Analysis of the Dialysis Dose in Different Clinical Situations: A Simulation-Based Approach

VALTUILLE, RODOLFO; SZTEJNBERG , MANUEL; FERNÁNDEZ, ELMER ANDRÉS

Hemodialysis

InTech

Año: 2013; p. 359 - 380

End Stage Renal Disease (ESRD) is an important public health concern around the globe. It is associated with high morbidity and mortality being Hemodialysis (HD) the main applied therapy. [1] A recent study (HEMO study) could not show any decrease in the morbidity and/or mortality associated with increases in the dose -expressed as equilibrated Kt/V (eqKt/V)- and/or the flow (comparing high versus low flux, where high flux is defined as a Kt/V of Beta 2 microglobulin (B2M) ≥ 20 ml/min) when utilizing the three-times-a-week (3-times/wk HD) schedule therapy. [2] This led to development of several HD schedules proposals based on the variation of the session time duration (TD) as well as on its weekly frequency (Fr). However, more frequent HD schedules require new indexes to measure the delivered dose. In this context, the Equivalent Renal Clearence (EKR) [Casino y López] [3] and Standard Kt/V (stdKt/V) [Gotch] [4] indexes have been proposed to quantify the dialysis dose for different HD frequency schedules. The EKR concept equalizes the time-averaged concentration (TAC) of Urea (U) for different therapies which is then normalized by U distribution Volume. Gotch has proposed that the weekly dialysis dose (WDD) is better expressed as standardized kt-V (stdKt/V) when dialysis is more frequent than 3-times/wk. Standard Kt/V combines treatment dose and frequency allowing comparison of intermittent (HD, High flux HD, Hemofiltration, etc) and continuous (Continuous Ambulatory Peritoneal Dialysis) therapies; the formula is expressed as U generation rate (G) rate divided by the average peak concentration. [4] EqKt/V is the true dialysis dose per session occurring when U rebound (R), which is related to compartments and flow disequilibrium produced during HD treatment, is completed 30-60 minutes after the end of the HD session. The determination of eqKt/V requires the measurement or the ?prediction? of the true Eq U because the value of sp (single pool)Kt/V - a dimensionless ratio which includes Clearence of dialyzer (K), duration of treatment (TD) and volume of total water of the patient (V) - is greater than the Kt/V achieved in the patient which is calculated using the immediate postHD blood U concentration. In the last decade, several formulas were developed to predict eq Kt/V trying to avoid the extraction of an additional blood sample. The Daugirdas and Schneditz ?rate formula? is the most popular and validated equation and it is based in the prediction of eqKt/V as a linear function of spKt/V and the rate of dialysis (K/V). [5] An alternative and robust formula, based in the double pool analysis by Smye, [6] is the equation of Tattersall where he described a soluble time constant: the patient equilibration time (tp). [7] The majority of these formulas of prediction have been validated in the 3-times/wk HD schedules. New formulas to predict eq Kt/V have been recently published. Examples include the eqKt/V formula based on observations of the HEMO [8] study and two others developed by Leypoldt (based on blood sample analysis during hemofiltration and short and daily HD) [9]. The high accuracy of the extracellular U concentration evolution during and after (UR) an HD session by double pool U kinetic model has been verified in several studies. [10] Access and cardio-pulmonary recirculation can both influence the UR, but the effect occurs in the first minutes after the end of HD and is considered to be mild. [10] Several factors other than clearance of U might play a role in morbidity and mortality of hemodialyzed patients. One of them, recently revised, is the role of the ?denominator? to normalize the Kt. The results derived from the HEMO study showed that Kt/V failed to explain the paradoxical outcomes related to size (underweight versus obese patients) and gender. This factor was considered in the Frequent Hemodialysis Network (FHN) study which is currently underway. The investigators included the body surface area (BSA) as a potential tool for a better normalization of Kt and to allow more appropriate comparison among different HD populations. [11] Since 1980 the idea of emulating reality in a computer environment by simulation rapidly spread among biomedical researchers, being accepted as one of the most powerful tools both for understanding phenomenological aspects of a chosen physics or physiological complex and for predicting functional or operative conditions of technological systems. The main concept of this approach relies in numerically solving a mathematical model that governs a chosen physical system, whose the analytical solution is not known or potentially dangerous to reach for a specific application. In spite of many efforts spent in the past for formulating accurate and robust algorithms for solving mathematical models, the effectiveness of that approach heavily dependent on computational resources. This led to only recent widespread use of simulation strategy both scientific and medical problems [12]. A variable volume double-compartment (VVDC) kinetic model can reflect the behavior of different molecules and can be used as a mirror to analyze the profile in vivo by taking blood samples during the HD procedure. [13] In this scenario, the computational simulation including all the variables which affect the dialysis procedure can be a safe and useful tool to mimic many treatment schemes to help improve our knowledge of the dialysis therapy. [14] The aim of this study is to utilize a variable volume double-compartment (VVDC) kinetic model to simulate: Several clinical situations that allow comparison between the true eqKt/V and all the developed predictors, including the effect of increasing the TD and Fr. Changes in Kt/V, EKR and stdKt/V related to changes in TD and Fr. Comparison between using V with BSA to normalize K