catabolism by 5%. The basic assumption of single-pool kinetics may be inappropriate during RHED, and further increases in dialyzer clearance will increase the discrepancy between projected and actual urea removal. Future comparisons of RHED prescriptions should employ mass balance data, or redesigned kinetic analyses.

Blood Urea Nitrogen↗
PubMed1989

Transient response of retinal rod outer segment phosphodiesterase to actinic light pulses. I. Simple quantitative kinetic model.

We present a quantitative kinetic model for the transient velocity (microM of cGMP hydrolyzed/s) response of retinal rod outer segment (ROS) cGMP phosphodiesterase (v(t) versus t) to a stimulating light pulse in the linear response range. The model gives an excellent fit to experimental v(t) versus t data for ROS suspensions at different concentrations of GTP and GDP and clarifies experimental results which are difficult to understand in the absence of such a model. It contains the minimum number of steps required to fit our experimental data and consists of one rate-limiting step with specific rate kL for the production of active phosphodiesterase (PDE), PDE*, by photoactivated rhodopsin, R*, and deactivation processes for R* and PDE* with lifetimes tau R and tau P, respectively. The experimental graphs of v(t) versus t at each concentration of GTP and GDP are characterized by a fast rise to a peak value, vpeak, followed by a slow decay to zero level. The minimal kinetic model allows us to characterized completely the effects of GTP and GDP, and any other pertinent species, in terms of their effects on the parameters kL, tau R, and tau P. Our kinetic model indicates that for "washed" ROS preparations (a) the risetime of v(t) is determined by tau P which has a value of about 2 s and is insensitive to [GTP]. (b) The decay of v(t) is determined by tau R which decreases with [GTP] and has a value greater than 300 s at low [GTP] and a limiting value of 50 s at high [GTP]. We attribute the greater than 300 s lifetime to the complex R*G (where G is ROS G protein) and the 50-s lifetime to free R*. (c) The rate kL increases hyperbolically with [GTP] with a half-maximal value of 56 microM and kL.max = 22-45 s-1. (d) Peak velocity is given by the expression vpeak alpha kL tau P which is consistent with the dependence of kL on [GTP] and the experimental finding that vpeak varies hyperbolically with [GTP]. The minimal model has also allowed us to (a) develop clear definitions of amplification for the light-triggered enzymatic cascade and (b) clarify experimental methods for measuring gain.(ABSTRACT TRUNCATED AT 400 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Pharmacokinetic and pharmacodynamic parameters for antimicrobial effects of cefotaxime and amoxicillin in an in vitro kinetic model.

An in vitro kinetic model was used to study the relation between pharmacokinetic and pharmacodynamic (PK-PD) parameters for antimicrobial effect, e.g., the time above MIC (T>MIC), maximum concentration in serum (C(max)), and area under the concentration-time curve (AUC). Streptococcus pyogenes and Escherichia coli were exposed to cefotaxime, and the activity of amoxicillin against four strains of Streptococcus pneumoniae with different susceptibilities to penicillin was studied. The drug elimination rate varied so that the T>MIC ranged from 20 to 100% during 24 h, while the AUC and/or the initial concentration (C(max)) were kept constant. For S. pyogenes and E. coli, the maximal antimicrobial effect (E(max)) at 24 h occurred when the antimicrobial concentration exceeded the MIC for 50 and 80% of the strains tested, respectively. The penicillin-susceptible pneumococci (MIC, 0.03 mg/liter) and the penicillin-intermediate strain (MIC, 0.25 mg/liter) showed maximal killing by amoxicillin at a T>MIC of 50%. For a strain for which the MIC was 2 mg/liter, C(max) needed to be increased to achieve the E(max). Under the condition that C(max) was 10 times the MIC, E(max) was obtained at a T>MIC of 60%, indicating that C(max), in addition to T>MIC, may be an important parameter for antimicrobial effect on moderately penicillin-resistant pneumococci. For the strain for which the MIC was 4 mg/liter, the reduction of bacteria varied from -0.4 to -3.6 log(10) CFU/ml at a T>MIC of 100%, despite an initial antimicrobial concentration of 10 times the MIC. Our studies have shown that the in vitro kinetic model is a useful complement to animal models for studying the PK-PD relationship for antimicrobial effect of antibiotics.

Amoxicillin↗
PubMed2000

Tendency modeling: a new approach to obtain simplified kinetic models of metabolism applied to Saccharomyces cerevisiae.

A novel approach to construct kinetic models of metabolic pathways, to be used in metabolic engineering, is presented: the tendency modeling approach. This approach greatly facilitates the construction of these models and can easily be applied to complex metabolic networks. The resulting models contain a minimal number of parameters; identification of their values is straightforward. Use of in vitro obtained information in the identification of the kinetic equations is minimized. The tendency modeling approach has been used to derive a dynamic model of primary metabolism for aerobic growth of Saccharomyces cerevisiae on glucose, in which compartmentation is included. Simulation results obtained with the derived model are satisfying for most of the carbon metabolites that have been measured. Compared to a more detailed model, the simulations of our model are less accurate, but taking into account the much smaller number of kinetic parameters (35 instead of 84), the tendency the modeling approach is considered promising.

Biomedical Engineering↗
PubMed1995

Dialysate-based kinetic modeling.

The focus of this review article is urea kinetic modeling based on the exploitation of concentration measurements in the spent dialysate stream. After a review of blood-based urea kinetic modeling, dialysate-based techniques are considered, beginning with dialysate collection techniques and their associated urea kinetic modeling equations. Partial dialysate collection methods and equations for the determination of protein catabolic rate based on a 7-day mass balance period are explored next. This is followed by a description of urea sensors and their application for dialysate-based modeling including the determination of protein catabolic rate, predialysis blood urea nitrogen (BUN), and KT/V. How the output of a urea sensor may allow the detection of significant changes in patient clearance during the course of dialysis is illustrated, as well as how double-pool urea kinetics may be accounted for in KT/V determination. Routine determination of patient lean body mass using creatinine kinetic modeling based on partial dialysate collection or a dialysate-based creatinine concentration sensor is demonstrated. Finally, the potential for complete automation of urea kinetic modeling in dialysis machines of the future is explored.

Blood Urea Nitrogen↗