Phosphate kinetic modelling in chronichaemodialysis therapy: PhD thesis

Publikation: Bog/antologi/rapport/kliniske retningslinjerBogForskningpeer review

Abstract

Hyperphosphataemia is one of the most common and challenging conditions in haemodialysis (HD) patients, affecting between ~50% and 80% of the patient population. The condition is accompanied by severe complications and premature death. Main interventions in the management of hyperphosphataemia include dietary phosphate restrictions, phosphate-binding agents and dialysis removal. However, the high prevalence of hyperphosphataemia indicates that these approaches are deficient. Current practise is challenged in various ways, for example by the risk of protein malnutrition following dietary restrictions, an insufficient effect of the phosphatebinding agents and ineffective dialytic removal of phosphate due to, for instance, lack of individualised dialysis prescriptions. Physiological modelling in the form of phosphate kinetic modelling may further our understanding of phosphate kinetics in HD patients. Furthermore, it can help quantify dialytic phosphate removal and has the potential to help individualise current or new treatment regimens and generate new inputs to the teaching part - overall with a view to improving hyperphosphataemia management. This PhD study evaluates current phosphate kinetic modelling approaches in chronic HD therapy and presents new perspectives. The aim is to improve our insight into intra- and post-dialytic phosphate kinetics and to provide novel modelling tools that can aid current practice in hyperphosphataemia management, including perhaps in the handling of dialysis prescribing. The thesis consists of four studies. The first study is a model study presenting the development and evaluation of a new phosphate kinetic model on average plasma phosphate samples. The model includes a predictive model of intra-dialytic (four- and eight-hour) and post-dialytic (two-hour) values of plasma phosphate in HD therapy. Distribution volume assessment was part of the modelling process. The second study is a systematic review of phosphate kinetic models in HD therapy. The review provides insight into and in-depth comparison of existing models. The review is followed by another model study. Hence, the third study includes modifications and validation of the most promising model variation of the first study, a threecompartment model. The study aims at individualising the model and validating the model on individual patient data with a view to assessing the precision and the temporal robustness of the model predictions. Furthermore, adjustments are made to make the model more consistent with physiological expectations. The fourth and final study is an addition to the model presented in the third study. The focus of this study is to evaluate and validate the addition of an assumed intra-dialytic coagulation component to the model by adding a linear clearance reduction (/h) to the transport component of phosphate between dialysate and plasma. The results of the thesis indicate that the modelling approaches (Study I, III and IV) seem promising in simulating phosphate kinetics in individual chronic HD patients; especially intra-dialytic phosphate kinetics. The temporal robustness of the model predictions is also cautiously concluded on the basis of Study III. Furthermore, the VI idea of adding a coagulation component to the model to simulate intra-dialytic coagulation could provide a promising input to current phosphate kinetic modelling, for instance as a potentially useful tool for detection of clotting problems. Thus, the perspectives and ideas emanating from this PhD study may inform existing knowledge and contribute to devising clinically useful solutions. However, even though promising, the model with and without the coagulation component need further validation, especially with a focus on post-dialytic kinetics. In this regard, it would be highly relevant to test the model on a larger sample and it could be relevant to consider implementing (and validating) other model components that might influence the intraand post-dialytic plasma phosphate concentration.
OriginalsprogEngelsk
ForlagAalborg Universitetsforlag
Antal sider77
ISBN (Elektronisk)978-87-7210-245-0
StatusUdgivet - 2020

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