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.
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.
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
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.
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.