In silico comparison of protein-bound uremic toxin removal by hemodialysis, hemodiafiltration, membrane adsorption, and binding competition.

Protein-bound uremic toxins (PBUTs) are poorly removed during hemodialysis (HD) due to their low free (dialyzable) plasma concentration. We compared PBUT removal between HD, hemodiafiltration (HDF), membrane adsorption, and PBUT displacement in HD. The latter involves infusing a binding competitor pre-dialyzer, which competes with PBUTs for their albumin binding sites and increases their free fraction.

A model of vascular refilling with inflammation.

Inflammation is prevalent in hemodialysis patients and is believed to significantly contribute to cardiovascular disease progression in end stage renal disease patients undergoing hemodialysis. Increased vascular permeability associated with inflammation is likely to influence the capillary wall properties, affecting vascular refilling during hemodialysis. In this paper, we present a model that incorporates inflammation into a vascular refilling model.

Prediction of hemoglobin levels in individual hemodialysis patients by means of a mathematical model of erythropoiesis.

Anemia commonly occurs in people with chronic kidney disease (CKD) and is associated with poor clinical outcomes. The management of patients with anemia in CKD is challenging, due to its severity, frequent hypo-responsiveness to treatment with erythropoiesis stimulating agents (ESA) and common hemoglobin cycling. Nonlinear dose-response curves and long delays in the effect of treatment on red blood cell population size complicate predictions of hemoglobin (Hgb) levels in individual patients.

The Virtual Anemia Trial: An Assessment of Model-Based In Silico Clinical Trials of Anemia Treatment Algorithms in Patients With Hemodialysis.

In silico approaches have been proposed as a novel strategy to increase the repertoire of clinical trial designs. Realistic simulations of clinical trials can provide valuable information regarding safety and limitations of treatment protocols and have been shown to assist in the cost-effective planning of clinical studies. In this report, we present a blueprint for the stepwise integration of internal, external, and ecological validity considerations in virtual clinical trials (VCTs).

A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis.

Protein-bound uremic toxins (PBUTs) are difficult to remove by conventional hemodialysis; a high degree of protein binding reduces the free fraction of toxins and decreases their diffusion across dialyzer membranes. Mechanistic understanding of PBUT kinetics can open new avenues to improve their dialytic removal. We developed a comprehensive model of PBUT kinetics that comprises: (1) a three-compartment patient model, (2) a dialyzer model.

Control aspects of the human cardiovascular-respiratory system under a nonconstant workload.

The human cardiovascular system (CVS) and respiratory system (RS) work together in order to supply oxygen (O) and other substrates needed for metabolism and to remove carbon dioxide (CO). Global and local control mechanisms act on the CVS in order to adjust blood flow to the different parts of the body. This, in turn, affects the RS since the amount of O and CO transported, respectively to and away from the tissues depends on the cardiac output and blood flow in both the systemic and pulmonary circuits of the CVS.

Intradialytic Hypoxemia and Clinical Outcomes in Patients on Hemodialysis.

Background And Objectives: Intradialytic hypoxemia has been recognized for decades, but its associations with outcomes have not yet been assessed in a large patient cohort.

Design, Setting, Participants, & Measurements: Our retrospective cohort study was conducted between January of 2012 and January of 2015. We recorded blood oxygen saturation every minute during hemodialysis in patients with arteriovenous access.

Estimation of arterio-venous access blood flow in hemodialysis patients using video image processing technique.

Assessment of arterio-venous fistula (AVF) blood flow (ABF) is vital in hemodialysis (HD) patients. Currently, no non-invasive and contact-free technique is available to accurately measure ABF in routine clinical practice. In this study, we developed a novel approach using video image processing (VIP) to measure the change in optic flow in the skin.

A physiologically based model of vascular refilling during ultrafiltration in hemodialysis.

An assessment of fluid status can be obtained by monitoring relative blood volume (RBV) during hemodialysis (HD) treatment. The dynamics of RBV is determined by fluid removal from the intravascular compartment by ultrafiltration (UF) and vascular refill from the interstitium. To characterize this dynamics, a two-compartment model describing the short-term dynamics of vascular refilling and UF is developed.

Accelerated or out of control: the final months on dialysis.

Mortality rates in dialysis patients are as high as 20% per year. Recent epidemiologic evidence indicates common patterns in biological and clinical indicators before death. Blood pressure, serum albumin levels, C-reactive protein, body weight, and other indicators change, at a population level, at an accelerated rate of change months before death.

Stabilizing control for a pulsatile cardiovascular mathematical model.

In this paper, we develop a pulsatile model for the cardiovascular system which describes the reaction of this system to a submaximal constant workload imposed on a person at a bicycle ergometer test after a period of rest. Furthermore, the model should allow to use measurements for the pulsatile pressure in fingertips which provide information on the diastolic and the systolic pressure for parameter estimation. Based on the assumption that the baroreceptor loop is the essential control loop in this case, we design a stabilizing feedback control for the pulsatile model which is obtained by solving a linear-quadratic regulator problem for the linearization of a non-pulsatile counterpart of the pulsatile model.

Modeling of change in blood volume and extracellular fluid volume during hemodialysis.

Knowledge of dynamics of shift of fluid volume between intra- and extravascular compartments during hemodialysis (HD) is important for managing HD treatment to help patients approach dry weight without hypotension. The Relative blood volume (RBV) monitor indicates change in plasma volume based on the difference between ultrafiltration rate (UFR) and plasma refilling rate (PRR) during HD. However, the absolute value of PRR cannot be obtained from RBV.

Absolute blood volume in hemodialysis patients: why is it relevant, and how to measure it?

Intradialytic hypotension (IDH) is the most common complication during hemodialysis and is associated with significant morbidity. It occurs as a consequence of a reduction in blood volume during ultrafiltration. Today, devices for monitoring relative blood volume (i.

Bridging different perspectives of the physiological and mathematical disciplines.

The goal of this report is to discuss educational approaches for bridging the different perspectives of the physiological and mathematical disciplines. These approaches can enhance the learning experience for physiology, medical, and mathematics students and simultaneously act to stimulate mathematical/physiological/clinical interdisciplinary research. While physiology education incorporates mathematics, via equations and formulas, it does not typically provide a foundation for interdisciplinary research linking mathematics and physiology.

A model of erythropoiesis in adults with sufficient iron availability.

In this paper we present a model for erythropoiesis under the basic assumption that sufficient iron availability is guaranteed. An extension of the model including a sub-model for the iron dynamics in the body is topic of present research efforts. The model gives excellent results for a number of important situations: recovery of the red blood cell mass after blood donation, adaptation of the number of red blood cells to changes in the altitude of residence and, most important, the reaction of the body to different administration regimens of erythropoiesis stimulating agents, as for instance in the case of pre-surgical administration of Epoetin-α.

Time delay in physiological systems: analyzing and modeling its impact.

This article examines the functional and clinical impact of time delays that arise in human physiological systems, especially control systems. An overview of the mathematical and physiological contexts for considering time delays will be illustrated, from the system level to cell level, by examining models that incorporate time delays. This examination will highlight how such delays in combination with other system structures and parameters influence system dynamics.

Comparison of Optimal Design Methods in Inverse Problems.

Typical optimal design methods for inverse or parameter estimation problems are designed to choose optimal sampling distributions through minimization of a specific cost function related to the resulting error in parameter estimates. It is hoped that the inverse problem will produce parameter estimates with increased accuracy using data collected according to the optimal sampling distribution. Here we formulate the classical optimal design problem in the context of general optimization problems over distributions of sampling times.

Patterns of cardiovascular control during repeated tests of orthostatic loading.

To investigate patterns of cardiovascular control, a protocol of head up tilt (HUT) followed by lower body negative pressure (LBNP), which represents a significant cardiovascular control challenge, was employed. Linear regression of beat-to-beat heart rate (HR) and mean blood pressure (MBP) data collected over repeated tests was used to analyze control response during the LBNP phase of the combined HUT + LBNP protocol. Four runs for each of 10 healthy young males reaching presyncope were analyzed.

Introduction to the special issues: Short-term cardiovascular-respiratory control mechanisms.

This and the following issue of Cardiovascular Engineering are special issues reflecting research discussed during an interdisciplinary focused workshop entitled The workshop was organized by Mette Olufsen and Hien Tran at the Department of Mathematics at North Carolina State University, Jerry Batzel and Franz Kappel at the Institute for Mathematics and Scientific Computing, University of Graz, and Vera Novak at the Department of Gerontology at Harvard Medical School, and hosted by the American Institute of Mathematics (AIM), Palo Alto, California, October 9–13, 2006. The workshop was co-sponsored by AIM and the National Science Foundation.

Receding horizon controller for the baroreceptor loop in a model for the cardiovascular system.

In this article, we discuss the design and implementation of a receding horizon control (RHC) which will be used to represent the control for the baroreceptor loop in the human cardiovascular system (CVS). This control will be applied to a model of the CVS developed in a previous work by Kappel and Peer. In that earlier work, a linear quadratic control strategy (LQR) was implemented to represent this baroreflex control which was designed to stabilize the system under an ergometric workload.

Sensitivity analysis of a model of the cardiovascular system.

In this paper we consider the sensitivity analysis of a model of the cardiovascular system (CVS) simulating the transition to aerobic exercise and where the control for the system is implemented via an optimal control. Classical and generalized sensitivity analysis are discussed and compared and their application to the CVS model is analyzed.

Aspects of control of the cardiovascular-respiratory system during orthostatic stress induced by lower body negative pressure.

This paper considers a model developed to study the cardiovascular control system response to orthostatic stress as induced by two variations of lower body negative pressure (LBNP) experiments. This modeling approach has been previously applied to study control responses to transition from rest to aerobic exercise, to transition to non-REM sleep and to orthostatic stress as produced by the head up tilt (HUT) experiment. LBNP induces a blood volume shift because negative pressure changes the volume loading characteristics of the compartment which is subject to the negative pressure.

A cardiovascular-respiratory control system model including state delay with application to congestive heart failure in humans.

This paper considers a model of the human cardiovascular-respiratory control system with one and two transport delays in the state equations describing the respiratory system. The effectiveness of the control of the ventilation rate is influenced by such transport delays because blood gases must be transported a physical distance from the lungs to the sensory sites where these gases are measured. The short term cardiovascular control system does not involve such transport delays although delays do arise in other contexts such as the baroreflex loop (see [46]) for example.