A Quantitative Systems Pharmacology Kidney Model of Diabetes Associated Renal Hyperfiltration and the Effects of SGLT Inhibitors.

ABSTRACT: The early stage of diabetes mellitus is characterized by increased glomerular filtration rate (GFR), known as hyperfiltration, which is believed to be one of the main causes leading to renal injury in diabetes. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to be able to reverse hyperfiltration in some patients. We developed a mechanistic computational model of the kidney that explains the interplay of hyperglycemia and hyperfiltration and integrates the pharmacokinetics/pharmacodynamics (PK/PD) of the SGLT2i dapagliflozin. Based on simulation results, we propose kidney growth as the necessary process for hyperfiltration progression. Further, the model indicates that renal SGLT1i could significantly improve hyperfiltration when added to SGTL2i. Integrated into a physiol

SUBMITTER: Balazki P 

PROVIDER: S-EPMC6310870 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature