Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schappacher-Tilp, G.
Mathematical models of mineral and bone metabolism in patients with end stage renal disease treated with hemodialysis
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2021. pp. 181
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Petek Erwin
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- Abstract:
- Chronic kidney disease - bone mineral disorder (CKD-MBD) is a complex disorder affecting the vast majority of chronic kidney disease patients. A hallmark of CKD-MBD is altered parathyroid gland biology resulting in secondary hyperparathyroidism, renal osteodystrophy, and vascular calcification. CKD-MBD evolves due to an imbalance in the highly complex and multi-dimensional regulatory system ensuring calcium and phosphate homeostasis. This regulatory system involves many ions and hormones and their actions on the kidney, bone, intestine, and parathyroid gland. Due to the disorder's complexity, mathematical models help gain new insight into the disorders' development. Moreover, they could prove useful in finding the optimal strategy regarding the combination of standard treatments such as calcimimetics, even under the aspect of genetic variances of the calcium-sensing receptor (CaSR), calcitriol therapy, or lifestyle changes including phosphate diet or the administration of phosphate binders. The aim of this thesis was to translate critical physiological properties of the primary regulators of calcium and phosphate homeostasis into mathematical models and integrate these models into a comprehensive model of calcium and phosphate homeostasis. The main focus lies on patients suffering from end-stage renal disease. We test the integrated model against various clinical manifestations during acute and chronic disturbances of homeostasis. For example, the model can explain hypocalcemia as a response to phosphate infusion or hypophosphatemia and hypercalcemia in primary hyperparathyroidism patients. In patients with chronic kidney disease (CKD) and hemodialysis (HD) patients, the model predicts secondary hyperparathyroidism and high bone turnover and bone loss. The divergence between model predictions and clinical observations regarding cinacalcet treatment suggests the existent of a point of no return regarding calcium-phosphate precipitation resulting in vascular calcification. All models and their parameters are physiologically meaningful such that adaptations of the models to different conditions are straightforward. Such adaptations would be mutations of the calcium-sensing receptor or changes such as low or high phosphate diet.