Michael J. Lysaght

Kinetic modeling as a prescription aid in peritoneal dialysis

Methods for calculating fluid and mass removal in peritoneal dialysis are presented in order to aid clinicians in their care and management of patients and to assist them in their understanding of the physiological mechanisms which govern peritoneal transport. These methods are based on the Pyle-Popovich peritoneal mass transport model which encompasses both diffuse and convective transport as well as lymphatic flow and residual renal function. Algebraic solutions to the mass balance equations governing solute transport are provided. Since these solutions are expressed explicitly as functions of time, they are easily programmed for use on a personal computer or calculator. This offers considerable advantage over the more computer-intensive numerical solutions which had been previously required since one can now calculate both mass removal and changes in blood concentration at the end of an exchange without requiring any intermediate calculations. This computational advantage and the ability to model changes in blood concentration are shown to be of particular importance when modeling more dynamic therapies such as CCPD or Tidal peritoneal dialysis. Finally, the model and solutions, when assessed clinically among 5 patients on two separate occasions, resulted in predicted fluid and mass removals which were in high concordance with measured fluid and mass removals (concordance correlation coefficients in excess of 0.97). Our findings suggest that kinetic modeling can provide the kind of analytical tools necessary to guide clinicians in their care and management of peritoneal dialysis patients.

Demographic scope and economic magnitude of contemporary organ replacement therapies.

This analysis draws upon a variety of sources to provide a tally of the number of patients receiving organ replacement therapies and the costs associated with the provision of such therapies. Constituent data were available from treatment-specific patient registries, peer reviewed reports in scientific literature, business publications, and industry sources. The magnitude and economic scope of the contemporary organ replacement enterprise were found to be much larger than is generally recognized. In the year 2000, the lives of over 20 million patients will be sustained, supported, or significantly improved by functional organ replacement. The impacted population grows at over 10% per year. Worldwide, first year and follow-up costs of organ prosthesis exceeds

Membrane phenomena and mass transfer kinetics in peritoneal dialysis

300 billion US dollars per year and represents between 7 and 8% of total worldwide health care spending. Remarkably, in the United States, the costs of therapies enabled by organ replacement technology exceed 1% of the Gross Domestic Product. These findings constitute an incontestable tribute to the scientific significance and medical impact of the still nascent field of substitutive medicine. At the same time, the enormous magnitude of resources dedicated to organ replacement raises several issues related to overall cost effectiveness of current modalities and raises challenges and opportunities for future technical developments.

Filtration Rates and Pressure Driving Force in AV Filtration

Abstract Continuous ambulatory peritoneal dialysis (CAPD) is a process for the treatment of chronic renal failure in which metabolic waste products and excess body water are removed through the peritoneum, an intricate membrane-like tissue that lines the internal abdominal walls and covers the liver, intestine and other internal organs. As the newest of the widely-utilized modalities for chronic renal disease, CAPD is the most rapidly growing and, in many respects, the most subtle and poorly understood treatment. The peritoneum is not a simple barrier between two phases but rather a heterogeneous mucopolysaccharide hydrogel containing a labyrinthine vasculature through which blood flows as it equilibrates with a stagnant pool of dialysate residing within the peritoneal cavity. Despite the complexity of this transport medium, investigators have found it not only possible but quite useful to characterize the peritoneum in terms analogous to the mass transfer properties of a planar membrane separating well-mixed pools of blood and dialysate. This review begins with a summary of peritoneal dialysis and its contemporary role in the treatment of kidney failure. Measurements of equivalent peritoneal hydraulic permeability and of sieving coefficients and diffusive permeabilities as functions of molecular weight are subsequently tabulated from the literature and compared and contrasted to similar values for hemodialysis membranes. In addition, several published kinetic models, both analytical and numerical, which use a knowledge of peritoneal barrier properties and baseline clinical parameters for predicting rates of toxin and fluid removal during CAPD, are described and critically evaluated.

In vitro characterization of TGF-beta1 release from genetically modified fibroblasts in Ca(2+)-alginate microcapsules.

The whole blood filtration rate of hemofilters were measured in in vitro circuits simulating the pressure and flow conditions of arteriovenous filtration. For all devices tested, filtration rate was f

The Stability and Kinetics of Peritoneal Mass Transfer

This study was undertaken to develop an in situ source of transforming growth factor-β1 (TGF-β1), one of several molecules potentially useful for a tissue-engineered bioartificial cartilage. Primary human fibroblasts and murine NIH 3T3 cells were genetically modified via viral transfection to express human TGF-β1. Two viral constructs were used, one expressing a gene encoding for the latent and the other for the constitutively active form of the growth factor. Unmodified cells served as controls. Four genetically modified cohorts and two controls were separately encapsulated in a 1.8% alginate solution using a vibrating nozzle and 0.15M calcium chloride crosslinking bath. Diameter of the spherical capsules was 410 ± 87 &mgr;m. In vitro release rate measured over 168 hours varied with cell types and ranged from 2–17 pg/(milligram of capsules·24 h) or 2-17 ng/(106 cells·24 h). None of the formulations exhibited a large initial bolus release. Even when serum-supplemented medium was not replenished, cell viabilities remained over 55% after 1 week for all cell types. Microencapsulated genetically modified cells were capable of a constitutive synthesis and delivery of biologically significant quantity of TGF-β1 for at least 168 hours and thus are of potential utility for artificial cartilage and other orthopedic tissue engineering applications.

Of sodium, symptomatology and syllogism

Adequacy of peritoneal dialysis is dependent upon optimal solute and water transfer from the capillaries to peritoneal dialysate within the peritoneal cavity. Mass transfer is governed by the permeability of the capillary wall, the peritoneal interstitium and the mesothelial layer. Long-term exposure of these tissues to the processes and complications of CAPD may have an adverse effect on mass transfer, deleteriously affecting CAPD efficacy.

Membrane technology applied to donor plasmapheresis

Symptomatic intratreatment tolerance of patients to hemofiltration as found to be quantitatively superior to their tolerance to equivalent dialysis in both acute and chronic treatment series at matche

An Experimental Model for the Ultrafiltration of Sodium Ion from Blood or Plasma

Abstract Membrane technology is being increasingly applied to the collection of plasma by plasmapheresis, a procedure in which plasma is separated from whole blood, and the cellular components reinfused to the donor. Although still somewhat controversial, there is a general understanding of the physics and fluid mechanics involved in the transport phenomena associated with the microporous filtration of whole blood. The filtration process is governed by concentration polarization, with the red blood cell being the polarizing species. Shear-enhanced cellular diffusion has been proposed to explain how such a large cell can depolarize to allow the observed separation rates. The filtration rate per unit area is proportional to the first power of the shear rate and therefore, can remain approximately constant if the shear rate is increased to accommodate a decrease in surface area. Three automated membrane-based plasmapheresis systems are currently in use, primarily at fixed-site locations. They all collect 500-600 cc of plasma within 30-50 min. Two use hollow fiber membrane filter modules, while the third uses a rotating cylinder which relies on Couette rather than Poiseuille flow to generate the required shear rates at the membrane surface. Two portable systems have been developed; one centrifuge-based system requires house current, the other membrane system uses gravity, augmented by a battery power source. Both of the latter systems, due to their size and low weight are well suited for use in an environment where the equipment is moved on a frequent basis.

Oral administration of biochemically active microcapsules to treat uremia: new insights into an old approach

The ultrafiltration of sodium ion, Na+, was studied in model aqueous quaternary solutions containing 7-14% albumin as a membrane-impermeable polyelectrolyte, 140 mEq/l NaCl as a membrane-pe