Abstract: FR-PO283

A Mathematical Model of Parathyroid Gland Biology in Uremic Patients

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23

Authors

  • Schappacher-Tilp, Gudrun, University of Graz, Graz, Austria
  • Preciado, Priscila, Renal Research Institute, New York, New York, United States
  • Maheshwari, Vaibhav, Renal Research Insitute, New York, New York, United States
  • Cherif, Alhaji, Renal Research Institute, New York, New York, United States
  • Fuertinger, Doris H., Renal Research Institute, New York, New York, United States
  • Thijssen, Stephan, Renal Research Institute, New York, New York, United States
  • Bushinsky, David A., University of Rochester Medical Center, Rochester, New York, United States
  • Kotanko, Peter, Renal Research Institute, New York, New York, United States
Background

Chronic kidney disease-mineral bone disorder (CKD-MBD) affects the vast majority of CKD patients. A hallmark of CKD-MBD is an altered parathyroid gland biology with increased parathyroid hormone (PTH) secretion, reduced expression of calcium-sensing receptor (CaSR), and cell hyperplasia and hypertrophy. The aim of this study was to develop a mathematical model of the parathyroid gland enabling long-term simulations of parathyroid gland function in hemodialysis (HD) patients.

Methods

The mathematical model employs two PTH-producing cell populations, namely active secretory and quiescent cells that can proliferate or undergo apoptosis. PTH secretion can be modulated both on a cellular level and by increasing the number of secretory cells. The first mechanism involves the release of stored PTH, the decrease of intracellular degradation as well as increased biosynthesis. The second mechanism involves shorter secretory quiescence time as well as hyperplasia. All mechanisms are associated with different time constants implemented by positive or negative feedback loops on the CaSR and vitamin D receptor.

Results

We can successfully predict complex acute responses to changes in plasma calcium concentrations like different PTH values for the same serum calcium concentration during induction of and recovery from hypocalcemia. Moreover, we can predict a steady rising PTH release in hemodialysis patients due to high phosphate and low calcitriol levels. Long-term simulations allow the prediction of the effects of hyperplasia on PTH levels.

Conclusion

The in silico model of the parathyroid gland can be used to analyze pathophysiological alterations of the parathyroid gland in HD patients. It provides a useful tool to analyze long-term effects of dosing regimens of standard drugs like calcimimetics and vitamin D analogues on the parathyroid gland.